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排序方式: 共有94条查询结果,搜索用时 46 毫秒
81.
K Pritchard-Jones S Fleming D Davidson W Bickmore D Porteous C Gosden J Bard A Buckler J Pelletier D Housman 《Nature》1990,346(6280):194-197
82.
Ghoreschi K Laurence A Yang XP Tato CM McGeachy MJ Konkel JE Ramos HL Wei L Davidson TS Bouladoux N Grainger JR Chen Q Kanno Y Watford WT Sun HW Eberl G Shevach EM Belkaid Y Cua DJ Chen W O'Shea JJ 《Nature》2010,467(7318):967-971
CD4(+) T-helper cells that selectively produce interleukin (IL)-17 (T(H)17), are critical for host defence and autoimmunity. Although crucial for T(H)17 cells in vivo, IL-23 has been thought to be incapable of driving initial differentiation. Rather, IL-6 and transforming growth factor (TGF)-β1 have been proposed to be the factors responsible for initiating specification. Here we show that T(H)17 differentiation can occur in the absence of TGF-β signalling. Neither IL-6 nor IL-23 alone efficiently generated T(H)17 cells; however, these cytokines in combination with IL-1β effectively induced IL-17 production in naive precursors, independently of TGF-β. Epigenetic modification of the Il17a, Il17f and Rorc promoters proceeded without TGF-β1, allowing the generation of cells that co-expressed RORγt (encoded by Rorc) and T-bet. T-bet(+)RORγt(+) T(H)17 cells are generated in vivo during experimental allergic encephalomyelitis, and adoptively transferred T(H)17 cells generated with IL-23 without TGF-β1 were pathogenic in this disease model. These data indicate an alternative mode for T(H)17 differentiation. Consistent with genetic data linking IL23R with autoimmunity, our findings re-emphasize the importance of IL-23 and therefore may have therapeutic implications. 相似文献
83.
Loveday C Turnbull C Ramsay E Hughes D Ruark E Frankum JR Bowden G Kalmyrzaev B Warren-Perry M Snape K Adlard JW Barwell J Berg J Brady AF Brewer C Brice G Chapman C Cook J Davidson R Donaldson A Douglas F Greenhalgh L Henderson A Izatt L Kumar A Lalloo F Miedzybrodzka Z Morrison PJ Paterson J Porteous M Rogers MT Shanley S Walker L;Breast Cancer Susceptibility Collaboration 《Nature genetics》2011,43(9):879-882
Recently, RAD51C mutations were identified in families with breast and ovarian cancer. This observation prompted us to investigate the role of RAD51D in cancer susceptibility. We identified eight inactivating RAD51D mutations in unrelated individuals from 911 breast-ovarian cancer families compared with one inactivating mutation identified in 1,060 controls (P = 0.01). The association found here was principally with ovarian cancer, with three mutations identified in the 59 pedigrees with three or more individuals with ovarian cancer (P = 0.0005). The relative risk of ovarian cancer for RAD51D mutation carriers was estimated to be 6.30 (95% CI 2.86-13.85, P = 4.8 × 10(-6)). By contrast, we estimated the relative risk of breast cancer to be 1.32 (95% CI 0.59-2.96, P = 0.50). These data indicate that RAD51D mutation testing may have clinical utility in individuals with ovarian cancer and their families. Moreover, we show that cells deficient in RAD51D are sensitive to treatment with a PARP inhibitor, suggesting a possible therapeutic approach for cancers arising in RAD51D mutation carriers. 相似文献
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L C Papadopoulou C M Sue M M Davidson K Tanji I Nishino J E Sadlock S Krishna W Walker J Selby D M Glerum R V Coster G Lyon E Scalais R Lebel P Kaplan S Shanske D C De Vivo E Bonilla M Hirano S DiMauro E A Schon 《Nature genetics》1999,23(3):333-337
Mammalian cytochrome c oxidase (COX) catalyses the transfer of reducing equivalents from cytochrome c to molecular oxygen and pumps protons across the inner mitochondrial membrane. Mitochondrial DNA (mtDNA) encodes three COX subunits (I-III) and nuclear DNA (nDNA) encodes ten. In addition, ancillary proteins are required for the correct assembly and function of COX (refs 2, 3, 4, 5, 6). Although pathogenic mutations in mtDNA-encoded COX subunits have been described, no mutations in the nDNA-encoded subunits have been uncovered in any mendelian-inherited COX deficiency disorder. In yeast, two related COX assembly genes, SCO1 and SCO2 (for synthesis of cytochrome c oxidase), enable subunits I and II to be incorporated into the holoprotein. Here we have identified mutations in the human homologue, SCO2, in three unrelated infants with a newly recognized fatal cardioencephalomyopathy and COX deficiency. Immunohistochemical studies implied that the enzymatic deficiency, which was most severe in cardiac and skeletal muscle, was due to the loss of mtDNA-encoded COX subunits. The clinical phenotype caused by mutations in human SCO2 differs from that caused by mutations in SURF1, the only other known COX assembly gene associated with a human disease, Leigh syndrome. 相似文献
88.
Nanoscale architecture of integrin-based cell adhesions 总被引:3,自引:0,他引:3
Kanchanawong P Shtengel G Pasapera AM Ramko EB Davidson MW Hess HF Waterman CM 《Nature》2010,468(7323):580-584
Cell adhesions to the extracellular matrix (ECM) are necessary for morphogenesis, immunity and wound healing. Focal adhesions are multifunctional organelles that mediate cell-ECM adhesion, force transmission, cytoskeletal regulation and signalling. Focal adhesions consist of a complex network of trans-plasma-membrane integrins and cytoplasmic proteins that form a?<200-nm plaque linking the ECM to the actin cytoskeleton. The complexity of focal adhesion composition and dynamics implicate an intricate molecular machine. However, focal adhesion molecular architecture remains unknown. Here we used three-dimensional super-resolution fluorescence microscopy (interferometric photoactivated localization microscopy) to map nanoscale protein organization in focal adhesions. Our results reveal that integrins and actin are vertically separated by a ~40-nm focal adhesion core region consisting of multiple protein-specific strata: a membrane-apposed integrin signalling layer containing integrin cytoplasmic tails, focal adhesion kinase and paxillin; an intermediate force-transduction layer containing talin and vinculin; and an uppermost actin-regulatory layer containing zyxin, vasodilator-stimulated phosphoprotein and α-actinin. By localizing amino- and carboxy-terminally tagged talins, we reveal talin's polarized orientation, indicative of a role in organizing the focal adhesion strata. The composite multilaminar protein architecture provides a molecular blueprint for understanding focal adhesion functions. 相似文献
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Zusammenfassung Zellkerne, die aus Kaninchengewebe mittels eines nichtwässrigen Verfahrens bereitet werden, enthalten in ihren säurelöslichen Bestandteilen Nukleotide von Adenin, Hypoxanthin, Guanin, Uracil und (in sehr geringen Mengen) von Cytosin. Diese Stoffe wurden in Lunge, Darm-Mucosa, Knochenmark, Appendix und Thymus in abnehmender Konzentration vorgefunden.
British Empire Cancer Campaign Research Fellow 相似文献
British Empire Cancer Campaign Research Fellow 相似文献