Alternative splicing of Bcl-2-related genes: functional consequences and potential therapeutic applications

Apoptosis is a morphologically distinct form of cell death. It is executed and regulated by several groups of proteins. Bcl-2 family proteins are the main regulators of the apoptotic process acting either to inhibit or promote it. More than 20 members of the family have been identified so far and most have two or more isoforms. Alternative splicing is one of the major mechanisms providing proteomic complexity and functional diversification of the Bcl-2 family proteins. Pro- and anti-apoptotic Bcl-2 family members should function in harmony for the regulation of the apoptosis machinery, and their relative levels are critical for cell fate. Any mechanism breaking down this harmony by changing the relative levels of these antagonistic proteins could contribute to many diseases, including cancer and neurodegenerative disorders. Recent studies have shown that manipulation of the alternative splicing mechanisms could provide an opportunity to restore the proper balance of these regulator proteins. This review summarises current knowledge on the alternative splicing products of Bcl-2-related genes and modulation of splicing mechanisms as a potential therapeutic approach.Received 5 January 2004; received after revision 31 March 2004; accepted 6 April 2004     

绝望边缘的体认与言说——以《伤逝》为个案解析鲁迅的时间观与生命意识

在《伤逝》中 ,启蒙身份的丢失是根源于面对家庭的困惑。用什么来维系家庭成员 ,这是整个五四时期启蒙者的困境。小说采用叙述与体验两种截然不同的方式建构文本 ,透露出人生的悲剧 ,更重要的是凸现出鲁迅独特的时间观。在乌托邦与反乌托邦的平衡中 ,鲁迅与现实之间难以分割的关系促使他形成了“死后之生”的人生哲学     

Protein folds: molecular systematics in three dimensions

Advances in methods of structure determination have led to the accumulation of large amounts of protein structural data. Some 500 distinct protein folds have now been characterized, representing one-third of all globular folds that exist. The range of known structural types and the relatively large fraction of the protein universe that has already been sampled have greatly facilitated the discovery of some unifying principles governing protein structure and evolutionary relationships. These include a highly skewed distribution of topological arrangements of secondary-structure elements that favors a few very common connectivities and a highly skewed distribution in the capacity of folds to accommodate unrelated sequences. These and other observations suggest that the number of folds is far fewer than the number of genes, and that the fold universe is dominated by a small number of giant attractors that accommodate large numbers of unrelated sequences. Thus all basic protein folds will likely be determined in the near future, laying the foundation for a comprehensive understanding of the biochemical and cellular functions of whole organisms.     

“新婚姻法现象”中婚外情等争论带来的启示

“新婚姻法现象”不仅是一个立法事件,更是当前我国婚姻家庭关系领域内伦理道德矛盾的集中反映。一部法律的修订并不能解决所有矛盾,我们迫切需要有针对性地研究新问题,加强婚姻家庭关系领域的道德建设。     

家庭心理治疗理论研究综述

在系统论的观念影响下,心理治疗理论越来越倾向于以系统的观点来指导临床治疗.依据"系统学"的观念,家庭心理治疗就是将个体置于家庭这一系统之中进行分析和治疗.其方法主要包括结构性家庭治疗、系统性家庭治疗、行为家庭治疗和策略性家庭治疗等.     

分担值与正规函数

研究函数的分担值与正规族的关系.证明了:设f(z)是复平面上的亚纯函数,a是一个非零的有穷复数,f零点的重数至少为k.且满足(Ⅰ)f(z)=0当且仅当f~(j)(z)=0;(Ⅱ)当f~(k)(z)=a时,f(z)=a.则f(z)是复平面上的正规函数.     

我国农村养老制度的缺失与重构

本文从政治学的角度分析我国农村的养老制度，探讨其缺失与重构。由于国家的一系列政策以及农民在养老保障上的失语，构成当前农村的养老模式是以土地为基础，以家庭为核心。但这种模式在当前受到了严重的挑战，家庭养老能力日渐削弱，土地的保障功能日益弱化，国家的养老保险政策存在制度缺陷。应采取一系列措施解决农村养老面临的问题。     

新的差族和几乎差族的构造

利用4阶分圆给出了新的差族,这类差族可以用来构造Hadamard矩阵;利用2阶分圆构造出了一类新的几乎差族,其在很多组合和统计问题中可以给出部分平衡的不完备区组设计.     

人才培养,从家庭开始

文章从素质教育观点出发,分析了家庭因素,对教育的影响.