简介:Circulargenomes,beingthelargestproportionofsequencedgenomes,playanimportantroleingenomeanalysis.However,traditional2Dcircularmaponlyprovidesanoverviewandannotationsofgenomebutdoesnotofferfeature-basedcomparison.Forremedyingtheseshortcomings,wedeveloped3DGenomeTuner,ahybridofcircularmapandcomparativemaptools.Itscapabilityofviewingcomparisonsbetweenmultiplecircularmapsina3Dspaceoffersgreatbenefitstothestudyofcomparativegenomics.Theprogramisfreelyavailable(underanLGPLlicence)athttp://sourceforge.net/projects/dgenometuner.
简介:流行性感冒A病毒(H1N1),人的地方性的紧张的一个基因分类,鸟并且猪流感,穿过种类障碍到人并且显然获得了人的能力到人的传播。因为NS1蛋白质禁止抗病毒的干扰素/生产,H5N1子类型的一些紧张是高度剧毒的。另一蛋白质NS2调停到通过出口的细胞质的从原子核的病毒的ribonucleoprotein的出口信号。在这份报纸,我们学习了H1N1子类型的这些蛋白质的结构功能关系并且决定了他们的致病力的原因。我们的结果证明非保守的变化稍微稳定了或使动摇NS1或NS1-dsRNA建筑群的结构的域,稍微因此增加了或减少NS1蛋白质并且因而的函数提高了或减少H1N1病毒的致病力。不同紧张的NS2蛋白质在不同领域带了非保守的变化,导致功能的细微损失。这些变化稍微减少了病毒的致病力。因此,结果证实这些病毒的蛋白质的结构功能关系。
简介:Ithasbeenshownthattheprogressinthedeterminationofmembraneproteinstructuregrowsexponentially,withapproximatelythesamegrowthrateasthatofthewater-solubleproteins.Inordertoinvestigatetheeffectofthis,ontheperformanceofpredictionalgorithmsforbothα-helicalandβ-barrelmembraneproteins,weconductedaprospectivestudybasedonhistoricalrecords.WetrainedseparatehiddenMarkovmodelswithdifferentsizedtrainingsetsandevaluatedtheirperformanceontopologypredictionforthetwoclassesoftransmembraneproteins.Weshowthattheexistingtop-scoringalgorithmsforpredictingthetransmembranesegmentsofα-helicalmembraneproteinsperformslightlybetterthanthatofβ-barreloutermembraneproteinsinallmeasuresofaccuracy.Withthesamerationale,ameta-analysisoftheperformanceofthesecondarystructurepredictionalgorithmsindicatesthatexistingalgorithmictechniquescannotbefurtherimprovedbyjustaddingmorenon-homologoussequencestothetrainingsets.Theupperlimitforsecondarystructurepredictionisestimatedtobenomorethan70%and80%ofcorrectlypredictedresiduesforsinglesequencebasedmethodsandmultiplesequencebasedones,respectively.Therefore,weshouldconcentrateoureffortsonutilizingnewtechniquesforthedevelopmentofevenbetterscoringpredictors.
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:Thesurfaceglycoproteinhemagglutinin(HA)helpstheinfluenzaAvirustoevadethehostimmunesystembyantigenicvariationandisamajordrivingforceforviralevolution.Inthisstudy,theselectionpressureonHAofH5N1influenzaAviruswasanalyzedusingbioinformaticsalgorithms.Mostoftheidentifiedpositiveselection(PS)siteswerefoundtobewithinoradjacenttoepitopesites.SomeoftheidentifiedPSsitesareconsistentwithpreviousexperimentalstudies,providingfurthersupporttothebiologicalsignificanceofourfindings.ThehighestfrequencyofPSsiteswasobservedinrecentstrainsisolatedduring2005–2007.PhylogeneticanalysiswasalsoconductedonHAsequencesfromvarioushosts.Viraldriftisalmostsimilarinbothavianandhumanspecieswithaprogressivetrendovertheyears.OurstudyreportsnewmutationsinfunctionalregionsofHAthatmightprovidemarkersforvaccinedesignorcanbeusedtopredictisolatesofpandemicpotential.
简介:在这研究,L1蛋白质定序的人的乳头状瘤病毒(HPV)的107种类型从可得到的数据库,和这些HPVL1蛋白质的原子本地化信号(NLS)被获得被生物信息的分析分析并且预言。从107种类型,39种类型的NLS被PredictNLS软件(由两部组成的NLS的35种类型和单音的深裂的NLS的4种类型)预言。留下的HPV类型的NLS象NLS的一般规则一样根据特征和已经预言的NLS的相同被预言。根据结果,HPVL1蛋白质的107种类型的NLS被分类进15个范畴。在一样的NLS范畴的HPVL1蛋白质的不同类型能分享类似或一样的nucleocytoplasmic运输小径。他们可能被用作一样的目标阻止并且对待HPV感染的不同类型。结果也证明生物信息的技术能被用来分析并且预言蛋白质的NLS。
简介:Asystematicphylogeneticfootprintingapproachwasperformedtoidentifycon-servedtranscriptionfactorbindingsites(TFBSs)inmammalianpromoterregionsusinghuman,mouseandratsequencealignments.Wefoundthatthescoredis-tributionsofmostbindingsitemodelsdidnotfollowtheGaussiandistributionrequiredbymanystatisticalmethods.Therefore,weperformedanempiricaltesttoestablishtheoptimalthresholdforeachmodel.WegaugedourcomputationalpredictionsbycomparingwithpreviouslyknownTFBSsinthePCK1genepro-moterofthecytosolicisoformofphosphoenolpyruvatecarboxykinase,andachievedasensitivityof75%andaspecificityofapproximately32%.Almostallknownsitesoverlappedwithpredictedsites,andseveralnewputativeTFBSswerealsoidentified.WevalidatedapredictedSP1bindingsiteinthecontrolofPCK1tran-scriptionusinggelshiftandreporterassays.Finally,weappliedourcomputationalapproachtothepredictionofputativeTFBSswithinthepromoterregionsofallavailableRefSeqgenes.OurfullsetofTFBSpredictionsisfreelyavailableathttp://bfgl.anri.barc.usda.gov/tfbsConsSites.
简介:Leishmaniaisassociatedwithabroadspectrumofdiseases,rangingfromsimplecutaneoustoinvasivevisceralleishmaniasis.Here,thesequencesoftencysteineproteasesoftypesA,BandCofLeishmaniamajorwereobtainedfromGeneDBdatabase.PredictionofMHCclassIepitopesofthesecysteineproteaseswasperformedbyNetCTLprogramversion1.2.Inaddition,byusingBcePredserver,differentstructuralpropertiesoftheproteinswerepredictedtofindouttheirpotentialBcellepitopes.Accordingtothiscomputationalanalysis,nineregionswerepredictedasBcellepitopes.Theresultsprovideusefulinformationfordesigningpeptide-basedvaccines.
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简介:染色体17q21.31倒置是普通结构的多型性首先在欧洲人口发现了的900-kb。尽管在倒置区域以内的基因流动被假定可观压制,它关于在H1(非转换的顺序)和H2(转换顺序)之间的基因交换的细节仍然是不清楚的这倒置的haplotypes。这里,我们在17q21.31区域以内描述在一些基因安排之间的基因交换的一张精制地图。用1,546单个核苷酸多型性的HapMap阶段II数据,我们成功地由加入邻居的树重建在欧洲样品推出了96H1和24H2haplotypes。而且,我们分别地与相互、非相互的基因交换识别了15和26条候选人道。在怀有相互的交换的所有15个区域,haplotypes由克隆定序重建了没支持这些交换事件,建议这在某些异质接合的个人在二个姐妹染色体之间的交换发信号被分阶段执行错误区域引起。在另一方面,与非相互的基因流动越过26条道中的4个定序的完成的克隆证实这种基因交换被基因变换引起。在摘要,更加作为在一些基因安排之间的转线路被压制了,基因变换可能是为在17q21.31的基因交换的最重要的机制。
简介:Leptospirosisisrecognizedasthemostwidespreadzoonosiswithaglobaldistribution.Inthisstudy,theantigenicvariationinLeptospirainterrogansandLeptospiraborgpeterseniiisolatedfromhumanurineandfieldratkidneywaspreliminarilyconfirmedbymicroscopicagglutinationtestusingmonoclonalantibodies,andwasfurthersubjectedtoamplificationandidentificationofoutermembranelipoproteinswithstructuralgenevariation.Sequencesimilarityanalysisrevealedthattheseproteinsequences,namelyOmpL1,LipL32andLipL41,showednomorehomologiestooutermembranelipoproteinsofnon-pathogenicLeptospiraandothercloselyrelatedSpirochetes,butshowedastrongidentitywithinL.interrogans,suggestingintra-specificphylogeneticlineagesthatmightbeoriginatedfromacommonpathogenicleptospiralorigin.Moreover,theompL1geneshowedmoreantigenicvariationthanlipL32andlipL41duetolessconservationinsecondarystructuralevolutionwithincloselyrelatedspecies.Phylogenetically,ompL1andlipL41ofthesestrainsgaveaconsiderableproximitytoL.weiliiandL.santarosai.TheompL1geneofL.interrogansclustereddistinctlyfromotherpathogenicandnon-pathogenicleptospiralspecies.ThediversityofompLgeneshasbeenanalyzedanditenvisagedthatsequence-specificvariationsatantigenicdeterminantsiteswouldresultinslowevolutionarychangesalongwithnewserovaroriginationwithincloselyrelatedspecies.Thus,acrucialworkoneffectiverecombinantvaccinedevelopmentandengineeredantibodieswillhopefullymeettosolvethetherapeuticchallenges.
简介:InFebruary2006,twooutbreaksofhighlypathogenicavianinfluenzaAvirussubtypeH5N1occurredinchickensintwoneighboringdistricts(firstinNandurbarandsecondinJalgaon)ofMaharashtra,India,inaspanof12days.Inthepresentstudy,theneuraminidase(NA)geneofthetwoIndianH5N1isolateswastakenintoconsiderationtofindifthetwostrainsaregeneticallysimilar.PhylogeneticanalysisoftheNAgeneshowedthattheH5N1strainsisolatedfromthetwooutbreakswerenotoriginatedfromthesamesource.ThefirstIndianisolate(Nandubar/7972/06)wasclusteredclosesttoanisolatefromchickeninVietnamin2004,whereasthesecondIndianisolate(Jalgaon/8824/06)showedresemblancetostrainsisolatedfromswaninItalyandIranin2006.Moreover,aminoacidsequenceanalysisshowedvaryinghotspotsforsubstitutionsbetweenthesetwoIndianisolates,andthreesubstitutionswerefoundatfunctionaldomainsites.Secondarystructurechangesduetothesesubstitutionswerealsoreported.ThisstudyrevealsthattheH5N1strainsisolatedfromchickensduring2006birdfluoutbreaksintwoneighboringdistrictsofMaharashtra,Indiaaregeneticallydifferent.