排序方式: 共有120条查询结果,搜索用时 15 毫秒
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Cyclin-dependent kinases (CDKs) limit the activation of DNA replication origins to once per cell cycle by preventing the assembly of pre-replicative complexes (pre-RCs) during S, G2 and M phases of the cell cycle in the budding yeast Saccharomyces cerevisiae. CDKs inhibit each pre-RC component (ORC, Cdc6, Cdt1/Mcm2-7) by different mechanisms. We show here that the mitotic CDK, Clb2/Cdc28, binds tightly to an amino-terminal domain (NTD) of Cdc6, and that Cdc6 in this complex is unable to assemble pre-RCs. We present evidence indicating that this Clb2-dependent mechanism contributes to preventing re-replication in vivo. CDK interaction with the NTD of Cdc6 is mediated by the cyclin subunit Clb2, and could be reconstituted with recombinant Clb2 protein and synthetic NTD peptides. Tight Clb2 binding occurred only when the NTD was phosphorylated on CDK consensus sites. Human CDKs containing cyclins A, B and E also bound specifically to phospho-NTD peptides. We propose that direct binding of cyclins to phosphopeptide motifs may be a widespread phenomenon contributing to the targeting of CDKs to substrates. 相似文献
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Microtubules are essential intracellular structures involved in several cellular phenomena, including polarity establishment and chromosome segregation. Because the nuclear envelope persists during mitosis (closed mitosis) in fission yeast (Schizosaccharomyces pombe), cytoplasmic microtubules must be reorganized into the spindle in the compartmentalized nucleus on mitotic entry. An ideal mechanism might be to take advantage of an evolutionarily conserved microtubule formation system that uses the Ran-GTPase nuclear transport machinery, but no targets of Ran for spindle formation have been identified in yeast. Here we show that a microtubule-associated protein, Alp7, which forms a complex with Alp14, is a target of Ran in yeast for spindle formation. The Ran-deficient pim1 mutant (pim1-F201S) failed to show mitosis-specific nuclear accumulation of Alp7. Moreover, this mutant exhibited compromised spindle formation and early mitotic delay. Importantly, these defects were suppressed by Alp7 that was artificially targeted to the nucleus by a Ran-independent and importin-alpha-mediated system. Thus, Ran targets Alp7-Alp14 to achieve nuclear spindle formation, and might differentiate its targets depending on whether the organism undergoes closed or open mitosis. 相似文献
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数值模拟冲击式水轮机内部非定常流动 总被引:2,自引:0,他引:2
提出了用动画解析法解析冲击式水轮机非定常内部流动的方法,此法提供了如何将非定常流动按照时间顺序离散成动画单元,并通过拉格郎日法对流体质点的加速度进行积分来求出水斗内非定常流动的分布首次解析了其内部流动. 相似文献
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冲击式水轮机水斗内非定常自由水膜的流动非常复杂,至今还没有足够精确的数值方法来模拟这种流动.文中分析了非定常水膜流的流动机理,根据N-S方程推导出了水斗表面流体粒子在转动坐标系中的相对运动控制微分方程,依据控制微分方程编写出了数值解析软件并对水斗内的水膜流动进行了数值模拟,定量地得到了某模型水轮机水斗内部流动的速度场、能量场.对比一系列水膜流态分布,数值解析得到的结果与试验观测结果基本相吻合,最优工况下的水力效率与模型试验数据的误差为0.33%. 相似文献
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Deletion of Peg10, an imprinted gene acquired from a retrotransposon, causes early embryonic lethality 总被引:11,自引:0,他引:11
Ono R Nakamura K Inoue K Naruse M Usami T Wakisaka-Saito N Hino T Suzuki-Migishima R Ogonuki N Miki H Kohda T Ogura A Yokoyama M Kaneko-Ishino T Ishino F 《Nature genetics》2006,38(1):101-106
By comparing mammalian genomes, we and others have identified actively transcribed Ty3/gypsy retrotransposon-derived genes with highly conserved DNA sequences and insertion sites. To elucidate the functions of evolutionarily conserved retrotransposon-derived genes in mammalian development, we produced mice that lack one of these genes, Peg10 (paternally expressed 10), which is a paternally expressed imprinted gene on mouse proximal chromosome 6. The Peg10 knockout mice showed early embryonic lethality owing to defects in the placenta. This indicates that Peg10 is critical for mouse parthenogenetic development and provides the first direct evidence of an essential role of an evolutionarily conserved retrotransposon-derived gene in mammalian development. 相似文献
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Miyagawa T Kawashima M Nishida N Ohashi J Kimura R Fujimoto A Shimada M Morishita S Shigeta T Lin L Hong SC Faraco J Shin YK Jeong JH Okazaki Y Tsuji S Honda M Honda Y Mignot E Tokunaga K 《Nature genetics》2008,40(11):1324-1328
Narcolepsy (hypocretin deficiency), a sleep disorder characterized by sleepiness, cataplexy and rapid eye movement (REM) sleep abnormalities, is tightly associated with HLA-DRB1*1501 (M17378) and HLA-DQB1*0602 (M20432). Susceptibility genes other than those in the HLA region are also likely involved. We conducted a genome-wide association study using 500K SNP microarrays in 222 Japanese individuals with narcolepsy and 389 Japanese controls, with replication of top hits in 159 Japanese individuals with narcolepsy and 190 Japanese controls, followed by the testing of 424 Koreans, 785 individuals of European descent and 184 African Americans. rs5770917, a SNP located between CPT1B and CHKB, was associated with narcolepsy in Japanese (rs5770917[C], odds ratio (OR) = 1.79, combined P = 4.4 x 10(-7)) and other ancestry groups (OR = 1.40, P = 0.02). Real-time quantitative PCR assays in white blood cells indicated decreased CPT1B and CHKB expression in subjects with the C allele, suggesting that a genetic variant regulating CPT1B or CHKB expression is associated with narcolepsy. Either of these genes is a plausible candidate, as CPT1B regulates beta-oxidation, a pathway involved in regulating theta frequency during REM sleep, and CHKB is an enzyme involved in the metabolism of choline, a precursor of the REM- and wake-regulating neurotransmitter acetylcholine. 相似文献
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Role of retrotransposon-derived imprinted gene, Rtl1, in the feto-maternal interface of mouse placenta 总被引:1,自引:0,他引:1
Sekita Y Wagatsuma H Nakamura K Ono R Kagami M Wakisaka N Hino T Suzuki-Migishima R Kohda T Ogura A Ogata T Yokoyama M Kaneko-Ishino T Ishino F 《Nature genetics》2008,40(2):243-248
Eutherian placenta, an organ that emerged in the course of mammalian evolution, provides essential architecture, the so-called feto-maternal interface, for fetal development by exchanging nutrition, gas and waste between fetal and maternal blood. Functional defects of the placenta cause several developmental disorders, such as intrauterine growth retardation in humans and mice. A series of new inventions and/or adaptations must have been necessary to form and maintain eutherian chorioallantoic placenta, which consists of capillary endothelial cells and a surrounding trophoblast cell layer(s). Although many placental genes have been identified, it remains unknown how the feto-maternal interface is formed and maintained during development, and how this novel design evolved. Here we demonstrate that retrotransposon-derived Rtl1 (retrotransposon-like 1), also known as Peg11 (paternally expressed 11), is essential for maintenance of the fetal capillaries, and that both its loss and its overproduction cause late-fetal and/or neonatal lethality in mice. 相似文献
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Aitman TJ Critser JK Cuppen E Dominiczak A Fernandez-Suarez XM Flint J Gauguier D Geurts AM Gould M Harris PC Holmdahl R Hubner N Izsvák Z Jacob HJ Kuramoto T Kwitek AE Marrone A Mashimo T Moreno C Mullins J Mullins L Olsson T Pravenec M Riley L Saar K Serikawa T Shull JD Szpirer C Twigger SN Voigt B Worley K 《Nature genetics》2008,40(5):516-522
The rat is an important system for modeling human disease. Four years ago, the rich 150-year history of rat research was transformed by the sequencing of the rat genome, ushering in an era of exceptional opportunity for identifying genes and pathways underlying disease phenotypes. Genome-wide association studies in human populations have recently provided a direct approach for finding robust genetic associations in common diseases, but identifying the precise genes and their mechanisms of action remains problematic. In the context of significant progress in rat genomic resources over the past decade, we outline achievements in rat gene discovery to date, show how these findings have been translated to human disease, and document an increasing pace of discovery of new disease genes, pathways and mechanisms. Finally, we present a set of principles that justify continuing and strengthening genetic studies in the rat model, and further development of genomic infrastructure for rat research. 相似文献