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.     

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.     

Global landscape of HIV-human protein complexes

Human immunodeficiency virus (HIV) has a small genome and therefore relies heavily on the host cellular machinery to replicate. Identifying which host proteins and complexes come into physical contact with the viral proteins is crucial for a comprehensive understanding of how HIV rewires the host's cellular machinery during the course of infection. Here we report the use of affinity tagging and purification mass spectrometry to determine systematically the physical interactions of all 18 HIV-1 proteins and polyproteins with host proteins in two different human cell lines (HEK293 and Jurkat). Using a quantitative scoring system that we call MiST, we identified with high confidence 497 HIV-human protein-protein interactions involving 435 individual human proteins, with ～40% of the interactions being identified in both cell types. We found that the host proteins hijacked by HIV, especially those found interacting in both cell types, are highly conserved across primates. We uncovered a number of host complexes targeted by viral proteins, including the finding that HIV protease cleaves eIF3d, a subunit of eukaryotic translation initiation factor 3. This host protein is one of eleven identified in this analysis that act to inhibit HIV replication. This data set facilitates a more comprehensive and detailed understanding of how the host machinery is manipulated during the course of HIV infection.     

Data Filtering and Statistical Process Modeling

AnewfilteringmethodwhichextendstheSureShrinkalgorithmispresentedinthispaper.Sincethedatafromplantsalwayscontainsomepeaknoise,thenormaldenoisealgorithmssuchasSureShrinkcannotalwaysachievegoodresults.WiththePeakCutalgorithm,thepeaknoisecanbesignificantlyeliminatedandgoodsmoothingcanbeobtainedusingtheSureShrinkalgorithm.InthispaperaProjectiontoLatentStructures(PLS)modelisestablishedaftertheprocessdataarefirstfilteredusingthePeakCutandSureShrinkalgorithms.DistributedControlSystems(DCS)an…     

Science policy and politics in post-war Japan: the establishment of the KEK high energy physics laboratory

This paper provides a detailed account of the prehistory of the KEK National Laboratory for High Energy Physics at Tsukuba in Japan. Attempts to establish Japan's first truly national laboratory marked the beginning of ‘big science’ in Japan. An examination of the debate and decision-making processes, which spanned over a decade, provide insight into the political aspects of policy making in the post-war period. History shows that even in Japan, self-interest has taken precedence over group interests in lobbying for research funds for science.     

Direct access to serum macromolecules by intraerythrocytic malaria parasites.

Trafficking pathways in malaria-infected erythrocytes are complex because the internal parasite is separated from the serum by the erythrocyte and parasitophorous vacuolar membranes. Intraerythrocytic Plasmodium falciparum parasites can endocytose dextrans, protein A and an IgG2a antibody. Here we show that these macromolecules do not cross the erythrocyte or parasitophorous vacuolar membranes, but rather gain direct access to the aqueous space surrounding the parasite through a parasitophorous duct. Evidence for this structure includes visualization of membranes that are continuous between the parasitophorous vacuolar and erythrocyte membranes, and surface labelling of the parasite with fluorescent macromolecules under conditions that block endocytosis. The parasite can internalize by fluid-phase endocytosis macromolecules from the aqueous compartment surrounding it. Thus, surface antigens on trophozoites and schizonts should be considered as targets for antibody-directed parasiticidal agents.