简介:G-proteincoupledreceptors(GPCRs)representoneofthemostimportantclassesofdrugtargetsforpharmaceuticalindustryandplayimportantrolesincellularsignaltransduction.PredictingthecouplingspecificityofGPCRstoG-proteinsisvitalforfurtherunderstandingthemechanismofsignaltransductionandthefunctionofthereceptorswithinacell,whichcanprovidenewcluesforpharmaceuticalresearchanddevelopment.Inthisstudy,thefeaturesofaminoacidcompositionsandphysiochemicalpropertiesofthefull-lengthGPCRsequenceshavebeenanalyzedandextracted.Basedonthesefeatures,classifiershavebeendevelopedtopredictthecouplingspecificityofGPCRstoG-proteinsusingsupportvectormachines.Thetestingresultsshowthatthismethodcouldobtainbetterpredictionaccuracy.
简介:东方田鼠(Microtusfortis)分布于我国东北、西北、华中、华南17个省区,在韩国及俄罗斯也见报道.国内对该鼠的5个亚种,即指名亚种(M.f.fortis)(西北)、东北亚种(M.f.pelliecus)、辽宁亚种(M.f.dolichocephalus)、长江亚种(M.f.calamorum)和福建亚种(M.f.fujianensis)(华南),作过一般生物学描述[1],对于东方田鼠研究得较多的是长江亚种,60年代有人对该种动物的生态学特点进行了报道,近期对洞庭湖区东方田鼠的种群动态、繁殖特性、迁移行为也有系列研究[2],特别是该种动物具有对日本血吸虫天然抗感染性,引起了学术界的广泛兴趣,本研究通过对人工繁殖的东方田鼠的细胞遗传学的观察,了解该种动物的染色体数目的范围、染色体核型以及染色体G带特征.
简介:Microarrayhasbecomeapopularbiotechnologyinbiologicalandmedicalresearch.However,systematicandstochasticvariabilitiesinmicroarraydataareexpectedandunavoidable,resultingintheproblemthattherawmeasurementshaveinherent"noise"withinmicroarrayexperiments.Currently,logarithmicratiosareusuallyanalyzedbyvariousclusteringmethodsdirectly,whichmayintroducebiasinterpretationinidentifyinggroupsofgenesorsamples.Inthispaper,astatisticalmethodbasedonmixedmodelapproacheswasproposedformicroarraydataclusteranalysis.TheunderlyingrationaleofthismethodistopartitiontheobservedtotalgeneexpressionlevelintovariousvariationscausedbydifferentfactorsusinganANOVAmodel,andtopredictthedifferentialeffectsofGV(genebyvariety)interactionusingtheadjustedunbiasedprediction(AUP)method.ThepredictedGVinteractioneffectscanthenbeusedastheinputsofclusteranalysis.Weillustratedtheapplicationofourmethodwithageneexpressiondatasetandelucidatedtheutilityofourapproachusinganexternalvalidation.
简介:Annotationsofcompletegenomesequencessubmitteddirectlyfromsequencingprojectsarediverseintermsofannotationstrategiesandupdatefrequencies.Theseinconsistenciesmakecomparativestudiesdifficult.Toallowrapiddataprepara-tionofalargenumberofcompletegenomes,automationandspeedareimpor-tantforgenomere-annotation.Hereweintroduceanopen-sourcerapidgenomere-annotationsoftwaresystem,Restauro-G,specializedforbacterialgenomes.Restauro-Gre-annotatesagenomebysimilaritysearchesutilizingtheBLAST-LikeAlignmentTool,referringtoproteindatabasessuchasUniProtKB,NCBInr,NCBICOGs,Pfam,andPSORTb.Re-annotationbyRestauro-Gachievedover98%accuracyformostbacterialchromosomesincomparisonwiththeoriginalmanuallycuratedannotationofEMBLreleases.Restauro-GwasdevelopedinthegenericbioinformaticsworkbenchG-languageGenomeAnalysisEnvironmentandisdistributedathttp://restauro-g.iab.keio.ac.jp/undertheGNUGeneralPublicLicense.
简介:heterotrimericguanine核苷酸绑定蛋白质(G蛋白质)被表明了各种各样的发信号调停在植物的小径。然而,它在发信号的phytochromeA(phyA)的角色留下逃犯。在这研究,我们发现新调停phyA的显型指明了far-red照耀(FR)preconditioned房间死亡,它仅仅在跟随暴露到白光(WL)的FR-grown幼苗的胚轴发生。房间死亡在G变异的gpa1被减轻,但是与野类型(WT)比较在G变异的agb1加重了,在调停phyA的房间死亡小径的GPA1和AGB1的对抗角色的陈述语气。进一步的调查显示nonphotoconvertibleprotochlorophyllide(Pchlide633)的导致FR的累积,在暴露上产生反应的氧种类(ROS)到WL,为前提FR的房间死亡被要求。而且,ROS主要在叶绿体被检测用荧光灯探查。有趣地,到黑暗成年的幼苗的H2O2的申请导致类似于前提FR的房间死亡的显型。这表明ROS是为房间死亡的一个批评调停人。另外,我们观察到agb1比WT幼苗对H2O2更敏感,显示G蛋白质可以也修改到ROS应力的幼苗的敏感。一起拿这些结果,我们推断G蛋白质可以涉及表明小径调整Arabidopsis胚轴的前提FR的房间死亡的phyA。在phyA位于G蛋白质的参与下面发信号的可能的机制在这研究被讨论。
简介:Thestudyofsmalldrugmoleculesinteractingwithnucleicacidsisanareaofintenseresearchthathasparticularrelevanceinourunderstandingofrelativemechanisminchemotherapeuticapplicationsandtheassociationbetweengenetics(includingsequencevariation)anddrugresponse.Inthiscontribution,wedemonstratehowthesequence-specificbindingofananticancerdrugDacarbazine(DTIC)tosinglebase(A-G)mismatchcouldbesensitivelydetectedbycombiningelectrochemicaldetectionwithbiosensingsurfacebasedongoldnanoparticles.
简介:UnderstandingthecouplingspecificitybetweenGprotein-coupledreceptors(GPCRs)andspecificclassesofGproteinsisimportantforfurtherelucidationofreceptorfunctionswithinacell.IncreasinginformationonGPCRsequencesandtheGproteinfamilywouldfacilitatepredictionofthecouplingpropertiesofGPCRs.Inthisstudy,wedescribeanovelapproachforpredictingthecouplingspecificitybetweenGPCRsandGproteins.ThismethodusesnotonlyGPCRsequencesbutalsothefunctionalknowledgegeneratedbynaturallanguagepro-cessing,andcanachieve92.2%predictionaccuracybyusingtheC4.5algorithm.Furthermore,rulesrelatedtoGPCR-Gproteincouplingaregenerated.Thecom-binationofsequenceanalysisandtextminingimprovesthepredictionaccuracyforGPCR-Gproteincouplingspecificity,andalsoprovidescluesforunderstandingGPCRsignaling.
简介:AcomputationalsystemforthepredictionandclassificationofhumanG-proteincoupledreceptors(GPCRs)hasbeendevelopedbasedonthesupportvectormachine(SVM)methodandproteinsequenceinformation.ThefeaturevectorsusedtodeveloptheSVMpredictionmodelsconsistofstatisticallysignificantfeaturesselectedfromsingleaminoacid,dipeptide,andtripeptidecompositionsofproteinsequences.Furthermore,thelengthdistributiondifferencebetweenGPCRsandnon-GPCRshasalsobeenexploitedtoimprovethepredictionperformance.ThetestingresultswithannotatedhumanproteinsequencesdemonstratethatthissystemcangetgoodperformanceforbothpredictionandclassificationofhumanGPCRs.
简介:G-proteincoupledreceptors(GPCRs)areaclassofseven-helixtransmembraneproteinsthathavebeenusedinbioinformaticsasthetargetstofacilitatedrugdiscoveryforhumandiseases.AlthoughthousandsofGPCRsequenceshavebeencollected,theligandspecificityofmanyGPCRsisstillunknownandonlyonecrystalstructureoftherhodopsin-likefamilyhasbeensolved.Therefore,identifyingGPCRtypesonlyfromsequencedatahasbecomeanimportantresearchissue.Inthisstudy,anoveltechniqueforidentifyingGPCRtypesbasedontheweightedLevenshteindistancebetweentworeceptorsequencesandthenearestneighbormethod(NNM)isintroduced,whichcandealwithreceptorsequenceswithdifferentlengthsdirectly.Inourexperimentsforclassifyingfourclasses(acetylcholine,adrenoceptor,dopamine,andserotonin)oftherhodopsin-likefamilyofGPCRs,theerrorratesfromtheleave-one-outprocedureandtheleave-half-outprocedurewere0.62%and1.24%,respectively.Theseresultsarepriortothoseofthecovariantdiscriminantalgorithm,thesupportvectormachinemethod,andtheNNMwithEuclideandistance.
简介:摘要目的:调查我院常用抗G^+致病菌的抗生素的种类效价情况,为抗G^+致病菌的合理用药提供依据。方法:从2978个样本中分离到953株G^+致病菌,用全自动微生物分析仪-VITEK32进行菌种鉴定及16种抗生素的药敏实验。结果:953株G^+致病菌经鉴定属于11大类,其中金黄色葡萄球菌、表皮葡萄球菌、溶血葡萄球菌、草绿色链球菌和肠球菌属是五类主要的G^+致病菌,依次分别占总分离量的30.3%、1713%、15.1%、9.8%和6.8%;在检测的16种抗生素对排在前五位的G.致病菌的平均效价最低的五类抗生素是:青霉素(24.22%)、红霉素(26.22%)、头孢唑林(28.06%)、与链霉素(30.52%)和庆大霉素(31.06%)。而抗口致病菌整体效果最好的是:螯合新泰林(93.72%)、万古霉素(82.62%)和四环素(78.68%)。结论:研究结果表明越来越多抗生素抗临床常见G^+致病菌的效价呈现逐年递减的趋势.
简介:Werecentlyreportedtheuseofagene-trappingapproachtoisolatecellclonesinwhichareportergenehadintegratedintogenesmodulatedbyT-cellactivation.WehavenowtestedapanelofclonesfromthatreportandidentifiedtheonethatrespondstoavarietyofG-proteincoupledreceptors(GPCR).TheβlactamasetaggedEGR-3JurkatcellwasusedtodissectspecificGPCRsignalinginvivo.ThreeGPCRswerestudied,includingthechemokinereceptorCXCR4(Gicoupled)thatwasendogenouslyexpressed,theplateletactivationfactor(PAF)receptor(Gq-coupled),andβ2adrenergicreceptor(Gs-coupled)thatwasbothstablytransfected.Agonistsforeachreceptoractivatedtranscriptionoftheβ-lactamasetaggedEGR-3gene.InductionofEGR-3throughCXCR4wasblockedbypertussistoxinandPD58059,aspecificinhibitorofMEK(MAPK/ERKkinase).NeitheroftheseinhibitorsblockedisoproterenolorPAF-mediatedactivationofEGR-3.Conversely,β2-andPAF-mediatedEGR-3activationwasblockedbythep38,specificinhibitorSB580.Inaddition,bothβ2-andPAF-mediatedEGR-3activationcouldbesynergisticallyactivatedbyCXCR4activation.ThiscombinedresultindicatesthatEGR-3canbeactivatedthroughdistinctsignaltransductionpathwaysbydifferentGPCRsandthatsignalscanbeintegratedandamplifiedtoefficientlytunethelevelofactivation.
简介:目的:探讨UCP2-866G/A和ADIPOQ+45T/G基因多态性的交互作用与2型糖尿病合并冠心病发病风险的关系。方法:随机选取2014年10月至2015年5月在佳木斯大学附属第一医院就诊的130例单纯2型糖尿病患者和128例2型糖尿病合并冠心病患者进行病例对照研究。分别采用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)方法和聚合酶链反应-高分辨率溶解曲线(PCR-HRM)方法检测UCP2-866G/A和ADIPOQ+45T/G的基因多态性,并用非条件Logistic回归分析两基因间的交互作用。结果:在两组间分别进行UCP2-866G/A和ADIPOQ+45T/G基因多态性的单独关联分析,两变异位点的基因型和等位基因的频率在两组间的分布及遗传模型关联分析均无统计学差异(P〉0.05)。两变异位点联合分析发现,UCP2-866G/A的GG、GA分别和ADIPOQ+45T/G的TG在2型糖尿病合并冠心病中存在正向交互作用(P=0.000,ORI=OR(AB)/(ORA×ORB)=30.533/(0.549×0.116)〉1;P=0.007,ORI=OR(AB)/(ORA×ORB)=13.914/(0.525×0.116)〉1。结论:该研究显示:UCP2-866G/A和ADIPOQ+45T/G单一基因的多态性与2型糖尿病合并冠心病患病风险无关,而两者之间的交互作用可能增加2型糖尿病合并冠心病的发病风险。
简介:WeliveintheAgeofExtinctions-thecallfornamingourtime"Anthropocene"isnomorethanhubrisandescapismfromthiscolossalsin.Althoughthe6thmassextinctionhaspossiblyalreadystarted(Barnoskyetal.,2011),anditmayprovethelargestsofartobeenduredbylifeonEarth,effortsareneedednottoturnthisintotheAgeofLoneliness,whenhumansmayfindthemselvesMastersoftheEarthbutalone(Wilson,2014).
简介:目的:概述国产伊曲康唑(商品名“美扶”)在国内10a的应用情况,为其在国内临床规范、合理应用提供循证学证据。方法检索复习10a来国产伊曲康唑在国内应用的各类文章。结果共计检索筛选获得48篇文献,手足体股癣10篇,共计治疗手足癣451例,总有效率为90.91℅;花斑癣6篇,共治疗340例,总有效率为92.94℅;糠秕孢子菌毛囊炎5篇,共治疗238例,单疗程单用国产伊曲康唑总有效率为71.05℅;头癣2篇,总有效率为80.00℅;甲真菌病6篇,治疗指甲甲真菌病患者2疗程法总治愈率为78.95℅(135例/171例),3疗程法治愈率为82.60℅(19例/23例),治疗趾甲真菌病患者总治愈率为79.94℅(275例/344例);生殖器念珠菌病21篇,共治疗念珠菌性外阴阴道炎2260例,总治愈率为94.32℅,有效率为97.27℅,男性念珠菌病409例,总痊愈率75.04℅;头皮脂溢性皮炎2篇,总痊愈率为81.18℅(69例/85例);小儿皮肤真菌病1篇,痊愈率68.2℅(30例/44例);真菌性眼炎1篇,56例患者全部有效。主要不良反应为胃肠道不适,其次为头晕头痛、乏力、食欲下降、可逆性肝酶升高等,总不良反应发生率为6.95℅。结论国产伊曲康唑在多种真菌病有效率高,不良反应小。