Crystal structure of a self-splicing group I intron with both exons

The discovery of the RNA self-splicing group I intron provided the first demonstration that not all enzymes are proteins. Here we report the X-ray crystal structure (3.1-A resolution) of a complete group I bacterial intron in complex with both the 5'- and the 3'-exons. This complex corresponds to the splicing intermediate before the exon ligation step. It reveals how the intron uses structurally unprecedented RNA motifs to select the 5'- and 3'-splice sites. The 5'-exon's 3'-OH is positioned for inline nucleophilic attack on the conformationally constrained scissile phosphate at the intron-3'-exon junction. Six phosphates from three disparate RNA strands converge to coordinate two metal ions that are asymmetrically positioned on opposing sides of the reactive phosphate. This structure represents the first splicing complex to include a complete intron, both exons and an organized active site occupied with metal ions.     

The RickA protein of Rickettsia conorii activates the Arp2/3 complex

Actin polymerization, the main driving force for cell locomotion, is also used by the bacteria Listeria and Shigella and vaccinia virus for intracellular and intercellular movements. Seminal studies have shown the key function of the Arp2/3 complex in nucleating actin and generating a branched array of actin filaments during membrane extension and pathogen movement. Arp2/3 requires activation by proteins such as the WASP-family proteins or ActA of Listeria. We previously reported that actin tails of Rickettsia conorii, another intracellular bacterium, unlike those of Listeria, Shigella or vaccinia, are made of long unbranched actin filaments apparently devoid of Arp2/3 (ref. 4). Here we identify a R. conorii surface protein, RickA, that activates Arp2/3 in vitro, although less efficiently than ActA. In infected cells, Arp2/3 is detected on the rickettsial surface but not in actin tails. When expressed in mammalian cells and targeted to the membrane, RickA induces filopodia. Thus RickA-induced actin polymerization, by generating long actin filaments reminiscent of those present in filopodia, has potential as a tool for studying filopodia formation.     

Proxy evidence for an El Niño-like response to volcanic forcing

Past studies have suggested a statistical connection between explosive volcanic eruptions and subsequent El Ni?o climate events. This connection, however, has remained controversial. Here we present support for a response of the El Ni?o/Southern Oscillation (ENSO) phenomenon to forcing from explosive volcanism by using two different palaeoclimate reconstructions of El Ni?o activity and two independent, proxy-based chronologies of explosive volcanic activity from ad 1649 to the present. We demonstrate a significant, multi-year, El Ni?o-like response to explosive tropical volcanic forcing over the past several centuries. The results imply roughly a doubling of the probability of an El Ni?o event occurring in the winter following a volcanic eruption. Our empirical findings shed light on how the tropical Pacific ocean-atmosphere system may respond to exogenous (both natural and anthropogenic) radiative forcing.     

英国国际合作格局

该报告运用文献计量学方法，对英国及其主要合作伙伴国的国际合作格局做了全面的分析。所选
择的主要国家包括美国、加拿大、法国、德国、日本、澳大利亚、中国与印度；数据覆盖领域有临床、医药
卫生、生物科学、环境科学、数学、物质科学以及工程技术领域；数据时间分为1996－2000年与2001－2005
年两个时间段。结果显示：国际论文数量增长显著；英国国际合作论文份额的增长比G7 国家更加快速； 德
国和美国是英国最大的国际合作伙伴；英国国际合作论文的平均影响力显著高于其科研论文的总体影响力；
中国与英国合作发表的论文数量超过了与其他欧洲各国的合作论文数。     

Evidence for two independent prostate cancer risk-associated loci in the HNF1B gene at 17q12

We carried out a fine-mapping study in the HNF1B gene at 17q12 in two study populations and identified a second locus associated with prostate cancer risk, approximately 26 kb centromeric to the first known locus (rs4430796); these loci are separated by a recombination hot spot. We confirmed the association with a SNP in the second locus (rs11649743) in five additional populations, with P = 1.7 x 10(-9) for an allelic test of the seven studies combined. The association at each SNP remained significant after adjustment for the other SNP.     

Structure and function of the type 1 insulin-like growth factor receptor

The type 1 insulin-like growth factor receptor (IGF-1R), a transmembrane tyrosine kinase, is widely expressed across many cell types in foetal and postnatal tissues. Activation of the receptor following binding of the secreted growth factor ligands IGF-1 and IGF-2 elicits a repertoire of cellular responses including proliferation, and the protection of cells from programmed cell death or apoptosis. As a result, signalling through the IGF-1R is the principal pathway responsible for somatic growth in foetal mammals, whereas somatic growth in postnatal animals is achieved through the synergistic interaction of growth hormone and the IGFs. Forced overexpression of the IGF-1R results in the malignant transformation of cultured cells: conversely, downregulation of IGF-1R levels can reverse the transformed phenotype of tumour cells, and may render them sensitive to apoptosis in vivo. Elevated levels of IGF-IR are observed in a variety of human tumour types, whereas epidemiological studies implicate the IGF-1 axis as a predisposing factor in the pathogenesis of human breast and prostate cancer. The IGF-1R has thus emerged as a therapeutic target for the development of antitumour agents. Recent progress towards the elucidation of the three-dimensional structure of the extracellular domain of the IGF-1R represents an opportunity for the rational assembly of small molecule antagonists of receptor function for clinical use.