怎样在国际权威杂志上发表科学论.ppt

M.F.Egan,M.Kojima,J.H.Callicott,T.E.Goldberg,B.S.Kolachana,E.Zaistev,A.Bertolino,B.Gold,D.Goldman,M.Dean,B.Lu,(co-correspondingauthor)andD.R.Weinberger.(2003)TheBDNFval66metpolymorphismaffectsactivity-dependentsecretionofBDNFandhumanmemoryandhippocampalfunction.Cell112,257-269.L.Ma,Y.-Z.Huang,J.Valtschanoff,L.Feng,B.Lu,W.Xiong,R.Weinberg,L.Mei.(2003)Ligand-dependentrecruitmentoftheneuregulinsignalingcomplexintoneuronallipidrafts.J.Neurosci.23,3164-3175.J.Wang,C.-Q.Chen,B.Lu,andC.-P.Wu.(2003)GDNFacutelypotentiatesCa2+channelsandexcitatorysynaptictransmissioninmidbraindopaminergicneurons.NeuroSignals12,78-88.M.Miura,S.Gronthos,M.Zhao,B.Lu,L.W.Fisher,P.G.Robey,andS.Shi(2003)SHED:Stemcellsfromhumanexfoliateddeciduousteeth.Proc.Natl.Acad.Sci.USA100,5807-5812.Y.X.Zhou,M.Zhao,K.Shimazu,K.Sakata,D.Li,C.-X.Deng,B.Lu.(2003)ImpairmentsincerebellumPurkinjecellsandmotorfunctioninmicelackingSmad4inthecentralnervoussystem.J.Biol.Chem.278,42313-42320.J.Du,L.Feng,E.Zaitsev,H.S.Je,X.Liu,andB.Lu.(2003)Activity-andtyrosinekinase-dependentfacilitationofTrkBreceptorinternalizationinhippocampalneurons.JCellBiol.Inpress.Z.G.Luo,H.-S.Je,F.Yang,W.C.Xiong,B.Lu,andL.Mei(2003)ActivationofgeranylgenanyltransferaseisessentialforAgrin-inducedAChRclustering.NeuronInpress.S.X.Bamji,K.Shimazu,N.Kimes,J.Huelsken,W.Birchmeier,B.Lu,L.F.Reichardt.(2003)Regulationofpresynapticassemblyandmaintenanceby-catenin.NeuronInPress.F.Yang,X.He,J.Russell,andB.Lu.(2003)Ca2+influxindependenttransmitterreleasemediatedbymitochondrialNa+-Ca2+exchangerandproteinkinaseC.J.CellBiol.Inpress.,2003researcharticles,WhatIsthePurposeofDoingResearch?,ItisnotaboutthenumberofpapersItisnotabouttheimpactfactorofthepapersItisnotabouttheNobelPrize,Publishorperish1Nature=10JBC,GoodResearchIstheKey,MyEnglishisnotgoodTheyarebiasedagainstChinese(foreigners),WhatIsaFirst-ClassPaper/Research?,Majoradvanceinaclassicfield干细胞是如何分化成特定组织细胞的，胆固醇在人体的正常功用Newtechniquesandmethodsthatcanbewidelyused人类基因组研究中的自动测序技术,PCR,Patchclamp,Ca2+Imaging,GFPDiscoverieswithobviouspracticalimplicationsAIDSvirusreceptor的发现,老年痴呆症基因的发现Conceptualbreakthrough,novelideas神经营养因子可以促进学习记忆,RNA干扰现象Challengetotraditionalviews,breakdogma脑内有可分裂的神经干细胞，打破了传统观念Openingupnewarea,crossboard“细胞凋亡”现象的发现,开辟了新的科研领域,WhatIsaMediocrePaper/Research?,HorizontalgrowthImadethediscoveryinrats,youfindthesameincat.FillinggapsEGFactivatesJNKwhichisknowntoinducec-Junexpression.YoushowthatEFGenhancesc-Junexpression.WorkingoutdetailsIfoundNOinducestheproductionofcGMP,youworkoutdoseresponseandtimecourse.Supportexistingidea,“metoo”EGF-Rendocytosisrequiresdynamin,PDGF-Rtoo.FollowupCREBbindstoCRE.WorkingoutCREsequence.Incompletestudy,preliminary,HowtoReadScientificPapers?,TheGilbertwayKeeptheseinmindwhenyoureadWhatisthemajorquestionaddressedinthispaper?Isthisquestionimportantandwhy?Whataretheapproachesusedinthispaper,andwhethertheyareadequateforthequestions?Whatarethenovelideaorusinginnovativeapproaches?Whatistheconceptcomingoutofthispaper?Dotheresultspresentedsupportthisnewconcept?WeeklyreadingofCNStitlesCritical,appreciative,WhatMakesGoodScience?,ImportantandsignificantOriginalandinnovativeSolidandrigorousUniqueandunusual,Noveltyisessential,语不惊人誓不休,Theevaluationprocess,EditorialstaffBoardofReviewingEditors,20-30%,REJECT,REVIEW,REJECT,70%,ACCEPT(10%),70%,20%,6%,4%,ShouldyourpapergotoCNS?,Isityourbestever?Willithaveabigimpact?Doesitinterestscientistsinotherfields?Doesitoverturnconventionalwisdom?Workthatrepresentsalargestepforwardsolutiontolong-standingproblemdifferentwayofthinkingbroadimplications,Whathelps:,ConvincingdataAppropriatecontrolsCarefulpresentationConsiderationofallviablealternatives,Whatdoesnthelp,Theminimalpublishableunit.ExcessiveorunfoundedspeculationRepeatexamplesofaknownphenomenonInsufficientadvanceoverpreviouslypublishedwork,EditorialPoliciesofDifferentJournals,Cell/Neuron/ImmunityEditorialboarddoesalotofreviews.EditorsdiscussanddecideNaturesisterjournalsEditorsdiscussanddecideScienceSpacemeeting,boardofrevieweditorsPNASCommunicate,contribute,TrackCOthers,ProceduresforHighProfileJournals,Pre-submissioninquirySubmit/coverletterInitialscreenSendoutforreviewsReject/softreject/reviseRebuttalReviseagainAccept,significance/importancegeneralinterestsunusual/surprise,Initialscreening,suggestreviewers,maytakeonefriendsmaynotalwayssupportyou“nottoreview”alwayshonored“soft”and“harsh”reviewers,Selectionofreviewers,You,Editors,CoverLetters,mainfindingssignificancesuggestedreviewers“nottoreview”listwhohaveread,DearEditor,WewouldliketosubmittheenclosedmanuscriptentitledGDNFAcutelyModulatesNeuronalExcitabilityandA-typePotassiumChannelsinMidbrainDopaminergicNeurons,whichwewishtobeconsideredforpublicationinNatureNeuroscience.GDNFhaslongbeenthoughttobeapotentneurotrophicfactorforthesurvivalofmidbraindopaminergicneurons,whicharedegeneratedinParkinsonsdisease.Inthispaper,wereportanunexpected,acuteeffectofGDNFonA-typepotassiumchannels,leadingtoapotentiationofneuronalexcitability,inthedopaminergicneuronsincultureaswellasinadultbrainslices.Further,weshowthatGDNFregulatestheK+channelsthroughamechanismthatinvolvesactivationofMAPkinase.Thus,thisstudyhasrevealed,forthefirsttime,anacutemodulationofionchannelsbyGDNF.OurfindingschallengetheclassicviewofGDNFasalong-termsurvivalfactorformidbraindopaminergicneurons,andsuggestthatthenormalfunctionofGDNFistoregulateneuronalexcitability,andconsequentlydopaminerelease.TheseresultsmayalsohaveimplicationsinthetreatmentofParkinsonsdisease.Duetoadirectcompetitionandconflictofinterest,werequestthatDrs.XXXofHarvardUniv.,andYYofYaleUniv.notbeconsideredasreviewers.Withthanksforyourconsideration,IamSincerelyyours,DearEditor,WewouldliketosubmittheenclosedmanuscriptentitledCa2+-bindingproteinfrequeninmediatesGDNF-inducedpotentiationofCa2+channelsandtransmitterrelease,whichwewishtobeconsideredforpublicationinNeuron.WebelievethattwoaspectsofthismanuscriptwillmakeitinterestingtogeneralreadersofNeuron.First,wereportthatGDNFhasalong-termregulatoryeffectonneurotransmitterreleaseattheneuromuscularsynapses.Thisprovidesthefirstphysiologicalevidenceforaroleofthisnewfamilyofneurotrophicfactorsinfunctionalsynaptictransmission.Second,weshowthattheGDNFeffectismediatedbyenhancingtheexpressionoftheCa2+-bindingproteinfrequenin.Further,GDNFandfrequeninfacilitatesynaptictransmissionbyenhancingCa2+channelactivity,leadingtoanenhancementofCa2+influx.Thus,thisstudyhasidentified,forthefirsttime,amoleculartargetthatmediatesthelong-term,synapticactionofaneurotrophicfactor.Ourfindingsmayalsohavegeneralimplicationsinthecellbiologyofneurotransmitterrelease.,DearEditor:EnclosedarecopiesofamanuscriptentitledBDNFandNT-4/5PromotetheDevelopmentofLong-TermPotentiationintheHippocampus,whichwewishtobeconsideredforpublicationinNature.Asyouknow,thereisagreatdealofinterestandexcitementrecentlyinunderstandingtheroleofneurotrophinsinsynapsedevelopmentandplasticity.Ourmanuscriptprovides,forthefirsttime,thephysiologicalevidencethatneurotrophinsregulatelong-termpotentiation(LTP).ThemainpointofthepaperisthattheneurotrophinsBDNFandNT-4induceanearlierappearanceofLTPindevelopinghippocampus.IncontrasttorecentSciencearticlebyXXsgroup,we(andseveralotherLTPgroups)didnotseethatBDNFenhancebasalsynaptictransmissioninadullthippocampus.However,wefoundthatinadulthippocampus,inhibitionofBDNF/TrkBactivityattenuatedLTP,andweaktetanusthatnormallycannotinduceLTPproducedenduringLTP.Thesefindingsmayhaveimplicationsinthebasicmechanismforregulationofsynapsedevelopmentandlong-termmodulationofsynapticefficacy.Becauseoftherathercompetitivenatureofthefieldandtheimportantimplicationofourfindings,wehavenotyetpresentedthisworkinanypublicforum.However,confidentialdiscussionwithseveralprominentneuroscientistssuchas111and222havegeneratedtremendousexcitement.Thus,wefeelthatthisworkisofgeneralinterestandissuitableforpublicationinNature.WewouldliketosuggestDrs.aaaofYaleUniv.,bbbofHarvardMedicalSchool,andcccofUniv.ofCalifornia-Berkeley,asreviewersforthismanuscript.Duetoadirectcompetitionandconflictofinterest,werequestthatDr.XXandYY.notbeconsideredasreviewers.Thankyouverymuchforyourconsideration.,Titles,Important/significantUnexpected/unusualFunctionMechanismsSimpleStraightforwardSpecific,Structure,mechanism,anregulationoftheNeurosporaplasmamembraneH+,ModulationofpostendocyticsortingofG-protein-coupledreceptors,DistinctmolecularmechanismforinitiatingTRAF6signaling,Identificationof;Roleof;Involvementof,Sequenceofwriting,AbstractFigurelayoutFigurelegendMaterialandmethodsResultsIntroductionDiscussion,Abstract,Rationale“remainunknown”;“Todetermine”Summarystatement“Hereweshow”BodyDontgointodetails;dontusemanyspecialtermsSignificanceMustpointout,butdontclaimtoomuch,FormationofthenormalmammaliancerebralcortexrequiresthemigrationofGABAergicinhibitoryinterneuronsfromanextracorticalorigin,thelateralganglioniceminence(LGE).Mechanismsguidingthemigratorydirectionoftheseneurons,orotherneuronsintheneocortex,arenotwellunderstood.WehaveusedanexplantassaytostudyGABAergicneuronalmigrationandfoundthattheventricularzone(VZ)oftheLGEisrepulsivetoGABAergicneurons.Furthermore,thesecretedproteinSlitisachemorepellentguidingthemigratorydirectionofGABAergicneurons,andblockadeofendogenousSlitsignalinginhibitstherepulsiveactivityintheVZ.TheseresultshaverevealedacellularsourceofguidanceforGABAergicneurons,demonstratedamolecularcueimportantforcorticaldevelopment,andsuggestedaguidancemechanismforthemigrationofextracorticalneuronsintotheneocortex.,Ithasnotescapedournoticethatthespecificpairingwehavepostulatedimmediatelysuggestsapossiblecopyingmechanismforthegeneticmaterial.-J.D.WatsonandF.H.C.Crick,Neuronalresponsestobrain-derivedneurotrophicfactor(BDNF)areinitiatedbytheactivationofthereceptorTrkBtyrosinekinase(1).Inthisstudyweexaminedwhethercholesterol-andglycolipid-richmicrodomains,lipidrafts,provideafunctionalplatformforBDNF-dependentsignaltransduction(2).Usingprimarycultureofcorticalneurons,wedemonstratedthatTrkBwasdramaticallytranslocatedintolipidraftsinBDNF-dependentmanner(3).ThistranslocationwasblockedbythepharmacologicaleffectofgeneralTrkinhibitors,indicatingthatTrkBactivationisrequiredforthetranslocationmechanism.WealsoshowedthatBDNFandTrkB-FLwerebothconcentratedinlipidraftsduringdevelopmentofcerebralcortex,concomitantwiththatofsynapticvesicleproteins,includingsolubleN-ethylmaleimide-sensitivefactorattachmentproteinreceptor(SNARE)proteinsandsynaptophysin(4).Thisresult,togetherwiththefindingsthatBDNFstimulationcausedtranslocationofsynaptophysinintolipidrafts(5)andthatBDNF-enhancedglutamatereleaseandexocytosiswerebothattenuatedbydepletionofcholesterolfromthecellsurfacewithmethyl-beta-cyclodextrin(MCD),indicatesthatlipidraftsareessentialforBDNFregulationofneurotransmitterrelease(6).,Brain-derivedneurotrophicfactor(BDNF)playsanimportantroleinsynapticplasticitybuttheunderlyingsignalingmechanismsremainunknown.HereweshowthatBDNFrapidlyrecruitsfull-lengthTrkB(TrkB-FL)receptorintocholesterol-richlipidraftsfromnon-raftregionsofneuronalplasmamembranes.TruncatedTrkBlackingtheintracellularkinasedomainwasnottranslocated,andthetranslocationofTrkB-FLwasblockedbyTrkinhibitors,suggestingaroleforTrkBtyrosinekinaseinthetranslocation.DisruptionoflipidraftsbydepletingcholesterolfromthecellsurfaceblockedBDNF-dependentTrkBtranslocation.DisruptionofraftsalsopreventedthepotentiatingeffectofBDNFontransmitterreleaseinculturedneurons,aswellasthatonsynapticresponsetotetanusinhippocampalslices.Incontrast,lipidraftsarenotrequiredforBDNFregulationofneuronalsurvival.Thus,ligand-inducedTrkBtranslocationintolipidraftsmayrepresentaselectivesignalingmechanismforsynapticmodulationbyBDNFintheCNS.,Acalcium-independentbutvoltage-dependentsecretion(CIVDS)coexistswiththecalciumdependentexocytosisindorsalrootganglion(DRG)neurons(1).HerewehaveinvestigatedtheCIVDS-coupledendocytosis(2).Usingopticalandmembranecapacitancemeasurements,weshowthat,incalcium-freemedium,eitherstepdepolarizationoratrainofaction-potential-likestimulationinduceanovelformofrapidendocytosis,whichoccursimmediatelyaftertheCIVDS.Surprisingly,thiscalcium-independentendocytosisisstronglydependentonthestimulationfrequency(3).H7suppresstheendocytosis,whilePKAagonistsenhanceit(4).Biochemicalexperimentsshowthatmembranedepolarizationdirectlyup-regulatePKAinDRGneurons.OurexperimentsalsoshowedthatthefrequencydependencyofCIVDS-REisdynamin-independent(5).Thus,ourdataindicatethatneuronalactivitymodulatesarapidendocytosisviaaCa2+-anddynamin-independentphosphorylation-dependentmannerinDRGneurons(6).,SynapticvesicleendocytosisisbelievedtorequireCa2+andtheGTPasedynamin.Herewereportanovelformofrapidendocytosis(RE)thatisindependentofCa2+anddynaminindorsalrootganglion(DRG)neurons.UsingFMdyelabelingandmembranecapacitancemeasurements,weshowthatbothstepdepolarizationandrepetitivestimulationinduceREinCa2+-freemedium.REalsooccursinthepresenceofaCa2+chelator(BAPTA).InhibitionofdynaminfunctionbythreedifferentapproachesdoesnotaffectRE.ProteinkinaseA(PKA)inhibitorssuppresstheendocytosis,whilePKAactivatorsenhanceit.Biochemicalexperimentsdemonstratethatmembranedepolarizationdirectlyup-regulatedPKAactivity.TheseresultsrevealaCa2+-anddynamin-independentformofendocytosisthatiscontrolledbyneuronalactivityandPKA-dependentphosphorylationinDRGneurons.,Introduction,Whatdoweknowaboutthesubjects?Onlyrelevantinformationshouldbeprovided;dontwriteareviewWhatwedontknowRationaleWhyyouwanttodoit?DontrepeatabstractApproachesHowyouaregoingtodoit.SignificanceMakeanappealtogeneralreaders,InthisstudywehaveexaminedtheroleofchromograninsCGAandCGB,indense-coresecretorygranulebiogenesis.WeanalyzedtheeffectofspecificdepletionofeitherCGAorCGB,usinganantisenseRNAstrategy,ondense-coresecretorygranuleformationinratpheochromocytoma(PC12)cells,amodelneuroendocrinecellline.WealsoexpressedCGAinapituitarycellline(6T3)lackingtheregulatedsecretorypathwayandnonendocrinefibroblastcellstodetermineitseffectoninductionofdense-coresecretorygranulebiogenesisandregulatedsecretion.Finally,wedeterminedwhetherCGAcouldregulatethelevelofothersecretorygranuleproteinsinneuroendocrineandendocrinecells,PC12and6T3.ThesestudiesidentifiedCGAasakeyregulatorofdense-coresecretorygranulebiogenesisandstorageofothergranuleproteinsinendocrinecells.,Results,LogicNeedtoexplaintherationalesinthebeginningConnectionsbetweenparagraphsDontjump,Previousstudieshaveshownthatmembranedepolarization-triggeredCa2+influxthroughL-typeVSCCsinducesanincreaseinBDNFmRNAexpressioninculturedneurons(Zafraetal.,1990;Ghoshetal.,1994).ThisincreaseinBDNFmRNAcouldbetheresultofincreasedtranscriptioninitiation,orincreasedBDNFmRNAstability,orboth.TodetermineifmembranedepolarizationstimulatesBDNFtranscription,we.,GiventhefindingthatCa2+influxthroughL-typeVSCCsinducesBDNFtranscription,experimentswerecarriedouttodeterminewhichofthefourBDNFpromotersiscapableofmediatingaCa2+response.Asdescribedabove,theratBDNFgeneconsistsoffourdistinct5exonseachdrivenbyaspecificpromoterandeachsplicedtoacommon3exonthatencodestheBDNFprotein.SinceeachofthefourprimaryBDNFtranscriptscanbepolyadenylatedatoneoftwosites,atotalofeightBDNFtranscriptsaregenerated.Inprinciple,theeighttranscriptscanbedistinguishedbyNorthernblottingusing5exonspecificprobes,sinceeachofthefour5exonprobesshoulddetectashortandalongBDNFtranscript.ByidentifyingthespecificBDNFmRNAsinduceduponCa2+influxthroughL-typeVSCCs,itshouldbepossibletoidentifywhichofthefourBDNFpromotersisCa2+responsive,sincetheCa2+-responsivepromoter(s)wouldbeexpectedtobelocatedjust5oftheinitiationsiteofBDNFmRNAsynthesis.,Discussion,SummaryofmainfindingsPapersthatsupportyou,butdontdowngradeyournoveltyPitfallsandwhySignificance.Dontspeculatetoomuch,Theresultsinthepresentstudymayhaveanumberofimplicationsinthecellbiologyoftyrosinekinasereceptors.First,wereportthe.Toourknowledge,thisisthefirstdemonstrationfor.Thus,ourresultssuggestacross-talkbetweenCa2+andtyrosinekinasesignalingpathways.Second,thepresentstudyrevealsanimportantregulatoryeffectof.Itwillbeinterestingtodeterminewhether.Finally,weshowthat.Xxx.Takentogether,theseresultssuggestageneralroleoftyrosinekinaseintheendocytosisofgrowthfactorreceptors.,Therearethreemainfindingsinthepresentstudy.First,wereportaGDNF-inducedlong-termfacilitationofneurotransmitterreleaseattheneuromuscularsynapses.Second,weshowthattheeffectofGDNFonsynaptictransmissionismediatedbyanincreaseintheexpressionoftheCa2+-bindingproteinfrequenin.Finally,wedemonstratethatGDNFandfrequeninfacilitatesynaptictransmissionbyenhancingN-typeCa2+channelactivation,leadingtoanenhancementofCa2+influx.Thus,thisstudyhasidentified,forthefirsttime,amoleculartargetthatmediatesthelong-term,synapticactionofaneurotrophicfactor.Ourfindingsmayalsoprovidenewinsightsintotheregulatorymechanismsofneurotransmitterrelease.,Invitethoroughcritique,RunyourownreviewprocessfirstaskfeedbackfromsomeoneinyourownspecialtysomeoneinanunrelatedspecialtyagoodeditorfortheEnglishlanguageAssessbothresearchandpresentation,Commonreasonsforrejection,BelongsinaspecializedjournalToosmallofanadvanceoverpreviouslypublishedworkUnconvincingdataObservationswithoutinterpretationsInterpretationswithoutdata,Reviseyourpaper,Becalmaboutreviewerscriticisms.AlwaysmakeeditoryourfriendNeverarguewithreviewersTrytodoeverythingthatreviewersaskSeizetheopportunitywhenreviewersmakemistakes,Whenyourpapergetsrejectedwithoutreview,DearEditor,Iwouldappreciateifyoucouldreconsidertoreviewourmanuscript,“111.Wefeelstronglythatthisisanimportantsubjectthattouchesoneofthecentraldogmasinneuroscience:xxx.Itisalsoverytimely,giventhepublicationofthepaperbyXandYentitled“222”inthelatestissueofNatureNeuroscience.Inthispaper,theauthorsxxx.Theyclaimedthatxxx.WhenapaperthisprovocativehasbeenpublishedbyahighprofilejournallikeNatureNeuroscience,webelievethatitisworthgivingabenefitofdoubts.Itwillbehelpfuliftherearepapersthatconsiderotheralternativeinterpretations,orattempttoreplicateinthesameordifferentsystems.Wehaveobservedsimilarxxx,butwehave