Killer cell immunoglobulin-like receptor 3DL1-mediated recognition of human leukocyte antigen B

Members of the killer cell immunoglobulin-like receptor (KIR) family, a large group of polymorphic receptors expressed on natural killer (NK) cells, recognize particular peptide-laden human leukocyte antigen (pHLA) class I molecules and have a pivotal role in innate immune responses. Allelic variation and extensive polymorphism within the three-domain KIR family (KIR3D, domains D0-D1-D2) affects pHLA binding specificity and is linked to the control of viral replication and the treatment outcome of certain haematological malignancies. Here we describe the structure of a human KIR3DL1 receptor bound to HLA-B*5701 complexed with a self-peptide. KIR3DL1 clamped around the carboxy-terminal end of the HLA-B*5701 antigen-binding cleft, resulting in two discontinuous footprints on the pHLA. First, the D0 domain, a distinguishing feature of the KIR3D family, extended towards β2-microglobulin and abutted a region of the HLA molecule with limited polymorphism, thereby acting as an 'innate HLA sensor' domain. Second, whereas the D2-HLA-B*5701 interface exhibited a high degree of complementarity, the D1-pHLA-B*5701 contacts were suboptimal and accommodated a degree of sequence variation both within the peptide and the polymorphic region of the HLA molecule. Although the two-domain KIR (KIR2D) and KIR3DL1 docked similarly onto HLA-C and HLA-B respectively, the corresponding D1-mediated interactions differed markedly, thereby providing insight into the specificity of KIR3DL1 for discrete HLA-A and HLA-B allotypes. Collectively, in association with extensive mutagenesis studies at the KIR3DL1-pHLA-B*5701 interface, we provide a framework for understanding the intricate interplay between peptide variability, KIR3D and HLA polymorphism in determining the specificity requirements of this essential innate interaction that is conserved across primate species.     

In situ small angle X-ray scattering investigation of the thermal expansion and related structural information of carbon nanotube composites

In-situ thermal expansion tests on a series of carbon nanotube bucky-paper composites were performed with direct heating within a synchrotron SAXS source. The impact of the samples density and morphology as well as the chemistry and degree of decoration of the carbon nanotubes on the scattering patterns were investigated and correlated to the materials macro-properties. The results demonstrate that simple densification techniques, such as acetone dipping or gold electroless deposition, could reduce greatly the displacements of the carbon nanotubes within the structure and lead to more thermally stable material.     

自然界的左手性

基本粒子物理与药物酞胺哌啶酮所引起的胎儿畸形事件有什么关系呢?在制酒工业,晶体形状,合成化学和理论物理学等方面都已经发现了这种关联的线索,所有这些都与自然界的左手性有关。     

The genome sequence of Schizosaccharomyces pombe

We have sequenced and annotated the genome of fission yeast (Schizosaccharomyces pombe), which contains the smallest number of protein-coding genes yet recorded for a eukaryote: 4,824. The centromeres are between 35 and 110 kilobases (kb) and contain related repeats including a highly conserved 1.8-kb element. Regions upstream of genes are longer than in budding yeast (Saccharomyces cerevisiae), possibly reflecting more-extended control regions. Some 43% of the genes contain introns, of which there are 4,730. Fifty genes have significant similarity with human disease genes; half of these are cancer related. We identify highly conserved genes important for eukaryotic cell organization including those required for the cytoskeleton, compartmentation, cell-cycle control, proteolysis, protein phosphorylation and RNA splicing. These genes may have originated with the appearance of eukaryotic life. Few similarly conserved genes that are important for multicellular organization were identified, suggesting that the transition from prokaryotes to eukaryotes required more new genes than did the transition from unicellular to multicellular organization.     

绿色基因——以生物工程创造新食物

当比尔·塔克在太阳落山的黄昏时分赶回堪萨斯农场中的家园时,他那一片长出了穗状雄花的玉米田预示着一场农业革命已落到了日暮途穷的境地:他的田地干得土壤在手掌中会一片片地剥落为粉末。他和邻近农场主的玉米产量骤然下降了三分之一,和十年前开始的增产趋势成了鲜明的对照。     

Effectiveness of the global protected area network in representing species diversity

The Fifth World Parks Congress in Durban, South Africa, announced in September 2003 that the global network of protected areas now covers 11.5% of the planet's land surface. This surpasses the 10% target proposed a decade earlier, at the Caracas Congress, for 9 out of 14 major terrestrial biomes. Such uniform targets based on percentage of area have become deeply embedded into national and international conservation planning. Although politically expedient, the scientific basis and conservation value of these targets have been questioned. In practice, however, little is known of how to set appropriate targets, or of the extent to which the current global protected area network fulfils its goal of protecting biodiversity. Here, we combine five global data sets on the distribution of species and protected areas to provide the first global gap analysis assessing the effectiveness of protected areas in representing species diversity. We show that the global network is far from complete, and demonstrate the inadequacy of uniform--that is, 'one size fits all'--conservation targets.     

Linkage disequilibrium of a type 1 diabetes susceptibility locus with a regulatory IL12B allele

Type 1 diabetes (T1D; or insulin-dependent diabetes mellitus, IDDM) is an autoimmune disease with both genetic and environmental components. In addition to the human leukocyte antigen (HLA) complex, the single major genetic contributor of susceptibility, an unknown number of other unidentified genes are required to mediate disease. Although many loci conferring susceptibility to T1D have been mapped, their identification has proven problematic due to the complex nature of this disease. Our strategy for finding T1D susceptibility genes has been to test for human homologues of loci implicated in diabetes-prone NOD (non-obese diabetic) mice, together with application of biologically relevant stratification methods. We report here a new susceptibility locus, IDDM18, located near the interleukin-12 (IL-12)p40 gene, IL12B. Significant bias in transmission of IL12B alleles was observed in affected sibpairs and was confirmed in an independent cohort of simplex families. A single base change in the 3' UTR showed strong linkage disequilibrium with the T1D susceptibility locus. The IL12B 3' UTR alleles showed different levels of expression in cell lines. Variation in IL-12p40 production may influence T-cell responses crucial for either mediating or protecting against this and other autoimmune diseases.     

学术研究的领域和重点

学术研究(academic research),尤其是自然科学的研究具有一些特性,这些特性如果不是普遍的标准,起码被作为全世界大学的标准。但是学术研究常受到挑战,不得不放弃既定的标准而屈从于经费来源施加的压力,尤其是在金融紧的阶段。五十年代到六十年代持续发展的阶段过后,发达国家学术研究经历了日益严重的金融紧,面临随之而来的压力,不得不放弃既定的标准。在不发达国家,那些从未富裕过的大学正面临更大的压力以适应科学界     

理论物理的尽头是否已经在望?

我在这个讲演里,打算探讨理论物理的目标,有否可能在不太远的将来,比如说在本世纪的末了,可以达到.我的意思是指,我们是否能够获得一个有关物理相互作用的、前后一致的、统一的理论,这样的一个理论,对所有可能观察到的现象,都能加以描述.当然,在作出这样的预言时,必须非常谨慎:我们以前曾经至     

时空的边缘

Stephen Hawking是剑桥大学Lucasian数学教授,国际著名理论物理学家。1985年5月对我国进行了学术访问,并在中国科技大学和北京师范大学作了学术讲演。本文概述了历史上的宇宙学观点,并介绍了宇宙学中的最新成就,这些成果在哲学上及物理学上都有重要的意义。