Research articles

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  • A genome-wide association study meta-analysis of more than 100,000 subjects of European and Asian ancestries reveals 42 new risk loci for rheumatoid arthritis, with follow-up studies identifying 98 biological candidate genes that are either already being targeted by drugs or could be in the future.

    • Yukinori Okada
    • Di Wu
    • Robert M. Plenge
    Letter
  • Whole-exome sequencing and analysis of 115 cervical carcinoma–normal paired samples, in addition to transcriptome and whole-genome sequencing for a subset of these tumours, reveal novel genes mutated at significant levels within this cohort and provide evidence that HPV integration is a common mechanism for target gene overexpression; results also compare mutational landscapes between squamous cell carcinomas and adenocarcinomas.

    • Akinyemi I. Ojesina
    • Lee Lichtenstein
    • Matthew Meyerson
    Letter
  • Replacement of the wingless (wg) gene in Drosophila with one that expresses a membrane-tethered form of Wg results in viable flies with normally patterned appendages of nearly the right size; early wg transcription and memory of signalling ensure continued target-gene expression in the absence of Wg release, even though the spread of Wg could boost cell proliferation.

    • Cyrille Alexandre
    • Alberto Baena-Lopez
    • Jean-Paul Vincent
    Article
  • Diffuse white matter injury is common in very preterm infants; here, enhanced epidermal growth factor receptor signalling in oligodendrocyte precursor cells in a mouse model of such injury is shown to increase cellular and functional recovery.

    • Joseph Scafidi
    • Timothy R. Hammond
    • Vittorio Gallo
    Letter
  • A risk haplotype for type 2 diabetes is identified with four amino acid substitutions in SLC16A11, which is present at ∼50% frequency in Native American samples and ∼10% in east Asian samples, but is rare in European and African samples; SLC16A11 may alter hepatic lipid metabolism, causing an increase in triacylglycerol levels.

    • Amy L. Williams
    • Suzanne B. R. Jacobs
    • Teresa Tusié-Luna
    Letter
  • The Tet family of dioxygenase enzymes convert 5-methylcytosine to 5-hydroxymethylcytosine, 5-formylcytosine and 5-carboxylcytosine, which has an effect on gene expression; here the structure of NgTet1, a Tet-like protein with the same activity as mammalian Tet1, is determined, showing that NgTet1 uses a base-flipping mechanism to access 5-methylcytosine.

    • Hideharu Hashimoto
    • June E. Pais
    • Xiaodong Cheng
    Letter
  • Intermolecular Coulombic decay transfers excess energy to neighbouring molecules, which then lose a low-energy (and, hence, genotoxic) electron; here the process is experimentally confirmed to be site-selective and highly efficient, possibly enabling more targeted radiation therapy.

    • F. Trinter
    • M. S. Schöffler
    • T. Jahnke
    Letter
  • A highly specific chemical crosslinking method is used to trap a complex between an acyl carrier protein and a fatty acid dehydratase during fatty acid biosynthesis; subsequent X-ray crystallography, NMR spectroscopy and molecular dynamics simulations techniques enable the detailed study of this complex.

    • Chi Nguyen
    • Robert W. Haushalter
    • Michael D. Burkart
    Letter
  • This large comparative phylogenetic study across angiosperms shows that species that are herbaceous or have small conduits evolved these traits before colonizing environments with freezing conditions, whereas deciduous species changed their climate niche before becoming deciduous.

    • Amy E. Zanne
    • David C. Tank
    • Jeremy M. Beaulieu
    Letter
  • Cryo-electron microscopy combined with chemical crosslinking and mass spectrometry is used to determine the structure of the large subunit of the mammalian mitoribosome; this structure provides detailed structural insight, particularly of the molecular architecture of the polypeptide exit site, which has been structurally remodelled during evolution, presumably to help facilitate the membrane insertion of the highly hydrophobic proteins encoded by the mitochondrial genome.

    • Basil J. Greber
    • Daniel Boehringer
    • Nenad Ban
    Article
  • Quiescent CD4 T cells in lymphoid tissues are shown to die after HIV-1 infection by caspase-1-mediated pyroptosis, a highly inflammatory form of programmed cell death; caspase 1 inhibitors, which are safe for human use, can rescue the cell death in vitro raising the possibility of new therapeutics targeting the host instead of the virus.

    • Gilad Doitsh
    • Nicole L. K. Galloway
    • Warner C. Greene
    Article
  • A single-flask, catalytic enantioselective conversion of terminal alkenes into a number of chiral products is described: this tandem diboration/cross-coupling reaction works on a broad range of substrates, requires small amounts of commercially available catalysts, and provides products in high yield and high selectivity.

    • Scott N. Mlynarski
    • Christopher H. Schuster
    • James P. Morken
    Letter
  • High-resolution measurements of electrons obtained by satellite during the geomagnetic storm of 9 October 2012 together with a data-driven global wave model are analysed to show that scattering by a magnetospheric electromagnetic emission, known as ‘chorus’, can explain the temporal evolution of the observed increase in relativistic electron flux.

    • R. M. Thorne
    • W. Li
    • S. G. Kanekal
    Letter
  • To establish what effect the Late Cenozoic cooling climate shift might have had on global erosion, inverse modelling of thermochronometric ages is used to show that erosion rates are increased by cooling, especially in glaciated mountain ranges.

    • Frédéric Herman
    • Diane Seward
    • Todd A. Ehlers
    Letter