简介:CleavageofchromosomalDNAintooligonucleosomalsizefragmentsisanintegralpartofapoptosis.ElegantbiochemicalworkidentifiedtheDNAfragmentationfactor(DFF)asamajorapoptoticendonucleaseforDNAfragmentationinvitroGeneticstudiesinmicesupporttheimportenceofDFFinDNAfragmentationandpossiblyinapoptosisinvivo.RecentworkalsosuggeststheexistenceofadditionalendonucleasesforDNAdegradation.Understandingtherolesofindividualendonucleasesinapoptosis,andhowtheymightcoordinatetodegradeDNAindifferenttissuesduringnormaldevelopmentandhomeostasis,aswellasinvariousdiseasedstates,willbeamajorresearchfocusinthenearfuture.
简介:<正>Apoptosisisahighlyregulatedphysiologicalprocesscriticalindevelopmentandtissuehomeostasis.Abnormalapoptosiscanleadtodiseaseconditionsincludingneurodegeneration,autoimmunityandcancer.DNAfragmentationisanintegralpartofapoptosisandhaslongbeensuspectedtobeofcriticalimportanceincleaninguppotentiallyantigenicDNAandgeneticmaterialcapableofinducingneoplasmictransformationinneighboringcells.DirectevidenceforthisfunctionofDNAfragmentationhowever,isstilllacking.TheidentificationofaheterodimericDNAfragmentationfactor45and40(DFF45andDFF40,alsocalledICADforInhibitorofCaspaseActivatedDNaseandCADforCaspaseActivatedDNaserespectively)aswellas
简介:AsthetopologicalpropertiesofeachspotinDNAmicroarrayimagesmayvaryfromoneanother,weemployedgranulometriestounderstandtheshape-sizecontentcontributedduetoasignificantintensityvaluewithinaspot.Analysiswasperformedonthemicroarrayimagethatconsistedof240spotsbyusingconceptsfrommathematicalmorphology.Inordertofindoutindicesforeachspotandtofurtherclassifythem,weadoptedmorphologicalmultiscaleopenings,whichprovidedmicroarraysatmultiplescales.Successiveopenedmicroarraysweresubtractedtoidentifytheprotrusionsthatweresmallerthanthesizeofstructuringelement.Spot-wisedetails,intermsofprobabilityoftheseobservedprotrusions,werecomputedbyplacingaregularlyspacedgridonmicroarraysuchthateachspotwascenteredineachgrid.Basedontheprobabilityofsizedistributionfunctionsoftheseprotrusionsisolatedateachlevel,weestimatedthemeansizeandtextureindexforeachspot.Withthesecharacteristics,weclassifiedthespotsinamicroarrayimageintobrightanddullcategoriesthroughpatternspectrumandshape-sizecomplexitymeasures.Thesesegregatedspotscanbecomparedwiththoseofhybridizationlevels.
简介:Apoptosiscanbetriggeredbyavarietyofstimuliincludingdeathfactors,anti-cancerdrugsandfactor-deprivation.Theseapoptoticcellsareswiftlyphagocytosedbymacrophagestopreventthereleaseofnoxiousorinflammatorymaterialsfromdyingcells.ThemolecularanalysisofFasligand(adeathfactor)-inducedapoptosisindicatedthatacascadeofproteases(caspases)isactivatedduringthisprocess,whicheventuallyactivatesaspecificDNase(caspase-activatedDNase).CADexistsasacomplexwithitsinhibitor(ICAD)inproliferatingcells.Whenthecellsaretriggeredtoapoptosis,caspases,inparticularcaspase3,inthedownstreamofthecaspasecascadecleaveICAD,whichreleasesCADtocauseDNAdegradationinnuclei.
简介:The2004SoutheastAsiaTsunamikillednearly5,400peopleinSouthernThailand,includingforeigntouristsandlocalresidents.TorecoverDNAevidenceasmuchaspossiblefromtheseriouslydecomposedbodies,weexploredproceduresofsamplepreparationfrombothboneandtoothsamplesaswellasbothmitochondrialandnuclearmarkers.DespitehavingfailedtorecoverenoughDNAfornuclearmarkertyping,wesucceededinobtainingfullyinformativeresultsformitochondrialmarkers(HV1andHV2)from258toothsampleswithasuccessrateof51%(258/507).UsinganorganicDNAextractionmethodcoupledwithanultrafiltrationstep,weobtained16STR(including13CODISloci,onesexdiscriminationlocus,andtwoIdentifilerloci)profilesfor834sampleswithasuccessrateof79%(834/1,062).Inaddition,bycomparingtheallelicfrequenciesbetweenthetypedsamplesasagroupandotherindexpopulations,weconcludethattheThaitsunamivictimsareacombinedgroupofseveralpopulations.Ourresultsprovidevaluableevidenceandprotocolsforthefutureforensicpractice.
简介:Heterogeneousnuclearribonucleoproteins(hnRNPs)arespliceosomalmacromolecularassemblagesandthusactivelyparticipateinpre-mRNAmetabolism.Theyarecomposedofevolutionarilyconservedandtandemlyrepeatedmotifs,wherebothRNA-bindingandprotein-proteinrecognitionoccurtoachievecellularactivities.Byyetunknownmechanisms,theseribonucleoprotein(RNP)particlesaretargetedbyautoantibodiesandhenceplaysignificantroleinavarietyofhumansystemicautoimmunediseases.Thisfeaturemakesthemimportantprognosticmarkersintermsofmolecularepidemiologyandpathogenesisofautoimmunity.SinceRNPdomainisoneofthemostconservedandwidespreadscaffolds,evolutionalysesoftheseRNA-bindingdomainscanprovidefurthercluesondisease-specificepitopeformation.ThestudypresentedhereinrepresentsasequencecomparisonofRNA-recognitionregionsofrecentlyclonedandcharacterizedhumanhnRNPA3withthoseofotherrelevanthnRNPA/B-typeproteins.Theirimplicationsinhumanautoimmunityareparticularlyemphasized.
简介:在不到10年里自从它的开始,RNA干扰(RNAi)在生物医学的科学上有非凡的影响。RNAi被表明了到影响众多生物并且疾病小径。RNAi技术的开发和采纳是丰富的从基本loss-of-function工具,到药品的目标确认的染色体宽的屏蔽图书馆和治疗学的开发。然而,RNAiis的分子的机制理解远非完全。这简短评论的目的是在阐明加亮关键成就导致RNA的silencing建筑群并且到的生化学机制为这块地构画出主要挑战。
简介:Eelfamilyisahugeone,inwhichmanykindsofeelsespeciallysomemigratoryeels,bearstrongresemblancetoeachother,andarethereforedifficulttobeidentified.Inthisstudy29randomprimerswereusedtomakeRAPDanalysisforJapaneseseel(Anguillajaponica),Europeaneel(Anguillaanguilla)andPikeeel(Muraenesoxcinereus).Andtotally299fragmentswerecounted.Sharedorspecificfragmentswerecountedandgeneticsimilarityorgeneticdistancewerecalculated.ThegeneticsimilaritybetweenJapaneseeelandPikeeelis0.68andthegeneticdistancebetweenthemis0.32;thosebetweenEuropeaneelandPikeeelare0.72and0.28respectively,andbetweenJapaneseeelandEuropeaneelare0.74and0.25respectively.Themethodhasbeenshowntobesuitabletomolecularidentificationofeels.Itprovidesanalternativeapproachtodeterminetherelationshipbetweenspecies.
简介:DNA聚合酶III是为DNA的复制负责的五eubacterialDNA聚合酶之一双。在DNA聚合酶III核心酶的十个子单元之中,高山哈子单元两个都为polymerizing催化反应DNA海滨。在这研究,我们提取了高山的genomic序列哈从159的子单元定序eubacterial染色体,并且执行了基于顺序的种系发生、结构的分析。我们发现所有eubacterial染色体有至少一座高山哈子单元,哪个形式homodimers或heterodimers。种系发生并且领域高山的结构的分析以及拷贝数字变化哈在每个细菌的子单元显示高山的分类哈子单元进四个基本的组:polC,dnaE1,dnaE2,和dnaE3。这个分类具有在染色体作文分析的本质。我们也巩固了命名惯例在基因注解避免进一步的混乱。
简介:在源于mitochondrial机能障碍的氧化phosphorylation的改变长被假设了涉及tumorigenesis。线粒体最近被显示了在调整规划房间死亡和房间增长起一个重要作用。而且,mitochondrialDNA(mtDNA)变化在各种各样的癌症房间被发现了。然而,在tumorigenesis的这些mtDNA变化的角色仍然保持大部分未知。这评论集中于基本mitochondrial遗传,mtDNA变化和与癌症联系的结果的mitochondrial机能障碍。潜在的分子的机制,调停从mtDNA变化的致病和到tumorigenesis的mitochondrial机能障碍也被讨论。
简介:Humanpolymorphonuclearleukocytes(PMN)havebeenreportedtocompletelylackofDNA-dependentproteinkinase(DNA-PK)whichiscomposedofKuproteinandthecatalyticsubunitDNA-PKcs,neededfornonhomologousend-joining(NHEJ)ofDNAdouble-strandbreaks.PromyelocyticHL-60cellsexpressavariantformofKuresultinginenhancedradiationsensitivity.ThisraisesthequestioniflowefficiencyofNHEJ,instrumentalforthecellularrepairofoxidativedamage,isanormalcharacteristicofmyeloiddifferentiation.HereweconfirmedthecompletelackofDNAPKinPMNproteinextracts,andtheexpressionofthetruncatedKu86variantforminHL-60.However,thisdegradationofDNA-PKwasshowntobeduetoaDNA-PK-degradingproteaseinPMNandHL-60.Inaddition,byusingaprotease-resistantwholecellassay,bothKu86andDNA-PKcscouldbedemonstratedinPMN,suggestingthepreviouslyreportedabsenceinPMNofDNA-PKtobeanartefact.ThelevelsofKu86andDNA-PKcsweremuchreducedinPMN,ascomparedwiththatofthelymphocytes,whereasHL-60displayedamarkedlyelevatedDNA-PKconcentration.Inconclusion,ourfindingsprovideevidenceofreduced,notdepletedexpressionofDNA-PKduringthematurestagesofmyeloiddifferentiation.