鲁白_如何在顶级科学杂志上发表论文.ppt

新视野系列研究生课程：科技论文的构思、撰写和发表,生物医学世纪讲坛,特邀报告：,HowtoPublishYourPapersintheTopScientificJournals,鲁白教授,WhatIsaFirst-ClassPaper?,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,PatchclampDiscoverieswithobviouspracticalimplicationsAIDSvirusreceptor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?,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,Articles,AnRNAThermosensorControlsExpressionofVirulenceGenesinListeriamonocytogenesJrgenJohansson,PierreMandin,AdrianaRenzoni,ClaudeChiaruttini,MathiasSpringer,andPascaleCossart,Single-StrandedAntisensesiRNAsGuideTargetRNACleavageinRNAiJavierMartinez,AgnieszkaPatkaniowska,HenningUrlaub,ReinhardLhrmann,andThomasTuschl,OcaBIsRequiredforNormalTranscriptionandV(D)JRecombinationofaSubsetofImmunoglobulingeneRafaelCasellas,MilaJankovic,GesaMeyer,AnnaGazumyan,YanLuo,RobertG.Roeder,andMichelC.Nussenzweig,Cell,September6,2002:110(5),AStructuralMechanismofIntegrinIIb3Inside-OutActivationasRegulatedbyItsCytoplasmicFaceOlgaVinogradova,AlgirdasVelyvis,AstaVelyviene,BinHu,ThomasA.Haas,EdwardF.Plow,andJunQin,GlobalConformationalRearrangementsinIntegrinExtracellularDomainsinOutside-InandInside-OutSignalingJunichiTakagi,BenjaminM.Petre,ThomasWalz,andTimothyA.Springer,AppAIsaBlueLightPhotoreceptorthatAntirepressesPhotosynthesisGeneExpressioninRhodobactersphaeroidesShinjiMasudaandCarlE.Bauer,WhatMakesGoodScience?,ImportantandsignificantOriginalandinnovativeSolidandrigorousUniqueandunusual,Noveltyisessential,EditorialPoliciesofDifferentJournals,Cell/Neuron/ImmunityEditorialboarddoesalotofreviews.EditorsdiscussanddecideNaturesisterjournalsEditorsdiscussanddecideScienceSpacemeeting,editorialboardPNASCommunicate,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.IncontrasttorecentSciencearticlebyErinSchumansgroup,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,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,MuSKplaysanessentialroleinpostsynapticdifferentiationattheneuromuscularjunction.However,theunderlyingmechanismsremainedunclear.WedemonstratetheinteractionofMuSKwithDishevelled1(Dvl1)inmusclecells.TheexpressionpatternofDvl1indevelopinganddenervatedmuscleissimilartothatofMuSK.Moreover,Dvl1isenrichedattheneuromuscularjunctionwhereMuSKisconcentrated.DisruptionoftheinteractionofMuSKwithDvlinhibitsAChRclusteringinmusclecellsinducedbyagrinandmotoneuronsandattenuatestheamplitudeofspontaneouspostsynapticcurrentsattheneuromuscularjunction.Inaddition,Dvl1interactswithPAK1andmediatesagrin-inducedactivationofPAK,whichisrequiredforAChRclustering.TheseresultsdemonstrateessentialrolesofDvlandPAKinagrin-inducedAChRclustering,revealingasignalingpathwaythatrequiredtheMuSK-Dvl-PAKcomplex.,Animportantaspectofsynapsedevelopmentistheclusteringofneurotransmitterreceptorsinthepostsynapticmembrane.AlthoughMuSKisrequiredforacetylcholinereceptor(AChR)clusteringattheneuromuscularjunction(NMJ),theunderlyingmolecularmechanismsremainunclear.Wereportherethatinmusclecells,MuSKinteractswithDishevelled(Dvl),asignalingmoleculeimportantforcellpolarity.Dvl1islocalizedattheneuromuscularsynapses.DisruptionoftheMuSK-DvlinteractioninhibitsAgrin-inducedandneuron-inducedAChRclustering.ExpressionofdominantnegativeDvl1inthepostsynapticmusclecellsreducestheamplitudeofspontaneoussynapticcurrentsattheNMJ.Moreover,Dvl1interactswithadownstreamkinasePAK1.AgrinactivatesPAK,andthisactivationrequiresDvl.InhibitionofPAK1activityattenuatesAChRclustering.TheseresultsdemonstrateimportantrolesofDvlandPAKinAgrin/MuSK-inducedAChRclustering,andrevealanovelfunctionofDvlinsynapsedevelopment.,Sequenceofwriting,AbstractFigurelayoutFigurelegendMaterialandmethodsResultsIntroductionDiscussion,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.,Reviseyourpaper,Becalmaboutreviewerscriticisms.AlwaysmakeeditoryourfriendNeverarguewithreviewersTrytodoeverythingthatreviewersaskSeizetheopportunitywhenreviewersmakemistakes,Whenyourpapergetsrejectedwithoutreview,DearEditor,Iwouldappreciateifyoucouldreconsidertoreviewourmanuscript,“111.Wefeelstronglythatthisisanimportantsubjectthattouchesoneofthecentraldogmasinneuroscience:xxx.Itisalsoverytimely,giventhepublicationofthepaperbyXandYentitled“222”inthelatestissueofNatureNeuroscience.Inthispaper,theauthorsxxx.Theyclaimedthatxxx.WhenapaperthisprovocativehasbeenpublishedbyahighprofilejournallikeNatureNeuroscience,webelievethatitisworthgivingabenefitofdoubts.Itwillbehelpfuliftherearepapersthatconsiderotheralternativeinterpretations,orattempttoreplicateinthesameordifferentsystems.Wehaveobservedsimilarxxx,butwehaveacompletelydifferentinterpretation.Wefoundthat1)xxx2)xxx;3)xxx.Thus,ourpaperraisesthepossibilitythatxxxreportedbyXandYwereduetoxxx.Specifically,wewouldlikeyoutoconsiderthefollowingtwoissues:First,XandYusedaaa,whileweusedbbb.sssssssss.Second,cccusedbyXandYmaynotbesospecific.Inadditiontothedrasticallydifferentopinionsregardingxxx,wefeelthatourf