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排序方式: 共有251条查询结果,搜索用时 15 毫秒
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Animal studies hint at staying power of SARS 总被引:2,自引:0,他引:2
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Repping S Skaletsky H Brown L van Daalen SK Korver CM Pyntikova T Kuroda-Kawaguchi T de Vries JW Oates RD Silber S van der Veen F Page DC Rozen S 《Nature genetics》2003,35(3):247-251
Many human Y-chromosomal deletions are thought to severely impair reproductive fitness, which precludes their transmission to the next generation and thus ensures their rarity in the population. Here we report a 1.6-Mb deletion that persists over generations and is sufficiently common to be considered a polymorphism. We hypothesized that this deletion might affect spermatogenesis because it removes almost half of the Y chromosome's AZFc region, a gene-rich segment that is critical for sperm production. An association study established that this deletion, called gr/gr, is a significant risk factor for spermatogenic failure. The gr/gr deletion has far lower penetrance with respect to spermatogenic failure than previously characterized Y-chromosomal deletions; it is often transmitted from father to son. By studying the distribution of gr/gr-deleted chromosomes across the branches of the Y chromosome's genealogical tree, we determined that this deletion arose independently at least 14 times in human history. We suggest that the existence of this deletion as a polymorphism reflects a balance between haploid selection, which culls gr/gr-deleted Y chromosomes from the population, and homologous recombination, which continues to generate new gr/gr deletions. 相似文献
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Post-translational modification by ubiquitin-like proteins (Ublps) is an essential cellular regulatory mechanism. The Ublp NEDD8 regulates cell division, signalling and embryogenesis. Ublps are conjugated to their targets by the sequential action of E1, E2 and often E3 enzymes. Each Ublp has a dedicated E1, or activating enzyme, that initiates its conjugation cascade. First, E1 associates with the Ublp and catalyses adenylation of the carboxy terminus of the Ublp. Second, E1 forms a thioester between its catalytic cysteine and the Ublp. Next, E1 is loaded with a second Ublp molecule, adenylating the C terminus of this second Ublp while still carrying the first thioester-bound Ublp. Last, E1 binds E2 and promotes Ublp transfer to the catalytic cysteine of E2. We report here the structure and mutational analysis of human APPBP1-UBA3, the heterodimeric E1 enzyme for NEDD8 (ref. 11). Each E1 activity is specified by a domain: an adenylation domain resembling bacterial adenylating enzymes, an E1-specific domain organized around the catalytic cysteine, and a domain involved in E2 recognition resembling ubiquitin. The domains are arranged around two clefts that coordinate protein and nucleotide binding so that each of E1's reactions drives the next, in an assembly-line fashion. 相似文献
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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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It is important that migration is measured accurately, for example to inform population estimates and projections. However, current sources of information make it difficult to produce robust estimates of emigration from Great Britain. Several other countries, including Ireland, make use of household surveys in their estimates of migration. To investigate the feasibility of obtaining information on emigration from those resident in Great Britain, three questions were included in the Omnibus Survey for two months. Respondents were asked whether they had plans to emigrate or whether anyone in their family had recently emigrated or intended to shortly. This article reports on the results of this pilot, providing evidence on response levels, comparison with the International Passenger Survey and feedback from interviewers on the questions asked. 相似文献