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441.
The locations and properties of common deletion variants in the human genome are largely unknown. We describe a systematic method for using dense SNP genotype data to discover deletions and its application to data from the International HapMap Consortium to characterize and catalogue segregating deletion variants across the human genome. We identified 541 deletion variants (94% novel) ranging from 1 kb to 745 kb in size; 278 of these variants were observed in multiple, unrelated individuals, 120 in the homozygous state. The coding exons of ten expressed genes were found to be commonly deleted, including multiple genes with roles in sex steroid metabolism, olfaction and drug response. These common deletion polymorphisms typically represent ancestral mutations that are in linkage disequilibrium with nearby SNPs, meaning that their association to disease can often be evaluated in the course of SNP-based whole-genome association studies.  相似文献   
442.
Commensal Escherichia coli form biofilms at body temperature by expressing the extracellular matrix components curli fimbriae and cellulose. The role of curli fimbriae and cellulose in the interaction of commensal E. coli with the intestinal epithelial cell line HT-29 was investigated. Expression of curli fimbriae by the typical commensal isolate E. coli TOB1 caused adherence and internalization of the bacteria and triggered IL-8 production in HT-29 cells. In particular, induction of IL-8 production was complex and involved curli-bound flagellin. While cellulose alone had no effect on the interaction of TOB1 with HT-29 cells, co-expression of cellulose with curli fimbriae decreased adherence to, internalization and IL-8 induction of HT-29 cells. Investigation of a panel of commensal isolates showed a partial correlation between expression of curli fimbriae and enhanced internalization and IL-8 production. In addition, a high immunostimulatory flagellin was identified. Thus, the consequences of expression of extracellular matrix components on commensal bacterial-host interactions are complex.  相似文献   
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445.
Memory     
Memories become stabilized through a time-dependent process that requires gene expression and is commonly known as consolidation. During this time, memories are labile and can be disrupted by a number of interfering events, including electroconvulsive shock, trauma and other learning or the transient effect of drugs such as protein synthesis inhibitors. Once consolidated, memories are insensitive to these disruptions. However, they can again become fragile if recalled or reactivated. Reactivation creates another time-dependent process, known as reconsolidation, during which the memory is restabilized. Here we discuss some of the questions currently debated in the field of memory consolidation and reconsolidation, the molecular and anatomical requirements for both processes and, finally, their functional relationship.  相似文献   
446.
Nadeau JH  Topol EJ 《Nature genetics》2006,38(10):1095-1098
Recent experience with several high-profile drugs demonstrates the great challenges in developing effective and safe therapeutics. A complementary approach to the popular paradigm of disease genetics is based on inherited factors that reduce the incidence and severity of disease among individuals who are genetically predisposed to disease. We propose testing specifically for modifier genes and protective alleles among at-risk individuals and studying the efficacy of therapeutics based on the genetics of health.  相似文献   
447.
The mammalian olfactory system is not uniformly organized but consists of several subsystems each of which probably serves distinct functions. Not only are the two major nasal chemosensory systems, the vomeronasal organ and the main olfactory epithelium, structurally and functionally separate entities, but the latter is further subcompartimentalized into overlapping expression zones and projection-related subzones. Moreover, the populations of ‘OR37’ neurons not only express a unique type of olfactory receptors but also are segregated in a cluster-like manner and generally project to only one receptor-specific glomerulus. The septal organ is an island of sensory epithelium on the nasal septum positioned at the nasoplatine duct; it is considered as a ‘mini-nose’ with dual function. A specific chemosensory function of the most recently discovered subsystem, the so-called Grueneberg ganglion, is based on the expression of olfactory marker protein and the axonal projections to defined glomeruli within the olfactory bulb. This complexity of distinct olfactory subsystems may be one of the features determining the enormous chemosensory capacity of the sense of smell.  相似文献   
448.
如何优化分配,合理调运,及时准确地完成后勤保障任务,是现代战争中战区物资调运面临的重要问题之一.基于运输问题,就现代战争条件下战区物资调运问题的各种情况建立了数学模型.该模型可用于后勤物资保障的决策支持系统及指挥自动化系统,为解决战时后勤保障供应问题提供了新的理论方法和思路.  相似文献   
449.
在分析了现有基线扣除算法的基础上,根据非基线对称类基线信号的特征提出了一种新的基线扣除算法--基于小波滤波和梯度直方图最佳分割的非基线对称类信号基线扣除新算法.考虑到信号总是存在着噪声,含噪的基线信号梯度值也较大,并且分布无规律,采用了多分辨率小波变换滤波技术.通过合理选择最佳分割阈值门限,算法可精确提取出该类信号的基线.  相似文献   
450.
引信全电子安全系统程序控制组件设计   总被引:3,自引:0,他引:3  
全电子安全系统是引信设计的发展方向,程序控制组件是实现引信安全控制的重要部件.介绍了一种引信全电子安全系统程序控制组件的技术要求、基本功能和工作顺序及原理,提出了提高系统可靠性的电路模式和设计原则,同时对程序控制组件的软件设计方法进行了介绍.采用先进的在系统可编程器件,实现系统逻辑功能的集成化、小型化,且具有易于功能扩展、设计升级等优点.  相似文献   
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