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Journal Cover Nature
   [2159 followers]  Follow    
   Full-text available via subscription Subscription journal
     ISSN (Print) 0028-0836 - ISSN (Online) 1476-4687
     Published by Nature Publishing Group Homepage  [109 journals]   [SJR: 14.747]   [H-I: 768]
  • Future computing
    • Pages: 113 - 113
      Abstract: Pushing the boundaries of current computing technologies will show the way to new ones.
      Citation: Nature 512, 7513 (2014)
      PubDate: 2014-08-13
      DOI: 10.1038/512113b
      Issue No: Vol. 512, No. 7513 (2014)
       
  • Save the children
    • Pages: 113 - 113
      Abstract: Infants and young people are being traumatized by armed conflict in their countries. Their resulting mental illnesses must be addressed, for the good of both the individuals and their society.
      Citation: Nature 512, 7513 (2014)
      PubDate: 2014-08-12
      DOI: 10.1038/512113a
      Issue No: Vol. 512, No. 7513 (2014)
       
  • China should aim for a total cap on emissions
    • Authors: Qiang Wang
      Pages: 115 - 115
      Abstract: A focus on carbon intensity alone will allow emissions to grow with the economy, argues Qiang Wang.
      Citation: Nature 512, 7513 (2014)
      PubDate: 2014-08-13
      DOI: 10.1038/512115a
      Issue No: Vol. 512, No. 7513 (2014)
       
  • Chemistry: Cleaner, greener ammonia
    • Pages: 116 - 116
      Abstract: A method of producing ammonia could yield a greener route to nitrogen-based fertilizers.Ammonia is currently synthesized by combining nitrogen and hydrogen under high pressures and temperatures in a reaction called the Haber–Bosch process. Making the hydrogen consumes around 5% of the world's natural-gas production,
      Citation: Nature 512, 7513 (2014)
      PubDate: 2014-08-13
      DOI: 10.1038/512116d
      Issue No: Vol. 512, No. 7513 (2014)
       
  • Astronomy: Another super-Earth found
    • Pages: 116 - 116
      Abstract: A 'super-Earth' planet — an extrasolar planet larger than Earth but smaller than Neptune — has been detected in the habitable zone of a star called Gliese 832.Robert Wittenmyer at the University of New South Wales in Sydney, Australia, and his colleagues used data
      Citation: Nature 512, 7513 (2014)
      PubDate: 2014-08-13
      DOI: 10.1038/512116c
      Issue No: Vol. 512, No. 7513 (2014)
       
  • Gene editing: CRISPR corrects β-thalassaemia
    • Pages: 116 - 116
      Abstract: A common genetic blood disorder has been corrected in cultured stem cells by using a cutting-edge genome-editing technique.The disorder β-thalassaemia is characterized by reduced levels of haemoglobin due to mutations in the gene for β-globin (HBB). Yuet Kan and his colleagues at
      Citation: Nature 512, 7513 (2014)
      PubDate: 2014-08-13
      DOI: 10.1038/512116b
      Issue No: Vol. 512, No. 7513 (2014)
       
  • Polar science: Arctic snowpack thins
    • Pages: 116 - 116
      Abstract: As Arctic sea ice has shrunk and thinned, so has the snowpack blanketing it.Melinda Webster at the University of Washington in Seattle and her colleagues studied data on spring snow depth gathered between 2009 and 2013 by radar surveys conducted from the air and
      Citation: Nature 512, 7513 (2014)
      PubDate: 2014-08-13
      DOI: 10.1038/512116a
      Issue No: Vol. 512, No. 7513 (2014)
       
  • Microbiology: Resistance genes mapped
    • Pages: 116 - 117
      Abstract: Researchers have pinpointed mutations encoding antibiotic resistance in bacteria that cause pneumonia, borrowing a technique more often used to hunt for gene variations linked to common human diseases.Streptococcus pneumoniae is a leading killer of children under five worldwide. The bacterium is prone to
      Citation: Nature 512, 7513 (2014)
      PubDate: 2014-08-13
      DOI: 10.1038/512116e
      Issue No: Vol. 512, No. 7513 (2014)
       
  • Imaging: Seeing through a mouse skull
    • Pages: 117 - 117
      Abstract: Glowing nanotubes have allowed researchers to peer through a mouse's skull and examine its living brain in real time.Calvin Kuo and Hongjie Dai of Stanford University in California and their colleagues injected fluorescent molecules based on carbon nanotubes into the tails of mice. The
      Citation: Nature 512, 7513 (2014)
      PubDate: 2014-08-13
      DOI: 10.1038/512117a
      Issue No: Vol. 512, No. 7513 (2014)
       
  • Seismology: From earthquakes to icequakes
    • Pages: 117 - 117
      Abstract: Big earthquakes on land can trigger small distant 'icequakes' in the Antarctic ice sheet.At magnitude 8.8, the 2010 Maule earthquake in Chile was the largest quake in the Southern Hemisphere for half a century. Zhigang Peng at the Georgia Institute of Technology in Atlanta
      Citation: Nature 512, 7513 (2014)
      PubDate: 2014-08-13
      DOI: 10.1038/512117b
      Issue No: Vol. 512, No. 7513 (2014)
       
  • Stem cells: Fresh growth from elderly cells
    • Pages: 117 - 117
      Abstract: Human skin cells can be reprogrammed into neural cells that form synapses with neurons in severed spinal cords in rats.A team led by Paul Lu and Mark Tuszynski at the University of California San Diego in La Jolla took skin fibroblasts from an 86-year-old
      Citation: Nature 512, 7513 (2014)
      PubDate: 2014-08-13
      DOI: 10.1038/512117c
      Issue No: Vol. 512, No. 7513 (2014)
       
  • Microbiology: Ecosystems afloat in asphalt
    • Pages: 117 - 117
      Abstract: Water droplets suspended in the world's largest tar 'lake' are teeming with diverse ecosystems of bacteria and methane-producing microorganisms, despite the inhospitable living conditions.Droplets just a few microlitres in volume that were isolated from Pitch Lake (pictured), a huge tar pit on
      Citation: Nature 512, 7513 (2014)
      PubDate: 2014-08-13
      DOI: 10.1038/512117d
      Issue No: Vol. 512, No. 7513 (2014)
       
  • Clash over the Kardashians of science
    • Authors: Chris Woolston
      Pages: 117 - 117
      Abstract: Nature's roundup of the papers and issues gaining traction on social media.Here's a novel approach for getting an article noticed: put 'Kardashian' in the title. A paper that compared Twitter-using researchers to the celebrity Kim Kardashian incited a backlash on social media. Online
      Citation: Nature 512, 7513 (2014)
      PubDate: 2014-08-13
      DOI: 10.1038/512117e
      Issue No: Vol. 512, No. 7513 (2014)
       
  • Seven days: 8–14 August 2014
    • Pages: 118 - 119
      Abstract: The week in science: Ebola declared an international public-health emergency; power-cut at UK’s Antarctic research station; and Rosetta space probe catches up with a comet.
      Citation: Nature 512, 7513 (2014)
      PubDate: 2014-08-12
      DOI: 10.1038/512118a
      Issue No: Vol. 512, No. 7513 (2014)
       
  • Native ecosystems blitzed by drought
    • Authors: Alexandra Witze
      Pages: 121 - 122
      Abstract: California’s current water crisis offers a preview of what climate change will bring.
      Citation: Nature 512, 7513 (2014)
      PubDate: 2014-08-12
      DOI: 10.1038/512121a
      Issue No: Vol. 512, No. 7513 (2014)
       
  • Health check for deep-sea mining
    • Authors: Katia Moskvitch
      Pages: 122 - 123
      Abstract: European project evaluates risks to delicate ecosystems.
      Citation: Nature 512, 7513 (2014)
      PubDate: 2014-08-13
      DOI: 10.1038/512122a
      Issue No: Vol. 512, No. 7513 (2014)
       
  • Teen drug use gets supersize study
    • Authors: Sara Reardon
      Pages: 123 - 124
      Abstract: US government programme will examine 10,000 adolescents to document effects on developing brains.
      Citation: Nature 512, 7513 (2014)
      PubDate: 2014-08-12
      DOI: 10.1038/512123a
      Issue No: Vol. 512, No. 7513 (2014)
       
  • US assesses virus of the Caribbean
    • Authors: Aleszu Bajak
      Pages: 124 - 125
      Abstract: Researchers warn that a change of mosquito host could accelerate spread of chikungunya across the Americas.
      Citation: Nature 512, 7513 (2014)
      PubDate: 2014-08-12
      DOI: 10.1038/512124a
      Issue No: Vol. 512, No. 7513 (2014)
       
  • Online collaboration: Scientists and the social network
    • Authors: Richard Van Noorden
      Pages: 126 - 129
      Abstract: Giant academic social networks have taken off to a degree that no one expected even a few years ago. A Nature survey explores why.
      Citation: Nature 512, 7513 (2014)
      PubDate: 2014-08-13
      DOI: 10.1038/512126a
      Issue No: Vol. 512, No. 7513 (2014)
       
  • Society: Don't blame the mothers
    • Authors: Sarah S. Richardson, Cynthia R. Daniels, Matthew W. Gillman, Janet Golden, Rebecca Kukla, Christopher Kuzawa, Janet Rich-Edwards
      Pages: 131 - 132
      Abstract: Careless discussion of epigenetic research on how early life affects health across generations could harm women, warn Sarah S. Richardson and colleagues.
      Citation: Nature 512, 7513 (2014)
      PubDate: 2014-08-13
      DOI: 10.1038/512131a
      Issue No: Vol. 512, No. 7513 (2014)
       
  • History of engineering: Wonder maker
    • Authors: Andrew Robinson
      Pages: 134 - 135
      Abstract: Andrew Robinson delves into a study inspired by James Watt's fascinating workshop.
      Citation: Nature 512, 7513 (2014)
      PubDate: 2014-08-13
      DOI: 10.1038/512134a
      Issue No: Vol. 512, No. 7513 (2014)
       
  • Books in brief
    • Authors: Barbara Kiser
      Pages: 135 - 135
      Abstract: Barbara Kiser reviews five of the week’s best science picks.
      Citation: Nature 512, 7513 (2014)
      PubDate: 2014-08-13
      DOI: 10.1038/512135a
      Issue No: Vol. 512, No. 7513 (2014)
       
  • Centenary: Russian stamp to honour physicist
    • Authors: Renad I. Zhdanov, Pascal Chardonnet
      Pages: 136 - 136
      Abstract: Russia has just issued a postage stamp to mark the centenary of the birth of the brilliant physicist and cosmologist Yakov Zel'dovich (1914–87).Among his many achievements, and despite never having received a university degree, Zel'dovich developed the theories of nuclear chain reactions and of
      Citation: Nature 512, 7513 (2014)
      PubDate: 2014-08-13
      DOI: 10.1038/512136a
      Issue No: Vol. 512, No. 7513 (2014)
       
  • Conservation: White possums must stay cool to survive
    • Authors: William F. Laurance, Susan Laurance, Christine Milne
      Pages: 136 - 136
      Abstract: It is ironic that Australia, one of the world's highest carbon emitters per capita, is giving up on a hard-won plan to reduce its greenhouse-gas emissions (see Nature511, 392; 201410.1038/511392a) just as climate change could be about to claim one
      Citation: Nature 512, 7513 (2014)
      PubDate: 2014-08-13
      DOI: 10.1038/512136b
      Issue No: Vol. 512, No. 7513 (2014)
       
  • Transgenic crops: Mexican GM maize rift is not so simple
    • Authors: Hugo Perales
      Pages: 136 - 136
      Abstract: You rightly point out that the issue of genetically modified (GM) maize (corn) is more sensitive and complex in Mexico than in other countries (Nature511, 16–17; 201410.1038/511016a), but you owe readers a more in-depth and balanced view.
      Citation: Nature 512, 7513 (2014)
      PubDate: 2014-08-13
      DOI: 10.1038/512136c
      Issue No: Vol. 512, No. 7513 (2014)
       
  • Sexual harassment: Create ethics codes to curb sex abuse
    • Authors: Margaret C. Hardy
      Pages: 136 - 136
      Abstract: A survey published last month found evidence of alarming levels of sexual violence (towards 26% of women and 6% of men) in the course of fieldwork by life scientists (see Naturehttp://doi.org/t3n; 2014). Meanwhile, more than 50 US higher-education institutions are under investigation
      Citation: Nature 512, 7513 (2014)
      PubDate: 2014-08-13
      DOI: 10.1038/512136d
      Issue No: Vol. 512, No. 7513 (2014)
       
  • Neuroscience: What females really want
    • Authors: Leslie C. Griffith
      Pages: 138 - 139
      Abstract: The identification of neural subcircuits used by female fruit flies to make a choice about whether to copulate with a potential mate provides a template for understanding how the brain integrates complex information to reach decisions.
      Citation: Nature 512, 7513 (2014)
      PubDate: 2014-08-13
      DOI: 10.1038/512138a
      Issue No: Vol. 512, No. 7513 (2014)
       
  • Solar system: Sandcastles in space
    • Authors: Daniel J. Scheeres
      Pages: 139 - 140
      Abstract: Analysis of a kilometre-sized, near-Earth asteroid shows that forces weaker than the weight of a penny can keep it from falling apart. This has implications for understanding the evolution of the Solar System. See Letter p.174
      Citation: Nature 512, 7513 (2014)
      PubDate: 2014-08-13
      DOI: 10.1038/512139a
      Issue No: Vol. 512, No. 7513 (2014)
       
  • Ageing: Old blood stem cells feel the stress
    • Authors: Jiri Bartek, Zdenek Hodny
      Pages: 140 - 141
      Abstract: Ageing is accompanied by deterioration in the haematopoietic stem cells that are responsible for regenerating the blood system. Cellular stress in the aged stem cells could be a cause of this decline. See Letter p.198
      Citation: Nature 512, 7513 (2014)
      PubDate: 2014-07-30
      DOI: 10.1038/nature13652
      Issue No: Vol. 512, No. 7513 (2014)
       
  • Condensed-matter physics: Glasses made from pure metals
    • Authors: Jan Schroers
      Pages: 142 - 143
      Abstract: The experimental realization of amorphous pure metals sets the stage for studies of the fundamental processes of glass formation, and suggests that amorphous structures are the most ubiquitous forms of condensed matter. See Letter P.177
      Citation: Nature 512, 7513 (2014)
      PubDate: 2014-08-06
      DOI: 10.1038/nature13653
      Issue No: Vol. 512, No. 7513 (2014)
       
  • Cancer: One cell at a time
    • Authors: Edward J. Fox, Lawrence A. Loeb
      Pages: 143 - 144
      Abstract: Single-cell DNA sequencing of two breast-cancer types has shown extensive mutational variation in individual tumours, confirming that generation of genetic diversity may be inherent in how tumours evolve. See Article p.155
      Citation: Nature 512, 7513 (2014)
      PubDate: 2014-07-30
      DOI: 10.1038/nature13650
      Issue No: Vol. 512, No. 7513 (2014)
       
  • Astronomical instrumentation: Atmospheric blurring has a new enemy
    • Authors: Brent Ellerbroek
      Pages: 144 - 145
      Abstract: A fully automated optics system that corrects atmospheric blurring of celestial objects has imaged 715 star systems thought to harbour planets, completing each observation in less time than it takes to read this article.
      Citation: Nature 512, 7513 (2014)
      PubDate: 2014-08-13
      DOI: 10.1038/512144a
      Issue No: Vol. 512, No. 7513 (2014)
       
  • Structural biology: Corralling a protein-degradation regulator
    • Authors: Raymond J. Deshaies
      Pages: 145 - 146
      Abstract: The crystal structure of the COP9 signalosome, a large protein complex that regulates intracellular protein degradation, reveals how the complex achieves exquisite specificity for its substrates. See Article p.161
      Citation: Nature 512, 7513 (2014)
      PubDate: 2014-07-16
      DOI: 10.1038/nature13644
      Issue No: Vol. 512, No. 7513 (2014)
       
  • Limits on fundamental limits to computation
    • Authors: Igor L. Markov
      Pages: 147 - 154
      Abstract: An indispensable part of our personal and working lives, computing has also become essential to industries and governments. Steady improvements in computer hardware have been supported by periodic doubling of transistor densities in integrated circuits over the past fifty years. Such Moore scaling now requires ever-increasing efforts, stimulating research in alternative hardware and stirring controversy. To help evaluate emerging technologies and increase our understanding of integrated-circuit scaling, here I review fundamental limits to computation in the areas of manufacturing, energy, physical space, design and verification effort, and algorithms. To outline what is achievable in principle and in practice, I recapitulate how some limits were circumvented, and compare loose and tight limits. Engineering difficulties encountered by emerging technologies may indicate yet unknown limits.
      Citation: Nature 512, 7513 (2014)
      PubDate: 2014-08-13
      DOI: 10.1038/nature13570
      Issue No: Vol. 512, No. 7513 (2014)
       
  • Clonal evolution in breast cancer revealed by single nucleus genome
           sequencing
    • Authors: Yong Wang, Jill Waters, Marco L. Leung, Anna Unruh, Whijae Roh, Xiuqing Shi, Ken Chen, Paul Scheet, Selina Vattathil, Han Liang, Asha Multani, Hong Zhang, Rui Zhao, Franziska Michor, Funda Meric-Bernstam, Nicholas E. Navin
      Pages: 155 - 160
      Abstract: Sequencing studies of breast tumour cohorts have identified many prevalent mutations, but provide limited insight into the genomic diversity within tumours. Here we developed a whole-genome and exome single cell sequencing approach called nuc-seq that uses G2/M nuclei to achieve 91% mean coverage breadth. We
      Citation: Nature 512, 7513 (2014)
      PubDate: 2014-07-30
      DOI: 10.1038/nature13600
      Issue No: Vol. 512, No. 7513 (2014)
       
  • Crystal structure of the human COP9 signalosome
    • Authors: Gondichatnahalli M. Lingaraju, Richard D. Bunker, Simone Cavadini, Daniel Hess, Ulrich Hassiepen, Martin Renatus, Eric S. Fischer, Nicolas H. Thomä
      Pages: 161 - 165
      Abstract: Ubiquitination is a crucial cellular signalling process, and is controlled on multiple levels. Cullin–RING E3 ubiquitin ligases (CRLs) are regulated by the eight-subunit COP9 signalosome (CSN). CSN inactivates CRLs by removing their covalently attached activator, NEDD8. NEDD8 cleavage by CSN is catalysed by CSN5, a
      Citation: Nature 512, 7513 (2014)
      PubDate: 2014-07-16
      DOI: 10.1038/nature13566
      Issue No: Vol. 512, No. 7513 (2014)
       
  • Three-dimensional structure of human γ-secretase
    • Authors: Peilong Lu, Xiao-chen Bai, Dan Ma, Tian Xie, Chuangye Yan, Linfeng Sun, Guanghui Yang, Yanyu Zhao, Rui Zhou, Sjors H. W. Scheres, Yigong Shi
      Pages: 166 - 170
      Abstract: The γ-secretase complex, comprising presenilin 1 (PS1), PEN-2, APH-1 and nicastrin, is a membrane-embedded protease that controls a number of important cellular functions through substrate cleavage. Aberrant cleavage of the amyloid precursor protein (APP) results in aggregation of amyloid-β, which accumulates in the brain and
      Citation: Nature 512, 7513 (2014)
      PubDate: 2014-06-29
      DOI: 10.1038/nature13567
      Issue No: Vol. 512, No. 7513 (2014)
       
  • The origin of the local 1/4-keV X-ray flux in both charge exchange and a
           hot bubble
    • Authors: M. Galeazzi, M. Chiao, M. R. Collier, T. Cravens, D. Koutroumpa, K. D. Kuntz, R. Lallement, S. T. Lepri, D. McCammon, K. Morgan, F. S. Porter, I. P. Robertson, S. L. Snowden, N. E. Thomas, Y. Uprety, E. Ursino, B. M. Walsh
      Pages: 171 - 173
      Abstract: The solar neighbourhood is the closest and most easily studied sample of the Galactic interstellar medium, an understanding of which is essential for models of star formation and galaxy evolution. Observations of an unexpectedly intense diffuse flux of easily absorbed 1/4-kiloelectronvolt X-rays, coupled with the discovery that interstellar space within about a hundred parsecs of the Sun is almost completely devoid of cool absorbing gas, led to a picture of a ‘local cavity’ filled with X-ray-emitting hot gas, dubbed the local hot bubble. This model was recently challenged by suggestions that the emission could instead be readily produced within the Solar System by heavy solar-wind ions exchanging electrons with neutral H and He in interplanetary space, potentially removing the major piece of evidence for the local existence of million-degree gas within the Galactic disk. Here we report observations showing that the total solar-wind charge-exchange contribution is approximately 40 per cent of the 1/4-keV flux in the Galactic plane. The fact that the measured flux is not dominated by charge exchange supports the notion of a million-degree hot bubble extending about a hundred parsecs from the Sun.
      Citation: Nature 512, 7513 (2014)
      PubDate: 2014-07-27
      DOI: 10.1038/nature13525
      Issue No: Vol. 512, No. 7513 (2014)
       
  • Cohesive forces prevent the rotational breakup of rubble-pile asteroid
           (29075) 1950 DA
    • Authors: Ben Rozitis, Eric MacLennan, Joshua P. Emery
      Pages: 174 - 176
      Abstract: Space missions and ground-based observations have shown that some asteroids are loose collections of rubble rather than solid bodies. The physical behaviour of such ‘rubble-pile’ asteroids has been traditionally described using only gravitational and frictional forces within a granular material. Cohesive forces in the form of small van der Waals forces between constituent grains have recently been predicted to be important for small rubble piles (ten kilometres across or less), and could potentially explain fast rotation rates in the small-asteroid population. The strongest evidence so far has come from an analysis of the rotational breakup of the main-belt comet P/2013 R3 (ref. 7), although that was indirect and poorly constrained by observations. Here we report that the kilometre-sized asteroid (29075) 1950 DA (ref. 8) is a rubble pile that is rotating faster than is allowed by gravity and friction. We find that cohesive forces are required to prevent surface mass shedding and structural failure, and that the strengths of the forces are comparable to, though somewhat less than, the forces found between the grains of lunar regolith.
      Citation: Nature 512, 7513 (2014)
      PubDate: 2014-08-13
      DOI: 10.1038/nature13632
      Issue No: Vol. 512, No. 7513 (2014)
       
  • Formation of monatomic metallic glasses through ultrafast liquid quenching
    • Authors: Li Zhong, Jiangwei Wang, Hongwei Sheng, Ze Zhang, Scott X. Mao
      Pages: 177 - 180
      Abstract: It has long been conjectured that any metallic liquid can be vitrified into a glassy state provided that the cooling rate is sufficiently high. Experimentally, however, vitrification of single-element metallic liquids is notoriously difficult. True laboratory demonstration of the formation of monatomic metallic glass has been lacking. Here we report an experimental approach to the vitrification of monatomic metallic liquids by achieving an unprecedentedly high liquid-quenching rate of 1014 K s−1. Under such a high cooling rate, melts of pure refractory body-centred cubic (bcc) metals, such as liquid tantalum and vanadium, are successfully vitrified to form metallic glasses suitable for property interrogations. Combining in situ transmission electron microscopy observation and atoms-to-continuum modelling, we investigated the formation condition and thermal stability of the monatomic metallic glasses as obtained. The availability of monatomic metallic glasses, being the simplest glass formers, offers unique possibilities for studying the structure and property relationships of glasses. Our technique also shows great control over the reversible vitrification–crystallization processes, suggesting its potential in micro-electromechanical applications. The ultrahigh cooling rate, approaching the highest liquid-quenching rate attainable in the experiment, makes it possible to explore the fast kinetics and structural behaviour of supercooled metallic liquids within the nanosecond to picosecond regimes.
      Citation: Nature 512, 7513 (2014)
      PubDate: 2014-08-06
      DOI: 10.1038/nature13617
      Issue No: Vol. 512, No. 7513 (2014)
       
  • The tidal–rotational shape of the Moon and evidence for polar wander
    • Authors: Ian Garrick-Bethell, Viranga Perera, Francis Nimmo, Maria T. Zuber
      Pages: 181 - 184
      Abstract: The origin of the Moon’s large-scale topography is important for understanding lunar geology, lunar orbital evolution and the Moon’s orientation in the sky. Previous hypotheses for its origin have included late accretion events, large impacts, tidal effects and convection processes. However, testing these hypotheses and quantifying the Moon’s topography is complicated by the large basins that have formed since the crust crystallized. Here we estimate the large-scale lunar topography and gravity spherical harmonics outside these basins and show that the bulk of the spherical harmonic degree-2 topography is consistent with a crust-building process controlled by early tidal heating throughout the Moon. The remainder of the degree-2 topography is consistent with a frozen tidal–rotational bulge that formed later, at a semi-major axis of about 32 Earth radii. The probability of the degree-2 shape having both tidal-heating and frozen shape characteristics by chance is less than 1%. We also infer that internal density contrasts eventually reoriented the Moon’s polar axis by 36 ± 4°, to the configuration we observe today. Together, these results link the geology of the near and far sides, and resolve long-standing questions about the Moon’s large-scale shape, gravity and history of polar wander.
      Citation: Nature 512, 7513 (2014)
      PubDate: 2014-07-30
      DOI: 10.1038/nature13639
      Issue No: Vol. 512, No. 7513 (2014)
       
  • Neuropsychosocial profiles of current and future adolescent alcohol
           misusers
    • Authors: Robert Whelan, Richard Watts, Catherine A. Orr, Robert R. Althoff, Eric Artiges, Tobias Banaschewski, Gareth J. Barker, Arun L. W. Bokde, Christian Büchel, Fabiana M. Carvalho, Patricia J. Conrod, Herta Flor, Mira Fauth-Bühler, Vincent Frouin, Juergen Gallinat, Gabriela Gan, Penny Gowland, Andreas Heinz, Bernd Ittermann, Claire Lawrence, Karl Mann, Jean-Luc Martinot, Frauke Nees, Nick Ortiz, Marie-Laure Paillère-Martinot, Tomas Paus, Zdenka Pausova, Marcella Rietschel, Trevor W. Robbins, Michael N. Smolka, Andreas Ströhle, Gunter Schumann, Hugh Garavan
      Pages: 185 - 189
      Abstract: A comprehensive account of the causes of alcohol misuse must accommodate individual differences in biology, psychology and environment, and must disentangle cause and effect. Animal models can demonstrate the effects of neurotoxic substances; however, they provide limited insight into the psycho-social and higher cognitive factors involved in the initiation of substance use and progression to misuse. One can search for pre-existing risk factors by testing for endophenotypic biomarkers in non-using relatives; however, these relatives may have personality or neural resilience factors that protect them from developing dependence. A longitudinal study has potential to identify predictors of adolescent substance misuse, particularly if it can incorporate a wide range of potential causal factors, both proximal and distal, and their influence on numerous social, psychological and biological mechanisms. Here we apply machine learning to a wide range of data from a large sample of adolescents (n = 692) to generate models of current and future adolescent alcohol misuse that incorporate brain structure and function, individual personality and cognitive differences, environmental factors (including gestational cigarette and alcohol exposure), life experiences, and candidate genes. These models were accurate and generalized to novel data, and point to life experiences, neurobiological differences and personality as important antecedents of binge drinking. By identifying the vulnerability factors underlying individual differences in alcohol misuse, these models shed light on the aetiology of alcohol misuse and suggest targets for prevention.
      Citation: Nature 512, 7513 (2014)
      PubDate: 2014-07-02
      DOI: 10.1038/nature13402
      Issue No: Vol. 512, No. 7513 (2014)
       
  • A common Greenlandic TBC1D4 variant confers muscle insulin resistance and
           type 2 diabetes
    • Authors: Ida Moltke, Niels Grarup, Marit E. Jørgensen, Peter Bjerregaard, Jonas T. Treebak, Matteo Fumagalli, Thorfinn S. Korneliussen, Marianne A. Andersen, Thomas S. Nielsen, Nikolaj T. Krarup, Anette P. Gjesing, Juleen R. Zierath, Allan Linneberg, Xueli Wu, Guangqing Sun, Xin Jin, Jumana Al-Aama, Jun Wang, Knut Borch-Johnsen, Oluf Pedersen, Rasmus Nielsen, Anders Albrechtsen, Torben Hansen
      Pages: 190 - 193
      Abstract: The Greenlandic population, a small and historically isolated founder population comprising about 57,000 inhabitants, has experienced a dramatic increase in type 2 diabetes (T2D) prevalence during the past 25 years. Motivated by this, we performed association mapping of T2D-related quantitative traits in up to 2,575 Greenlandic individuals without known diabetes. Using array-based genotyping and exome sequencing, we discovered a nonsense p.Arg684Ter variant (in which arginine is replaced by a termination codon) in the gene TBC1D4 with an allele frequency of 17%. Here we show that homozygous carriers of this variant have markedly higher concentrations of plasma glucose (β = 3.8 mmol l−1, P = 2.5 × 10−35) and serum insulin (β = 165 pmol l−1, P = 1.5 × 10−20) 2 hours after an oral glucose load compared with individuals with other genotypes (both non-carriers and heterozygous carriers). Furthermore, homozygous carriers have marginally lower concentrations of fasting plasma glucose (β = −0.18 mmol l−1, P = 1.1 × 10−6) and fasting serum insulin (β = −8.3 pmol l−1, P = 0.0014), and their T2D risk is markedly increased (odds ratio (OR) = 10.3, P = 1.6 × 10−24). Heterozygous carriers have a moderately higher plasma glucose concentration 2 hours after an oral glucose load than non-carriers (β = 0.43 mmol l−1, P = 5.3 × 10−5). Analyses of skeletal muscle biopsies showed lower messenger RNA and protein levels of the long isoform of TBC1D4, and lower muscle protein levels of the glucose transporter GLUT4, with increasing number of p.Arg684Ter alleles. These findings are concomitant with a severely decreased insulin-stimulated glucose uptake in muscle, leading to postprandial hyperglycaemia, impaired glucose tolerance and T2D. The observed effect sizes are several times larger than any previous findings in large-scale genome-wide association studies of these traits and constitute further proof of the value of conducting genetic association studies outside the traditional setting of large homogeneous populations.
      Citation: Nature 512, 7513 (2014)
      PubDate: 2014-06-18
      DOI: 10.1038/nature13425
      Issue No: Vol. 512, No. 7513 (2014)
       
  • Altitude adaptation in Tibetans caused by introgression of Denisovan-like
           DNA
    • Authors: Emilia Huerta-Sánchez, Xin Jin, Asan, Zhuoma Bianba, Benjamin M. Peter, Nicolas Vinckenbosch, Yu Liang, Xin Yi, Mingze He, Mehmet Somel, Peixiang Ni, Bo Wang, Xiaohua Ou, Huasang, Jiangbai Luosang, Zha Xi Ping Cuo, Kui Li, Guoyi Gao, Ye Yin, Wei Wang, Xiuqing Zhang, Xun Xu, Huanming Yang, Yingrui Li, Jian Wang, Jun Wang, Rasmus Nielsen
      Pages: 194 - 197
      Abstract: As modern humans migrated out of Africa, they encountered many new environmental conditions, including greater temperature extremes, different pathogens and higher altitudes. These diverse environments are likely to have acted as agents of natural selection and to have led to local adaptations. One of the most celebrated examples in humans is the adaptation of Tibetans to the hypoxic environment of the high-altitude Tibetan plateau. A hypoxia pathway gene, EPAS1, was previously identified as having the most extreme signature of positive selection in Tibetans, and was shown to be associated with differences in haemoglobin concentration at high altitude. Re-sequencing the region around EPAS1 in 40 Tibetan and 40 Han individuals, we find that this gene has a highly unusual haplotype structure that can only be convincingly explained by introgression of DNA from Denisovan or Denisovan-related individuals into humans. Scanning a larger set of worldwide populations, we find that the selected haplotype is only found in Denisovans and in Tibetans, and at very low frequency among Han Chinese. Furthermore, the length of the haplotype, and the fact that it is not found in any other populations, makes it unlikely that the haplotype sharing between Tibetans and Denisovans was caused by incomplete ancestral lineage sorting rather than introgression. Our findings illustrate that admixture with other hominin species has provided genetic variation that helped humans to adapt to new environments.
      Citation: Nature 512, 7513 (2014)
      PubDate: 2014-07-02
      DOI: 10.1038/nature13408
      Issue No: Vol. 512, No. 7513 (2014)
       
  • Replication stress is a potent driver of functional decline in ageing
           haematopoietic stem cells
    • Authors: Johanna Flach, Sietske T. Bakker, Mary Mohrin, Pauline C. Conroy, Eric M. Pietras, Damien Reynaud, Silvia Alvarez, Morgan E. Diolaiti, Fernando Ugarte, E. Camilla Forsberg, Michelle M. Le Beau, Bradley A. Stohr, Juan Méndez, Ciaran G. Morrison, Emmanuelle Passegué
      Pages: 198 - 202
      Abstract: Haematopoietic stem cells (HSCs) self-renew for life, thereby making them one of the few blood cells that truly age. Paradoxically, although HSCs numerically expand with age, their functional activity declines over time, resulting in degraded blood production and impaired engraftment following transplantation. While many drivers of HSC ageing have been proposed, the reason why HSC function degrades with age remains unknown. Here we show that cycling old HSCs in mice have heightened levels of replication stress associated with cell cycle defects and chromosome gaps or breaks, which are due to decreased expression of mini-chromosome maintenance (MCM) helicase components and altered dynamics of DNA replication forks. Nonetheless, old HSCs survive replication unless confronted with a strong replication challenge, such as transplantation. Moreover, once old HSCs re-establish quiescence, residual replication stress on ribosomal DNA (rDNA) genes leads to the formation of nucleolar-associated γH2AX signals, which persist owing to ineffective H2AX dephosphorylation by mislocalized PP4c phosphatase rather than ongoing DNA damage. Persistent nucleolar γH2AX also acts as a histone modification marking the transcriptional silencing of rDNA genes and decreased ribosome biogenesis in quiescent old HSCs. Our results identify replication stress as a potent driver of functional decline in old HSCs, and highlight the MCM DNA helicase as a potential molecular target for rejuvenation therapies.
      Citation: Nature 512, 7513 (2014)
      PubDate: 2014-07-30
      DOI: 10.1038/nature13619
      Issue No: Vol. 512, No. 7513 (2014)
       
  • Historical contingency and its biophysical basis in glucocorticoid
           receptor evolution
    • Authors: Michael J. Harms, Joseph W. Thornton
      Pages: 203 - 207
      Abstract: Understanding how chance historical events shape evolutionary processes is a central goal of evolutionary biology. Direct insights into the extent and causes of evolutionary contingency have been limited to experimental systems, because it is difficult to know what happened in the deep past and to characterize other paths that evolution could have followed. Here we combine ancestral protein reconstruction, directed evolution and biophysical analysis to explore alternative ‘might-have-been’ trajectories during the ancient evolution of a novel protein function. We previously found that the evolution of cortisol specificity in the ancestral glucocorticoid receptor (GR) was contingent on permissive substitutions, which had no apparent effect on receptor function but were necessary for GR to tolerate the large-effect mutations that caused the shift in specificity. Here we show that alternative mutations that could have permitted the historical function-switching substitutions are extremely rare in the ensemble of genotypes accessible to the ancestral GR. In a library of thousands of variants of the ancestral protein, we recovered historical permissive substitutions but no alternative permissive genotypes. Using biophysical analysis, we found that permissive mutations must satisfy at least three physical requirements—they must stabilize specific local elements of the protein structure, maintain the correct energetic balance between functional conformations, and be compatible with the ancestral and derived structures—thus revealing why permissive mutations are rare. These findings demonstrate that GR evolution depended strongly on improbable, non-deterministic events, and this contingency arose from intrinsic biophysical properties of the protein.
      Citation: Nature 512, 7513 (2014)
      PubDate: 2014-06-15
      DOI: 10.1038/nature13410
      Issue No: Vol. 512, No. 7513 (2014)
       
  • DENR–MCT-1 promotes translation re-initiation downstream of uORFs to
           control tissue growth
    • Authors: Sibylle Schleich, Katrin Strassburger, Philipp Christoph Janiesch, Tatyana Koledachkina, Katharine K. Miller, Katharina Haneke, Yong-Sheng Cheng, Katrin Küchler, Georg Stoecklin, Kent E. Duncan, Aurelio A. Teleman
      Pages: 208 - 212
      Abstract: During cap-dependent eukaryotic translation initiation, ribosomes scan messenger RNA from the 5′ end to the first AUG start codon with favourable sequence context. For many mRNAs this AUG belongs to a short upstream open reading frame (uORF), and translation of the main downstream ORF requires re-initiation, an incompletely understood process. Re-initiation is thought to involve the same factors as standard initiation. It is unknown whether any factors specifically affect translation re-initiation without affecting standard cap-dependent translation. Here we uncover the non-canonical initiation factors density regulated protein (DENR) and multiple copies in T-cell lymphoma-1 (MCT-1; also called MCTS1 in humans) as the first selective regulators of eukaryotic re-initiation. mRNAs containing upstream ORFs with strong Kozak sequences selectively require DENR–MCT-1 for their proper translation, yielding a novel class of mRNAs that can be co-regulated and that is enriched for regulatory proteins such as oncogenic kinases. Collectively, our data reveal that cells have a previously unappreciated translational control system with a key role in supporting proliferation and tissue growth.
      Citation: Nature 512, 7513 (2014)
      PubDate: 2014-07-06
      DOI: 10.1038/nature13401
      Issue No: Vol. 512, No. 7513 (2014)
       
  • Histone H4 tail mediates allosteric regulation of nucleosome remodelling
           by linker DNA
    • Authors: William L. Hwang, Sebastian Deindl, Bryan T. Harada, Xiaowei Zhuang
      Pages: 213 - 217
      Abstract: Imitation switch (ISWI)-family remodelling enzymes regulate access to genomic DNA by mobilizing nucleosomes. These ATP-dependent chromatin remodellers promote heterochromatin formation and transcriptional silencing by generating regularly spaced nucleosome arrays. The nucleosome-spacing activity arises from the dependence of nucleosome translocation on the length of extranucleosomal linker DNA, but the underlying mechanism remains unclear. Here we study nucleosome remodelling by human ATP-dependent chromatin assembly and remodelling factor (ACF), an ISWI enzyme comprising a catalytic subunit, Snf2h, and an accessory subunit, Acf1 (refs 2, 11, 12, 13). We find that ACF senses linker DNA length through an interplay between its accessory and catalytic subunits mediated by the histone H4 tail of the nucleosome. Mutation of AutoN, an auto-inhibitory domain within Snf2h that bears sequence homology to the H4 tail, abolishes the linker-length sensitivity in remodelling. Addition of exogenous H4-tail peptide or deletion of the nucleosomal H4 tail also diminishes the linker-length sensitivity. Moreover, Acf1 binds both the H4-tail peptide and DNA in an amino (N)-terminal domain dependent manner, and in the ACF-bound nucleosome, lengthening the linker DNA reduces the Acf1-H4 tail proximity. Deletion of the N-terminal portion of Acf1 (or its homologue in yeast) abolishes linker-length sensitivity in remodelling and leads to severe growth defects in vivo. Taken together, our results suggest a mechanism for nucleosome spacing where linker DNA sensing by Acf1 is allosterically transmitted to Snf2h through the H4 tail of the nucleosome. For nucleosomes with short linker DNA, Acf1 preferentially binds to the H4 tail, allowing AutoN to inhibit the ATPase activity of Snf2h. As the linker DNA lengthens, Acf1 shifts its binding preference to the linker DNA, freeing the H4 tail to compete AutoN off the ATPase and thereby activating ACF.
      Citation: Nature 512, 7513 (2014)
      PubDate: 2014-06-29
      DOI: 10.1038/nature13380
      Issue No: Vol. 512, No. 7513 (2014)
       
  • Visualization of arrestin recruitment by a G-protein-coupled receptor
    • Authors: Arun K. Shukla, Gerwin H. Westfield, Kunhong Xiao, Rosana I. Reis, Li-Yin Huang, Prachi Tripathi-Shukla, Jiang Qian, Sheng Li, Adi Blanc, Austin N. Oleskie, Anne M. Dosey, Min Su, Cui-Rong Liang, Ling-Ling Gu, Jin-Ming Shan, Xin Chen, Rachel Hanna, Minjung Choi, Xiao Jie Yao, Bjoern U. Klink, Alem W. Kahsai, Sachdev S. Sidhu, Shohei Koide, Pawel A. Penczek, Anthony A. Kossiakoff, Virgil L. Woods Jr, Brian K. Kobilka, Georgios Skiniotis, Robert J. Lefkowitz
      Pages: 218 - 222
      Abstract: G-protein-coupled receptors (GPCRs) are critically regulated by β-arrestins, which not only desensitize G-protein signalling but also initiate a G-protein-independent wave of signalling. A recent surge of structural data on a number of GPCRs, including the β2 adrenergic receptor (β2AR)–G-protein complex, has provided novel insights into the structural basis of receptor activation. However, complementary information has been lacking on the recruitment of β-arrestins to activated GPCRs, primarily owing to challenges in obtaining stable receptor–β-arrestin complexes for structural studies. Here we devised a strategy for forming and purifying a functional human β2AR–β-arrestin-1 complex that allowed us to visualize its architecture by single-particle negative-stain electron microscopy and to characterize the interactions between β2AR and β-arrestin 1 using hydrogen–deuterium exchange mass spectrometry (HDX-MS) and chemical crosslinking. Electron microscopy two-dimensional averages and three-dimensional reconstructions reveal bimodal binding of β-arrestin 1 to the β2AR, involving two separate sets of interactions, one with the phosphorylated carboxy terminus of the receptor and the other with its seven-transmembrane core. Areas of reduced HDX together with identification of crosslinked residues suggest engagement of the finger loop of β-arrestin 1 with the seven-transmembrane core of the receptor. In contrast, focal areas of raised HDX levels indicate regions of increased dynamics in both the N and C domains of β-arrestin 1 when coupled to the β2AR. A molecular model of the β2AR–β-arrestin signalling complex was made by docking activated β-arrestin 1 and β2AR crystal structures into the electron microscopy map densities with constraints provided by HDX-MS and crosslinking, allowing us to obtain valuable insights into the overall architecture of a receptor–arrestin complex. The dynamic and structural information presented here provides a framework for better understanding the basis of GPCR regulation by arrestins.
      Citation: Nature 512, 7513 (2014)
      PubDate: 2014-06-22
      DOI: 10.1038/nature13430
      Issue No: Vol. 512, No. 7513 (2014)
       
  • Mental health: Stressed students reach out for help
    • Authors: Julie Gould
      Pages: 223 - 224
      Abstract: Graduate students struggling with the stresses of their work and lives can tap into multiple avenues of support.
      Citation: Nature 512, 7513 (2014)
      PubDate: 2014-08-13
      DOI: 10.1038/nj7513-223a
      Issue No: Vol. 512, No. 7513 (2014)
       
  • The death of immortality
    • Authors: Kyle L. Wilson, Andrew B. Barbour
      Pages: 226 - 226
      Abstract: Life lessons.
      Citation: Nature 512, 7513 (2014)
      PubDate: 2014-08-13
      DOI: 10.1038/512226a
      Issue No: Vol. 512, No. 7513 (2014)
       
 
 
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