Zhao G

References (45)

Title : Colocalization of Increased Midbrain Signals in Neuroinflammation and Tau PET Imaging Suggests the Diagnosis of Progressive Supranuclear Palsy - Lu_2024_Clin.Nucl.Med__
Author(s) : Lu J , Ge J , Yu H , Zhao G , Chen X
Ref : Clin Nucl Med , : , 2024
Abstract : Clinical overlap with multiple other neurological diseases makes the diagnosis of autoimmune encephalitis challenging; consequently, a broad range of neurological diseases are misdiagnosed as autoimmune encephalitis. A 58-year-old man presented with abnormal behavior, irritability for 3 years, oculomotor disturbance, unsteady walking, and dysphagia and was suspected as having anti-dipeptidyl-peptidase-like protein 6 (DPPX) encephalitis as the anti-DPPX antibody was positive in the serum. However, the therapeutic effect of immunotherapy was unsatisfactory. Subsequently, colocalization of increased midbrain signals was observed in neuroinflammation PET using [ 18 F]DPA-714 and in tau PET using [ 18 F]florzolotau, suggesting the diagnosis of progressive supranuclear palsy.
ESTHER : Lu_2024_Clin.Nucl.Med__
PubMedSearch : Lu_2024_Clin.Nucl.Med__
PubMedID: 38271226
Gene_locus related to this paper: human-DPP6

Title : DAGLbeta is the principal synthesizing enzyme of 2-AG and promotes aggressive intrahepatic cholangiocarcinoma via AP-1\/DAGLbeta\/miR4516 feedforward circuitry - Ma_2023_Am.J.Physiol.Gastrointest.Liver.Physiol__
Author(s) : Ma M , Zeng G , Tan B , Zhao G , Su Q , Zhang W , Song Y , Liang J , Xu B , Wang Z , Chen J , Hou M , Yang C , Yun J , Huang Y , Lin Y , Chen D , Han Y , DeMorrow S , Liang L , Lai J , Huang L
Ref : American Journal of Physiology Gastrointest Liver Physiol , : , 2023
Abstract : The endocannabinoid system (ECS) is dysregulated in various liver diseases. Previously we had shown that the major endocannabinoid 2-arachidonoyl glycerol (2-AG) promoted tumorigenesis of intrahepatic cholangiocarcinoma (ICC). However, biosynthesis regulation and clinical significance of 2-AG remain elusive. In present study we quantified 2-AG by gas chromatography/mass spectrometry (GC/MS) and showed that 2-AG was enriched in ICC patients' samples as well as in thioacetamide-induced orthotopic rat ICC model. Moreover, we found that diacylglycerol lipase beta (DAGLbeta) was the principal synthesizing enzyme of 2-AG which significantly upregulated in ICC. DAGLbeta promoted tumorigenesis and metastasis of ICC in vitro and in vivo, and positively correlated with clinical stage and poor survival in ICC patients. Functional studies showed that AP-1 (heterodimers of c-Jun and FRA1) directly binded to the promoter and regulated transcription of DAGLbeta, which can be enhanced by lipopolysaccharide (LPS). miR-4516 was identified as the tumor-suppressing miRNA of ICC which can be significantly suppressed by LPS, 2-AG or ectopic DAGLbeta overexpression. FRA1 and STAT3 were targets of miR-4516 and overexpression of miRNA-4516 significantly suppressed expression of FRA1, SATA3 and DAGLbeta. Expression of miRNA-4516 was negatively correlated with FRA1, SATA3 and DAGLbeta in ICC patients' samples. Our findings identify DAGLbeta as the principal synthesizing enzyme of 2-AG in ICC. DAGLbeta promotes oncogenesis and metastasis of ICC and is transcriptionally regulated by a novel AP-1/DAGLbeta/miR4516 feedforward circuitry.
ESTHER : Ma_2023_Am.J.Physiol.Gastrointest.Liver.Physiol__
PubMedSearch : Ma_2023_Am.J.Physiol.Gastrointest.Liver.Physiol__
PubMedID: 37366545
Gene_locus related to this paper: human-DAGLB

Title : The N-terminal hydrophobicity modulates a distal structural domain conformation of zearalenone lacton hydrolase and its application in protein engineering - Wang_2023_Enzyme.Microb.Technol_165_110195
Author(s) : Wang H , Lu Z , Lin X , Wang M , Jiang T , Zhao G , La X , Xv J , Jiang S , Zhang G
Ref : Enzyme Microb Technol , 165 :110195 , 2023
Abstract : Zearalenone (ZEN) is one of the most common mycotoxins in maize, wheat, barley, sorghum, rye and other grains. ZEN contamination in feed is an international health issue due to its estrogenicity by competitively binding to estrogen receptors. Enzymatic detoxification of ZEN is superior to physical and chemical methods in terms of safety, environmental impact and preserving nutritional value and palatability, but is hampered by both the currently limited repertoire of detoxifying enzymes and the lack of knowledge about their structure-function relationships. In this study, a ZEN lacton hydrolase candidate (ZHD11C) was identified from thermo-tolerant Fonsecaea multimorphosa CBS 102226, and characterized to be more thermostable than these reported homologues. An intriguing feature of ZHD11C is that the N-terminal hydrophobicity affects its thermal stability and causes conformational change of a domain far from the N-terminal. This finding was successfully applied to enhance the thermostability of the most active ZEN lacton hydrolase ZHD518 through rationally tailoring its N-terminal hydrophobicity. Our results not only provide more insights into the structure-function relationships of ZEN lacton hydrolases, but generate better candidate for bio-decontamination of zearalenone in feed industries.
ESTHER : Wang_2023_Enzyme.Microb.Technol_165_110195
PubMedSearch : Wang_2023_Enzyme.Microb.Technol_165_110195
PubMedID: 36764030

Title : In vitro absorption and lipid-lowering activity of baicalin esters synthesized by whole-cell catalyzed esterification - Zhang_2022_Bioorg.Chem_120_105628
Author(s) : Zhang M , Xin X , Zhao G , Zou Y , Li XF
Ref : Bioorg Chem , 120 :105628 , 2022
Abstract : Baicalin, a phenolic glycoside with good lipid-lowering activity, has poor intestinal absorption due to low lipophilicity. In this study, six ester derivatives of baicalin, named BECn (n = 2, 3, 4, 6, 8, and 10) based on their fatty chain lengths, were synthesized by whole-cell catalyzed esterification to improve lipophilicity, and the intestinal absorption and lipid-lowering activity of the synthesized esters were investigated using cell models in vitro. BEC2, BEC3, and BEC4 exhibited higher P(app) values than baicalin in Caco-2 cell monolayers. The lipid-lowering activity of the three esters was stronger than baicalin in the cell models of hepatic steatosis, adipocytes and foam macrophages, and was attributed to their higher intracellular accumulation and stronger direct activation of the carnitine palmitoyltransferase 1A. Moreover, these esters were easily hydrolyzed by carboxylesterase and were unstable at pH 7.4, which significantly weakened their absorption and lipid-lowering activity. This study laid the foundation for industrial production and practical application of BAI esters.
ESTHER : Zhang_2022_Bioorg.Chem_120_105628
PubMedSearch : Zhang_2022_Bioorg.Chem_120_105628
PubMedID: 35066316

Title : Employing Engineered Enolase Promoter for Efficient Expression of Thermomyces lanuginosus Lipase in Yarrowia lipolytica via a Self-Excisable Vector - Jiao_2022_Int.J.Mol.Sci_24_
Author(s) : Jiao L , Li W , Li Y , Zhou Q , Zhu M , Zhao G , Zhang H , Yan Y
Ref : Int J Mol Sci , 24 : , 2022
Abstract : Yarrowia lipolytica is progressively being employed as a workhouse for recombinant protein expression. Here, we expanded the molecular toolbox by engineering the enolase promoter (pENO) and developed a new self-excisable vector, and based on this, a combined strategy was employed to enhance the expression of Thermomyces lanuginosus lipase (TLL) in Y. lipolytica. The strength of 11 truncated enolase promoters of different length was first identified using eGFP as a reporter. Seven of the truncated promoters were selected to examine their ability for driving TLL expression. Then, a series of enolase promoters with higher activities were developed by upstream fusing of different copies of UAS1B, and the recombinant strain Po1f/hp16e(100)-tll harboring the optimal promoter hp16e(100) obtained a TLL activity of 447 U/mL. Additionally, a new self-excisable vector was developed based on a Cre/loxP recombination system, which achieved efficient markerless integration in Y. lipolytica. Subsequently, strains harboring one to four copies of the tll gene were constructed using this tool, with the three-copy strain Po1f/3tll showing the highest activity of 579 U/mL. The activity of Po1f/3tll was then increased to 720 U/mL by optimizing the shaking flask fermentation parameters. Moreover, the folding-related proteins Hac1, Pdi, and Kar2 were employed to further enhance TLL expression, and the TLL activity of the optimal recombinant strain Po1f/3tll-hac1-pdi-kar2 reached 1197 U/mL. By using this combined strategy, TLL activity was enhanced by approximately 39.9-fold compared to the initial strain. Thus, the new vector and the combined strategy could be a useful tool to engineer Y. lipolytica for high-level expression of heterologous protein.
ESTHER : Jiao_2022_Int.J.Mol.Sci_24_
PubMedSearch : Jiao_2022_Int.J.Mol.Sci_24_
PubMedID: 36614159

Title : Acetylcholinesterase inhibition with Pyridostigmine attenuates hypertension and neuroinflammation in the paraventricular nucleus in rat model for Preeclampsia - Issotina_2021_Int.Immunopharmacol__108365
Author(s) : Issotina Zibrila A , Li Y , Wang Z , Zhao G , Liu H , Leng J , Ahasan Ali M , Ampofo Osei J , Kang YM , Liu J
Ref : Int Immunopharmacol , :108365 , 2021
Abstract : Preeclampsia (PE) is characterized by hypertension, autonomic imbalance and inflammation. The subfornical organ (SFO) reportedly relays peripheral inflammatory mediator's signals to the paraventricular nucleus (PVN), a brain autonomic center shown to mediate hypertension in hypertensive rat but not yet in PE rat models. Additionally, we previously showed that Pyridostigmine (PYR), an acetylcholinesterase inhibitor, attenuated placental inflammation and hypertension in PE models. In this study, we investigated the effect of PYR on the activities of these brain regions in PE model. PYR (20 mg/kg/day) was administered to reduced uterine perfusion pressure (RUPP) Sprague-Dawley rat from gestational day (GD) 14 to GD19. On GD19, the mean arterial pressure (MAP) was recorded and samples were collected for analysis. RUPP rats exhibited increased MAP (P = 0.0025), elevated circulating tumor necrosis factor-alpha (TNF-alpha, P = 0.0075), reduced baroreflex sensitivity (BRS), increased neuroinflammatory markers including TNF-alpha, interleukin-1beta (IL-1beta), microglial activation (P = 0.0039), oxidative stress and neuronal excitation within the PVN and the SFO. Changes in MAP, in molecular and cellular expression induced by RUPP intervention were improved by PYR. The ability of PYR to attenuate TNF-alpha mediated central effect was evaluated in TNF-alpha-infused pregnant rats. TNF-alpha infusion-promoted neuroinflammation in the PVN and SFO in dams was abolished by PYR. Collectively, our data suggest that PYR improves PE-like symptoms in rat by dampening placental ischemia and TNF-alpha-promoted inflammation and pro-hypertensive activity in the PVN. This broadens the therapeutical potential of PYR in PE.
ESTHER : Issotina_2021_Int.Immunopharmacol__108365
PubMedSearch : Issotina_2021_Int.Immunopharmacol__108365
PubMedID: 34815190

Title : Efficient Enzymatic Synthesis of Lipophilic Phenolic Glycoside Azelaic Acid Esters and Their Depigmenting Activity - Xu_2021_J.Agric.Food.Chem_69_13102
Author(s) : Xu H , Li X , Xin X , Mo L , Zou Y , Zhao G
Ref : Journal of Agricultural and Food Chemistry , 69 :13102 , 2021
Abstract : In this paper, an enzymatic route for synthesizing phenolic glycoside azelaic acid esters was successfully set up via lipase-catalyzed esterification and transesterification. Among the lipases tested, Candida antarctica lipase B (Novozyme 435) showed the highest activity in catalyzing esterification and Thermomyces lanuginosus (Lipozyme TLIM) gave the highest substrate conversion in catalyzing transesterification for the synthesis of ester. The addition of 4A molecular sieves into the reaction system is found to be an effective method for in situ absorption of the byproduct water and methanol, with which the substrate conversions of the enzymatic esterification and transesterification were 98.7 and 95.1%, respectively. Also, the main product ratios in transesterification were above 99.0% with lipozyme TLIM as a catalyst because the hydrolysis reaction was hindered. The results of the physical and biological properties indicate that all esters had higher Clog p values than their parent compounds. Also, the esters showed higher intracellular tyrosinase inhibitory and depigmentating activities than phenolic glycosides, azelaic acid (AA), and their physical mixtures due to their higher membrane penetration and tyrosinase inhibitory effects. In particular, piceid 6''-O-azelaic acid ester (PIA) showed the strongest inhibitory effect against melanin production. Its inhibitory rate was 77.4% at a concentration of 0.25 mM, about 4.2 times higher than that of arbutin (18.5%).
ESTHER : Xu_2021_J.Agric.Food.Chem_69_13102
PubMedSearch : Xu_2021_J.Agric.Food.Chem_69_13102
PubMedID: 34705451

Title : Detection of organophosphorus pesticides by nanogold\/mercaptomethamidophos multi-residue electrochemical biosensor - Zhao_2021_Food.Chem_354_129511
Author(s) : Zhao G , Zhou B , Wang X , Shen J , Zhao B
Ref : Food Chem , 354 :129511 , 2021
Abstract : Based on the successful synthesis of mercaptomethamidophos as a substrate, a novel nanogold/mercaptomethamidophos multi-residue electrochemical biosensor was designed and fabricated by combining nanoscale effect, strong Au-S bonds as well as interaction between acetylcholinesterase (AChE) and mercaptomethamidophos, which can simultaneously detect 11 kinds of organophosphorus pesticides (OPPs) and total amount of OPPs using indirect competitive method. Electrochemical behavior of the modified electrode was characterized by differential pulse voltammetry (DPV) and electrochemical impedance spectroscopy (EIS). The AChE concentration and incubation time were optimized at 37.4 degreesC to achieve the best detection effect. This biosensor exhibits excellent electrochemical properties with a wider linear range of 0.1 ~ 1500 ng.mL(-1), lower detection limit of 0.019 ~ 0.077 ng.mL(-1), better stability and repeatability, which realizes the rapid detection of total amount of OPPs, and can simultaneously detect a large class of OPPs rather than one kind of OPP. Two OPPs (trichlorfon, dichlorvos) were detected in actual samples of apple and cabbage and achieved satisfactory test results.
ESTHER : Zhao_2021_Food.Chem_354_129511
PubMedSearch : Zhao_2021_Food.Chem_354_129511
PubMedID: 33735695

Title : Structure-Guided Rational Design of a Mono- and Diacylglycerol Lipase from Aspergillus oryzae: A Single Residue Mutant Increases the Hydrolysis Ability - Lan_2021_J.Agric.Food.Chem_69_5344
Author(s) : Lan D , Zhao G , Holzmann N , Yuan S , Wang J , Wang Y
Ref : Journal of Agricultural and Food Chemistry , 69 :5344 , 2021
Abstract : Engineering of enzymes on the basis of protein structures are rational and efficient approaches to acquire biocatalysts of desired performances. In this study, we focused on a special mono- and diacylglycerol lipase (MDGL) isolated from the lipolytic enzyme-enriched fungus Aspergillus oryzae and discovered improved variants based on its crystal structure. We first solved the crystal structure of Aspergillus oryzae lipase (AOL) at 1.7 A resolution. Structure analysis and sequence alignment of AOL and other MDGLs revealed that the residue V269 is of vital importance for catalysis. Replacement of the V269 in AOL with the corresponding residues in other MDGLs has led to noticeable changes in hydrolysis without sacrificing the thermostability and substrate specificity. Among the investigated variants, V269D exhibited about a six-fold higher hydrolysis activity compared to the wild type. Molecular dynamics simulations and protein-ligand interaction frequency analyses revealed that the Asp substitution enhanced the substrate affinity of AOL. Our work sheds light on understanding the catalytic process of AOL and helps tailoring MDGLs with desired catalytic performance to fulfill the demand for biotechnological applications.
ESTHER : Lan_2021_J.Agric.Food.Chem_69_5344
PubMedSearch : Lan_2021_J.Agric.Food.Chem_69_5344
PubMedID: 33929832
Gene_locus related to this paper: aspor-MDLB

Title : Ratiometric two-photon fluorescent probe for in situ imaging of carboxylesterase (CE)-mediated mitochondrial acidification during medication - Jiang_2019_Chem.Commun.(Camb)_55_11358
Author(s) : Jiang A , Chen G , Xu J , Liu Y , Zhao G , Liu Z , Chen T , Li Y , James TD
Ref : Chem Commun (Camb) , 55 :11358 , 2019
Abstract : We report on a dual ratiometric two-photon fluorescent probe for in situ sensing of mitochondrial CE activity and pH. Using the probe it is possible to visualize the CE-mediated acidification of hepatoma cells and hepatic tissues during medication with antipyretic anti-inflammatory drugs.
ESTHER : Jiang_2019_Chem.Commun.(Camb)_55_11358
PubMedSearch : Jiang_2019_Chem.Commun.(Camb)_55_11358
PubMedID: 31482158

Title : Complement Receptor C5aR1 Inhibition Reduces Pyroptosis in hDPP4-Transgenic Mice Infected with MERS-CoV - Jiang_2019_Viruses_11_
Author(s) : Jiang Y , Li J , Teng Y , Sun H , Tian G , He L , Li P , Chen Y , Guo Y , Zhao G , Zhou Y , Sun S
Ref : Viruses , 11 : , 2019
Abstract : Middle East respiratory syndrome coronavirus (MERS-CoV) is a highly pathogenic virus with a crude mortality rate of ~35%. Previously, we established a human DPP4 transgenic (hDPP4-Tg) mouse model in which we studied complement overactivation-induced immunopathogenesis. Here, to better understand the pathogenesis of MERS-CoV, we studied the role of pyroptosis in THP-1 cells and hDPP4 Tg mice with MERS-CoV infection. We found that MERS-CoV infection induced pyroptosis and over-activation of complement in human macrophages. The hDPP4-Tg mice infected with MERS-CoV overexpressed caspase-1 in the spleen and showed high IL-1beta levels in serum, suggesting that pyroptosis occurred after infection. However, when the C5a-C5aR1 axis was blocked by an anti-C5aR1 antibody (Ab), expression of caspase-1 and IL-1beta fell. These data indicate that MERS-CoV infection induces overactivation of complement, which may contribute to pyroptosis and inflammation. Pyroptosis and inflammation were suppressed by inhibiting C5aR1. These results will further our understanding of the pathogenesis of MERS-CoV infection.
ESTHER : Jiang_2019_Viruses_11_
PubMedSearch : Jiang_2019_Viruses_11_
PubMedID: 30634407

Title : Enhancing the atypical esterase promiscuity of the gamma-lactamase Sspg from Sulfolobus solfataricus by substrate screening - Wang_2019_Appl.Microbiol.Biotechnol_103_4077
Author(s) : Wang J , Zhao H , Zhao G , Chen D , Tao Y , Wu S
Ref : Applied Microbiology & Biotechnology , 103 :4077 , 2019
Abstract : Promiscuous enzymes can be modified by protein engineering, which enables the catalysis of non-native substrates. gamma-lactamase Sspg from Sulfolobus solfataricus is an enzyme with high activity, high stability, and pronounced tolerance of high concentrations of the gamma-lactam substrate. These characteristics suggest Sspg as a robust enzymatic catalyst for the preparation of optically pure gamma-lactam. This study investigated the modification of this enzyme to expand its application toward resolving chiral esters. gamma-Lactamase-esterase conversion was performed by employing a three-step method: initial sequence alignment, followed by substrate screening, and protein engineering based on the obtained substrate-enzyme docking results. This process of fine-tuning of chemical groups on substrates has been termed "substrate screening." Steric hindrance and chemical reactivity of the substrate are major concerns during this step, since both are determining factors for the enzyme-substrate interaction. By employing this three-step method, gamma-lactamase Sspg was successfully converted into an esterase with high enantioselectivity towards phenylglycidate substrates (E value > 300). However, since both wild-type Sspg and Sspg mutants did not hydrolyze para-nitrophenyl substrates (pNPs), this esterase activity was termed "atypical esterase activity." The gamma-lactamase activity and stability of the Sspg mutants were not severely compromised. The proposed method can be applied to find novel multi-functional enzyme catalysts within existing enzyme pools.
ESTHER : Wang_2019_Appl.Microbiol.Biotechnol_103_4077
PubMedSearch : Wang_2019_Appl.Microbiol.Biotechnol_103_4077
PubMedID: 30955078

Title : Diagnostic value of complete blood count in paraquat and organophosphorus poisoning patients - Tang_2018_Toxicol.Ind.Health__748233718770896
Author(s) : Tang Y , Hu L , Hong G , Zhong D , Song J , Zhao G , Lu Z
Ref : Toxicol Ind Health , :748233718770896 , 2018
Abstract : Complete blood count (CBC) is one of the most extensively used tests in clinical practice. In order to determine the diagnostic value of the CBC in paraquat (PQ) and organophosphorus (OPPs) poisoning, the CBC indices of PQ- and OPPs-poisoned patients were investigated in this study. A total of 96 PQ poisoning patients, 90 OPPs poisoning patients, and 188 healthy subjects were included in this study. The PQ- and OPPs-poisoned patients were divided into different groups according to their clinical symptoms. All CBC indices were analyzed by Fisher discriminant, partial least-squares discriminant analysis (PLS-DA), variance analysis, and receiver operating characteristic (ROC). The discriminant results showed that 87.7% of original grouped cases correctly classified between PQ-poisoned patients, OPPs-poisoned patients, and healthy subjects. The PLS-DA results showed that the important variable order was different in PQ- and OPPs-poisoned patients. Both white blood cell (WBC) and neutrophil (NE) counts were the most important indexes in PQ- and OPPs-poisoned patients. In OPPs poisoning patients, WBC and NE showed statistical differences between the severe poisoning group and the moderate poisoning group. Their areas under the ROC curve (AUC) were 0.673 (WBC) and 0.669 (NE), which were higher than cholinesterase (CHE; AUC 0.326). In conclusion, the CBC indices had a diagnostic value in PQ and OPPs poisoning; WBC and NE were the first responses and had clinical significance in PQ and OPPs poisoning; moreover, they are better than CHE in diagnosing OPPs poisoning.
ESTHER : Tang_2018_Toxicol.Ind.Health__748233718770896
PubMedSearch : Tang_2018_Toxicol.Ind.Health__748233718770896
PubMedID: 29669481

Title : Blockade of the C5a-C5aR axis alleviates lung damage in hDPP4-transgenic mice infected with MERS-CoV - Jiang_2018_Emerg.Microbes.Infect_7_77
Author(s) : Jiang Y , Zhao G , Song N , Li P , Chen Y , Guo Y , Li J , Du L , Jiang S , Guo R , Sun S , Zhou Y
Ref : Emerg Microbes Infect , 7 :77 , 2018
Abstract : The pathogenesis of highly pathogenic Middle East respiratory syndrome coronavirus (MERS-CoV) remains poorly understood. In a previous study, we established an hDPP4-transgenic (hDPP4-Tg) mouse model in which MERS-CoV infection causes severe acute respiratory failure and high mortality accompanied by an elevated secretion of cytokines and chemokines. Since excessive complement activation is an important factor that contributes to acute lung injury after viral infection, in this study, we investigated the role of complement in MERS-CoV-induced lung damage. Our study showed that complement was excessively activated in MERS-CoV-infected hDPP4-Tg mice through observations of increased concentrations of the C5a and C5b-9 complement activation products in sera and lung tissues, respectively. Interestingly, blocking C5a production by targeting its receptor, C5aR, alleviated lung and spleen tissue damage and reduced inflammatory responses. More importantly, anti-C5aR antibody treatment led to decreased viral replication in lung tissues. Furthermore, compared with the sham treatment control, apoptosis of splenic cells was less pronounced in the splenic white pulp of treated mice, and greater number of proliferating splenic cells, particularly in the red pulp, was observed. These data indicate that (1) dysregulated host immune responses contribute to the severe outcome of MERS; (2) excessive complement activation, triggered by MERS-CoV infection, promote such dysregulation; and (3) blockade of the C5a-C5aR axis lead to the decreased tissue damage induced by MERS-CoV infection, as manifested by reduced apoptosis and T cell regeneration in the spleen. Therefore, the results of this study suggest a new strategy for clinical intervention and adjunctive treatment in MERS-CoV cases.
ESTHER : Jiang_2018_Emerg.Microbes.Infect_7_77
PubMedSearch : Jiang_2018_Emerg.Microbes.Infect_7_77
PubMedID: 29691378

Title : The Aegilops tauschii genome reveals multiple impacts of transposons - Zhao_2017_Nat.Plants_3_946
Author(s) : Zhao G , Zou C , Li K , Wang K , Li T , Gao L , Zhang X , Wang H , Yang Z , Liu X , Jiang W , Mao L , Kong X , Jiao Y , Jia J
Ref : Nat Plants , 3 :946 , 2017
Abstract : Wheat is an important global crop with an extremely large and complex genome that contains more transposable elements (TEs) than any other known crop species. Here, we generated a chromosome-scale, high-quality reference genome of Aegilops tauschii, the donor of the wheat D genome, in which 92.5% sequences have been anchored to chromosomes. Using this assembly, we accurately characterized genic loci, gene expression, pseudogenes, methylation, recombination ratios, microRNAs and especially TEs on chromosomes. In addition to the discovery of a wave of very recent gene duplications, we detected that TEs occurred in about half of the genes, and found that such genes are expressed at lower levels than those without TEs, presumably because of their elevated methylation levels. We mapped all wheat molecular markers and constructed a high-resolution integrated genetic map corresponding to genome sequences, thereby placing previously detected agronomically important genes/quantitative trait loci (QTLs) on the Ae. tauschii genome for the first time.
ESTHER : Zhao_2017_Nat.Plants_3_946
PubMedSearch : Zhao_2017_Nat.Plants_3_946
PubMedID: 29158546
Gene_locus related to this paper: horvv-m0utz9 , wheat-a0a3b6c2m6 , wheat-a0a3b5zwb6 , wheat-a0a3b6bzs8 , wheat-a0a1d5zte7 , wheat-a0a1d5uwn5

Title : Recombinant Receptor-Binding Domains of Multiple Middle East Respiratory Syndrome Coronaviruses (MERS-CoVs) Induce Cross-Neutralizing Antibodies against Divergent Human and Camel MERS-CoVs and Antibody Escape Mutants - Tai_2017_J.Virol_91_
Author(s) : Tai W , Wang Y , Fett CA , Zhao G , Li F , Perlman S , Jiang S , Zhou Y , Du L
Ref : J Virol , 91 : , 2017
Abstract : Middle East respiratory syndrome coronavirus (MERS-CoV) binds to cellular receptor dipeptidyl peptidase 4 (DPP4) via the spike (S) protein receptor-binding domain (RBD). The RBD contains critical neutralizing epitopes and serves as an important vaccine target. Since RBD mutations occur in different MERS-CoV isolates and antibody escape mutants, cross-neutralization of divergent MERS-CoV strains by RBD-induced antibodies remains unknown. Here, we constructed four recombinant RBD (rRBD) proteins with single or multiple mutations detected in representative human MERS-CoV strains from the 2012, 2013, 2014, and 2015 outbreaks, respectively, and one rRBD protein with multiple changes derived from camel MERS-CoV strains. Like the RBD of prototype EMC2012 (EMC-RBD), all five RBDs maintained good antigenicity and functionality, the ability to bind RBD-specific neutralizing monoclonal antibodies (MAbs) and the DPP4 receptor, and high immunogenicity, able to elicit S-specific antibodies. They induced potent neutralizing antibodies cross-neutralizing 17 MERS pseudoviruses expressing S proteins of representative human and camel MERS-CoV strains identified during the 2012-2015 outbreaks, 5 MAb escape MERS-CoV mutants, and 2 live human MERS-CoV strains. We then constructed two RBDs mutated in multiple key residues in the receptor-binding motif (RBM) of RBD and demonstrated their strong cross-reactivity with anti-EMC-RBD antibodies. These RBD mutants with diminished DPP4 binding also led to virus attenuation, suggesting that immunoevasion after RBD immunization is accompanied by loss of viral fitness. Therefore, this study demonstrates that MERS-CoV RBD is an important vaccine target able to induce highly potent and broad-spectrum neutralizing antibodies against infection by divergent circulating human and camel MERS-CoV strains. IMPORTANCE: MERS-CoV was first identified in June 2012 and has since spread in humans and camels. Mutations in its spike (S) protein receptor-binding domain (RBD), a key vaccine target, have been identified, raising concerns over the efficacy of RBD-based MERS vaccines against circulating human and camel MERS-CoV strains. Here, we constructed five vaccine candidates, designated 2012-RBD, 2013-RBD, 2014-RBD, 2015-RBD, and Camel-RBD, containing single or multiple mutations in the RBD of representative human and camel MERS-CoV strains during the 2012-2015 outbreaks. These RBD-based vaccine candidates maintained good functionality, antigenicity, and immunogenicity, and they induced strong cross-neutralizing antibodies against infection by divergent pseudotyped and live MERS-CoV strains, as well as antibody escape MERS-CoV mutants. This study provides impetus for further development of a safe, highly effective, and broad-spectrum RBD-based subunit vaccine to prevent MERS-CoV infection.
ESTHER : Tai_2017_J.Virol_91_
PubMedSearch : Tai_2017_J.Virol_91_
PubMedID: 27795425

Title : Human intestinal tract serves as an alternative infection route for Middle East respiratory syndrome coronavirus - Zhou_2017_Sci.Adv_3_eaao4966
Author(s) : Zhou J , Li C , Zhao G , Chu H , Wang D , Yan HH , Poon VK , Wen L , Wong BH , Zhao X , Chiu MC , Yang D , Wang Y , Au-Yeung RKH , Chan IH , Sun S , Chan JF , To KK , Memish ZA , Corman VM , Drosten C , Hung IF , Zhou Y , Leung SY , Yuen KY
Ref : Sci Adv , 3 :eaao4966 , 2017
Abstract : Middle East respiratory syndrome coronavirus (MERS-CoV) has caused human respiratory infections with a high case fatality rate since 2012. However, the mode of virus transmission is not well understood. The findings of epidemiological and virological studies prompted us to hypothesize that the human gastrointestinal tract could serve as an alternative route to acquire MERS-CoV infection. We demonstrated that human primary intestinal epithelial cells, small intestine explants, and intestinal organoids were highly susceptible to MERS-CoV and can sustain robust viral replication. We also identified the evidence of enteric MERS-CoV infection in the stool specimen of a clinical patient. MERS-CoV was considerably resistant to fed-state gastrointestinal fluids but less tolerant to highly acidic fasted-state gastric fluid. In polarized Caco-2 cells cultured in Transwell inserts, apical MERS-CoV inoculation was more effective in establishing infection than basolateral inoculation. Notably, direct intragastric inoculation of MERS-CoV caused a lethal infection in human DPP4 transgenic mice. Histological examination revealed MERS-CoV enteric infection in all inoculated mice, as shown by the presence of virus-positive cells, progressive inflammation, and epithelial degeneration in small intestines, which were exaggerated in the mice pretreated with the proton pump inhibitor pantoprazole. With the progression of the enteric infection, inflammation, virus-positive cells, and live viruses emerged in the lung tissues, indicating the development of sequential respiratory infection. Taken together, these data suggest that the human intestinal tract may serve as an alternative infection route for MERS-CoV.
ESTHER : Zhou_2017_Sci.Adv_3_eaao4966
PubMedSearch : Zhou_2017_Sci.Adv_3_eaao4966
PubMedID: 29152574

Title : A recombinant receptor-binding domain of MERS-CoV in trimeric form protects human dipeptidyl peptidase 4 (hDPP4) transgenic mice from MERS-CoV infection - Tai_2016_Virology_499_375
Author(s) : Tai W , Zhao G , Sun S , Guo Y , Wang Y , Tao X , Tseng CK , Li F , Jiang S , Du L , Zhou Y
Ref : Virology , 499 :375 , 2016
Abstract : Middle East respiratory syndrome (MERS) coronavirus (MERS-CoV) was first identified in 2012, and it continues to threaten human health worldwide. No MERS vaccines are licensed for human use, reinforcing the urgency to develop safe and efficacious vaccines to prevent MERS. MERS-CoV spike protein forms a trimer, and its receptor-binding domain (RBD) serves as a vaccine target. Nevertheless, the protective efficacy of RBD in its native trimeric form has never been evaluated. In this study, a trimeric protein, RBD-Fd, was generated by fusing RBD with foldon trimerization motif. It bound strongly to the receptor of MERS-CoV, dipeptidyl peptidase 4 (DPP4), and elicited robust RBD-specific neutralizing antibodies in mice, maintaining long-term neutralizing activity against MERS-CoV infection. RBD-Fd potently protected hDPP4 transgenic mice from lethal MERS-CoV challenge. These results suggest that MERS-CoV RBD in its trimeric form maintains native conformation and induces protective neutralizing antibodies, making it a candidate for further therapeutic development.
ESTHER : Tai_2016_Virology_499_375
PubMedSearch : Tai_2016_Virology_499_375
PubMedID: 27750111

Title : Pioglitazone reduces lipid droplets in cholesterolosis of the gallbladder by increasing ABCA1 and NCEH1 expression - Wang_2015_Mol.Cell.Biochem_399_7
Author(s) : Wang JM , Wang D , Tan YY , Zhao G , Ji ZL
Ref : Molecular & Cellular Biochemistry , 399 :7 , 2015
Abstract : As a cholesterol-induced metabolic disease, cholesterolosis of the gallbladder is often resected clinically, which could lead to many complications. The histopathology of cholesterolosis is due to excessive lipid droplet accumulation in epithelial and subcutaneous tissues. The main components of lipid droplets are cholesterol esters (CEs). Removal of CEs from gallbladder epithelial cells (GBECs) is very important for maintaining intracellular cholesterol homeostasis and for treating cholesterol-related diseases. In this study, pioglitazone was used to reduce intracellular CEs. To further elucidate the mechanism, cholesterolosis GBECs were treated with pioglitazone, 22-(R)-hydroxycholesterol (a liver X receptor alpha (LXRalpha) agonist), or peroxisome proliferator-activated receptor gamma (PPARgamma) siRNA. Western blotting for PPARgamma, LXRalpha, ATP-binding cassette transporter A1 (ABCA1), and neutral cholesteryl ester hydrolase 1 (NCEH1) was performed. At length, cholesterol efflux to apoA-I was measured, and oil red O staining was used to visualize lipid droplet variations in cells. In conclusion, we observed that pioglitazone increased ABCA1 expression in an LXR-dependent manner and NCEH1 expression in an LXRalpha-independent manner, which mobilized CE hydrolysis and cholesterol efflux to reduce lipid droplet content in cholesterolosis GBECs. Our data provide a plausible alternative to human gallbladder cholesterolosis.
ESTHER : Wang_2015_Mol.Cell.Biochem_399_7
PubMedSearch : Wang_2015_Mol.Cell.Biochem_399_7
PubMedID: 25280398

Title : [Effect of PON1 overexpression on mouse diaphragmatic muscle cells injury caused by acute dichlorvos poisoning] - Wu_2015_Zhonghua.Yi.Xue.Za.Zhi_95_2955
Author(s) : Wu B , Wang F , Zhou J , Hou Y , Hong G , Zhao G , Ge Y , Liu Y , Qiu Q , Lu Z
Ref : Zhonghua Yi Xue Za Zhi , 95 :2955 , 2015
Abstract : OBJECTIVE: To investigate the effect of paraoxonase1 (PON1) overexpression on mouse diaphragmatic muscle cells injury caused by acute dichlorvos poisoning.
METHODS: Mouse diaphragmatic muscle cells were cultured routinely and infected with overexpression lentivirus. Cells were divided into normal control group, DDVP group, LV-GFP + DDVP group, LV-PON1 + DDVP group. Cell viability was determined by CCK-8 assay. Flow cytometry was used to detect cell apoptosis. The mRNA and protein expression of PON1 and Nrf2 in mouse diaphragmatic muscle cells was measured by RT-PCR and Western blot. Enzyme-linked immunosorbent assay was used to determine levels of acetyl cholinesterase (AchE), heme oxygenase 1 (HO-1) and quinone oxidoreductase-1 (NQO-1) in mouse diaphragmatic muscle cells. The activity of superoxide dismutase (SOD) and catalase (CAT) as well as malondialdehyde (MDA) content in cells was measured by chemical colorimetry.
RESULTS: After induced by 0, 80, 160, 320, 640 micromol/L DDVP for 24 hours, the viability of mouse diaphragmatic muscle cells was (100 +/- 3.82)%, (82.13 +/- 2.60)%, (53.57 +/- 5.05)%, (30.77 +/- 3.30)%, (14.20 +/- 2.19)% respectively, changing in a concentration-dependent manner (P < 0.05). After induced by 160 micromol/L DDVP for 0, 6, 12, 24 hours, the viability of mouse diaphragmatic muscle cells was (100.17 +/- 2.74)%, (76.13 +/- 6.01)%, (66.53 +/- 3.55)%, (53.57 +/- 5.05)%, changing in a time-dependent manner (P < 0.05). The PON1 protein level in LV-PON1 group was higher than that of blank control group (0.370 +/- 0.015 vs 0.232 +/- 0.004, 0.197 +/- 0.015 vs 0.037 +/- 0.003, P < 0.05). The cell viability of LV-PON1 group is higher than that of DDVP group at different time point after induction of DDVP (P < 0.05). After induced by DDVP for 24 hours, the cell apoptosis rate and MDA content in LV-PON1 group were lower than those of DDVP group (P < 0.05). While levels of AchE, PON1 and Nrf2 protein expression, SOD and CAT, HO-1 and NQO-1 were higher than those of DDVP group (P < 0.05).
CONCLUSIONS: The overexpression of PON1 could effectively alleviate AchE inhibition by DDVP and induce Nrf2 expression to exert antioxidant effect, thus protected the mouse diaphragmatic muscle cells.
ESTHER : Wu_2015_Zhonghua.Yi.Xue.Za.Zhi_95_2955
PubMedSearch : Wu_2015_Zhonghua.Yi.Xue.Za.Zhi_95_2955
PubMedID: 26814074

Title : Multi-Organ Damage in Human Dipeptidyl Peptidase 4 Transgenic Mice Infected with Middle East Respiratory Syndrome-Coronavirus - Zhao_2015_PLoS.One_10_e0145561
Author(s) : Zhao G , Jiang Y , Qiu H , Gao T , Zeng Y , Guo Y , Yu H , Li J , Kou Z , Du L , Tan W , Jiang S , Sun S , Zhou Y
Ref : PLoS ONE , 10 :e0145561 , 2015
Abstract : The Middle East Respiratory Syndrome Coronavirus (MERS-CoV) causes severe acute respiratory failure and considerable extrapumonary organ dysfuction with substantial high mortality. For the limited number of autopsy reports, small animal models are urgently needed to study the mechanisms of MERS-CoV infection and pathogenesis of the disease and to evaluate the efficacy of therapeutics against MERS-CoV infection. In this study, we developed a transgenic mouse model globally expressing codon-optimized human dipeptidyl peptidase 4 (hDPP4), the receptor for MERS-CoV. After intranasal inoculation with MERS-CoV, the mice rapidly developed severe pneumonia and multi-organ damage, with viral replication being detected in the lungs on day 5 and in the lungs, kidneys and brains on day 9 post-infection. In addition, the mice exhibited systemic inflammation with mild to severe pneumonia accompanied by the injury of liver, kidney and spleen with neutrophil and macrophage infiltration. Importantly, the mice exhibited symptoms of paralysis with high viral burden and viral positive neurons on day 9. Taken together, this study characterizes the tropism of MERS-CoV upon infection. Importantly, this hDPP4-expressing transgenic mouse model will be applicable for studying the pathogenesis of MERS-CoV infection and investigating the efficacy of vaccines and antiviral agents designed to combat MERS-CoV infection.
ESTHER : Zhao_2015_PLoS.One_10_e0145561
PubMedSearch : Zhao_2015_PLoS.One_10_e0145561
PubMedID: 26701103

Title : DL0410 can reverse cognitive impairment, synaptic loss and reduce plaque load in APP\/PS1 transgenic mice - Yang_2015_Pharmacol.Biochem.Behav_139_15
Author(s) : Yang RY , Zhao G , Wang DM , Pang XC , Wang SB , Fang JS , Li C , Liu AL , Wu S , Du GH
Ref : Pharmacol Biochem Behav , 139 :15 , 2015
Abstract : Cholinesterase inhibitors are first-line therapy for Alzheimer's disease (AD). DL0410 is an AChE/BuChE dual inhibitor with a novel new structural scaffold. It has been demonstrated that DL0410 could improve memory deficits in both Abeta1-42-induced and scopolamine-induced amnesia in mice. In the present study, the therapeutic effect of DL0410 and its action mechanism were investigated in APP/PS1 transgenic mice. Six-month old APP/PS1 transgenic mice were orally administered with DL0410 (3, 10, 30mg/kg/day). After 60days, several behavioural tests, including the Morris water maze and step-down tests, were used to investigate the effects of DL0410 on mice behaviours. All the behavioural experimental results showed that DL0410 significantly ameliorated memory deficits. Meanwhile, DL0410 attenuated neural cell damage and reduced senile plaques significantly in the hippocampus of APP/PS1 transgenic mice. In addition, DL0410 significantly decreased Abeta plaques, while increasing the number of synapses and the thickness of PSD in the hippocampus. We also found DL0410 decreased the expression of APP, NMDAR1B and the phosphorylation level of NMDAR2B, and increased the phosphorylation level of CAMKII and the expression of PSD-95. In this study, the results of behavioural tests demonstrated for the first time that DL0410 could improve learning and memory dysfunction in APP/PS1 transgenic mice. The mechanism of its beneficial effects might be related to cholinesterase inhibition, Abeta plaques inhibition, improvement of synapse loss by regulating of expression of proteins related to synapses. As a result, DL0410 could be considered as a candidate drug for the therapy of AD.
ESTHER : Yang_2015_Pharmacol.Biochem.Behav_139_15
PubMedSearch : Yang_2015_Pharmacol.Biochem.Behav_139_15
PubMedID: 26476132

Title : Pseudomonas aeruginosa homoserine lactone triggers apoptosis and Bak\/Bax-independent release of mitochondrial cytochrome C in fibroblasts - Schwarzer_2014_Cell.Microbiol_16_1094
Author(s) : Schwarzer C , Fu Z , Shuai S , Babbar S , Zhao G , Li C , Machen TE
Ref : Cell Microbiol , 16 :1094 , 2014
Abstract : Pseudomonas aeruginosa use N-(3-oxododecanoyl)-homoserine lactone (C12) as a quorum-sensing molecule to regulate gene expression in the bacteria. It is expected that in patients with chronic infections with P. aeruginosa, especially as biofilms, local [C12] will be high and, since C12 is lipid soluble, diffuse from the airways into the epithelium and underlying fibroblasts, capillary endothelia and white blood cells. Previous work showed that C12 has multiple effects in human host cells, including activation of apoptosis. The present work tested the involvement of Bak and Bax in C12-triggered apoptosis in mouse embryo fibroblasts (MEF) by comparing MEF isolated from embryos of wild-type (WT) and Bax(-/-) /Bak(-/-) (DKO) mice. In WT MEF C12 rapidly triggered (minutes to 2 h): activation of caspases 3/7 and 8, depolarization of mitochondrial membrane potential (Deltapsimito ), release of cytochrome C from mitochondria into the cytosol, blebbing of plasma membranes, shrinkage/condensation of cells and nuclei and, subsequently, cell killing. A DKO MEF line that was relatively unaffected by the Bak/Bax-dependent proapoptotic stimulants staurosporine and etoposide responded to C12 similarly to WT MEF: activation of caspase 3/7, depolarization of Deltapsimito and release of cytochrome C and cell death. Re-expression of Bax or Bak in DKO MEF did not alter the WT-like responses to C12 in DKO MEF. These data showed that C12 triggers novel, rapid proapoptotic Bak/Bax-independent responses that include events commonly associated with activation of both the intrinsic pathway (depolarization of Deltapsimito and release of cytochrome C from mitochondria into the cytosol) and the extrinsic pathway (activation of caspase 8). Unlike the proapoptotic agonists staurosporine and etoposide that release cytochrome C from mitochondria, C12's effects do not require participation of either Bak or Bax.
ESTHER : Schwarzer_2014_Cell.Microbiol_16_1094
PubMedSearch : Schwarzer_2014_Cell.Microbiol_16_1094
PubMedID: 24438098

Title : Substituted piperidinyl glycinyl 2-cyano-4,5-methano pyrrolidines as potent and stable dipeptidyl peptidase IV inhibitors - Zhao_2013_Bioorg.Med.Chem.Lett_23_1622
Author(s) : Zhao G , Kwon C , Wang A , Robertson JG , Marcinkeviciene J , Parker RA , Kirby MS , Hamann LG
Ref : Bioorganic & Medicinal Chemistry Lett , 23 :1622 , 2013
Abstract : Synthesis and structure-activity relationship of a series of substituted piperidinyl glycine 2-cyano-4,5-methano pyrroline DPP-IV inhibitors are described. Improvement of the inhibitory activity and chemical stability of this series of compounds was respectively achieved by the introduction of bulky groups at the 4-position and 1-position of the piperidinyl glycine, leading to a series of potent and stable DPP-IV inhibitors.
ESTHER : Zhao_2013_Bioorg.Med.Chem.Lett_23_1622
PubMedSearch : Zhao_2013_Bioorg.Med.Chem.Lett_23_1622
PubMedID: 23416006

Title : The genome of the hydatid tapeworm Echinococcus granulosus - Zheng_2013_Nat.Genet_45_1168
Author(s) : Zheng H , Zhang W , Zhang L , Zhang Z , Li J , Lu G , Zhu Y , Wang Y , Huang Y , Liu J , Kang H , Chen J , Wang L , Chen A , Yu S , Gao Z , Jin L , Gu W , Wang Z , Zhao L , Shi B , Wen H , Lin R , Jones MK , Brejova B , Vinar T , Zhao G , McManus DP , Chen Z , Zhou Y , Wang S
Ref : Nat Genet , 45 :1168 , 2013
Abstract : Cystic echinococcosis (hydatid disease), caused by the tapeworm E. granulosus, is responsible for considerable human morbidity and mortality. This cosmopolitan disease is difficult to diagnose, treat and control. We present a draft genomic sequence for the worm comprising 151.6 Mb encoding 11,325 genes. Comparisons with the genome sequences from other taxa show that E. granulosus has acquired a spectrum of genes, including the EgAgB family, whose products are secreted by the parasite to interact and redirect host immune responses. We also find that genes in bile salt pathways may control the bidirectional development of E. granulosus, and sequence differences in the calcium channel subunit EgCavbeta1 may be associated with praziquantel sensitivity. Our study offers insights into host interaction, nutrient acquisition, strobilization, reproduction, immune evasion and maturation in the parasite and provides a platform to facilitate the development of new, effective treatments and interventions for echinococcosis control.
ESTHER : Zheng_2013_Nat.Genet_45_1168
PubMedSearch : Zheng_2013_Nat.Genet_45_1168
PubMedID: 24013640
Gene_locus related to this paper: echgr-k4epc5 , echmu-u6hbw4 , echgr-w6ugl0 , echgr-w6u7y4 , echgr-w6vaq5 , echgr-a0a068wxj3 , echgr-a0a068wgw1 , echgr-a0a068wl60

Title : Identification of a receptor-binding domain in the S protein of the novel human coronavirus Middle East respiratory syndrome coronavirus as an essential target for vaccine development - Du_2013_J.Virol_87_9939
Author(s) : Du L , Zhao G , Kou Z , Ma C , Sun S , Poon VK , Lu L , Wang L , Debnath AK , Zheng BJ , Zhou Y , Jiang S
Ref : J Virol , 87 :9939 , 2013
Abstract : A novel human Middle East respiratory syndrome coronavirus (MERS-CoV) caused outbreaks of severe acute respiratory syndrome (SARS)-like illness with a high mortality rate, raising concerns of its pandemic potential. Dipeptidyl peptidase-4 (DPP4) was recently identified as its receptor. Here we showed that residues 377 to 662 in the S protein of MERS-CoV specifically bound to DPP4-expressing cells and soluble DPP4 protein and induced significant neutralizing antibody responses, suggesting that this region contains the receptor-binding domain (RBD), which has a potential to be developed as a MERS-CoV vaccine.
ESTHER : Du_2013_J.Virol_87_9939
PubMedSearch : Du_2013_J.Virol_87_9939
PubMedID: 23824801

Title : ContigScape: a Cytoscape plugin facilitating microbial genome gap closing - Tang_2013_BMC.Genomics_14_289
Author(s) : Tang B , Wang Q , Yang M , Xie F , Zhu Y , Zhuo Y , Wang S , Gao H , Ding X , Zhang L , Zhao G , Zheng H
Ref : BMC Genomics , 14 :289 , 2013
Abstract : BACKGROUND: With the emergence of next-generation sequencing, the availability of prokaryotic genome sequences is expanding rapidly. A total of 5,276 genomes have been released since 2008, yet only 1,692 genomes were complete. The final phase of microbial genome sequencing, particularly gap closing, is frequently the rate-limiting step either because of complex genomic structures that cause sequence bias even with high genomic coverage, or the presence of repeat sequences that may cause gaps in assembly.
RESULTS: We have developed a Cytoscape plugin to facilitate gap closing for high-throughput sequencing data from microbial genomes. This plugin is capable of interactively displaying the relationships among genomic contigs derived from various sequencing formats. The sequence contigs of plasmids and special repeats (IS elements, ribosomal RNAs, terminal repeats, etc.) can be displayed as well.
CONCLUSIONS: Displaying relationships between contigs using graphs in Cytoscape rather than tables provides a more straightforward visual representation. This will facilitate a faster and more precise determination of the linkages among contigs and greatly improve the efficiency of gap closing.
ESTHER : Tang_2013_BMC.Genomics_14_289
PubMedSearch : Tang_2013_BMC.Genomics_14_289
PubMedID: 23627759
Gene_locus related to this paper: myctu-cut3 , myctu-cutas1 , myctu-cutas2 , myctu-Rv0160c , myctu-Rv1069c , myctu-RV1215C , myctu-Rv2045c , myctu-RV3452 , myctu-Rv3802c , amyor-r4tdn6 , amyor-r4sys4 , amyor-r4svp2 , amyor-r4t193 , amyor-r4t8c7 , amyor-r4t8w6 , amyor-r4t1x8 , amyor-r4stv4 , amyor-r4t7z6 , 9pseu-r4sx12

Title : A truncated receptor-binding domain of MERS-CoV spike protein potently inhibits MERS-CoV infection and induces strong neutralizing antibody responses: implication for developing therapeutics and vaccines - Du_2013_PLoS.One_8_e81587
Author(s) : Du L , Kou Z , Ma C , Tao X , Wang L , Zhao G , Chen Y , Yu F , Tseng CT , Zhou Y , Jiang S
Ref : PLoS ONE , 8 :e81587 , 2013
Abstract : An emerging respiratory infectious disease with high mortality, Middle East respiratory syndrome (MERS), is caused by a novel coronavirus (MERS-CoV). It was first reported in 2012 in Saudi Arabia and has now spread to eight countries. Development of effective therapeutics and vaccines is crucial to save lives and halt the spread of MERS-CoV. Here, we show that a recombinant protein containing a 212-amino acid fragment (residues 377-588) in the truncated receptor-binding domain (RBD: residues 367-606) of MERS-CoV spike (S) protein fused with human IgG Fc fragment (S377-588-Fc) is highly expressed in the culture supernatant of transfected 293T cells. The purified S377-588-Fc protein efficiently binds to dipeptidyl peptidase 4 (DPP4), the receptor of MERS-CoV, and potently inhibited MERS-CoV infection, suggesting its potential to be further developed as a therapeutic modality for treating MERS-CoV infection and saving the patients' lives. The recombinant S377-588-Fc is able to induce in the vaccinated mice strong MERS-CoV S-specific antibodies, which blocks the binding of RBD to DPP4 receptor and effectively neutralizes MERS-CoV infection. These findings indicate that this truncated RBD protein shows promise for further development as an effective and safe vaccine for the prevention of MERS-CoV infection.
ESTHER : Du_2013_PLoS.One_8_e81587
PubMedSearch : Du_2013_PLoS.One_8_e81587
PubMedID: 24324708

Title : Draft genome sequence of Aspergillus oryzae strain 3.042 - Zhao_2012_Eukaryot.Cell_11_1178
Author(s) : Zhao G , Yao Y , Qi W , Wang C , Hou L , Zeng B , Cao X
Ref : Eukaryot Cell , 11 :1178 , 2012
Abstract : Aspergillus oryzae is the most important fungus for the traditional fermentation in China and is particularly important in soy sauce fermentation. We report the 36,547,279-bp draft genome sequence of A. oryzae 3.042 and compared it to the published genome sequence of A. oryzae RIB40.
ESTHER : Zhao_2012_Eukaryot.Cell_11_1178
PubMedSearch : Zhao_2012_Eukaryot.Cell_11_1178
PubMedID: 22933657
Gene_locus related to this paper: aspor-q2uj83

Title : Complete sequencing and pan-genomic analysis of Lactobacillus delbrueckii subsp. bulgaricus reveal its genetic basis for industrial yogurt production - Hao_2011_PLoS.One_6_e15964
Author(s) : Hao P , Zheng H , Yu Y , Ding G , Gu W , Chen S , Yu Z , Ren S , Oda M , Konno T , Wang S , Li X , Ji ZS , Zhao G
Ref : PLoS ONE , 6 :e15964 , 2011
Abstract : Lactobacillus delbrueckii subsp. bulgaricus (Lb. bulgaricus) is an important species of Lactic Acid Bacteria (LAB) used for cheese and yogurt fermentation. The genome of Lb. bulgaricus 2038, an industrial strain mainly used for yogurt production, was completely sequenced and compared against the other two ATCC collection strains of the same subspecies. Specific physiological properties of strain 2038, such as lysine biosynthesis, formate production, aspartate-related carbon-skeleton intermediate metabolism, unique EPS synthesis and efficient DNA restriction/modification systems, are all different from those of the collection strains that might benefit the industrial production of yogurt. Other common features shared by Lb. bulgaricus strains, such as efficient protocooperation with Streptococcus thermophilus and lactate production as well as well-equipped stress tolerance mechanisms may account for it being selected originally for yogurt fermentation industry. Multiple lines of evidence suggested that Lb. bulgaricus 2038 was genetically closer to the common ancestor of the subspecies than the other two sequenced collection strains, probably due to a strict industrial maintenance process for strain 2038 that might have halted its genome decay and sustained a gene network suitable for large scale yogurt production.
ESTHER : Hao_2011_PLoS.One_6_e15964
PubMedSearch : Hao_2011_PLoS.One_6_e15964
PubMedID: 21264216
Gene_locus related to this paper: lacda-q1g8l1 , lacdl-pip

Title : Draft genome sequence of the marine bacterium Streptomyces griseoaurantiacus M045, which produces novel manumycin-type antibiotics with a pABA core component - Li_2011_J.Bacteriol_193_3417
Author(s) : Li F , Jiang P , Zheng H , Wang S , Zhao G , Qin S , Liu Z
Ref : Journal of Bacteriology , 193 :3417 , 2011
Abstract : Streptomyces griseoaurantiacus M045, isolated from marine sediment, produces manumycin and chinikomycin antibiotics. Here we present a high-quality draft genome sequence of S. griseoaurantiacus M045, the first marine Streptomyces species to be sequenced and annotated. The genome encodes several gene clusters for biosynthesis of secondary metabolites and has provided insight into genomic islands linking secondary metabolism to functional adaptation in marine S. griseoaurantiacus M045.
ESTHER : Li_2011_J.Bacteriol_193_3417
PubMedSearch : Li_2011_J.Bacteriol_193_3417
PubMedID: 21551298
Gene_locus related to this paper: 9acto-f3ngb7 , 9acto-f3nim7 , 9acto-f3ntg3 , 9acto-f3nmw3 , 9actn-f3nh76 , 9actn-f3nh94

Title : Comparative genomic and transcriptomic analysis revealed genetic characteristics related to solvent formation and xylose utilization in Clostridium acetobutylicum EA 2018 - Hu_2011_BMC.Genomics_12_93
Author(s) : Hu S , Zheng H , Gu Y , Zhao J , Zhang W , Yang Y , Wang S , Zhao G , Yang S , Jiang W
Ref : BMC Genomics , 12 :93 , 2011
Abstract : BACKGROUND: Clostridium acetobutylicum, a gram-positive and spore-forming anaerobe, is a major strain for the fermentative production of acetone, butanol and ethanol. But a previously isolated hyper-butanol producing strain C. acetobutylicum EA 2018 does not produce spores and has greater capability of solvent production, especially for butanol, than the type strain C. acetobutylicum ATCC 824.
RESULTS: Complete genome of C. acetobutylicum EA 2018 was sequenced using Roche 454 pyrosequencing. Genomic comparison with ATCC 824 identified many variations which may contribute to the hyper-butanol producing characteristics in the EA 2018 strain, including a total of 46 deletion sites and 26 insertion sites. In addition, transcriptomic profiling of gene expression in EA 2018 relative to that of ATCC824 revealed expression-level changes of several key genes related to solvent formation. For example, spo0A and adhEII have higher expression level, and most of the acid formation related genes have lower expression level in EA 2018. Interestingly, the results also showed that the variation in CEA_G2622 (CAC2613 in ATCC 824), a putative transcriptional regulator involved in xylose utilization, might accelerate utilization of substrate xylose.
CONCLUSIONS: Comparative analysis of C. acetobutylicum hyper-butanol producing strain EA 2018 and type strain ATCC 824 at both genomic and transcriptomic levels, for the first time, provides molecular-level understanding of non-sporulation, higher solvent production and enhanced xylose utilization in the mutant EA 2018. The information could be valuable for further genetic modification of C. acetobutylicum for more effective butanol production.
ESTHER : Hu_2011_BMC.Genomics_12_93
PubMedSearch : Hu_2011_BMC.Genomics_12_93
PubMedID: 21284892
Gene_locus related to this paper: cloab-CAC2917 , cloab-q97db4 , cloac-CAC0719 , cloac-CAC1022 , cloac-CAC1962 , cloac-CAC2246 , cloac-CAC3407 , cloac-CAP0071 , cloac-pnbae

Title : Age-related pulmonary emphysema in mice lacking alpha\/beta hydrolase domain containing 2 gene - Jin_2009_Biochem.Biophys.Res.Commun_380_419
Author(s) : Jin S , Zhao G , Li Z , Nishimoto Y , Isohama Y , Shen J , Ito T , Takeya M , Araki K , He P , Yamamura K
Ref : Biochemical & Biophysical Research Communications , 380 :419 , 2009
Abstract : The alpha/beta hydrolase family genes have been identified as down-regulated genes in human emphysematous lungs. Although proteins in the alpha/beta hydrolase family generally act as enzymes, such as lipases, the specific functions of the Abhd2 protein are unknown. To examine the role of Abhd2 in the lung, we analyzed Abhd2 deficient mice obtained by gene trap mutagenesis. Abhd2 was expressed in the alveolar type II cells. Abhd2 deficiency resulted in a decreased level of phosphatidylcholine in the bronchoalveolar lavage. These mice developed spontaneous gradual progression of emphysema, due to increased macrophage infiltration, increased inflammatory cytokines, a protease/anti-protease imbalance and enhanced apoptosis. This phenotype is more akin to the pace of emphysema that develops in humans. Our findings suggest that derangement in alveolar phospholipid metabolism can induce emphysema, and that Abhd2 plays a critical role in maintaining lung structural integrity.
ESTHER : Jin_2009_Biochem.Biophys.Res.Commun_380_419
PubMedSearch : Jin_2009_Biochem.Biophys.Res.Commun_380_419
PubMedID: 19250629
Gene_locus related to this paper: human-ABHD2 , mouse-ABHD2

Title : Genome sequence of the versatile fish pathogen Edwardsiella tarda provides insights into its adaptation to broad host ranges and intracellular niches - Wang_2009_PLoS.One_4_e7646
Author(s) : Wang Q , Yang M , Xiao J , Wu H , Wang X , Lv Y , Xu L , Zheng H , Wang S , Zhao G , Liu Q , Zhang Y
Ref : PLoS ONE , 4 :e7646 , 2009
Abstract : BACKGROUND: Edwardsiella tarda is the etiologic agent of edwardsiellosis, a devastating fish disease prevailing in worldwide aquaculture industries. Here we describe the complete genome of E. tarda, EIB202, a highly virulent and multi-drug resistant isolate in China. METHODOLOGY/PRINCIPAL FINDINGS: E. tarda EIB202 possesses a single chromosome of 3,760,463 base pairs containing 3,486 predicted protein coding sequences, 8 ribosomal rRNA operons, and 95 tRNA genes, and a 43,703 bp conjugative plasmid harboring multi-drug resistant determinants and encoding type IV A secretion system components. We identified a full spectrum of genetic properties related to its genome plasticity such as repeated sequences, insertion sequences, phage-like proteins, integrases, recombinases and genomic islands. In addition, analysis also indicated that a substantial proportion of the E. tarda genome might be devoted to the growth and survival under diverse conditions including intracellular niches, with a large number of aerobic or anaerobic respiration-associated proteins, signal transduction proteins as well as proteins involved in various stress adaptations. A pool of genes for secretion systems, pili formation, nonfimbrial adhesions, invasions and hemagglutinins, chondroitinases, hemolysins, iron scavenging systems as well as the incomplete flagellar biogenesis might feature its surface structures and pathogenesis in a fish body. CONCLUSION/SIGNIFICANCE: Genomic analysis of the bacterium offered insights into the phylogeny, metabolism, drug-resistance, stress adaptation, and virulence characteristics of this versatile pathogen, which constitutes an important first step in understanding the pathogenesis of E. tarda to facilitate construction of a practical effective vaccine used for combating fish edwardsiellosis.
ESTHER : Wang_2009_PLoS.One_4_e7646
PubMedSearch : Wang_2009_PLoS.One_4_e7646
PubMedID: 19865481
Gene_locus related to this paper: edwte-d0zav8 , edwte-d0zg19 , edwtf-e0t1p5 , edwte-d0za01 , edwte-d0z9v1

Title : A neuroligin-4 missense mutation associated with autism impairs neuroligin-4 folding and endoplasmic reticulum export - Zhang_2009_J.Neurosci_29_10843
Author(s) : Zhang C , Milunsky JM , Newton S , Ko J , Zhao G , Maher TA , Tager-Flusberg H , Bolliger MF , Carter AS , Boucard AA , Powell CM , Sudhof TC
Ref : Journal of Neuroscience , 29 :10843 , 2009
Abstract : Neuroligins (NLs) are postsynaptic cell-adhesion molecules essential for normal synapse function. Mutations in neuroligin-4 (NL4) (gene symbol: NLGN4) have been reported in some patients with autism spectrum disorder (ASD) and other neurodevelopmental impairments. However, the low frequency of NL4 mutations and the limited information about the affected patients and the functional consequences of their mutations cast doubt on the causal role of NL4 mutations in these disorders. Here, we describe two brothers with classical ASD who carry a single amino-acid substitution in NL4 (R87W). This substitution was absent from the brothers' asymptomatic parents, suggesting that it arose in the maternal germ line. R87 is conserved in all NL isoforms, and the R87W substitution is not observed in control individuals. At the protein level, the R87W substitution impaired glycosylation processing of NL4 expressed in HEK293 and COS cells, destabilized NL4, caused NL4 retention in the endoplasmic reticulum in non-neuronal cells and neurons, and blocked NL4 transport to the cell surface. As a result, the R87W substitution inactivated the synapse-formation activity of NL4 and abolished the functional effect of NL4 on synapse strength. Viewed together, these observations suggest that a point mutation in NL4 can cause ASD by a loss-of-function mechanism.
ESTHER : Zhang_2009_J.Neurosci_29_10843
PubMedSearch : Zhang_2009_J.Neurosci_29_10843
PubMedID: 19726642

Title : Encapsulated in silica: genome, proteome and physiology of the thermophilic bacterium Anoxybacillus flavithermus WK1 - Saw_2008_Genome.Biol_9_R161
Author(s) : Saw JH , Mountain BW , Feng L , Omelchenko MV , Hou S , Saito JA , Stott MB , Li D , Zhao G , Wu J , Galperin MY , Koonin EV , Makarova KS , Wolf YI , Rigden DJ , Dunfield PF , Wang L , Alam M
Ref : Genome Biol , 9 :R161 , 2008
Abstract : BACKGROUND: Gram-positive bacteria of the genus Anoxybacillus have been found in diverse thermophilic habitats, such as geothermal hot springs and manure, and in processed foods such as gelatin and milk powder. Anoxybacillus flavithermus is a facultatively anaerobic bacterium found in super-saturated silica solutions and in opaline silica sinter. The ability of A. flavithermus to grow in super-saturated silica solutions makes it an ideal subject to study the processes of sinter formation, which might be similar to the biomineralization processes that occurred at the dawn of life. RESULTS: We report here the complete genome sequence of A. flavithermus strain WK1, isolated from the waste water drain at the Wairakei geothermal power station in New Zealand. It consists of a single chromosome of 2,846,746 base pairs and is predicted to encode 2,863 proteins. In silico genome analysis identified several enzymes that could be involved in silica adaptation and biofilm formation, and their predicted functions were experimentally validated in vitro. Proteomic analysis confirmed the regulation of biofilm-related proteins and crucial enzymes for the synthesis of long-chain polyamines as constituents of silica nanospheres. CONCLUSIONS: Microbial fossils preserved in silica and silica sinters are excellent objects for studying ancient life, a new paleobiological frontier. An integrated analysis of the A. flavithermus genome and proteome provides the first glimpse of metabolic adaptation during silicification and sinter formation. Comparative genome analysis suggests an extensive gene loss in the Anoxybacillus/Geobacillus branch after its divergence from other bacilli.
ESTHER : Saw_2008_Genome.Biol_9_R161
PubMedSearch : Saw_2008_Genome.Biol_9_R161
PubMedID: 19014707
Gene_locus related to this paper: anofw-b7ghw8 , anofw-b7gk10 , anofw-b7gk45 , anofw-b7gln5 , anofw-b7glx5 , anofw-b7gm70

Title : Isolation and characterization of N98-1272 A, B and C, selective acetylcholinesterase inhibitors from metabolites of an actinomycete strain - Zheng_2007_J.Enzyme.Inhib.Med.Chem_22_43
Author(s) : Zheng ZH , Dong YS , Zhang H , Lu XH , Ren X , Zhao G , He JG , Si SY
Ref : J Enzyme Inhib Med Chem , 22 :43 , 2007
Abstract : A high throughput screening was carried out in order to search for inhibitors of acetylcholinesterase (AChE) from microorganism metabolites. An actinomycete strain was found to produce active compounds named N98-1272 A, B and C with IC50 of 15.0, 11.5, 12.5 microM, respectively. Structural studies revealed that the three compounds are identical to the known antibiotics, Manumycin C, B and A. Kinetic analyses showed that N98-1272 C (Manumycin A) acted as a reversible noncompetitive inhibitor of acetylcholinesterase, with a Ki value of 7.2 microM. The cyclohexenone epoxide part of the structure plays a crucial role in the inhibitory activity against AChE. Compared with Tacrine, N98-1272 A, B, and C exhibit much better selectivity toward AChE over BuChE.
ESTHER : Zheng_2007_J.Enzyme.Inhib.Med.Chem_22_43
PubMedSearch : Zheng_2007_J.Enzyme.Inhib.Med.Chem_22_43
PubMedID: 17373546

Title : Genome and proteome of long-chain alkane degrading Geobacillus thermodenitrificans NG80-2 isolated from a deep-subsurface oil reservoir - Feng_2007_Proc.Natl.Acad.Sci.U.S.A_104_5602
Author(s) : Feng L , Wang W , Cheng J , Ren Y , Zhao G , Gao C , Tang Y , Liu X , Han W , Peng X , Liu R , Wang L
Ref : Proc Natl Acad Sci U S A , 104 :5602 , 2007
Abstract : The complete genome sequence of Geobacillus thermodenitrificans NG80-2, a thermophilic bacillus isolated from a deep oil reservoir in Northern China, consists of a 3,550,319-bp chromosome and a 57,693-bp plasmid. The genome reveals that NG80-2 is well equipped for adaptation into a wide variety of environmental niches, including oil reservoirs, by possessing genes for utilization of a broad range of energy sources, genes encoding various transporters for efficient nutrient uptake and detoxification, and genes for a flexible respiration system including an aerobic branch comprising five terminal oxidases and an anaerobic branch comprising a complete denitrification pathway for quick response to dissolved oxygen fluctuation. The identification of a nitrous oxide reductase gene has not been previously described in Gram-positive bacteria. The proteome further reveals the presence of a long-chain alkane degradation pathway; and the function of the key enzyme in the pathway, the long-chain alkane monooxygenase LadA, is confirmed by in vivo and in vitro experiments. The thermophilic soluble monomeric LadA is an ideal candidate for treatment of environmental oil pollutions and biosynthesis of complex molecules.
ESTHER : Feng_2007_Proc.Natl.Acad.Sci.U.S.A_104_5602
PubMedSearch : Feng_2007_Proc.Natl.Acad.Sci.U.S.A_104_5602
PubMedID: 17372208
Gene_locus related to this paper: geotd-g3jwz2 , geoka-q5l1n0 , geotn-a4ijt0 , geotn-a4ilq0 , geotn-a4is13 , geotn-a4isp0 , geotn-a4isp3

Title : Potent non-nitrile dipeptidic dipeptidyl peptidase IV inhibitors - Simpkins_2007_Bioorg.Med.Chem.Lett_17_6476
Author(s) : Simpkins LM , Bolton S , Pi Z , Sutton JC , Kwon C , Zhao G , Magnin DR , Augeri DJ , Gungor T , Rotella DP , Sun Z , Liu Y , Slusarchyk WS , Marcinkeviciene J , Robertson JG , Wang A , Robl JA , Atwal KS , Zahler RL , Parker RA , Kirby MS , Hamann LG
Ref : Bioorganic & Medicinal Chemistry Lett , 17 :6476 , 2007
Abstract : The synthesis and structure-activity relationships of novel dipeptidyl peptidase IV inhibitors replacing the classical cyanopyrrolidine P1 group with other small nitrogen heterocycles are described. A unique potency enhancement was achieved with beta-branched natural and unnatural amino acids, particularly adamantylglycines, linked to a (2S,3R)-2,3-methanopyrrolidine based scaffold.
ESTHER : Simpkins_2007_Bioorg.Med.Chem.Lett_17_6476
PubMedSearch : Simpkins_2007_Bioorg.Med.Chem.Lett_17_6476
PubMedID: 17937986

Title : The DNA sequence, annotation and analysis of human chromosome 3 - Muzny_2006_Nature_440_1194
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
Ref : Nature , 440 :1194 , 2006
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.
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

Title : Diprolyl nitriles as potent dipeptidyl peptidase IV inhibitors - Zhao_2005_Bioorg.Med.Chem.Lett_15_3992
Author(s) : Zhao G , Taunk PC , Magnin DR , Simpkins LM , Robl JA , Wang A , Robertson JG , Marcinkeviciene J , Sitkoff DF , Parker RA , Kirby MS , Hamann LG
Ref : Bioorganic & Medicinal Chemistry Lett , 15 :3992 , 2005
Abstract : Dipeptidyl peptidase IV (DPP4) is a multifunctional type II transmembrane serine peptidase which regulates various physiological processes, most notably plasma glucose homeostasis by cleaving peptide hormones glucagon-like peptide-1 and glucose-dependent insulinotropic polypeptide. Inhibition of DPP4 is a potentially valuable therapy for type 2 diabetes. Synthesis and structure-activity relationships of a series of substituted diprolyl nitriles are described, leading to the identification of compound 1 with a measured DPP4 K(i) of 3.6 nM.
ESTHER : Zhao_2005_Bioorg.Med.Chem.Lett_15_3992
PubMedSearch : Zhao_2005_Bioorg.Med.Chem.Lett_15_3992
PubMedID: 16046120

Title : A single residual replacement improves the folding and stability of recombinant cassava hydroxynitrile lyase in E. coil - Yan_2003_Biotechnol.Lett_25_1041
Author(s) : Yan G , Cheng S , Zhao G , Wu S , Liu Y , Sun W
Ref : Biotechnol Lett , 25 :1041 , 2003
Abstract : Substitution of Ser113 for Gly113 in the cap domain of hydroxynitrile lyase from Manihot esculenta (MeHNL) was performed by site-directed mutagenesis to improve its self-generated folding and stability under denaturation conditions. The yield of the recombinant mutant HNL1 (mut-HNL1), which had higher specific activity than the wild type HNL0 (wt-HNL0), was increased by 2 to 3-fold. Thermostability of MeHNL was also enhanced, probably due to an increase in content of the beta-strand secondary structure according to CD analysis. Our data in this report suggest that Ser113 significantly contributes to the in vivo folding and stability of MeHNL and demonstrates an economic advantage of mut-HNL1 over the wt-HNL0.
ESTHER : Yan_2003_Biotechnol.Lett_25_1041
PubMedSearch : Yan_2003_Biotechnol.Lett_25_1041
PubMedID: 12889812
Gene_locus related to this paper: manes-hnl

Title : Genome of the bacterium Streptococcus pneumoniae strain R6 - Hoskins_2001_J.Bacteriol_183_5709
Author(s) : Hoskins J , Alborn WE, Jr. , Arnold J , Blaszczak LC , Burgett S , DeHoff BS , Estrem ST , Fritz L , Fu DJ , Fuller W , Geringer C , Gilmour R , Glass JS , Khoja H , Kraft AR , Lagace RE , LeBlanc DJ , Lee LN , Lefkowitz EJ , Lu J , Matsushima P , McAhren SM , McHenney M , McLeaster K , Mundy CW , Nicas TI , Norris FH , O'Gara M , Peery RB , Robertson GT , Rockey P , Sun PM , Winkler ME , Yang Y , Young-Bellido M , Zhao G , Zook CA , Baltz RH , Jaskunas SR , Rosteck PR, Jr. , Skatrud PL , Glass JI
Ref : Journal of Bacteriology , 183 :5709 , 2001
Abstract : Streptococcus pneumoniae is among the most significant causes of bacterial disease in humans. Here we report the 2,038,615-bp genomic sequence of the gram-positive bacterium S. pneumoniae R6. Because the R6 strain is avirulent and, more importantly, because it is readily transformed with DNA from homologous species and many heterologous species, it is the principal platform for investigation of the biology of this important pathogen. It is also used as a primary vehicle for genomics-based development of antibiotics for gram-positive bacteria. In our analysis of the genome, we identified a large number of new uncharacterized genes predicted to encode proteins that either reside on the surface of the cell or are secreted. Among those proteins there may be new targets for vaccine and antibiotic development.
ESTHER : Hoskins_2001_J.Bacteriol_183_5709
PubMedSearch : Hoskins_2001_J.Bacteriol_183_5709
PubMedID: 11544234
Gene_locus related to this paper: strp2-q04l35 , strpj-b8zns7 , strpn-AXE1 , strpn-b2dz20 , strpn-pepx , strpn-SP0614 , strpn-SP0777 , strpn-SP0902 , strpn-SP1343

Title : Biochemical Mechanisms and Diagnostic Microassays for Pyrethroid, Carbamate, and Organophosphate Insecticide Resistance\/Cross-Resistance in the Tobacco Budworm, Heliothis virescens - Zhao_1996_Pestic.Biochem.Physiol_56_183
Author(s) : Zhao G , Rose RL , Hodgson E , Roe RM
Ref : Pesticide Biochemistry and Physiology , 56 :183 , 1996
Abstract : Tobacco budworm, Heliothis virescens, larvae were collected from wild velvet leaf in Macon Ridge (LA) where insecticide resistance in cotton was previously reported. The initial resistance levels were 58.0-fold for thiodicarb and 16.0-fold for cypermethrin compared to a susceptible laboratory population. Selection of this Macon Ridge population with thiodicarb on cotton increased resistance for thiodicarb to 172.9-fold and resulted in cross-resistance for cypermethrin to 161.3-fold compared to the susceptible control. Thiodicarb-selected Macon Ridge budworms were also resistant to methyl parathion (7.6-fold), profenofos (59.9-fold), and azinphosmethyl (>38.8-fold). Cytochrome P450 metabolism ofp-nitroanisole was elevated 30.1-, 16.8-, and 18.8-fold in midgut, fat body, and carcass, respectively, of the selected Macon Ridge budworms. The P450 content was also increased. Ester hydrolysis of 1-naphthyl acetate andp-nitrophenyl acetate as well as 1-chloro-2,4-dinitrobenzene and 1,2-dichloro-4-nitrobenzene glutathioneS-transferase activity were elevated approximately 2-fold with some variability among the specific tissues examined. Piperonyl butoxide increased thiodicarb toxicity by 14.8-fold, methyl parathion by 9.3-fold, and cypermethrin by 19.4-fold.S,S,S-Tributylphosphorothioate increased thiodicarb toxicity by 14.5-fold, methyl parathion by 6.6-fold, and profenofos by 7.2-fold. These results suggests that both cytochrome P450 and esterase play an important role in tobacco budworm resistance and cross-resistance between carbamates, organophosphates, and pyrethroids. Acetylthiocholine hydrolysis was 3.4- and 3.5-fold insensitive to paraoxon and methomyl, respectively, in the thiodicarb-selected Macon Ridge strain. Microassays based onp-nitroanisole andp-nitrophenyl acetate metabolism were successfully used to diagnose resistance in field populations of the tobacco budworm in different geographical areas of the U.S.
ESTHER : Zhao_1996_Pestic.Biochem.Physiol_56_183
PubMedSearch : Zhao_1996_Pestic.Biochem.Physiol_56_183

Title : Mechanisms conferring resistance of Western flower thrips to bendiocarb - Zhao_1995_Pest.Sci_44_293
Author(s) : Zhao G , Liu W , Knowles CO
Ref : Pest Sci , 44 :293 , 1995
Abstract : Mechanisms associated with bendiocarb resistance were examined in two strains of western flower thrips, Frankliniella occidentalis (Pergande), that differed in their susceptibility to this carbamate by 13.6-fold. No appreciable differences between the two strains in [14C] bendiocarb penetration and excretion were detected; however, bendiocarb was metabolised substantially faster by the resistant KCM thrips than by the more susceptible UMC thrips. No appreciable difference between the two strains was found in the sensitivity of acetylcholinesterase activity to inhibition by bendiocarb. It was concluded that bendiocarb resistance in KCM western flower thrips was due to enhanced metabolism that probably was mainly oxidative in nature.
ESTHER : Zhao_1995_Pest.Sci_44_293
PubMedSearch : Zhao_1995_Pest.Sci_44_293