Receptor communication within the lymphocyte plasma membrane: a role for the thrombospondin family of matricellular proteins

Lymphocytes, the principal cells of the immune system, carry out immune surveillance throughout the body by their unique capacity to constantly reposition themselves between a free-floating vascular state and a tissue state characterized by migration and frequent adhesive interactions with endothelial cells and components of the extracellular matrix. Therefore, mechanisms co-ordinating adhesion and migration with signals delivered through antigen recognition probably play a pivotal role for the regulation of lymphocyte behaviour and function. Endogenous thrombospondin-1 (TSP-1) seems to be the hub in such a mechanism for autocrine regulation of T cell adhesion and migration. TSP-1 functions as a mediator of cis interaction of vital receptors within the T lymphocyte plasma membrane, including integrins, low density lipoprotein receptor-related protein, calreticulin and integrin-associated protein. Received 1 June 2006; received after revision 28 June 2006; accepted 11 October 2006     

Genetic studies of diseases

Genomic alterations lead to cancer complexity and form a major hurdle for comprehensive understanding of the molecular mechanisms underlying oncogenesis. In this review, we describe recent advances in studying cancer-associated genes from a systems biology point of view. The integration of known cancer genes onto protein and signaling networks reveals the characteristics of cancer genes within networks. This approach shows that cancer genes often function as network hub proteins which are involved in many cellular processes and form focal nodes in information exchange between many signaling pathways. Literature mining allows constructing gene-gene networks, in which new cancer genes can be identified. The gene expression profiles of cancer cells are used for reconstructing gene regulatory networks. By doing so, genes which are involved in the regulation of cancer progression can be picked up from these networks, after which their functions can be further confirmed in the laboratory.     

tRNase Z: the end is not in sight

Although the enzyme tRNase Z has only recently been isolated, a plethora of data has already been acquired concerning the enzyme. tRNase Z is the endonuclease that catalyzes the removal of the tRNA 3′ trailer, yielding the mature tRNA 3′ end ready for CCA addition and aminoacylation. Another substrate cleaved by tRNase Z is the small chromogenic phosphodiester bis(p-nitrophenyl)phosphate (bpNPP), which is the smallest tRNase Z substrate known so far. Hitherto the biological function as tRNA 3′-end processing enzyme has been shown only in one prokaryotic and one eukaryotic organism, respectively. This review summarizes the present information concerning the two tRNase Z substrates pre-tRNA and bpNPP, as well as the metal requirements of tRNase Z enzymes. Received 29 March 2007; received after revision 15 May 2007; accepted 21 May 2007     

Computational protein function prediction: Are we making progress?

The computational prediction of gene and protein function is rapidly gaining ground as a central undertaking in computational biology. Making sense of the flood of genomic data requires fast and reliable annotation. Many ingenious algorithms have been devised to infer a protein's function from its amino acid sequence, 3D structure and chromosomal location of the encoding genes. However, there are significant challenges in assessing how well these programs perform. In this article we explore those challenges and review our own attempt at assessing the performance of those programs. We conclude that the task is far from complete and that a critical assessment of the performance of function prediction programs is necessary to make true progress in computational function prediction.     

Displacement Discontinuity Method in 3D Problems of Fracture Mechanics

The present paper suggests a modification of boundary elements numerical method, which uses displacement discontinuity method in 3D space. The current method can effectively decrease the computational elements number in 3D space because final elements are placed only on the surface of a fracture simulating the discontinuity of elastic medium. Thus the dimension of the problem is decreased. The new fundamental solutions were developed based on double layer potentials. The method proved to be effective for hydraulic fractures modeling and their interaction with natural faults in host rock formations.     

THEMIS星座对2008年2月26日磁层亚暴的观测--磁尾重联触发的亚暴分析研究

本文利用THEMIS卫星结合地面极光和地磁的观测,研究了2008年2月26日04：05和04：55UT的两次亚暴事件.Angelopoulos已经对发生在04：55UT的第二个亚暴事件做了分析.本文对两次亚暴的相关活动进行了详细研究,特别对第一次做了深入讨论,并着重分析了磁重联与亚暴活动的关系.在两次亚暴的初始阶段,第一次极光增亮发生在中磁尾磁重联后2～3min,但是持续时间较短,极向膨胀缓慢,与伪暴的特征相似,标志了亚暴的初突发（initial onset）.两次亚暴都存在第二次极光增亮和极光的极向膨胀,且时间与近地磁尾观测的地向流和磁场偶极化同时发生,并与亚暴膨胀相的其他活动的发生同步,标志了亚暴的主突发（major onset）.在两次亚暴的增长相期间,极盖区开放磁通量持续增加;在亚暴膨胀相和恢复相中,极盖区磁通量迅速减少.表明两次亚暴膨胀相的演化分别与两次尾瓣开放磁力线重联过程相联系的.从亚暴活动的参数分析,这两次亚暴都属于小亚暴范围;从重联率分析,两次磁重联都属于弱重联.本文的观测结果表明,中磁尾磁尾重联首先触发伪暴;高速流将磁通量和能量传输到近地磁尾;高速流减速最终导致亚暴...更多电流楔（substorm current wedge,简称SCW）的形成和电流中断,产生近地偶极化和极光膨胀,引起亚暴膨胀相突发.本文的观测结果是对近地中性线模型（near earth neutral line,简称NENL）和重联-电流中断协同模型（synthesis scenario of MR and CD,简称RCS）模型及亚暴膨胀相两步突发观点的有力支持.     

Cluster卫星对磁尾电流片运动特性的统计分析

地球磁尾电流片拍动的起源和运动方式一直是磁尾动力学研究中的重要问题之一.本文利用Cluster卫星数据,统计分析了2001年和2003年的磁尾电流片运动特性,利用我们最近发展的分析结构特征方向和运动速度的新方法,计算了磁尾电流片的运动速度,并给出了磁尾电流片在GSE坐标系中XY平面内的速度分布图.我们发现磁尾电流片存在着两种不同性质的运动,除了磁尾电流片向晨昏方向的运动,分析表明,磁尾电流片还存在着明显朝向子夜方向的运动（即GSE坐标系中Y=0平面）.观测还进一步表明,位于磁尾中间区域（｜Y_GSE｜〈8Re）的电流片的扰动,其南北向的速度分量相对较大,这从另一个方面说明磁尾中性片的中间区域可能是导致大部分磁尾电流片拍动事件中电流片朝向晨昏两侧运动的源区.对于运动方向朝向子夜方向（Y=0平面）的电流片,其运动方式与运动方向朝向晨昏两侧的电流片存在着明显的不同,因此我们推测,它们应具有不同的起源.本文的统计结果,为我们深入研究地球磁尾电流片拍动源区等物理问题提供了的参考依据.     

Exome sequencing identifies ACAD9 mutations as a cause of complex I deficiency

An isolated defect of respiratory chain complex I activity is a frequent biochemical abnormality in mitochondrial disorders. Despite intensive investigation in recent years, in most instances, the molecular basis underpinning complex I defects remains unknown. We report whole-exome sequencing of a single individual with severe, isolated complex I deficiency. This analysis, followed by filtering with a prioritization of mitochondrial proteins, led us to identify compound heterozygous mutations in ACAD9, which encodes a poorly understood member of the mitochondrial acyl-CoA dehydrogenase protein family. We demonstrated the pathogenic role of the ACAD9 variants by the correction of the complex I defect on expression of the wildtype ACAD9 protein in fibroblasts derived from affected individuals. ACAD9 screening of 120 additional complex I-defective index cases led us to identify two additional unrelated cases and a total of five pathogenic ACAD9 alleles.     

Genome-wide association studies of 14 agronomic traits in rice landraces

Uncovering the genetic basis of agronomic traits in crop landraces that have adapted to various agro-climatic conditions is important to world food security. Here we have identified ～ 3.6 million SNPs by sequencing 517 rice landraces and constructed a high-density haplotype map of the rice genome using a novel data-imputation method. We performed genome-wide association studies (GWAS) for 14 agronomic traits in the population of Oryza sativa indica subspecies. The loci identified through GWAS explained ～ 36% of the phenotypic variance, on average. The peak signals at six loci were tied closely to previously identified genes. This study provides a fundamental resource for rice genetics research and breeding, and demonstrates that an approach integrating second-generation genome sequencing and GWAS can be used as a powerful complementary strategy to classical biparental cross-mapping for dissecting complex traits in rice.