Phosphorylation by aurora kinase A induces Mdm2-mediated destabilization and inhibition of p53

Aurora kinase A (also called STK15 and BTAK) is overexpressed in many human cancers. Ectopic overexpression of aurora kinase A in mammalian cells induces centrosome amplification, chromosome instability and oncogenic transformation, a phenotype characteristic of loss-of-function mutations of p53. Here we show that aurora kinase A phosphorylates p53 at Ser315, leading to its ubiquitination by Mdm2 and proteolysis. p53 is not degraded in the presence of inactive aurora kinase A or ubiquitination-defective Mdm2. Destabilization of p53 by aurora kinase A is abrogated in the presence of mutant Mdm2 that is unable to bind p53 and after repression of Mdm2 by RNA interference. Silencing of aurora kinase A results in less phosphorylation of p53 at Ser315, greater stability of p53 and cell-cycle arrest at G2-M. Cells depleted of aurora kinase A are more sensitive to cisplatin-induced apoptosis, and elevated expression of aurora kinase A abolishes this response. In a sample of bladder tumors with wild-type p53, elevated expression of aurora kinase A was correlated with low p53 concentration. We conclude that aurora kinase A is a key regulatory component of the p53 pathway and that overexpression of aurora kinase A leads to increased degradation of p53, causing downregulation of checkpoint-response pathways and facilitating oncogenic transformation of cells.     

Subduction and collision processes in the Central Andes constrained by converted seismic phases

The Central Andes are the Earth's highest mountain belt formed by ocean-continent collision. Most of this uplift is thought to have occurred in the past 20 Myr, owing mainly to thickening of the continental crust, dominated by tectonic shortening. Here we use P-to-S (compressional-to-shear) converted teleseismic waves observed on several temporary networks in the Central Andes to image the deep structure associated with these tectonic processes. We find that the Moho (the Mohorovici? discontinuity--generally thought to separate crust from mantle) ranges from a depth of 75 km under the Altiplano plateau to 50 km beneath the 4-km-high Puna plateau. This relatively thin crust below such a high-elevation region indicates that thinning of the lithospheric mantle may have contributed to the uplift of the Puna plateau. We have also imaged the subducted crust of the Nazca oceanic plate down to 120 km depth, where it becomes invisible to converted teleseismic waves, probably owing to completion of the gabbro-eclogite transformation; this is direct evidence for the presence of kinetically delayed metamorphic reactions in subducting plates. Most of the intermediate-depth seismicity in the subducting plate stops at 120 km depth as well, suggesting a relation with this transformation. We see an intracrustal low-velocity zone, 10-20 km thick, below the entire Altiplano and Puna plateaux, which we interpret as a zone of continuing metamorphism and partial melting that decouples upper-crustal imbrication from lower-crustal thickening.     

论我国企业破产重整制度的完善

《中华人民共和国企业破产法》重要的创新点之一便是设立了破产重整制度,本文拟从《中华人民共和国企业破产法》对重整制度的现行规定入手,结合我国经济法制建设的要求和相关法律规则,分析其存在的立法不足,并提出相应的建议,以便使该法在司法实践中得到进一步的充实和完善,对我国新时期的经济发展发挥最大的促进作用。     

“八荣八耻”荣辱观研究综述

“八荣八耻”荣辱观提出后随即引起社会普遍关注，成为“2006年中国十大学术热点问题”之一。综观一年来的研究概况，其研究重心主要集中于“八荣八耻”荣辱观的价值和意义、深刻内涵、时代特征、建设路径和方法对策、荣辱观教育以及与传统荣辱观的关系等方面。系统梳理当下的研究现状，对“八荣八耻”荣辱观的深化研究，无疑将具有启示价值。     

TCP 数据流超时研究

Claffy于1994年基于一个小时的主干数据分析,提出了主干网数据流超时时间以64 s为宜的结论,这个结论被广泛沿用至今.在此期间互联网发生了翻天覆地的变化,这个结论是否仍然适用呢?本文以CERNET某2.5 G省网边界链路近期连续1 h报文数据构成的trace为对象,采用Claffy相似的方法进行了统计分析,得出的结论是:目前的数据流超时间隔取值16 s时就可以达到理想的效果.这个结论将对所有与网络数据流有关的工程和研究具有借鉴意义.在实验数据量方面,相对于Claffy的平均每秒1 118个报文(下文简称PPS),本次试验所采用的TRACE数据量为650 k PPS,约是前者的581倍.本文将详细介绍试验和结果产生的过程.     

数控机床现状及发展中的主要问题

简述了数控机床在中国的地位及现状，分析了数控机床发展的趋势及我国现存的主要问题。     

MR成像技术在脊柱压缩骨折研究中的应用

目的 探讨MR 多种成像技术对脊柱压缩骨折病因研究的价值.方法 48例(共88个椎体)脊柱椎体压缩行MR平扫T1,T2及T2脂肪抑制,DWI及T1增强扫描.其中病理性骨折28例(55个椎体,包括转移性肿瘤24例、骨髓瘤1例、结核4例);单纯性骨折20例(33个椎体,包括单纯外伤所致14例,骨质疏松6例).病理性骨折者,经穿刺检查或手术病理证实,部分临床证实;外伤或骨质疏松所致椎体压缩骨折均符合临床、实验室检查及MRI表现,部分随访证实.结果 单纯性骨折20例共33个椎体,T2WI呈高、混杂信号27个,低、等信号6个,DWI呈高、混杂信号5个,低、等信号28个.病理性骨折28例共55个椎体,T2WI呈高、混杂信号42个,低、等信号13个,DWI呈高、混杂信号51个,低、等信号4个,T1 T2组合确诊数为82.3%,多种组合T1 T2 T1增强 T2抑脂 DWI,确诊数为98.6%.结论 MR 多种成像技术联合应用对单纯性骨折和病理性骨折的鉴别可提供很大帮助.     

爱情的神经生理机制

爱情是一种跨文化普遍存在的现象.从20世纪90年代以来,爱情已经成为神经生物学、认知神经科学、心理学等多学科的新研究焦点.对爱情及其相关行为的脑功能成像研究发现,爱情主要激活奖赏环路,尤其是腹侧被盖区和尾状核;抑制与社会判断、负性情绪有关的脑区活动,如外侧前额叶皮层、后扣带皮层、杏仁核等.这提示爱情并不是一种单一情绪,而是一种类似于金钱奖赏的激励动机;同时爱情会降低人们对所爱对象的社会判断力.爱情所激活和抑制的脑区既有跨文化的一致性,也有差异性.另一方面,爱情也会导致人体内多种激素和神经递质的变化,包括皮质醇、多巴胺、五羟色胺、后叶催产素和加压素、神经生长因子等.最后,我们从爱情的测量方法、研究手段以及爱情对行为决策的可能影响等方面,讨论了爱情领域未来研究的可能方向.     

不同Ca~(2+)浓度对斑节对虾光感受器细胞内储存的Ca~(2+)的影响

应用草酸-焦锑酸盐结合的沉淀技术研究了在不同Ca^2 浓度条件下斑节对虾光感受器细胞胞内储存的Ca^2 的变化，电镜观察表明：在高钙溶液培育后，细胞内的多囊体、色素颗粒、板膜体中都存在大量的焦锑酸钙沉淀的黑色颗粒，线粒体中则无；在生理溶液培育后，线粒体中出现沉淀，而其他Ca^2 储存器中焦锑酸钙沉淀的黑色颗粒则大量减少，低钙溶液培育后焦锑酸钙沉淀的黑色颗粒情况与生理溶液条件下的相似，研究证实光感受器细胞内储存的Ca^2 受到胞外Ca^2 浓度的影响。     

USBCAN总线转换设备在Stateflow下的建模和仿真

USBCAN总线转换设备作为USB总线和CAN总线之间的连接设备,其运行状况和软件设计是否能达到设计的需求,一般的方法很难进行验证,本文通过在Stateflow工具箱下对一种USBCAN总线转换设备进行建模,并且在Matlab/Simulink环境下对整个转换设备运行状态进行仿真验证,实现了USBCAN总线转换设备运行状态的验证,提出了一种新的总线转换设备的仿真和验证方法。