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排序方式: 共有105条查询结果,搜索用时 312 毫秒
71.
Mutations in SEPT9 cause hereditary neuralgic amyotrophy 总被引:7,自引:0,他引:7
Kuhlenbäumer G Hannibal MC Nelis E Schirmacher A Verpoorten N Meuleman J Watts GD De Vriendt E Young P Stögbauer F Halfter H Irobi J Goossens D Del-Favero J Betz BG Hor H Kurlemann G Bird TD Airaksinen E Mononen T Serradell AP Prats JM Van Broeckhoven C De Jonghe P Timmerman V Ringelstein EB Chance PF 《Nature genetics》2005,37(10):1044-1046
Hereditary neuralgic amyotrophy (HNA) is an autosomal dominant recurrent neuropathy affecting the brachial plexus. HNA is triggered by environmental factors such as infection or parturition. We report three mutations in the gene septin 9 (SEPT9) in six families with HNA linked to chromosome 17q25. HNA is the first monogenetic disease caused by mutations in a gene of the septin family. Septins are implicated in formation of the cytoskeleton, cell division and tumorigenesis. 相似文献
72.
Transmission ratio distortion in the mouse is caused by several t-complex distorters (Tcds) acting in trans on the t-complex responder (Tcr). Tcds additively affect the flagellar movement of all spermatozoa derived from t/+ males; sperm carrying Tcr are rescued, resulting in an advantage for t sperm in fertilization. Here we show that Tagap1, a GTPase-activating protein, can act as a distorter. Tagap1 maps to the Tcd1 interval and has four t loci, which encode altered proteins including a C-terminally truncated form. Overexpression of wild-type Tagap1 in sperm cells phenocopied Tcd function, whereas a loss-of-function Tagap1 allele reduced the transmission rate of the t6 haplotype. The combined data strongly suggest that the t loci of Tagap1 produce Tcd1a. Our results unravel the molecular nature of a Tcd and demonstrate the importance of small G proteins in transmission ratio distortion in the mouse. 相似文献
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STAT3 signalling is required for leptin regulation of energy balance but not reproduction 总被引:33,自引:0,他引:33
Bates SH Stearns WH Dundon TA Schubert M Tso AW Wang Y Banks AS Lavery HJ Haq AK Maratos-Flier E Neel BG Schwartz MW Myers MG 《Nature》2003,421(6925):856-859
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Distinct molecular mechanism for initiating TRAF6 signalling 总被引:20,自引:0,他引:20
Ye H Arron JR Lamothe B Cirilli M Kobayashi T Shevde NK Segal D Dzivenu OK Vologodskaia M Yim M Du K Singh S Pike JW Darnay BG Choi Y Wu H 《Nature》2002,418(6896):443-447
Tumour-necrosis factor (TNF) receptor-associated factor 6 (TRAF6) is the only TRAF family member that participates in signal transduction of both the TNF receptor (TNFR) superfamily and the interleukin-1 receptor (IL-1R)/Toll-like receptor (TLR) superfamily; it is important for adaptive immunity, innate immunity and bone homeostasis. Here we report crystal structures of TRAF6, alone and in complex with TRAF6-binding peptides from CD40 and TRANCE-R (also known as RANK), members of the TNFR superfamily, to gain insight into the mechanism by which TRAF6 mediates several signalling cascades. A 40 degrees difference in the directions of the bound peptides in TRAF6 and TRAF2 shows that there are marked structural differences between receptor recognition by TRAF6 and other TRAFs. The structural determinant of the petide TRAF6 interaction reveals a Pro-X-Glu-X-X-(aromatic/acidic residue) TRAF6-binding motif, which is present not only in CD40 and TRANCE-R but also in the three IRAK adapter kinases for IL-1R/TLR signalling. Cell-permeable peptides with the TRAF6-binding motif inhibit TRAF6 signalling, which indicates their potential as therapeutic modulators. Our studies identify a universal mechanism by which TRAF6 regulates several signalling cascades in adaptive immunity, innate immunity and bone homeostasis. 相似文献
78.
Integrated genomic and epigenomic analyses pinpoint biallelic gene inactivation in tumors 总被引:14,自引:0,他引:14
Zardo G Tiirikainen MI Hong C Misra A Feuerstein BG Volik S Collins CC Lamborn KR Bollen A Pinkel D Albertson DG Costello JF 《Nature genetics》2002,32(3):453-458
Aberrant methylation of CpG islands and genomic deletion are two predominant mechanisms of gene inactivation in tumorigenesis, but the extent to which they interact is largely unknown. The lack of an integrated approach to study these mechanisms has limited the understanding of tumor genomes and cancer genes. Restriction landmark genomic scanning (RLGS; ref. 1) is useful for global analysis of aberrant methylation of CpG islands, but has not been amenable to alignment with deletion maps because the identity of most RLGS fragments is unknown. Here, we determined the nucleotide sequence and exact chromosomal position of RLGS fragments throughout the genome using the whole chromosome of origin of the fragments and in silico restriction digestion of the human genome sequence. To study the interaction of these gene-inactivation mechanisms in primary brain tumors, we integrated RLGS-based methylation analysis with high-resolution deletion maps from microarray-based comparative genomic hybridization (array CGH; ref. 3). Certain subsets of gene-associated CpG islands were preferentially affected by convergent methylation and deletion, including genes that exhibit tumor-suppressor activity, such as CISH1 (encoding SOCS1; ref. 4), as well as genes such as COE3 that have been missed by traditional non-integrated approaches. Our results show that most aberrant methylation events are focal and independent of deletions, and the rare convergence of these mechanisms can pinpoint biallelic gene inactivation without the use of positional cloning. 相似文献
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吴江海 《上饶师范学院学报》1989,(2)
4 暴涨宇宙4.1 暴涨宇宙的基本思想为了解决以上宇宙学的疑难问题。1981年古思(Guth)首先提出高温相变导致极早期宇宙暴涨的方案。他的这一方案的基本思想是:假设在宇宙极早期的某一段时间内(一般认为从10~(-34)秒到10~(-32)秒),宇宙的标度因子按指数规律增长(the inflation universe 一词由此而来),即 R(t)~e~(Ht)。而标准模型中 R(t)~t~(1/2)。借助于这一思想就可解决一些宇宙学的疑难问题。现在的问题是如何用具体的物理图象来实现这一思想。4.2 暴涨宇宙的具体物理图象 相似文献