天才一秒记住【狂风中文网】地址：https://www.kfzw.net
（b）Inanimalcellsrepliisstartedsimultamanypoiop（1）isdoublestrandedDrand，blad）showingtheplacesiionstarts（X）.DNApintocopybothstraiohearrows（2，3）.AnumberofDNApolymeraseeeeadresultingihehesizedDNAstrand（3）.AsthereplibubblesgrowthesefragmeogetherandcheckedforaaketiesofthestartingDNA（4）
11.RNApolymeraseisalargeplexofproteins，whidstospecificsitesatthestartofgeunwindstheDNAhelixarandtogiveaentaryRNAstrand.ThesugarmoleRNAaredifferenttothosefoundinDhefourbases（A，C，G）arethesamebutTissubstitutedforU.AstheRNApolymerasemovesalosstraoformahelix
Althoughthemeisareuood，howgeedfortransislessclear.Thephenomenonof‘geneexpression’hasoccupiedthousandsofmistsformanydecades.Basiesrequiredtomaintainthegorder（housekeepinggenes）arealressedbutmanyeneswillospecifictimesduringthelifeanisSomegenes，suchasthetwoglobimakeuphaemoglobin，arerequiredinsutsthatredcellsswitchtlobinprodu.Thealsoswitesonandoffinaveryplexpatterionornon-produofproteinsahecell’smainondingtoanystance.Wehavearound200differeypesinourbodies，allwithspecializedroles.Thesedifferentiatedcellsresultfreoroffiissues.Cellsalsohavetobeabletorespondrapidlytesbyswitesonandoff.Theseswitchesaretrolledbyagroupofaround3000differentproteiransfaegenesrequiremanyfactors，othersoransfactorsresideioplasmaheoaccesstheirgeransfactorsrequiredforrapidrespoleinandoutofthenuaintainingatstateofreadiness.
Howcellsmove
Muchofofthemeismsofhowaesfromwatgfibroblasttissueculture.Thecellmovesbyextendingabroadleadingedge，alamellipodium（seeFigure3c）whichmovesbyaeoftheundersidemembrasurface，ratherliketheiningtidemoviheuppersurfaellipodiumhasruffles，activewavesoffoldedmembrane，ardstherearofthecell.Allthisactivityisgehecellmembraionofsubunitstothefrontendsworkofafilaments.Attherearofthecell，theafilamentsbreakdowoberecycledtothefrontofthelamellipodiuFiionstermedfilopodia（similartomicrovilli）‘feelout’gapsbetweencells，allowingfibroblaststhsolidtissue.Thismigratihtissuesisentirelynormalforbothfibroblastsandwhitebloodcellsastheygoabouttheirnormaldutiesoftenandimmuthesametimerepresentsthemajorproblemiumoursareinitiatedbyalocallossoftrolofcelldivision.Ifthemassofnewlydividedcellsstaysput，theumnandusuallybesuccessfullyremovedbysurgeryorkilledbyradiatiohebiggestproblemwithcerismetastasis，wherecellsdissotheprimarytumour，pehesurroundiimatelyaccessthebloodstream，fromwhittheyerateseoursvirtuallyahebody.Aalyhowalandtumour）mhtissuebarriersisthefirststeptofiswhichhibitmetastasis，andnewdrugswhichcouldstopthespreadofcercellawayfrinal（primary）site.Ifewyears，sresshasbeeifyiareametastasis（unsurprisiarealsoinvolvediion）andinhibitorsoftheirmeisms.suchdiversesourcesascitruspeel（modifiedcitruspedoliveoil（oleamides）haveshowicproperties.
&，aproperty?
&roeofthepioneersofarkedin1824that‘life，asfarasphysicalorderised，isnothiha;ahissimplytheofthismovement’.Nearly200yearslater，justhowbihevariouspohecytoskeletontofunasasinglemoviyisstillabitofamystery.entrequiresbiochemicalals），anenergysupply，aionofstructuralelements.Cytoskeletalelemeogrowandshrinkandtethemselvesfora，butmuchfordwhentostue-BuehlerfromeryinChicago，acellbiologiststudyingthebehaviourofculture，‘thefunsanismiroltheiiosmolecules’—whichisawayofsayingthewholeisgreaterthaheparts.Somethingthathappeheiionofmaemsisemergey.Iheclassicexamplessosects，suchasthemassivecathedral-likestructuresproducedbytermiteies，oreveionofahohemovementofacellcouldbesideredapropertyofthemoleculesofthecytoskeleton，supportedbyenergyproduitodria，andinformationstoredinDNA.Thusitseemsfeasiblethatthemilliohinatissuepreofulfllthepurposeofthetissue，andthenaddaissuesfaherlevelsasaireanisThisviewmaygosomewaytoagfor（iflyexplaining）theplexitiesofourowence.
Iseelyrandom?
After30yearsexaminingthebehaviourofindividualculture，andreenormousamountoftimelapsefootage，thestudiesofAlbrecht-Buehlerhaveproduefasgobservationswhichmaysuggestthatcellsbothrequireandindeedpossess‘iheirsurroundingstoactastheydo.Theideathataoingisreiheirbehaviourwheherdthe，moveoffiions.Thisshowsa‘choithereatoaedeveio-Buehler’spublishedobservationsofthebehaviourofaculturedishappeartoiedmovemeappreofothercellsatadistanceofseveralcelldiameters.Albrecht-Buehlertermsthis‘telligendpointsoutthatthisbehaviourrequiresininginformation，whichhesuggestsmayinvht.Hesuggeststhatsigheroveradistanceofseveralcelldiametersbytheemissioiht.Intheabsenygreatbodyofworkinthisareaofresearch，itishardtoassessthetruesighesestudies，buttheyareextremelyintriguing.Inhisownwords，Albrecht-Buehlersuggeststhat‘cellbehaviouristrolledbyveryplexdataiioare，sofar，unknowntobiology’.
Ifwhatovemeivesimplicityofaplasticdishisplex，thensoisentwithinthehumanbody.Bloodcellsarepumpedarouiontoprovideoxygenationoftissuesbyreddtomaintainimmunesurveillahavarietyofwhitebloodcellscalledleucocytes.Toreachsitesofinjuryoriioesmustleavethecirculatoryflow.Thisisachievedbyattagthemselvestothewallofsmallbloodvessels，firstrollingtoastopusingadhesivemoleculescalledles，abitlikegrapplingiroabiliziatusingstroeiegrins.Atthispoiesmigratebetweehelialcellsthatlihebloodvessels（ratherlikeelbowingawaythroughacrowd），readytotinvadingbadmaybeitsuicidebyburstiheiraents（thiswillbedesmoredetailinChapter6）.Oeriahavesuccumbed，theirculfedbymacrophagesthathavealsomigratedtothesite.Thespeedayofthisresponseisimpressive，albeitthatthereare‘patrolliantlygthroughthewholebloodsysteThereisalsulardirectedmigratioionofanotherclassofwhitebloodcells（Tcells），whichleavethebonemarrorecursordpletetheirdevelopmehymususingsimilarhomingandadhesiohethemeigrationsinthebody，wearefarfrthewholepicture.
Howoldareourcells?
BenjaminFranklihattheoiesihandtaxesonlypartiallyappliestocells.Theoptionsfor‘theeermsaretodivideordie.Acell‘avoids’deathbydividihelesssacrificesitsowewodaughtercells.Mostdaughtercellsareidentidwillhaveidenticalfates，whichistodiffereoperformaparti，eventuallydie，ahismayinvolvealifespanofhanafewhours，asistheewhitebloodeutrophils），orupto120daysforredbloodcells.Mostcellsthroughoutourbodieswillbereplacedoverthecourseofourlifetime，withanaverageofseventotenyearsagtoJoheKarolinskaIo.Thereare，however，threetypesofcellthatwethecottothegrave:theneuronsofthecerebralcortexofthebraiheioftheeyelens;and，perhapssurprisimusclecells，whichmusthavetradbogglingthreebilliontimesinanyonewhoreaches1e.ThetheioftheleurallyverysimilartokeratinizedskihattheyarelargelyfilledwithkeratilaiddowninahighlyaalliallowingthemaximumamountoflighttotravelthroughtheIhiseanizationmaybreakdownaheeyelensbeeincataracts.
&h
Aswehaveseen，thelifespahinthehumanbodymayvarybetweenhoursaheactualproayeaboutiyofwaysfromavarietyofcauses.Directtraumasuchasmeicaldamage，orextremeheatorcold，produtassuchasruptureofthecellmembraaiohisproducesabalanceofdisorderoverorderthatotbereversed，sothecelldies，ratherlikethesuddenandusuallyviolehofanindividual，maybeinaroadatorwarsituatiohistypeofdeathistermednecrosis.
Adifferentariguihisonewhichisaverynecessaryproallmultis，iifiedinstudiesofdevelopmentbutsubsequentlyasa‘suicidepathway’forallcellsthathavefailedtoreproducethemselvesinasatisfaanner，endingaposedbytheuedrepliue’cells.Thisisknrammedcelldeath，or‘apoptreek，‘thefallingoftheleaves’），firstreizedinthe1970sbyAlastairCurrie，JohnKerr，andAndreathologistsinAberdeey，whoobserved（maironmicroscopy）acharacteristicseriesofgesleadih.Ittookoveradecadebeforethisprocesswasfullyacceptedasamajiismformaintaiusquooftissues.Apoptosisderanimmuneresponse（asocecrosis），astheteively‘recycled’，withthefragmesofthedeadup（phagocytosed）bytheirhealthyneighbours.Apoptosisisroutialprocessessuchastheremovalofwebbiweenfingersinhumans，thelossoftadpoletailsinamphibians，aamorphosis.Cellsthatarenolongerrequiredduribegintoshrink，andtheirsurfaeratesphericalprotuberancescalledblebs（Figure12a），averyactiveproobservedbytime-lapsemicroscopy，withthesurfaceofthecellresemblingboilingmudpoolsinvolicsites.Iheutentsbreakdowiocharacteristisemassesthatbecamethebenchmarkappearaoticcells（Figure 12c），astheDNAischoppedupintosmallpieces.
12.Apoptrammedcelldeath）.（a）Initially，thesurfaceofaesblebbed，（b）mitodrialosetheiriructure，（tentsofthenucleusaggregate，and（d）poresdevelopinthesurfaitodria
&wasrealizedthatapoptosiswasauniversalprothedemiseofcells，theseariofindhowthis‘cellsuicide’wasiwopathwaysemerged，depeoosiswastriggeredexterrinsiternally（intririnsicapoptosisresultsfromsighecellmembrane，whidto‘deathreceptors’onthecellsurfacethattheheprocessofcellsuicide.Thistypeofapoptosisusuallyoccursasamethodofcellkillinginimmunologicalreatrinsicapoptembryowhereitisprogrammedforaparticularstageor，alterriggeredasaresultofexteoDNA，suchasthatcausedbyionizingradiation.Apoptosisisalseredlipromisedahepresenceofrepairmeisms，theprqualitysstillfindiroduutatedproteins.
Themeicsofcellsuicide
Sohowdoesacellgoaboutendingitsowheactualmeismof‘cellsuicide’dependsuponmitodria，termedthe‘angelsofdeath’byNihisbook，Power，SexaodriaandtheMeanihefirstgeothemitodrialinnermembrane，whiagedbyaberraivity，leadiiohemitoembrane（Figure 12b，d）.Atthispoioesittedterapoptosis，aoe c（aproteinalfunyprodu）whichexitsthroughthenewlyformedpores.Thisinformatioasaresultofsomesintotidriawereioperfectlyhealthycells，resultinginapoptosis.Thereleasede dstoseveralotherproteioplasmtoformaplexcalledtheapoptosomewhiturn，activatesacascadeof‘exees’whilykillthecellbutcausefragmentationofthenudintobite-sizepiecesreadytobephagocytosedbyneighbcells.
&rihoccursaspartofadevelopmentalprogramme，itseemedlikelythattherewereactuallygenesforapoptwith orhabditiselegans（amuchstudiedodeworm），whereitisknowly131ofthetotalof1090cellsdiebyapoptdevelopment，BobHorovitzfreintheUSAframmedcelldeathgeudiesledtothearizein2002，sharedwithJohnSulstonandSydneyBrennerfreintheUK.
&hese‘celldeath’gehosegewereroutiedinmanymammalianceringthatapoptosiswasameismtodeletecellswithdamagedDNA.Mutationsihgeosis，allowihdamagedormutatedDNAtodevelopabnormallyaumours.DavidLane，wholosthisfathertohewasoedhisresearcheffortstoexplorethegesthatonormale1979，hefoundp53，aproteinthatisinactivatedordefialmostallcercells.Ifnormalp53ispreselevelsindividingdacellhasdamagedDesitsDNAiheriggersapoptthat，ihwaytoseingalldivision，henspiriionasatumoursuppressorandthe‘guardianofthegeotiestcellsarereizedbyuem（seeer）andremovedbyphagocytosis.Thus，evenatadvaagesofcer，arestorationofthe‘p53response’willbringpowerfuldefensesintoplaytoshrinktumoursandstrowth.Uingnormalp53intocerotasimpleprodseveralmicalstrategiesaretlyuion.Thepromiseofgeheaiplediseaseshasstilltoberealized，largelybecausethepracticalitieseheirprodutotherightamountsaimewithoutuablesideeffectsarestillproviremelydiffiterestingly，aappearstohavemadethemressiments，withadrugdigbeenapprovedforheadandne2003，whereastheUSFoodandDrinkAdministrationby2010hadnotapprovedanyp53-basedtreatments.
本章未完，请点击下一章继续阅读！若浏览器显示没有新章节了，请尝试点击右上角↗️或右下角↘️的菜单，退出阅读模式即可，谢谢！