排序方式: 共有198条查询结果,搜索用时 46 毫秒
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McGregor L Makela V Darling SM Vrontou S Chalepakis G Roberts C Smart N Rutland P Prescott N Hopkins J Bentley E Shaw A Roberts E Mueller R Jadeja S Philip N Nelson J Francannet C Perez-Aytes A Megarbane A Kerr B Wainwright B Woolf AS Winter RM Scambler PJ 《Nature genetics》2003,34(2):203-208
Fraser syndrome (OMIM 219000) is a multisystem malformation usually comprising cryptophthalmos, syndactyly and renal defects. Here we report autozygosity mapping and show that the locus FS1 at chromosome 4q21 is associated with Fraser syndrome, although the condition is genetically heterogeneous. Mutation analysis identified five frameshift mutations in FRAS1, which encodes one member of a family of novel proteins related to an extracellular matrix (ECM) blastocoelar protein found in sea urchin. The FRAS1 protein contains a series of N-terminal cysteine-rich repeat motifs previously implicated in BMP metabolism, suggesting that it has a role in both structure and signal propagation in the ECM. It has been speculated that Fraser syndrome is a human equivalent of the blebbed phenotype in the mouse, which has been associated with mutations in at least five loci including bl. As mapping data were consistent with homology of FRAS1 and bl, we screened DNA from bl/bl mice and identified a premature termination of mouse Fras1. Thus, the bl mouse is a model for Fraser syndrome in humans, a disorder caused by disrupted epithelial integrity in utero. 相似文献
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Pace ML Cole JJ Carpenter SR Kitchell JF Hodgson JR Van De Bogert MC Bade DL Kritzberg ES Bastviken D 《Nature》2004,427(6971):240-243
Ecosystems are supported by organic carbon from two distinct sources. Endogenous carbon is produced by photosynthesis within an ecosystem by autotrophic organisms. Exogenous carbon is produced elsewhere and transported into ecosystems. Consumers may use exogenous carbon with consequent influences on population dynamics, predator-prey relationships and ecosystem processes. For example, exogenous inputs provide resources that may enhance consumer abundance beyond levels supported by within-system primary production. Exogenous fluxes of organic carbon to ecosystems are often large, but this material is recalcitrant and difficult to assimilate, in contrast to endogenously produced organic matter, which is used more easily. Here we show, by the experimental manipulation of dissolved inorganic (13)C in two lakes, that internal primary production is insufficient to support the food webs of these ecosystems. Additions of NaH(13)CO(3) enriched the (13)C content of dissolved inorganic carbon, particulate organic carbon, zooplankton and fish. Dynamics of (13)C indicate that 40-55% of particulate organic carbon and 22-50% of zooplankton carbon are derived from terrestrial sources, showing that there is significant subsidy of these ecosystems by organic carbon produced outside their boundaries. 相似文献
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Loss of integrin alpha(v)beta8 on dendritic cells causes autoimmunity and colitis in mice 总被引:1,自引:0,他引:1
Travis MA Reizis B Melton AC Masteller E Tang Q Proctor JM Wang Y Bernstein X Huang X Reichardt LF Bluestone JA Sheppard D 《Nature》2007,449(7160):361-365
The cytokine transforming growth factor-beta (TGF-beta) is an important negative regulator of adaptive immunity. TGF-beta is secreted by cells as an inactive precursor that must be activated to exert biological effects, but the mechanisms that regulate TGF-beta activation and function in the immune system are poorly understood. Here we show that conditional loss of the TGF-beta-activating integrin alpha(v)beta8 on leukocytes causes severe inflammatory bowel disease and age-related autoimmunity in mice. This autoimmune phenotype is largely due to lack of alpha(v)beta8 on dendritic cells, as mice lacking alpha(v)beta8 principally on dendritic cells develop identical immunological abnormalities as mice lacking alpha(v)beta8 on all leukocytes, whereas mice lacking alpha(v)beta8 on T cells alone are phenotypically normal. We further show that dendritic cells lacking alpha(v)beta8 fail to induce regulatory T cells (T(R) cells) in vitro, an effect that depends on TGF-beta activity. Furthermore, mice lacking alpha(v)beta8 on dendritic cells have reduced proportions of T(R) cells in colonic tissue. These results suggest that alpha(v)beta8-mediated TGF-beta activation by dendritic cells is essential for preventing immune dysfunction that results in inflammatory bowel disease and autoimmunity, effects that are due, at least in part, to the ability of alpha(v)beta8 on dendritic cells to induce and/or maintain tissue T(R) cells. 相似文献
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