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1.
Mochida S  Hunt T 《Nature》2007,449(7160):336-340
Fertilization induces a transient increase in cytoplasmic Ca2+ concentration in animal eggs that releases them from cell cycle arrest in the second meiotic metaphase. In frog eggs, Ca2+ activates Ca2+/calmodulin-activated kinase, which inactivates cytostatic factor, allowing the anaphase-promoting factor to turn on and ubiquitinate cyclins and securin, which returns the cell cycle to interphase. Here we show that the calcium-activated protein phosphatase calcineurin is also important in this process. Calcineurin is transiently activated after adding Ca2+ to egg extracts, and inhibitors of calcineurin such as cyclosporin A (ref. 8) delay the destruction of cyclins, the global dephosphorylation of M-phase-specific phosphoproteins and the re-formation of a fully functional nuclear envelope. We found that a second wave of phosphatase activity directed at mitotic phosphoproteins appears after the spike of calcineurin activity. This activity disappeared the next time the extract entered M phase and reappeared at the end of mitosis. We surmise that inhibition of this second phosphatase activity is important in allowing cells to enter mitosis, and, conversely, that its activation is required for a timely return to interphase. Calcineurin is required to break the deep cell cycle arrest imposed by the Mos-MAP (mitogen-activated protein) kinase pathway, and we show that Fizzy/Cdc20, a key regulator of the anaphase-promoting factor, is an excellent substrate for this phosphatase.  相似文献   

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The Cdc25A phosphatase is essential for cell-cycle progression because of its function in dephosphorylating cyclin-dependent kinases. In response to DNA damage or stalled replication, the ATM and ATR protein kinases activate the checkpoint kinases Chk1 and Chk2, which leads to hyperphosphorylation of Cdc25A. These events stimulate the ubiquitin-mediated proteolysis of Cdc25A and contribute to delaying cell-cycle progression, thereby preventing genomic instability. Here we report that beta-TrCP is the F-box protein that targets phosphorylated Cdc25A for degradation by the Skp1/Cul1/F-box protein complex. Downregulation of beta-TrCP1 and beta-TrCP2 expression by short interfering RNAs causes an accumulation of Cdc25A in cells progressing through S phase and prevents the degradation of Cdc25A induced by ionizing radiation, indicating that beta-TrCP may function in the intra-S-phase checkpoint. Consistent with this hypothesis, suppression of beta-TrCP expression results in radioresistant DNA synthesis in response to DNA damage--a phenotype indicative of a defect in the intra-S-phase checkpoint that is associated with an inability to regulate Cdc25A properly. Our results show that beta-TrCP has a crucial role in mediating the response to DNA damage through Cdc25A degradation.  相似文献   

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Molecular events during maturation of the immune response to oxazolone   总被引:10,自引:0,他引:10  
C Berek  G M Griffiths  C Milstein 《Nature》1985,316(6027):412-418
Sequence analysis of the heavy- and light-chain messenger RNA of hybridomas immunized with a specific hapten yields important clues about the interplay between genetic and selective events during the onset and maturation of the immune response. The maturation of the primary response to the hapten 2-phenyl-5-oxazolone is characterized by a drift to higher-affinity somatic variants of a germline-encoded basic sequence, whereas hybridomas from the secondary response demonstrate a further maturation dominated by a shift to alternative germline combinations.  相似文献   

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"素质教育"在当今学校教育中已经成为一个受到广泛关注的课题,在由应试教育向素质教育的转轨中,广大教育工作者认真研究并全面理解素质教育理论,积极推进素质教育,深化学校教育改革.学校体育是学校教育的重要组成部分,是素质教育不可缺少的重要内容.在体育教学中:1)转变教育思想,更新教育观念是实施素质教育的前提;2)课程体系的改革是实施素质教育的重要因素;3)提高体育教师队伍的整体水平是实施素质教育的基础.  相似文献   

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Hiiragi T  Solter D 《Nature》2004,430(6997):360-364
Studies of experimentally manipulated embryos have led to the long-held conclusion that the polarity of the mouse embryo remains undetermined until the blastocyst stage. However, recent studies reporting that the embryonic-abembryonic axis of the blastocyst arises perpendicular to the first cleavage plane, and hence to the animal-vegetal axis of the zygote, have led to the claim that the axis of the mouse embryo is already specified in the egg. Here we show that there is no specification of the axis in the egg. Time-lapse recordings show that the second polar body does not mark a stationary animal pole, but instead, in half of the embryos, moves towards a first cleavage plane. The first cleavage plane coincides with the plane defined by the two apposing pronuclei once they have moved to the centre of the egg. Pronuclear transfer experiments confirm that the first cleavage plane is not determined in early interphase but rather is specified by the newly formed topology of the two pronuclei. The microtubule networks that allow mixing of parental chromosomes before dividing into two may be involved in these processes.  相似文献   

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采用Western blotting检测p90rsk-1在绵羊卵母细胞体外成熟过程中的表达.实验分别在0h、8h、16h、24h检测绵羊卵母细胞p90rsk-1的表达量的变化,并进行统计学分析.结果p90rsk-1在绵羊卵母细胞体外成熟过程中均为阳性表达.随着成熟时间的延长,卵母细胞p90rsk-1在16h的相对表达量显著升高(P<0.05),但在24h又下降.因此推测Rsk在绵羊卵母细胞体外成熟过程中起一定的作用.  相似文献   

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Hoege C  Pfander B  Moldovan GL  Pyrowolakis G  Jentsch S 《Nature》2002,419(6903):135-141
The RAD6 pathway is central to post-replicative DNA repair in eukaryotic cells; however, the machinery and its regulation remain poorly understood. Two principal elements of this pathway are the ubiquitin-conjugating enzymes RAD6 and the MMS2-UBC13 heterodimer, which are recruited to chromatin by the RING-finger proteins RAD18 and RAD5, respectively. Here we show that UBC9, a small ubiquitin-related modifier (SUMO)-conjugating enzyme, is also affiliated with this pathway and that proliferating cell nuclear antigen (PCNA) -- a DNA-polymerase sliding clamp involved in DNA synthesis and repair -- is a substrate. PCNA is mono-ubiquitinated through RAD6 and RAD18, modified by lysine-63-linked multi-ubiquitination--which additionally requires MMS2, UBC13 and RAD5--and is conjugated to SUMO by UBC9. All three modifications affect the same lysine residue of PCNA, suggesting that they label PCNA for alternative functions. We demonstrate that these modifications differentially affect resistance to DNA damage, and that damage-induced PCNA ubiquitination is elementary for DNA repair and occurs at the same conserved residue in yeast and humans.  相似文献   

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在以培养能力为核心的素质教育中,课程实习在能力培养中具有更重要的意义,因为课程实习是学生所学知识的直接应用,培养学生的能力也就更具体,效果也就更明显。因此,能力培养就贯穿了课程实习的整个过程。  相似文献   

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讨论利用现成的光电效应实验仪来测量孵化早期鸡蛋的透光性的实验组装的技术问题和基本原理,提出了利用贝叶斯决策理论把孵化早期无精蛋鉴别出来的方法.  相似文献   

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Contrary to the traditional view that microtubules pull chromosomes polewards during the anaphase stage of meiotic and mitotic cell divisions, new evidence suggests that the chromosome movements are driven by a motor located at the kinetochore. The process of chromosome segregation involves proper arrangement of kinetochores for spindle attachment, followed by spindle attachment and chromosome movement. Mechanisms in Drosophila for chromosome segregation in meiosis differ in males and females, implying the action of different gene products in the two sexes. A product encoded at the claret locus in Drosophila is required for normal chromosome segregation in meiosis in females and in early mitotic divisions of the embryo. Here we show that the predicted amino-acid sequence of this product is related to the heavy chain of kinesin. The conserved region corresponds to the kinesin motor domain and includes the ATP-binding site and a region that can bind microtubules. A second region contains a leucine repeat motif which may mediate protein-subunit interactions necessary for attachment of chromosomes to the spindle. The mutant phenotype of chromosome nondisjunction and loss, and its similarity to the kinesin ATP-binding domain, suggest that the product encoded at claret not only stabilizes chromosome attachments to the spindle, but may also be a motor that drives chromosome segregation in female meiosis.  相似文献   

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如何在系统实时控制时间限制范围内精确、快速地实施解耦计算,是并联机器人实时控制中急待解决的一个关键问题。以往一般采用解析法(先建立复杂的数学模型,然后计算机编程求解),但是这种解耦方法实际可行性较差。因此,寻求解耦新思路、新方法已成为并联机器人研究工作中急待解决的问题。这里就此问题,提出了利用三维技术进行运动解耦的新思路、新方法。该方法简捷方便,开发周期短,其解耦精度与解析法相当接近。  相似文献   

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Visintin R  Hwang ES  Amon A 《Nature》1999,398(6730):818-823
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要提高高职院校学生的英语语用能力,教师应摈弃传统的教学模式,以学生为中心,采用任务型的教学方法,注重语料的输入,提升学生的语音语调水平,并且要创造使用英语的环境,为学生提供更多用英语与人交流的机会。  相似文献   

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和谐社会的建立对于现存的政府行政能力提出了挑战,它要求政府的能力进行改革与提升。为适应形势发展的需要,在建设人民满意的政府的同时,必须注重经济与社会的协调发展,科学地化解矛盾,造就高素质的公务员队伍,妥善处理不同利益主体之间的利益关系,化解社会上的不和谐因素,使政府在构建和谐社会的进程中起到及到积极的促进作用。  相似文献   

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和谐社会的建立对于现存的政府行政能力提出了挑战,它要求政府的能力进行改革与提升。为适应形势发展的需要,在建设人民满意的政府的同时,必须注重经济与社会的协调发展,科学地化解矛盾,造就高素质的公务员队伍,妥善处理不同利益主体之间的利益关系,化解社会上的不和谐因素,使政府在构建和谐社会的进程中起到及到积极的促进作用。  相似文献   

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