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  • 简介:Prestinisthemotorproteinofcochlearouterhaircells(OHCs).ItisabletoperformrapidandreciprocalelectromechanicalconversionthatunderliesOHCelectromotility.Duetotheinadequatesizeofasingleprestinmoleculetoformthe~12nmintramembraneousproteinparticles(IMPs)intheOHClateralmembrane(LM),thepossibilityofprestinoligomerizationhasbeenproposed.Ithasbeensuggestedthatprestinmoleculesformhighorderoligomers,mostlikelyasthetetramer,inheterologoussystems.InOHCs,however,theoligomericstructureofprestinremainsunclear.Herewecalculatedtheprestin-relatedchargedensityinbothgerbilandguineapigOHCsthroughmeasuringtheirnonlinearcapacitance(NLC)andLMsurfacearea,showingthattheaveragechargedensity(22,608μm-2ingerbils;19,460μm-2inguineapigs)isstatistically4timestheaveragedensityofIMPs(5,686μm-2ingerbils;5,000μm-2inguineapigs).ThissuggeststhateachIMPcontainsfourprestinmoleculesbaseduponthenotionthateachprestintransfersasingleelementarycharge,implyingthatprestinformstetramersinOHCs.Todeterminewhethertheprestintetramerfunctionsasamechanicalunit,wesubsequentlycomparedtheslopefactors(α)ofelectromotilityandNLCsimultaneouslymeasuredfromthesameOHC,showingthattheαvaluesofthetwoarestatisticallythesame.ThissuggeststhateachprestinmoleculeinthetetramerismechanicallyindependentandequallycontributestoOHCelectromotility.

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  • 简介:Theintroductionofnext-generationsequencing(NGS)technologyintestingforhereditarycancersusceptibilityallowstestingofmultiplecancersusceptibilitygenessimultaneously.Whiletherearemanypotentialbenefitstoutilizingthistechnologyinthehereditarycancerclinic,includingefficiencyoftimeandcost,therearealsoimportantlimitationsthatmustbeconsidered.Thebestpanelforthegivenclinicalsituationshouldbeselectedtominimizethenumberofvariantsofunknownsignificance.Theinclusioninpanelsoflowpenetranceornewlyidentifiedgeneswithoutspecificactionabilitycanbeproblematicforinterpretation.Geneticcounselorsareanessentialpartofthehereditarycancerriskassessmentteam,helpingthemedicalteamselectthemostappropriatetestandinterprettheoftencomplexresults.Geneticcounselorsobtainanextendedfamilyhistory,counselpatientsontheavailabletestsandthepotentialimplicationsofresultsforthemselvesandtheirfamilymembers(pre-testcounseling),explaintopatientstheimplicationsofthetestresults(post-testcounseling),andassistintestingfamilymembersatrisk.

  • 标签: 遗传性 癌症 遗传评价 检测 测序 基因测试
  • 简介:BACKGROUND:Duringthecellularagingprocess,thenumberofmitochondria,generationofadenosinetriphosphate(ATP),activityofrespiratorychainenzymecomplex1and4,andoxidationdecrease.OBJECTIVE:Toobservetheeffectsofaqueousandspirituousextract,aswellaspolysaccharidesfromFructusschizandrae(MagnoliaVine)onenergymetabolismandmitochondrialanti-oxidationincranialnervecellsofaD-gal-inducedagingmousemodel.DESIGN,TIMEANDSETTING:Arandomized,controlled,animalstudy.TheexperimentwasconductedattheDepartmentofBiochemistry,QiqiharMedicalCollegebetweenMarchandJuly2006.MATERIALS:Fiftyhealthy,Kunmingmiceofbothsexes,aged2-3monthsoldandweighing18-22g,wereusedforthepresentstudy.FructusschizandraewaspurchasedfromtheMedicalCollegeofJiamusiUniversity.Aqueousextracts,spirituousextracts,andpolysaccharidesfromFructusschizandraewereprepared.D-galactose(D-gal)isaproductoftheSecondReagentFactory,ShanghaiCity,China.Mn-superoxidedismutase(Mn-SOD)kit,malonaldehyde(MDA)kit,proteinquantificationkit,andinorganicphosphorustestingkitwerepurchasedfromJianChengBioeng.Co.,China.METHODS:Fiftymicewererandomlydividedintofivegroups,with10miceineachgroup:youngcontrol,agingmodel,aqueousFructusschizandraeextract,spirituousFructusschizandraeextract,andFructusschizandraepolysaccharides.Overacourseof30days,miceinagingmodel,aqueousFructusschizandraeextract,spirituousFructusschizandraeextract,andFructusschizandraepolysaccharidesgroupswereinjectedsubcutaneouslywithD-gal(100mg/kg)intothenapeoftheneckdaily,andadministeredintragastricallywithanequalvolumeofsterile,warmwater(agingmodel),aqueousFructusschizandraeextract(2g/kg),spirituousFructusschizandraeextract(2g/kg),orFructusschizandraepolysaccharides(0.2g/kg),respectively.Miceintheyoungcontrolgroupwereinjectedintothenapeoftheneckwithphysiologicalsaline

  • 标签: 成年人 线粒体 神经细胞 复合酶
  • 简介:Ginkgoditerpenelactonesmeglumineinjection(GDLI)isacommerciallyavailableproductusedforneuroprotection.However,thepharmacokineticpropertiesoftheprototypesandhydrolyzedcarboxylicformsoftheprimarycomponentsinGDLI,i.e.,ginkgolideA(GA),ginkgolideB(GB),andginkgolideK(GK),haveneverbeenfullyevaluatedinbeagledogs.Inthiswork,asimple,sensitive,andreliablemethodbasedonultra-fastliquidchromatography-tandemmassspectrometry(UFLC-MS/MS)wasdeveloped,andtheprototypesandtotalamountsofGA,GB,andGKweredeterminedinbeagledogplasma.Theplasmaconcentrationsofthehydrolyzedcarboxylicformswerecalculatedbysubtractingtheprototypeconcentrationsfromthetotallactoneconcentrations.Forthefirsttime,thepharmacokineticsofGA,GB,andGKwerefullyassessedinthreeforms,i.e.,theprototypes,thehydrolyzedcarboxylicforms,andthetotalamounts,afterintravenousadministrationofGDLIinbeagledogs.Itwasshownthatginkgolidesprimarilyexistedinthehydrolyzedforminplasma,andtheratioofhydrolysatestoprototypeformsofGAandGBdecreasedgraduallytoahomeostaticratio.AllofthethreeformsofthethreeginkgolidesshowedlinearexposureofAUCtothedosages.GA,GB,andGKshowedaconstanthalf-lifeapproximately2.7,3.4,and1.2h,respectively,whichwereconsistentfortheformsatthreedoselevels(0.3,1.0,and3.0mg·kg~(-1))andafteraconsecutiveinjectionofGDLIfor7days(1.0mg·kg~(-1)).

  • 标签: HYDROLYSATES of GINKGOLIDES LC-MS/MS PHARMACOKINETICS GINKGO
  • 简介:Interfacedebondingbetweenprosthesesandabutmentswasthemostfrequentfailuremodeofresin-bondedfixedpartialsdentures(RBFPDs)inclinic.ThepurposeofthisstudywastoinvestigatetheeffectofaccessoryretentionformsonthebondstrengthofRBFPDs.Threetypesof3Dfiniteelementmodelswereconstructed.ThemodelofposteriormetalplateRBFPDwithspoon-shapedocclusalrestseatsservedasthecontrol.Theremainingtwotypesofmodelsbasedonthecontroladdedtheretentionformdesignofthepinholeandaxialgrooverespectively.Theaxialorbuccolingualloadof150Nwasappliedontheprosthesis,firstpremolarandfirstmolarrespectively.Themaximumprincipalstressesoftheadhesivelayerindifferentmodelswerecalculated.Undertheloadofthesamemagnitude,thestressduetothebuccolingualloadwassignificantlyhigherthanthatduetotheaxialloadintheadhesivelayer.Theproximalshoulder,occlusalrestseatswallandtheproximalmarginadjacenttotheshoulderwerethehighriskregionwheretheadhesivelayerdamagedeasily.Comparedwiththecontrolmodel,thepinandgroovemodelscouldslightlydecreasethestressintheadhesivelayeraftertheaxialloading,whilethestressintheadhesivelayerdrasticallydecreasedafterhorizontalloadingandreducedby22%and31%respectively.TheseresultsindicatethatthehorizontalocclusalforcehasamoreseriousharmtothedebondingofRBFPDs.Inaddition,theaccessoryretentionforms(e.g.pinandaxialgrooveretentionforms)candecreasethestresslevelintheadhesivelayer,whichareconducivetoincreasetheload-bearingcapacityofRBFPDs.

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