Genome-wide association analysis identifies 20 loci that influence adult height

Adult height is a model polygenic trait, but there has been limited success in identifying the genes underlying its normal variation. To identify genetic variants influencing adult human height, we used genome-wide association data from 13,665 individuals and genotyped 39 variants in an additional 16,482 samples. We identified 20 variants associated with adult height (P < 5 x 10(-7), with 10 reaching P < 1 x 10(-10)). Combined, the 20 SNPs explain approximately 3% of height variation, with a approximately 5 cm difference between the 6.2% of people with 17 or fewer 'tall' alleles compared to the 5.5% with 27 or more 'tall' alleles. The loci we identified implicate genes in Hedgehog signaling (IHH, HHIP, PTCH1), extracellular matrix (EFEMP1, ADAMTSL3, ACAN) and cancer (CDK6, HMGA2, DLEU7) pathways, and provide new insights into human growth and developmental processes. Finally, our results provide insights into the genetic architecture of a classic quantitative trait.     

Rapid X-ray flaring from the direction of the supermassive black hole at the Galactic Centre.

The nuclei of most galaxies are now believed to harbour supermassive black holes. The motions of stars in the central few light years of our Milky Way Galaxy indicate the presence of a dark object with a mass of about 2.6 x 106 solar masses (refs 2, 3). This object is spatially coincident with the compact radio source Sagittarius A* (Sgr A*) at the dynamical centre of the Galaxy, and the radio emission is thought to be powered by the gravitational potential energy released by matter as it accretes onto a supermassive black hole. Sgr A* is, however, much fainter than expected at all wavelengths, especially in X-rays, which has cast some doubt on this model. The first strong evidence for X-ray emission was found only recently. Here we report the discovery of rapid X-ray flaring from the direction of Sgr A*, which, together with the previously reported steady X-ray emission, provides compelling evidence that the emission is coming from the accretion of gas onto a supermassive black hole at the Galactic Centre.     

High levels of mitochondrial DNA deletions in substantia nigra neurons in aging and Parkinson disease

Here we show that in substantia nigra neurons from both aged controls and individuals with Parkinson disease, there is a high level of deleted mitochondrial DNA (mtDNA) (controls, 43.3% +/- 9.3%; individuals with Parkinson disease, 52.3% +/- 9.3%). These mtDNA mutations are somatic, with different clonally expanded deletions in individual cells, and high levels of these mutations are associated with respiratory chain deficiency. Our studies suggest that somatic mtDNA deletions are important in the selective neuronal loss observed in brain aging and in Parkinson disease.     

Primitive deuterostomes from the Chengjiang Lagerst?tte (Lower Cambrian, China).

Cambrian fossil-Lagerst?tten (sites of exceptional fossil preservation), such as those from Chengjiang (Lower Cambrian) and the Burgess Shale (Middle Cambrian), provide our best window into the Cambrian 'explosion'. Such faunas are known from about 40 localities, and have yielded a widely disparate series of taxa ranging from ctenophores to agnathan fish. Recent excavations of the Chengjiang fossil-Lagerst?tte, known from a series of sites near Kunming in Yunnan, south China, have resulted in the discovery of several new forms. In conjunction with material described earlier, these provide evidence for a new group of metazoans, the vetulicolians. Several features, notably a series of gill slits, suggest that this group can throw light on an early stage of deuterostome diversification.     

Systems and Environmental Decision Making—Postgraduate Open Learning with the Open University

Environmental issues affect everyone though the ways in which people engage with them varies a great deal. The Open University's Masters program in environmental decision making has at its core a modular course that enables students to incorporate environmental factors into their decision making from a starting point of identifying their own environmental issues using a systems approach. Students carry out a project based on their own experience in a decision-making situation of their own choice. A framework for environmental decision making is introduced and students learn how to use the framework systematically, systemically and critically. The course has evolved since it was first introduced in 1997 as both students and the course team have learnt about environmental decision making together. This paper analyses and interprets some of the data that have emerged from students projects since the course began.     

Structural basis for the subunit assembly of the anaphase-promoting complex

The anaphase-promoting complex or cyclosome (APC/C) is an unusually large E3 ubiquitin ligase responsible for regulating defined cell cycle transitions. Information on how its 13 constituent proteins are assembled, and how they interact with co-activators, substrates and regulatory proteins is limited. Here, we describe a recombinant expression system that allows the reconstitution of holo APC/C and its sub-complexes that, when combined with electron microscopy, mass spectrometry and docking of crystallographic and homology-derived coordinates, provides a precise definition of the organization and structure of all essential APC/C subunits, resulting in a pseudo-atomic model for 70% of the APC/C. A lattice-like appearance of the APC/C is generated by multiple repeat motifs of most APC/C subunits. Three conserved tetratricopeptide repeat (TPR) subunits (Cdc16, Cdc23 and Cdc27) share related superhelical homo-dimeric architectures that assemble to generate a quasi-symmetrical structure. Our structure explains how this TPR sub-complex, together with additional scaffolding subunits (Apc1, Apc4 and Apc5), coordinate the juxtaposition of the catalytic and substrate recognition module (Apc2, Apc11 and Apc10 (also known as Doc1)), and TPR-phosphorylation sites, relative to co-activator, regulatory proteins and substrates.     

澳大利亚科研诚信管理探析

全球范围内的科研诚信管理越来越重要,尤其是随着机构间和国家间的合作越来越频繁.由于研究经费的申请和论文的发表竞争日趋激烈,科研诚信管理的风险也随之加大.科研管理供应链上的所有参与者,包括政府、基金资助机构、研究机构、研究人员以及学生都应该被纳入科研诚信管理体系.该文分别从政府和机构层面对澳大利亚科研诚信管理结构和政策进...