Ultrastructure
Ultrastructure
批准号:
9068773
负责人:
CLARA FRANZINI-ARMSTRONG
金额:
$12.81万
依托单位国家:
美国
项目类别:
财政年份:
2006
资助国家:
美国
项目状态:
已结题
起止时间:
2006-04-14 至 2018-05-31
关键词:
AffectAgeAgingAnimal ModelApoptosisAreaBehaviorBiopsyCalciumCellsCollaborationsConfocal MicroscopyCouplingDataDependenceDetectionDevelopmentElectron MicroscopyElectronsEmbryoEvaluationExtravasationFeedbackFiberFoundationsFreeze FracturingFrequenciesGenderGoalsGrantGuidelinesHeterozygoteHomozygoteHumanHuman PathologyImageIndividualInduced MutationInstructionLight MicroscopeLinkMalignant hyperpyrexia due to anesthesiaMicrotomyMitochondriaModelingMolecularMouse StrainsMusMuscleMuscle FibersMutateMutationOrganellesPathologyPatientsPermeabilityPhaseProteinsReactionRyR1Ryanodine Receptor Calcium Release ChannelSERCA1SamplingSarcoplasmic ReticulumSkeletal MuscleStagingSurfaceTechniquesTestingTriad Acrylic ResinVariantWorkbasedensityearly onsetexperiencehigh standardhuman tissueinsightinterestmorphometrymouse modeloverexpressionprotein protein interactionresponsesex
中文摘要
核心 D 将执行支持所有其他项目所必需的定性和定量组织学和超微结构检查。该核心不仅将提供各种电子、相差和共焦显微镜技术,而且还将以高质量标准运行,并对实验和分子改变的结果提供专家的批判性评估。高质量图像的统一和一致使用将允许检测蛋白质-蛋白质相互作用和单个细胞器反应的细微变化,这些变化要么是功能改变的基础,要么是这种改变的长期结果。很明显,肌纤维对影响兴奋-收缩耦合的突变的整体超微结构反应是非常具体的,并且为因果效应提供了相当多的见解。在过去的一段时间里,我们已经证明了病理学的强烈纤维类型和性别依赖性,这与类似的功能变化很好地对应。提出了两种通用方法。一是定义突变背景下钙释放单位(CRU、骨骼肌中的三联体)主要蛋白质成分之间关系的任何变化,另一个是通过发育和衰老跟踪病理学的发展(最具体的是线粒体、肌原纤维和 CRU 的变化),以及与突变对 CRU 通道的已知功能影响相关。这将通过结合光学显微镜技术(纤维整体相差和荧光共聚焦成像)来实现免疫标记纤维),具有用于电子显微镜的薄切片和冷冻断裂,并辅以定量形态测量技术。核心目标是确定每个突变在短期内对钙释放单元大分子组装的主要影响,以及长期对 SR、线粒体和收缩材料的次要影响。
英文摘要
Core D will perform the qualitative and quantitative histological and ultrastructural checks that are necessary to support all other Projects. The Core will not only supply various techniques of electron, phase contrast and confocal microscopy, but it will also operate at a high standard of quality and offer an expert critical evaluation of the results of experimental and molecular alterations. The uniform and consistent use of high quality images will allow the detection of even subtle alterations in protein-protein interactions and in the response of individual cell organelles that either are at the basis of altered functions or are the long term results of such alterations. It is clear that the overall ultrastructural response of the muscle fiber to mutations affecting excitation-contraction coupling are quite specific and offer considerable insight into causative effects. In the past period we have evidenced a strong fiber type- and gender-dependence of the pathology, that correspindes quite well with similar variations in function. Two general approaches are proposed. One is to define any alterations in the relationships between the major protein components of calcium release units (CRUs, triads in skeletal muscle) within the context of the mutation and the other is to follow the development of pathology (most specifically mitochondrial, myofibrillar and CRUs' alterations) through development and aging and in relation to the known functional effects of the mutation on CRUs' channels.This will be achieved by combining light microscope techniques (phase contrast of fibers whole mounts and confocal imaging of fluorescently immunolabeled fibers) with thin sectioning and freeze-fracture for electron microscopy supplemented by quantitative morphometry techniques. The core aims at defining the primary impact of each mutation on the macromelcular assembly of calcium release units within a short term and the secondary impact on SR, mitochondria and contractile material on the long term.
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会议论文
TOMOGRAPHY OF SKELETAL MUSCLE TRIADIC JUNCTION
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批准号:8172283
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项目类别:
-
资助金额:$0.54万
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财政年份:2010
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负责人:CLARA FRANZINI-ARMSTRONG
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依托单位:
TOMOGRAPHY OF SKELETAL MUSCLE TRIADIC JUNCTION
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批准号:7721716
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项目类别:
-
资助金额:$3.34万
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财政年份:2008
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负责人:CLARA FRANZINI-ARMSTRONG
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依托单位:
Core D
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批准号:7436122
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项目类别:
-
资助金额:$11.6万
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财政年份:2007
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负责人:CLARA FRANZINI-ARMSTRONG
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依托单位:
TOMOGRAPHY OF SKELETAL MUSCLE TRIADIC JUNCTION
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批准号:7598376
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项目类别:
-
资助金额:$1.15万
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财政年份:2007
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负责人:CLARA FRANZINI-ARMSTRONG
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依托单位:
Electron Microscopy
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批准号:7504346
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项目类别:
-
资助金额:$10.26万
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财政年份:2007
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负责人:CLARA FRANZINI-ARMSTRONG
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依托单位:
Ultrastructure
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批准号:8478060
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项目类别:
-
资助金额:$13.46万
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财政年份:2006
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负责人:CLARA FRANZINI-ARMSTRONG
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依托单位:
Ultrastructure
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批准号:8667321
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项目类别:
-
资助金额:$12.48万
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财政年份:2006
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负责人:CLARA FRANZINI-ARMSTRONG
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依托单位:
Core D
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批准号:7137175
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项目类别:
-
资助金额:$8.77万
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财政年份:2005
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负责人:CLARA FRANZINI-ARMSTRONG
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依托单位:
MOLECULAR ARCHITECTURE OF E C COUPLING UNITS
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批准号:6338667
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项目类别:
-
资助金额:$20.29万
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财政年份:2000
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负责人:CLARA FRANZINI-ARMSTRONG
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依托单位:
MYOSIN MOTOR IN ACTION
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批准号:6353510
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项目类别:
-
资助金额:$28.89万
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财政年份:2000
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负责人:CLARA FRANZINI-ARMSTRONG
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依托单位:
MYOSIN MOTOR IN ACTION
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批准号:6202159
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项目类别:
-
资助金额:$28.89万
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财政年份:1999
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负责人:CLARA FRANZINI-ARMSTRONG
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依托单位:
MOLECULAR ARCHITECTURE OF E C COUPLING UNITS
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批准号:6201524
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项目类别:
-
资助金额:$20.29万
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财政年份:1999
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负责人:CLARA FRANZINI-ARMSTRONG
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依托单位:
MYOSIN MOTOR IN ACTION
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批准号:6109392
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项目类别:
-
资助金额:$28.89万
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财政年份:1998
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负责人:CLARA FRANZINI-ARMSTRONG
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依托单位:
MOLECULAR ARCHITECTURE OF E C COUPLING UNITS
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批准号:6100669
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项目类别:
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资助金额:$20.29万
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财政年份:1998
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负责人:CLARA FRANZINI-ARMSTRONG
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依托单位:
CONTRACTION AND E-C COUPLING IN STRIATED MUSCLE
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批准号:6241528
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项目类别:
-
资助金额:$21.84万
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财政年份:1997
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负责人:CLARA FRANZINI-ARMSTRONG
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依托单位:
MOLECULAR ARCHITECTURE OF E C COUPLING UNITS
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批准号:6235874
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项目类别:
-
资助金额:$20.88万
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财政年份:1997
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负责人:CLARA FRANZINI-ARMSTRONG
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依托单位:
CALCIUM RELEASE UNITS IN CARDIAC MUSCLE
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批准号:2224148
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项目类别:
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资助金额:$17.83万
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财政年份:1993
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负责人:CLARA FRANZINI-ARMSTRONG
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依托单位:
CALCIUM RELEASE UNITS IN CARDIAC MUSCLE
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批准号:6389206
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项目类别:
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资助金额:$21.5万
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财政年份:1993
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负责人:CLARA FRANZINI-ARMSTRONG
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依托单位:
CALCIUM RELEASE UNITS IN CARDIAC MUSCLE
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批准号:3367220
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项目类别:
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资助金额:$16.16万
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财政年份:1993
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负责人:CLARA FRANZINI-ARMSTRONG
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依托单位:
CALCIUM RELEASE UNITS IN CARDIAC MUSCLE
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批准号:6537025
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项目类别:
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资助金额:$21.99万
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财政年份:1993
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负责人:CLARA FRANZINI-ARMSTRONG
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依托单位:
国内基金
海外基金
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