简介：Nitricoxide(NO)isapleiotropicregulator,criticaltonumerousbiologicalprocesses,includingva-sodilatation,neurotransmissionandmacrophage-mediatedimmunity.Thefamilyofnitricoxidesynthases(NOS)comprisesinducibleNOS(iNOS),endothelialNOS(eNOS),andneuronalNOS(nNOS).Interest-ingly,variousstudieshaveshownthatallthreeisoformscanbeinvolvedinpromotingorinhibitingtheetiologyofcancer.NOSactivityhasbeendetectedintumourcellsofvarioushistogeneticoriginsandhasbeenassociatedwithtumourgrade,proliferationrateandexpressionofimportantsignalingcomponentsassociatedwithcancerdevelopmentsuchastheoestrogenreceptor.ItappearsthathighlevelsofNOSexpression(forexample,generatedbyactivatedmacrophages)maybecytostaticorcytotoxicfortumorcells,whereaslowlevelactivitycanhavetheoppositeeffectandpromotetumourgrowth.Paradoxicallytherefore,NO(andrelatedreactivenitrogenspecies)mayhavebothgenotoxicandangiogenicproperties.IncreasedNO-generationinacellmayselectmutantp53cellsandcontributetotumourangiogenesisbyupregulatingVEGF.Inaddition,NOmaymodulatetumourDNArepairmechanismsbyupregulatingp53,poly(ADP-ribose)polymerase(PARP)andtheDNA-dependentproteinkinase(DNA-PK).Anunderstand-ingatthemolecularleveloftheroleofNOincancerwillhaveprofoundtherapeuticimplicationsforthediagnosisandtreatmentofdisease.

简介：Matrixmetalloproteinases(MMPs)andtissueinhibitorsofmetalloproteinases(TIMPs)playasignificantroleinregulatingangiogenesis,theprocessofnewbloodvesselformation.Interstitialcollagenase(MMP-1),72kDagelatinaseA/typeIVcollagenase(MMP-2),and92kDAgelatinaseB/typeIVcollagenase(MMP-9)dissolveextracellularmatrix(ECM)andmayinitiateandpromoteangiogenesis.TIMP-1,TIMP-2,TIMP-3,andpossibly,TIMP-4inhibitneovascularization.Anewparadignisemergingthatmatrilysin(MMP-7),MMP-9,andmetalloelastase(MMP-12)mayblockangiogenesisbyconvertingplasminogentoangiostatin,whichisoneofthemostpotentangiogenesisantagonists.MMPsandTIMPsplayacomplexroleinregulatingangiogenesis.Anunderstandingofthebiochemicalandcellularpathwaysandmechanismsofangiogenesiswillprovideimportantinformationtoallowthecontrolofangiogenesis,e.g.thestimulationofangiogenesisforcoronarycollateralcirculationformation;whiletheinhibitionfortreatingarthritisandcancer.

简介：ApoptosisplaysanessentialroleinTcellbiology.ThymocytesexpressingnonfunctionalorautoreactiveTCRsareeliminatedbyapoptosisduringdevelopment.ApoptosisalsoleadstothedeletionofexpandedeffectorTcellsduringimmuneresponses.Thedysregulationofapoptosisintheimmunesystemresultsinautoimmunity,tumorogenesisandimmunodeficiency.Twomajorpathwaysleadtoapoptosis:theintrinsiccelldeathpathwaycontrolledbyBcl-2familymembersandtheextrinsiccelldeathpathwaycontrolledbydeathreceptorsignaling.Thesetwopathwaysworktogethertoregu

简介：PML基因涉及t(15；17)尖锐promyelocytic白血球过多症(APL)的translocation，它产生oncogenic熔化蛋白质PML(promyelocytic白血球过多症蛋白质)-retinoic酸受体高山哈。PML蛋白质本地化称为PML原子领域(PML-ND)的原子结构到一个代用品，哪个PML是必要结构的部件。在APL，PML-NDs被破坏，因此含有在这白血球过多症的致病的这些结构。出人意料地，最近的研究显示PML和PML-ND玩一个瘤在除了APL的人的瘤的几种不同类型的镇压角色。因为PML在多重细胞的小径的极端通用性和参与，理解位于它的功能下面的机制，并且因此在瘤抑制的角色，是一项挑战性的任务。在这评论，我们试图非常在这个领域里估价更最近的进展并且建议调查的新大街。

简介：Itiswellrecognizedthatcelldeathplaysanimportantroleduringthematurationofthenervoussystemaswellasinmanyneurologicaldiseases.Apoptosishasbeenshowntobeimportantparticularyduringembryogenesisasameanstoeliminatingunwantedneurons.SeveredaxonshavealsobeenshowntodegenerateinanorganizedfashiontermedWalleriandegeneration.Excitotoxicdeathisanotherformofcelldeathinthenervoussystemwhichisinducedbyhighconcentrationsofneurotransmitterssuchasglutamate.Itisnotknownwhetherthesamemolecularmechanismsunderliethesedifferentformsofcelldeathinthenervoussystem.TheBax-/-Bak-/-doubleknock-outmouseprovidesanidealsystemtostudy

简介：补充系统对普通病原体在天生的防卫起一个关键作用。补充的激活导致柔韧、有效的解朊的串联，它通过有势力proinflammatory分子的生产在病原体以及在古典煽动性的反应的产生的opsonization和细胞溶解终止。然而，更最近，在有免疫力的反应的补充的角色由于连接补充激活到适应有免疫力的回答的观察被扩展了。补充是在允许综合主人防卫到病原的挑战的天生、适应的有免疫力的回答之间的一座功能的桥，这现在被欣赏。因此，它的函数的研究象主机免疫者反应的组织和组织一样允许卓见进主人病原体相互作用的分子的underpinnings。这评论试图总结在主人防卫上在天生、适应的有免疫力的回答和这些相互作用的后果补充戏的角色。

简介：Stableisotopesofmostimportantbiologicalelements,suchasC,H,NandO,affectlivingorganisms.Inrapidlygrowingspecies,deuteriumandtoalesserextentotherheavyisotopesreducethegrowthrate.Atleastfordeuteriumitisknownthatitsdepletionalsonegativelyimpactsthespeedofbiologicalprocesses.Asarule,livingorganisms'resist'changesintheirisotopicenvironment,preferringnaturalisotopicabundances.Thispreferencecouldbeduetoevolutionaryoptimization;anadditionaleffectcouldbeduetothepresenceofthe'isotopicreso-nance'.Theisotopicresonancephenomenonhasbeenlinkedtothechoiceofearliestaminoacids,andthusaffectedtheevolutionofgeneticcode.Totesttheisotopicresonancehypothesis,literaturedatawereanalyzedagainstquantitativeandqualitativepredictionsofthehypothesis.Fourstudiesprovidedfiveindependentdatasets,eachinverygoodquantitativeagreementwiththepredictions.Thus,theisotopicresonancehypothesisisnolongersimplyplausible;itcannowbedeemedlikely.Additionaltestingisneeded,however,beforefullacceptanceofthishypothesis.

简介：植物发展了复杂生物化学的机制从昆虫herbivory阻止威胁。最近的研究表明了在对上面的植物回答的根的一个重要角色扎根了herbivory(AGH)。根的参与是不可分的种抵抗和忍耐机制。根不仅由为各种各样的毒素的生合成充当地点在植物防卫起一个活跃作用并且而且由存储photoassimilates启用未来生长贡献忍耐。有有益的忍受土壤的微生物的根的相互作用也影响在植物和昆虫草食动物之间的相互作用的结果。Shoot-to-root通讯信号为对AGH的植物反应是批评的。在对AGH的植物反应的根的角色的更好的理解是必要的以便开发植物昆虫相互作用的一幅全面图画。这里，我们在对AGH的植物反应总结关于根的角色的研究的当前的地位并且也讨论涉及shoot-to-root通讯的可能的信号。

简介：Weconductedacomprehensivestudytoinvestigatetheaerodynamiccharacteristicsandforcegenerationoftheelytraofabeetle,Allomyrinadichotoma.Ouranalysisincludedwindtunnelexperimentsandthree-dimensionalcomputationalfluiddynamicssimulationsusingANSYS-CFXsoftware.Ourfirstapproachwasaquasi-staticstudythatconsideredtheeffectofinducedflappingflowduetotheflappingmotionofthefore-wings(elytra)atafrequencyofaround30Hzto40Hz.Thedihedralanglewasvariedtorepresentflappingmotionduringtheupstrokeanddownstroke.Wefoundthatanelytronproducespositiveliftat0°geometricangleofattack,negativeliftduringtheupstroke,andalwaysproducesdragduringboththeupstrokeanddownstroke.Wealsofoundthattheliftcoefficientofanelytrondoesnotdropevenataveryhighgeometricangleofattack.Forabeetlewithabodyweightof5g,basedonthequasi-staticmethod,thefore-wings(elytra)canproduceliftoflessthan1%ofitsbodyweight.

简介：在病原体识别的像使用费的受体(TLR)的角色在最近的年里是快速地先进的。然而，进在非传染的织物损害的TLR的功能的调查刚开始了。以前，我们和其它表明了那碎裂的hyaluronan(哈)在织物损害期间积累。CD44被要求在织物损害期间清除HA，并且损害了清理哈在不停的发炎的结果。另外，碎裂哈在损害地点由煽动性的房间刺激煽动性的基因的表示。最近，我们识别了那哈碎片要求TLR2和TLR4刺激老鼠巨噬细胞生产煽动性的chemokines和cytokines。在一个非传染的肺损害模型，在TLR2和TLR4缺乏的老鼠显示出煽动性的房间的损害transepithelial迁居，增加的织物损害，提高的肺上皮的房间apoptosis，和减少的幸存。在高分子的质量的表示上的肺上皮的房间哈对尖锐的肺损害和apoptosis的保护的老鼠，部分地通过NF-kappaB的TLR依赖的基础激活。在TLR2和TLR4的夸大的损害缺乏的老鼠看起来由于上皮的房间上的损害HA-TLR相互作用。这些研究识别那个主机矩阵部件哈并且TLR相互作用提供开始煽动性的回答的信号，维持上皮的房间完整，并且支持从尖锐的肺损害的恢复。房间研究(2006)16：693-701。做i：10.1038/sj.cr.7310085；出版联机2006年8月8日。

简介：QuestionsconcerningthefunctionalroleofthehollowregionofthebutterflyPyrameisatalanta(L.)scaleareexperimentallyinvestigated.Attentionwasinitiallydirectedtothisproblembyobservationofthecomplexmicrostructureofthebutterflyscaleaswellasotherstudiesindicatinghigherliftonbutterflywingscoveredwithscale.Theaerodynamicforcesweremeasuredfortwooscillatingscalemodels.ResultsindicatedthattheaircavityofanoscillatingmodelofthePyrameisatalanta(L.)scaleincreasedtheliftbyafactorof1.15andreducedthedampingcoefficientsbyafactorof1.38.Themodificationoftheaerodynamiceffectsonthemodelofbutterflyscalewasduetoanincreaseofthevirtualairmass,whichinfluencedthebody.Thehollowregionofthescaleincreasedthevirtualairmassbyafactorof1.2.Thevirtualmassofthebutterflyscalewiththehollowregionwasrepresentedasthesumofairmassoftwoimaginarygeometricalfigures:acircularcylinderaroundthescaleandaright-angledparallelepipedwithinthehollowregion.TheinteractionmechanismofthebutterflyPyrameisatalanta(L.)scalewithaflowwasdescribed.Thisnovelinteractionmechanismexplainedmostgeometricalfeaturesoftheairpermeablebutterflyscale(invertedV-profileoftheridges,nozzleofthetipedge,hollowregion,andopeningsoftheupperlamina)andtheirarrangement.

简介：在为处理可变环境条件的昆虫的关键改编是diapause的能力。老虎燕子尾巴蝴蝶，Papilioglaucus和P。canadensis是理想的种类探索基因原因和人口diapause的基因后果因为这个特点地的分叉被相信是在维持在这些之间的一个混合地区的一个突出的因素种类。然而，很少对因素被知道影响在这个系统感应的diapause。这里，我们探索了怎么空间(纬度)，环境(温度)并且基因(杂交)因素影响在这个系统感应的diapause。明确地，用从越过东方美国的野蛮抓住的个人的一系列生长房间实验被执行到：(1)评估批评光周期怎么与纬度变化，(2)孤立在哪个正式就职发生的阶段，(3)测试在温度的变化是否影响了diapause正式就职的率，并且(4)探索diapause的发生怎么在混合后代被影响。我们发现那正式就职发生在幼虫的阶段，不对温度的一个相对宽广的范围敏感，看起来有一个复杂基因基础(即，不简单地是跟随一个孟德尔的继承模式的一个主导的特点)并且批评光周期在纬度与每增加的度由0.4h增加。这个工作加深我们空间、环境、基因的变化怎么在生态的模型系统和愿望使探索气候的变化怎么影响人口动力学和这个系统的遗传的未来研究可能的welldeveloped影响关键季节的改编(diapause正式就职)的理解。

简介：Thesurfaceglycoproteinhemagglutinin(HA)helpstheinfluenzaAvirustoevadethehostimmunesystembyantigenicvariationandisamajordrivingforceforviralevolution.Inthisstudy,theselectionpressureonHAofH5N1influenzaAviruswasanalyzedusingbioinformaticsalgorithms.Mostoftheidentifiedpositiveselection(PS)siteswerefoundtobewithinoradjacenttoepitopesites.SomeoftheidentifiedPSsitesareconsistentwithpreviousexperimentalstudies,providingfurthersupporttothebiologicalsignificanceofourfindings.ThehighestfrequencyofPSsiteswasobservedinrecentstrainsisolatedduring2005–2007.PhylogeneticanalysiswasalsoconductedonHAsequencesfromvarioushosts.Viraldriftisalmostsimilarinbothavianandhumanspecieswithaprogressivetrendovertheyears.OurstudyreportsnewmutationsinfunctionalregionsofHAthatmightprovidemarkersforvaccinedesignorcanbeusedtopredictisolatesofpandemicpotential.

简介：Thehedgehog-patched(hh-ptc)intercellularsignalingpathwayhasrecentlybeenshowntocontroltheproliferationofepithelialstemcellsinbothDrosophilaandVertebrated.MutantandectopicexpressionanalysesinDrosophilasuggestthattheHHproteindiffusesfromthesignalingcellstopromotetheproliferationofnearbyovariansomaticstemcellsbyantagonizingthesuppressionofitsreceptorPTCtowardstheCItranscriptionfactorinthestemcells.Consequently,thetranscriptionofCIdependentgenesleadstostemcellproliferation.Thisregulatorypathwayappearstofunctionalsoinvertebrates,wheredefectsinptccausebasalcellcarcinoma,tumorsofepidermalstemcellorigin.BasalcellcarcinomacanalsobeinducedbyectopicexpressionofSonichedgehog(shh)orGlil,thevertebratehomologofci.Thesestudiessuggesttheconservationofthehhsignalingpathwayincontrollingepithelialstemcelldivisionsamongdifferentorganisma.

简介：在Brassicaceae的摘要，myrosinase催化glucosinolate的水解作用并且在反草食动物防卫起一个重要作用。我们从从另外的Brassica种类与myrosinase基因展出高顺序身份的Brassicaparachinensis克隆并且描绘myrosinase基因的全身的互补DNA。对有菱形斑纹的蛾(Plutellaxylostella)在防卫调查这myrosinase的角色，我们构造了RNA干扰(RNAi)表示指向了myrosinase和transfected的双strandedRNA的盒子它进B。parachinensis。Myrosinase在结果被压制转基因的工厂。在转基因的工厂上喂的有菱形斑纹的蛾幼虫比在非转基因的工厂上喂的那些有更低的幼虫、蛹的重量，更长蛹的持续时间，和更低的肥沃，建议有菱形斑纹的蛾使防御系统适应了glucosinolate-myrosinase。因此，myrosinase的抑制是为控制有菱形斑纹的蛾的一条潜在的途径。

简介：在braconid和姬蜂标志黄蜂的恶意和卵巢的蛋白质在产卵离子以后立即在他们的主人的成功的寄生状态起一个重要作用，特别为有免疫力的抑制。在这研究，我们比较了从Macrocentrus瓣环的女黄蜂收集的恶意和卵巢的蛋白质的效果，Ostriniafunacalis的幼虫的polyembryonicparasitoid，在在4h和24hpost注射的SephadexA-25祷告的封装能力上体内和试管内。结果证明卵巢的蛋白质显著地以一种剂量依赖者方式防碍血球的封装能力。传播并且在O的血球的生存能力。furnacalis没被恶意和卵巢的蛋白质在注射的各种各样的集中破坏。它似乎可能从M的卵巢的蛋白质。瓣环玩在压制主人血球的封装能力的一个角色。

简介：<正>Uponactivation,naiveT-helpercellscandifferentiateintotwomajordistinctsubsets,Thelper1(Th1)andThelper2(Th2),asdefinedbytheireffectorfunctionsandcytokinesecretionpatterns.CytokinemilieuandcostimulatorymoleculeshavebeenshowntoplayanessentialroleindeterminingThelperdifferentiation.However,itisstillunclearhowtheeffectsofsignalsofco-stimulatorymoleculesandcytokinesareexertedduringThelperdifferentiation.Weshowevidencesuggestingthatwhilecytokinesignalsinitiatedifferentiationprogram,theselectiveactionofdeatheffectorsdeterminestheendpointbalanceofdifferenti-