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排序方式: 共有134条查询结果,搜索用时 640 毫秒
31.
Todd JA Walker NM Cooper JD Smyth DJ Downes K Plagnol V Bailey R Nejentsev S Field SF Payne F Lowe CE Szeszko JS Hafler JP Zeitels L Yang JH Vella A Nutland S Stevens HE Schuilenburg H Coleman G Maisuria M Meadows W Smink LJ Healy B Burren OS Lam AA Ovington NR Allen J Adlem E Leung HT Wallace C Howson JM Guja C Ionescu-Tîrgovişte C;Genetics of Type Diabetes in Finland Simmonds MJ Heward JM Gough SC;Wellcome Trust Case Control Consortium Dunger DB Wicker LS Clayton DG 《Nature genetics》2007,39(7):857-864
The Wellcome Trust Case Control Consortium (WTCCC) primary genome-wide association (GWA) scan on seven diseases, including the multifactorial autoimmune disease type 1 diabetes (T1D), shows associations at P < 5 x 10(-7) between T1D and six chromosome regions: 12q24, 12q13, 16p13, 18p11, 12p13 and 4q27. Here, we attempted to validate these and six other top findings in 4,000 individuals with T1D, 5,000 controls and 2,997 family trios independent of the WTCCC study. We confirmed unequivocally the associations of 12q24, 12q13, 16p13 and 18p11 (P(follow-up) 相似文献
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Stanton H Rogerson FM East CJ Golub SB Lawlor KE Meeker CT Little CB Last K Farmer PJ Campbell IK Fourie AM Fosang AJ 《Nature》2005,434(7033):648-652
Aggrecan is the major proteoglycan in cartilage, endowing this tissue with the unique capacity to bear load and resist compression. In arthritic cartilage, aggrecan is degraded by one or more 'aggrecanases' from the ADAMTS (a disintegrin and metalloproteinase with thrombospondin motifs) family of proteinases. ADAMTS1, 8 and 9 have weak aggrecan-degrading activity. However, they are not thought to be the primary aggrecanases because ADAMTS1 null mice are not protected from experimental arthritis, and cleavage by ADAMTS8 and 9 is highly inefficient. Although ADAMTS4 and 5 are expressed in joint tissues, and are known to be efficient aggrecanases in vitro, the exact contribution of these two enzymes to cartilage pathology is unknown. Here we show that ADAMTS5 is the major aggrecanase in mouse cartilage, both in vitro and in a mouse model of inflammatory arthritis. Our data suggest that ADAMTS5 may be a suitable target for the development of new drugs designed to inhibit cartilage destruction in arthritis, although further work will be required to determine whether ADAMTS5 is also the major aggrecanase in human arthritis. 相似文献
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Buchanan JD Cowburn RP Jausovec AV Petit D Seem P Xiong G Atkinson D Fenton K Allwood DA Bryan MT 《Nature》2005,436(7050):475
We have found that almost all paper documents, plastic cards and product packaging contain a unique physical identity code formed from microscopic imperfections in the surface. This covert 'fingerprint' is intrinsic and virtually impossible to modify controllably. It can be rapidly read using a low-cost portable laser scanner. Most forms of document and branded-product fraud could be rendered obsolete by use of this code. 相似文献
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Curran JE Jowett JB Elliott KS Gao Y Gluschenko K Wang J Abel Azim DM Cai G Mahaney MC Comuzzie AG Dyer TD Walder KR Zimmet P MacCluer JW Collier GR Kissebah AH Blangero J 《Nature genetics》2005,37(11):1234-1241
Chronic inflammation has a pathological role in many common diseases and is influenced by both genetic and environmental factors. Here we assess the role of genetic variation in selenoprotein S (SEPS1, also called SELS or SELENOS), a gene involved in stress response in the endoplasmic reticulum and inflammation control. After resequencing SEPS1, we genotyped 13 SNPs in 522 individuals from 92 families. As inflammation biomarkers, we measured plasma levels of IL-6, IL-1beta and TNF-alpha. Bayesian quantitative trait nucleotide analysis identified associations between SEPS1 polymorphisms and all three proinflammatory cytokines. One promoter variant, -105G --> A, showed strong evidence for an association with each cytokine (multivariate P = 0.0000002). Functional analysis of this polymorphism showed that the A variant significantly impaired SEPS1 expression after exposure to endoplasmic reticulum stress agents (P = 0.00006). Furthermore, suppression of SEPS1 by short interfering RNA in macrophage cells increased the release of IL-6 and TNF-alpha. To investigate further the significance of the observed associations, we genotyped -105G --> A in 419 Mexican American individuals from 23 families for replication. This analysis confirmed a significant association with both TNF-alpha (P = 0.0049) and IL-1beta (P = 0.0101). These results provide a direct mechanistic link between SEPS1 and the production of inflammatory cytokines and suggest that SEPS1 has a role in mediating inflammation. 相似文献
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Zusammenfassung An der isolierten Kaninchenherzvorkammer verursacht Sauerstoffmangel Verminderung der diastolischen Erregbarkeit, Verlängerung der refraktären Phase sowie Herabsetzung der Kontraktionsfähigkeit. Herzmuskelflimmern wurde während dieser Anoxie nicht beobachtet. Sauerstoffzufuhr führte zu einer vollständigen Aufhebung der Anoxieauswirkung auf die absolute Refraktärperiode, zu einer teilweisen Aufhebung dieser Auswirkungen auf die Dauer der refraktären Gesamtpause, die diastolische Erregbarkeit und das Kontraktionsvermögen. 相似文献
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Apoptosis disables CD31-mediated cell detachment from phagocytes promoting binding and engulfment 总被引:19,自引:0,他引:19
Macrophage recognition and ingestion of 'self' cells undergoing apoptosis in vivo protects tissues from the toxic contents of dying cells and modulates macrophage regulation of inflammatory and immune responses. However, the complex molecular mechanisms mediating macrophage discrimination between viable and apoptotic cells are poorly understood. In particular, little is known of why viable nucleated cells are not engulfed by macrophages. To reveal active repulsion of viable cells and to seek specific capture or 'tethering' of apoptotic cells, we studied macrophage binding of viable and apoptotic leukocytes under conditions of flow. We found that homophilic ligation of CD31 (ref. 4) on viable leukocytes promoted their active, temperature-dependent detachment under low shear, whereas such CD31-mediated detachment was disabled in apoptotic leukocytes, promoting tight binding and macrophage ingestion of dying cells. Here we propose that CD31 (also known as platelet-endothelial cell adhesion molecule-1, PECAM-1) is an example of a cell-surface molecule that prevents phagocyte ingestion of closely apposed viable cells by transmitting 'detachment' signals, and which changes function on apoptosis, promoting tethering of dying cells to phagocytes. 相似文献