排序方式: 共有7条查询结果,搜索用时 296 毫秒
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Willer CJ Sanna S Jackson AU Scuteri A Bonnycastle LL Clarke R Heath SC Timpson NJ Najjar SS Stringham HM Strait J Duren WL Maschio A Busonero F Mulas A Albai G Swift AJ Morken MA Narisu N Bennett D Parish S Shen H Galan P Meneton P Hercberg S Zelenika D Chen WM Li Y Scott LJ Scheet PA Sundvall J Watanabe RM Nagaraja R Ebrahim S Lawlor DA Ben-Shlomo Y Davey-Smith G Shuldiner AR Collins R Bergman RN Uda M Tuomilehto J Cao A Collins FS Lakatta E Lathrop GM Boehnke M Schlessinger D Mohlke KL 《Nature genetics》2008,40(2):161-169
To identify genetic variants influencing plasma lipid concentrations, we first used genotype imputation and meta-analysis to combine three genome-wide scans totaling 8,816 individuals and comprising 6,068 individuals specific to our study (1,874 individuals from the FUSION study of type 2 diabetes and 4,184 individuals from the SardiNIA study of aging-associated variables) and 2,758 individuals from the Diabetes Genetics Initiative, reported in a companion study in this issue. We subsequently examined promising signals in 11,569 additional individuals. Overall, we identify strongly associated variants in eleven loci previously implicated in lipid metabolism (ABCA1, the APOA5-APOA4-APOC3-APOA1 and APOE-APOC clusters, APOB, CETP, GCKR, LDLR, LPL, LIPC, LIPG and PCSK9) and also in several newly identified loci (near MVK-MMAB and GALNT2, with variants primarily associated with high-density lipoprotein (HDL) cholesterol; near SORT1, with variants primarily associated with low-density lipoprotein (LDL) cholesterol; near TRIB1, MLXIPL and ANGPTL3, with variants primarily associated with triglycerides; and a locus encompassing several genes near NCAN, with variants strongly associated with both triglycerides and LDL cholesterol). Notably, the 11 independent variants associated with increased LDL cholesterol concentrations in our study also showed increased frequency in a sample of coronary artery disease cases versus controls. 相似文献
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Speliotes EK Willer CJ Berndt SI Monda KL Thorleifsson G Jackson AU Lango Allen H Lindgren CM Luan J Mägi R Randall JC Vedantam S Winkler TW Qi L Workalemahu T Heid IM Steinthorsdottir V Stringham HM Weedon MN Wheeler E Wood AR Ferreira T Weyant RJ Segrè AV Estrada K Liang L Nemesh J Park JH Gustafsson S Kilpeläinen TO Yang J Bouatia-Naji N Esko T Feitosa MF Kutalik Z Mangino M Raychaudhuri S Scherag A Smith AV Welch R Zhao JH Aben KK Absher DM Amin N Dixon AL Fisher E Glazer NL Goddard ME 《Nature genetics》2010,42(11):937-948
Obesity is globally prevalent and highly heritable, but its underlying genetic factors remain largely elusive. To identify genetic loci for obesity susceptibility, we examined associations between body mass index and ~ 2.8 million SNPs in up to 123,865 individuals with targeted follow up of 42 SNPs in up to 125,931 additional individuals. We confirmed 14 known obesity susceptibility loci and identified 18 new loci associated with body mass index (P < 5 × 10??), one of which includes a copy number variant near GPRC5B. Some loci (at MC4R, POMC, SH2B1 and BDNF) map near key hypothalamic regulators of energy balance, and one of these loci is near GIPR, an incretin receptor. Furthermore, genes in other newly associated loci may provide new insights into human body weight regulation. 相似文献
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Sanna S Jackson AU Nagaraja R Willer CJ Chen WM Bonnycastle LL Shen H Timpson N Lettre G Usala G Chines PS Stringham HM Scott LJ Dei M Lai S Albai G Crisponi L Naitza S Doheny KF Pugh EW Ben-Shlomo Y Ebrahim S Lawlor DA Bergman RN Watanabe RM Uda M Tuomilehto J Coresh J Hirschhorn JN Shuldiner AR Schlessinger D Collins FS Davey Smith G Boerwinkle E Cao A Boehnke M Abecasis GR Mohlke KL 《Nature genetics》2008,40(2):198-203
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Verónica Parrillas Laura Martínez-Muñoz Borja L. Holgado Amit Kumar Graciela Cascio Pilar Lucas José Miguel Rodríguez-Frade Marcos Malumbres Ana C. Carrera Karel HM van Wely Mario Mellado 《Cellular and molecular life sciences : CMLS》2013,70(3):545-558
Hypermethylation of SOCS genes is associated with many human cancers, suggesting a role as tumor suppressors. As adaptor molecules for ubiquitin ligases, SOCS proteins modulate turnover of numerous target proteins. Few SOCS targets identified so far have a direct role in cell cycle progression; the mechanism by which SOCS regulate the cell cycle thus remains largely unknown. Here we show that SOCS1 overexpression inhibits in vitro and in vivo expansion of human melanoma cells, and that SOCS1 associates specifically with Cdh1, triggering its degradation by the proteasome. Cells therefore show a G1/S transition defect, as well as a secondary blockade in mitosis and accumulation of cells in metaphase. SOCS1 expression correlated with a reduction in cyclin D/E levels and an increase in the tumor suppressor p19, as well as the CDK inhibitor p53, explaining the G1/S transition defect. As a result of Cdh1 degradation, SOCS1-expressing cells accumulated cyclin B1 and securin, as well as apparently inactive Cdc20, in mitosis. Levels of the late mitotic Cdh1 substrate Aurora A did not change. These observations comprise a hitherto unreported mechanism of SOCS1 tumor suppression, suggesting this molecule as a candidate for the design of new therapeutic strategies for human melanoma. 相似文献
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Blanco A Chomski E Grabtchak S Ibisate M John S Leonard SW Lopez C Meseguer F Miguez H Mondia JP Ozin GA Toader O van Driel HM 《Nature》2000,405(6785):437-440
Photonic technology, using light instead of electrons as the information carrier, is increasingly replacing electronics in communication and information management systems. Microscopic light manipulation, for this purpose, is achievable through photonic bandgap materials, a special class of photonic crystals in which three-dimensional, periodic dielectric constant variations controllably prohibit electromagnetic propagation throughout a specified frequency band. This can result in the localization of photons, thus providing a mechanism for controlling and inhibiting spontaneous light emission that can be exploited for photonic device fabrication. In fact, carefully engineered line defects could act as waveguides connecting photonic devices in all-optical microchips, and infiltration of the photonic material with suitable liquid crystals might produce photonic bandgap structures (and hence light-flow patterns) fully tunable by an externally applied voltage. However, the realization of this technology requires a strategy for the efficient synthesis of high-quality, large-scale photonic crystals with photonic bandgaps at micrometre and sub-micrometre wavelengths, and with rationally designed line and point defects for optical circuitry. Here we describe single crystals of silicon inverse opal with a complete three-dimensional photonic bandgap centred on 1.46 microm, produced by growing silicon inside the voids of an opal template of dose-packed silica spheres that are connected by small 'necks' formed during sintering, followed by removal of the silica template. The synthesis method is simple and inexpensive, yielding photonic crystals of pure silicon that are easily integrated with existing silicon-based microelectronics. 相似文献
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