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Journal Cover Nature
  [SJR: 21.936]   [H-I: 948]   [3460 followers]  Follow
    
   Full-text available via subscription Subscription journal
   ISSN (Print) 0028-0836 - ISSN (Online) 1476-4687
   Published by NPG Homepage  [124 journals]
  • Consistency in large pharmacogenomic studies
    • Authors: Paul Geeleher, Eric R. Gamazon, Cathal Seoighe, Nancy J. Cox, R. Stephanie Huang
      Abstract: arising fromB.Haibe-Kainset al. Nature504, 389–393 (2013); doi:10.1038/nature12831Haibe-Kains et al. reported inconsistency between two large-scale pharmacogenomic studies—the Cancer Cell Line Encyclopedia (CCLE) and the Cancer Genome Project (CGP). Upon careful analysis of the
      Citation: Nature 540, 7631 (2016)
      PubDate: 2016-11-30
      DOI: 10.1038/nature19838
      Issue No: Vol. 540, No. 7631 (2016)
       
  • Safikhani et al. reply
    • Authors: Zhaleh Safikhani, Nehme El-Hachem, Petr Smirnov, Mark Freeman, Anna Goldenberg, Nicolai J. Birkbak, Andrew H. Beck, Hugo J. W. L. Aerts, John Quackenbush, Benjamin Haibe-Kains
      Abstract: replying toP.Geeleher, E. R.Gamazon, C.Seoighe, N. J.Cox & R. S.HuangNature540, http://dx.doi.org/10.1038/nature19838 (2016).In the accompanying Comment, Geeleher et al. claim to have discovered overall consistency between the
      Citation: Nature 540, 7631 (2016)
      PubDate: 2016-11-30
      DOI: 10.1038/nature19839
      Issue No: Vol. 540, No. 7631 (2016)
       
  • Consistency in drug response profiling
    • Authors: John Patrick Mpindi, Bhagwan Yadav, Päivi Östling, Prson Gautam, Disha Malani, Astrid Murumägi, Akira Hirasawa, Sara Kangaspeska, Krister Wennerberg, Olli Kallioniemi, Tero Aittokallio
      Abstract: arising fromB.Haibe-Kainset al. Nature504, 389–393 (2013); doi:10.1038/nature12831The comparative analysis by Haibe-Kains et al. concluded that data from two large-scale studies of cancer cell lines showed highly discordant results for drug sensitivity measurements, whereas
      Citation: Nature 540, 7631 (2016)
      PubDate: 2016-11-30
      DOI: 10.1038/nature20171
      Issue No: Vol. 540, No. 7631 (2016)
       
  • Safikhani et al. reply
    • Authors: Zhaleh Safikhani, Nehme El-Hachem, Petr Smirnov, Mark Freeman, Anna Goldenberg, Nicolai J. Birkbak, Andrew H. Beck, Hugo J. W. L. Aerts, John Quackenbush, Benjamin Haibe-Kains
      Abstract: replying toJ. P.Mpindiet al. Nature540, http://dx.doi.org/10.1038/nature20171 (2016).The accompanying Comment by Mpindi et al. is an important contribution to the discussion of pharmacogenomic consistency for several reasons. Mpindi et al. were able
      Citation: Nature 540, 7631 (2016)
      PubDate: 2016-11-30
      DOI: 10.1038/nature20172
      Issue No: Vol. 540, No. 7631 (2016)
       
  • Drug response consistency in CCLE and CGP
    • Authors: Mehdi Bouhaddou, Matthew S. DiStefano, Eric A. Riesel, Emilce Carrasco, Hadassa Y. Holzapfel, DeAnalisa C. Jones, Gregory R. Smith, Alan D. Stern, Sulaiman S. Somani, T. Victoria Thompson, Marc R. Birtwistle
      Abstract: arising fromB.Haibe-Kainset al. Nature504, 389–393 (2013); doi:10.1038/nature12831The Cancer Cell Line Encyclopedia (CCLE) and Cancer Genome Project (CGP) are two independent large-scale efforts to characterize genomes, mRNA expression, and anti-cancer drug dose–responses across cell lines,
      Citation: Nature 540, 7631 (2016)
      PubDate: 2016-11-30
      DOI: 10.1038/nature20580
      Issue No: Vol. 540, No. 7631 (2016)
       
  • Safikhani et al. reply
    • Authors: Zhaleh Safikhani, Nehme El-Hachem, Petr Smirnov, Mark Freeman, Anna Goldenberg, Nicolai J. Birkbak, Andrew H. Beck, Hugo J. W. L. Aerts, John Quackenbush, Benjamin Haibe-Kains
      Abstract: replying toM.Bouhaddouet al. Nature540, http://dx.doi.org/10.1038/nature20580 (2016).In the accompanying Comment, the authors make two main claims: (1) that viability metrics computed over the drug concentration range shared between datasets yield higher consistency than the same
      Citation: Nature 540, 7631 (2016)
      PubDate: 2016-11-30
      DOI: 10.1038/nature20581
      Issue No: Vol. 540, No. 7631 (2016)
       
  • Post-publication criticism is crucial, but should be constructive
    • Pages: 7 - 8
      Abstract: In an era of online discussion, debate must remain nuanced and courteous.
      Citation: Nature 540, 7631 (2016)
      PubDate: 2016-11-30
      DOI: 10.1038/540007b
      Issue No: Vol. 540, No. 7631 (2016)
       
  • Academia must resist political confirmation bias
    • Pages: 7 - 7
      Abstract: It is crucial to fight discrimination in all its forms, but it is unhelpful to exclude conservative voices from debate.
      Citation: Nature 540, 7631 (2016)
      PubDate: 2016-11-29
      DOI: 10.1038/540007a
      Issue No: Vol. 540, No. 7631 (2016)
       
  • Researchers serve up suggestions to reduce food waste
    • Pages: 8 - 8
      Abstract: A change in cultural and social factors — such as overcoming a distaste for doggy bags — will be required to shift people’s behaviour.
      Citation: Nature 540, 7631 (2016)
      PubDate: 2016-11-30
      DOI: 10.1038/540008a
      Issue No: Vol. 540, No. 7631 (2016)
       
  • Post-truth: a guide for the perplexed
    • Authors: Kathleen Higgins
      Pages: 9 - 9
      Abstract: If politicians can lie without condemnation, what are scientists to do? Kathleen Higgins offers some explanation.
      Citation: Nature 540, 7631 (2016)
      PubDate: 2016-11-28
      DOI: 10.1038/540009a
      Issue No: Vol. 540, No. 7631 (2016)
       
  • Cancer: 'Jet lag' increases mouse cancer risk
    • Pages: 10 - 10
      Abstract: Mice with simulated jet lag have an increased risk of developing liver cancer.Sleeping out of step with the day–night cycle has been linked to various health disorders in humans. David Moore, Loning Fu and their colleagues at Baylor College of Medicine in Houston, Texas,
      Citation: Nature 540, 7631 (2016)
      PubDate: 2016-11-30
      DOI: 10.1038/540010c
      Issue No: Vol. 540, No. 7631 (2016)
       
  • Seismology: Gravity changes before quake hits
    • Pages: 10 - 10
      Abstract: Researchers have for the first time detected temporary changes in Earth's gravitational field just before an earthquake.Jean-Paul Montagner at the CNRS Institute of Earth Physics in Paris and his team analysed gravimetric and seismic data recorded during the massive 2011 Tohoku earthquake in Japan.
      Citation: Nature 540, 7631 (2016)
      PubDate: 2016-11-30
      DOI: 10.1038/540010d
      Issue No: Vol. 540, No. 7631 (2016)
       
  • Catalysts: Silicon added to life's toolbox
    • Pages: 10 - 10
      Abstract: Molecules containing both carbon and silicon have become a standard part of synthetic chemistry, but life uses silicon only in inorganic compounds such as the shells of diatoms.Now, Frances Arnold and her collaborators at the California Institute of Technology in Pasadena have engineered bacteria
      Citation: Nature 540, 7631 (2016)
      PubDate: 2016-11-30
      DOI: 10.1038/540010b
      Issue No: Vol. 540, No. 7631 (2016)
       
  • Immunology: Macaque social status alters immunity
    • Pages: 10 - 10
      Abstract: Changing the social status of macaques also changes their immune systems.Low social status has been linked to multiple health problems in humans and other primates, some of which may not be linked to the accessibility of food and other resources.Jenny Tung of Duke
      Citation: Nature 540, 7631 (2016)
      PubDate: 2016-11-30
      DOI: 10.1038/540010a
      Issue No: Vol. 540, No. 7631 (2016)
       
  • Climate change: Shifting niches spell trouble
    • Pages: 10 - 11
      Abstract: Plants and animals will probably be unable to respond to changes in environmental conditions fast enough to keep pace with climate change.Tereza Jezkova and John Wiens of the University of Arizona, Tucson, looked at 56 plant and animal species and documented shifts in their
      Citation: Nature 540, 7631 (2016)
      PubDate: 2016-11-30
      DOI: 10.1038/540010e
      Issue No: Vol. 540, No. 7631 (2016)
       
  • Palaeontology: Ancient reptile had a diaphragm
    • Pages: 11 - 11
      Abstract: The muscle that allows mammals to breathe deeply — the diaphragm — may have been present in some reptiles 300 million years ago, about 50 million years before it was thought to have appeared.Markus Lambertz at the University of Bonn in Germany and his
      Citation: Nature 540, 7631 (2016)
      PubDate: 2016-11-30
      DOI: 10.1038/540011a
      Issue No: Vol. 540, No. 7631 (2016)
       
  • Quantum physics: Record set for linked photons
    • Pages: 11 - 11
      Abstract: Particles that have linked quantum states, known as 'entangled' particles, can affect each other's states even if they are physically separated. Now scientists have set a record by entangling ten photons — two more than achieved previously.Entangled particles should one day enable quantum computing
      Citation: Nature 540, 7631 (2016)
      PubDate: 2016-11-30
      DOI: 10.1038/540011b
      Issue No: Vol. 540, No. 7631 (2016)
       
  • Materials science: Atom-thick coats for copper
    • Pages: 11 - 11
      Abstract: Coating metals with a high-quality, single-atom-thick layer of 2D boron nitride can protect them from corrosion.Layers of 2D materials have been touted for use as protective coatings on surfaces but have shown mixed results, with some apparently even increasing corrosion rates in the long
      Citation: Nature 540, 7631 (2016)
      PubDate: 2016-11-30
      DOI: 10.1038/540011c
      Issue No: Vol. 540, No. 7631 (2016)
       
  • Materials: Sensor detects UV exposure
    • Pages: 11 - 11
      Abstract: A sensor that sticks to the skin can give colour-coded readouts of ultraviolet light levels from the Sun, the leading cause of skin cancer.John Rogers at the University of Illinois at Urbana–Champaign and his colleagues developed the stretchable device (pictured), which is
      Citation: Nature 540, 7631 (2016)
      PubDate: 2016-11-30
      DOI: 10.1038/540011d
      Issue No: Vol. 540, No. 7631 (2016)
       
  • Epigenetics: Gut microbes shape DNA
    • Pages: 11 - 11
      Abstract: Gut microbes and the fatty acids they produce can regulate gene expression by influencing the 3D shape of their hosts' DNA.Intestinal bacteria are known to affect several aspects of host health, including the risk of cardiovascular and metabolic diseases. To study the mechanisms by
      Citation: Nature 540, 7631 (2016)
      PubDate: 2016-11-30
      DOI: 10.1038/540011e
      Issue No: Vol. 540, No. 7631 (2016)
       
  • Chernobyl's shield, dodo skeleton and HIV vaccines
    • Pages: 12 - 13
      Abstract: The week in science: 25 November–1 December 2016.
      Citation: Nature 540, 7631 (2016)
      PubDate: 2016-11-30
      DOI: 10.1038/540012a
      Issue No: Vol. 540, No. 7631 (2016)
       
  • Failed Alzheimer’s trial does not kill leading theory of disease
    • Authors: Alison Abbott, Elie Dolgin
      Pages: 15 - 16
      Abstract: The drug, and others based on the ‘amyloid hypothesis’, are still being tested in other, different trials.
      Citation: Nature 540, 7631 (2016)
      PubDate: 2016-11-23
      DOI: 10.1038/nature.2016.21045
      Issue No: Vol. 540, No. 7631 (2016)
       
  • UK scientists excited by surprise £2-billion government windfall
    • Authors: Elizabeth Gibney
      Pages: 16 - 17
      Abstract: Cash to include fund modelled on DARPA, the US defence department’s research arm — but how much will go to basic research is unclear.
      Citation: Nature 540, 7631 (2016)
      PubDate: 2016-11-23
      DOI: 10.1038/nature.2016.21038
      Issue No: Vol. 540, No. 7631 (2016)
       
  • Experimental treatments aim to prevent brain damage in babies
    • Authors: Erika Check Hayden
      Pages: 17 - 18
      Abstract: Advances in neuroscience are driving the development of therapies that could save thousands of the most vulnerable patients.
      Citation: Nature 540, 7631 (2016)
      PubDate: 2016-11-30
      DOI: 10.1038/540017a
      Issue No: Vol. 540, No. 7631 (2016)
       
  • Speedy Antarctic drills start hunt for Earth’s oldest ice
    • Authors: Quirin Schiermeier
      Pages: 18 - 19
      Abstract: British team is first to seek site of 1.5-million-year-old sample.
      Citation: Nature 540, 7631 (2016)
      PubDate: 2016-11-29
      DOI: 10.1038/540018a
      Issue No: Vol. 540, No. 7631 (2016)
       
  • Weaponized antibodies use new tricks to fight cancer
    • Authors: Heidi Ledford
      Pages: 19 - 20
      Abstract: Next generation of Trojan-horse drugs designed to minimize damage to healthy cells.
      Citation: Nature 540, 7631 (2016)
      PubDate: 2016-11-29
      DOI: 10.1038/540019a
      Issue No: Vol. 540, No. 7631 (2016)
       
  • Updated: NgAgo gene-editing controversy escalates in peer-reviewed papers
    • Authors: David Cyranoski
      Pages: 20 - 21
      Abstract: String of publications describes attempts — mostly unsuccessful — to use proposed CRISPR rival.
      Citation: Nature 540, 7631 (2016)
      PubDate: 2016-11-23
      DOI: 10.1038/nature.2016.21023
      Issue No: Vol. 540, No. 7631 (2016)
       
  • Four routes to better maritime governance
    • Authors: Zheng Wan, Jihong Chen, Abdel El Makhloufi, Daniel Sperling, Yang Chen
      Pages: 27 - 29
      Abstract: Challenges in preventing pollution from ballast water highlight reforms needed in global shipping regulation, write Zheng Wan and colleagues.
      Citation: Nature 540, 7631 (2016)
      PubDate: 2016-11-28
      DOI: 10.1038/540027a
      Issue No: Vol. 540, No. 7631 (2016)
       
  • A new global research agenda for food
    • Authors: Lawrence Haddad, Corinna Hawkes, Patrick Webb, Sandy Thomas, John Beddington, Jeff Waage, Derek Flynn
      Pages: 30 - 32
      Abstract: Lawrence Haddad, Corinna Hawkes and colleagues propose ten ways to shift the focus from feeding people to nourishing them.
      Citation: Nature 540, 7631 (2016)
      PubDate: 2016-11-30
      DOI: 10.1038/540030a
      Issue No: Vol. 540, No. 7631 (2016)
       
  • Fix food metrics
    • Authors: Pavan Sukhdev, Peter May, Alexander Müller
      Pages: 33 - 34
      Abstract: For sustainable, equitable nutrition we must count the true global costs and benefits of food production, urge Pavan Sukhdev, Peter May and Alexander Müller.
      Citation: Nature 540, 7631 (2016)
      PubDate: 2016-11-30
      DOI: 10.1038/540033a
      Issue No: Vol. 540, No. 7631 (2016)
       
  • Book publishing: University presses adapt
    • Authors: Roger Schonfeld
      Pages: 35 - 37
      Abstract: Roger Schonfeld analyses how the sector's scientific books are faring in the digitized, open-access era.
      Citation: Nature 540, 7631 (2016)
      PubDate: 2016-11-30
      DOI: 10.1038/540035a
      Issue No: Vol. 540, No. 7631 (2016)
       
  • Books in brief
    • Authors: Barbara Kiser
      Pages: 37 - 37
      Abstract: Barbara Kiser reviews five of the week's best science picks.
      Citation: Nature 540, 7631 (2016)
      PubDate: 2016-11-30
      DOI: 10.1038/540037a
      Issue No: Vol. 540, No. 7631 (2016)
       
  • Phylogeny: 'Tree of life' took root 150 years ago
    • Authors: Uwe Hossfeld, Georgy S. Levit
      Pages: 38 - 38
      Abstract: As thousands of scientists and policymakers gather in Mexico this month for the COP13 summit on biodiversity (see www.cbd.int/cop2016), we should take a moment to celebrate the earliest 'tree of life' model of biodiversity.Charles Darwin published the idea of a tree of life
      Citation: Nature 540, 7631 (2016)
      PubDate: 2016-11-30
      DOI: 10.1038/540038a
      Issue No: Vol. 540, No. 7631 (2016)
       
  • Conservation: smart advocacy needs data
    • Authors: Douglas J. McCauley, Francis H. Joyce, Jane Lubchenco
      Pages: 38 - 38
      Abstract: We agree that data alone will not save species (A. M.EllisonNature538, 141;10.1038/538141a2016). However, using data in combination with smart advocacy can make a difference.For example, ecologists specializing in seabirds, fishes and coral reefs shared their
      Citation: Nature 540, 7631 (2016)
      PubDate: 2016-11-30
      DOI: 10.1038/540038b
      Issue No: Vol. 540, No. 7631 (2016)
       
  • Conservation: big data boost in China
    • Authors: Ruidong Wu
      Pages: 38 - 38
      Abstract: I disagree with Aaron Ellison's contention that biodiversity data only rarely drive conservation decisions (Nature538, 141;10.1038/538141a2016). In China, better data are guiding changes in conservation policies and on-the-ground actions.For instance, huge long-term data sets on species, ecosystems
      Citation: Nature 540, 7631 (2016)
      PubDate: 2016-11-30
      DOI: 10.1038/540038c
      Issue No: Vol. 540, No. 7631 (2016)
       
  • Conservation: thrive on slings and arrows
    • Authors: David Lindenmayer
      Pages: 38 - 39
      Abstract: Aaron Ellison rightly calls for conservation scientists to engage more actively in the political process (Nature538, 141;10.1038/538141a2016). Unfortunately, those doing so can become targets for physical and verbal threats, personal abuse, bullying and trolling on social media.As
      Citation: Nature 540, 7631 (2016)
      PubDate: 2016-11-30
      DOI: 10.1038/540038d
      Issue No: Vol. 540, No. 7631 (2016)
       
  • Cities: factor in their biological impact
    • Authors: Alexandre Antonelli, Allison Perrigo
      Pages: 39 - 39
      Abstract: Richard Forman and Jianguo Wu identify several zones around the world that might be suitable for future urbanization (Nature537, 608–611;10.1038/537608a2016). We suggest that the problem of supporting a growing population needs to be considered from a
      Citation: Nature 540, 7631 (2016)
      PubDate: 2016-11-30
      DOI: 10.1038/540039a
      Issue No: Vol. 540, No. 7631 (2016)
       
  • Cities: new fringes to act as safety nets
    • Authors: Pranab Chatterjee, Manish Kakkar, Tamoghna Biswas
      Pages: 39 - 39
      Abstract: Richard Forman and Jianguo Wu suggest that sustainable city expansion should be restricted to selected urban peripheries (Nature537, 608–611;10.1038/537608a2016). Our investigations across five Indian cities indicate that proper planning of such peri-urban areas is crucial.We
      Citation: Nature 540, 7631 (2016)
      PubDate: 2016-11-30
      DOI: 10.1038/540039b
      Issue No: Vol. 540, No. 7631 (2016)
       
  • Trump: voters show importance of SDGs
    • Authors: David Griggs
      Pages: 39 - 39
      Abstract: Many of the factors that contributed to Donald Trump's win in the 2016 US presidential election are those that make achievement of the United Nations' Sustainable Development Goals (SDGs) so pressing. Drawn up to end poverty (goal 1) and inequality (goal 10) and to ensure
      Citation: Nature 540, 7631 (2016)
      PubDate: 2016-11-30
      DOI: 10.1038/540039c
      Issue No: Vol. 540, No. 7631 (2016)
       
  • Trump: offset fracking risks
    • Authors: Madelon Finkel
      Pages: 39 - 39
      Abstract: Unconventional gas extraction ('fracking') is likely to be central to the energy policy of president-elect Donald Trump. I urge the US Congress to tighten current regulations and strike a balance between energy independence and the safeguarding of public health and the environment (see also J.
      Citation: Nature 540, 7631 (2016)
      PubDate: 2016-11-30
      DOI: 10.1038/540039d
      Issue No: Vol. 540, No. 7631 (2016)
       
  • Trump: polls right, models wrong
    • Authors: Brandon Steelman
      Pages: 39 - 39
      Abstract: Contrary to popular opinion, the polls were not wrong in last month's US presidential election (see also Nature539, 339;10.1038/539339a2016). The most recent polls in each state predicted the outcome for individual states — but only when the 95% confidence
      Citation: Nature 540, 7631 (2016)
      PubDate: 2016-11-30
      DOI: 10.1038/540039e
      Issue No: Vol. 540, No. 7631 (2016)
       
  • Susan Lee Lindquist (1949–2016)
    • Authors: James Shorter, Aaron D. Gitler
      Pages: 40 - 40
      Abstract: Biologist who found unexpected power in protein folding.
      Citation: Nature 540, 7631 (2016)
      PubDate: 2016-11-30
      DOI: 10.1038/540040a
      Issue No: Vol. 540, No. 7631 (2016)
       
  • Planetary science: Pluto's telltale heart
    • Authors: Amy C. Barr
      Pages: 42 - 43
      Abstract: Studies of a large frost-filled basin on Pluto show that this feature altered the dwarf planet's spin axis, driving tectonic activity on its surface, and hint at the presence of a subsurface ocean. See Letters p.86, p.90, p.94 & p.97
      Citation: Nature 540, 7631 (2016)
      PubDate: 2016-11-30
      DOI: 10.1038/540042a
      Issue No: Vol. 540, No. 7631 (2016)
       
  • Cell biology: Double agents for mitochondrial division
    • Authors: Heidi M. McBride, Adam Frost
      Pages: 43 - 44
      Abstract: Mitochondrial organelles — the energy powerhouses of the cell — must divide and fuse dynamically to function. It emerges that two distinct dynamin enzymes enable mitochondrial division. See Letter p.139
      Citation: Nature 540, 7631 (2016)
      PubDate: 2016-11-23
      DOI: 10.1038/nature20482
      Issue No: Vol. 540, No. 7631 (2016)
       
  • Quantum computing: Efficient fault tolerance
    • Authors: Daniel Gottesman
      Pages: 44 - 45
      Abstract: Dealing with errors in a quantum computer typically requires complex programming and many additional quantum bits. A technique for controlling errors has been proposed that alleviates both of these problems.
      Citation: Nature 540, 7631 (2016)
      PubDate: 2016-11-16
      DOI: 10.1038/nature20479
      Issue No: Vol. 540, No. 7631 (2016)
       
  • Cell biology: Sort of unexpected
    • Authors: Martin R. Pool
      Pages: 45 - 46
      Abstract: To reach the cell surface, membrane proteins are first targeted to an organelle called the endoplasmic reticulum. Several targeting pathways are known, but it now emerges that there is yet another pathway. See Letter p.134
      Citation: Nature 540, 7631 (2016)
      PubDate: 2016-11-30
      DOI: 10.1038/540045a
      Issue No: Vol. 540, No. 7631 (2016)
       
  • Biogeochemistry: Projections of the soil-carbon deficit
    • Authors: Eric A. Davidson
      Pages: 47 - 48
      Abstract: Changes in the amount of carbon stored in soil might be a crucial feedback to climate change. Experimental field studies show that warming-induced soil carbon losses are greatest where carbon stocks are largest. See Letter p.104
      Citation: Nature 540, 7631 (2016)
      PubDate: 2016-11-30
      DOI: 10.1038/540047a
      Issue No: Vol. 540, No. 7631 (2016)
       
  • Astronomy: A black hole changes its feeding habits
    • Authors: Stephanie LaMassa
      Pages: 48 - 49
      Abstract: In the 1980s, the gas surrounding a black hole in a nearby galaxy began to emit much more radiation than before. This change has unexpectedly reversed in the past five years, questioning our understanding of these extreme phenomena.
      Citation: Nature 540, 7631 (2016)
      PubDate: 2016-11-23
      DOI: 10.1038/nature20480
      Issue No: Vol. 540, No. 7631 (2016)
       
  • Biological rhythms: Wild times
    • Authors: C. Loren Buck
      Pages: 49 - 50
      Abstract: Little is known about the biological rhythms that emerge from social behaviours in the wild. A study of shorebird pairs shows that rhythms of nest-incubation duties are mainly governed by strategies to avoid predators. See Letter p.109
      Citation: Nature 540, 7631 (2016)
      PubDate: 2016-11-23
      DOI: 10.1038/nature20481
      Issue No: Vol. 540, No. 7631 (2016)
       
  • The genomic basis of circadian and circalunar timing adaptations in a
           midge
    • Authors: Tobias S. Kaiser, Birgit Poehn, David Szkiba, Marco Preussner, Fritz J. Sedlazeck, Alexander Zrim, Tobias Neumann, Lam-Tung Nguyen, Andrea J. Betancourt, Thomas Hummel, Heiko Vogel, Silke Dorner, Florian Heyd, Arndt von Haeseler, Kristin Tessmar-Raible
      Pages: 69 - 73
      Abstract: Organisms use endogenous clocks to anticipate regular environmental cycles, such as days and tides. Natural variants resulting in differently timed behaviour or physiology, known as chronotypes in humans, have not been well characterized at the molecular level. We sequenced the genome of Clunio marinus,
      Citation: Nature 540, 7631 (2016)
      PubDate: 2016-11-21
      DOI: 10.1038/nature20151
      Issue No: Vol. 540, No. 7631 (2016)
       
  • Correcting mitochondrial fusion by manipulating mitofusin conformations
    • Authors: Antonietta Franco, Richard N. Kitsis, Julie A. Fleischer, Evripidis Gavathiotis, Opher S. Kornfeld, Guohua Gong, Nikolaos Biris, Ann Benz, Nir Qvit, Sara K. Donnelly, Yun Chen, Steven Mennerick, Louis Hodgson, Daria Mochly-Rosen, Gerald W. Dorn II
      Pages: 74 - 79
      Abstract: Mitochondria are dynamic organelles that exchange contents and undergo remodelling during cyclic fusion and fission. Genetic mutations in MFN2 (the gene encoding mitofusin 2) interrupt mitochondrial fusion and cause the untreatable neurodegenerative condition Charcot-Marie-Tooth disease type 2A (CMT2A). It has not yet been possible
      Citation: Nature 540, 7631 (2016)
      PubDate: 2016-10-24
      DOI: 10.1038/nature20156
      Issue No: Vol. 540, No. 7631 (2016)
       
  • The pathway to GTPase activation of elongation factor SelB on the ribosome
    • Authors: Niels Fischer, Piotr Neumann, Lars V. Bock, Cristina Maracci, Zhe Wang, Alena Paleskava, Andrey L. Konevega, Gunnar F Schröder, Helmut Grubmüller, Ralf Ficner, Marina V. Rodnina, Holger Stark
      Pages: 80 - 85
      Abstract: In all domains of life, selenocysteine (Sec) is delivered to the ribosome by selenocysteine-specific tRNA (tRNASec) with the help of a specialized translation factor, SelB in bacteria. Sec-tRNASec recodes a UGA stop codon next to a downstream mRNA stem–loop. Here we
      Citation: Nature 540, 7631 (2016)
      PubDate: 2016-11-14
      DOI: 10.1038/nature20560
      Issue No: Vol. 540, No. 7631 (2016)
       
  • Observed glacier and volatile distribution on Pluto from
           atmosphere–topography processes
    • Authors: Tanguy Bertrand, François Forget
      Pages: 86 - 89
      Abstract: Pluto has a variety of surface frosts and landforms as well as a complex atmosphere. There is ongoing geological activity related to the massive Sputnik Planitia glacier, mostly made of nitrogen (N2) ice mixed with solid carbon monoxide and methane, covering the 4-kilometre-deep, 1,000-kilometre-wide basin of Sputnik Planitia near the anti-Charon point. The glacier has been suggested to arise from a source region connected to the deep interior, or from a sink collecting the volatiles released planetwide. Thin deposits of N2 frost, however, were also detected at mid-northern latitudes and methane ice was observed to cover most of Pluto except for the darker, frost-free equatorial regions. Here we report numerical simulations of the evolution of N2, methane and carbon monoxide on Pluto over thousands of years. The model predicts N2 ice accumulation in the deepest low-latitude basin and the threefold increase in atmospheric pressure that has been observed to occur since 1988. This points to atmospheric–topographic processes as the origin of Sputnik Planitia’s N2 glacier. The same simulations also reproduce the observed quantities of volatiles in the atmosphere and show frosts of methane, and sometimes N2, that seasonally cover the mid- and high latitudes, explaining the bright northern polar cap reported in the 1990s and the observed ice distribution in 2015. The model also predicts that most of these seasonal frosts should disappear in the next decade.
      Citation: Nature 540, 7631 (2016)
      PubDate: 2016-09-19
      DOI: 10.1038/nature19337
      Issue No: Vol. 540, No. 7631 (2016)
       
  • Reorientation and faulting of Pluto due to volatile loading within Sputnik
           Planitia
    • Authors: James T. Keane, Isamu Matsuyama, Shunichi Kamata, Jordan K. Steckloff
      Pages: 90 - 93
      Abstract: Pluto is an astoundingly diverse, geologically dynamic world. The dominant feature is Sputnik Planitia—a tear-drop-shaped topographic depression approximately 1,000 kilometres in diameter possibly representing an ancient impact basin. The interior of Sputnik Planitia is characterized by a smooth, craterless plain three to four kilometres beneath the surrounding rugged uplands, and represents the surface of a massive unit of actively convecting volatile ices (N2, CH4 and CO) several kilometres thick. This large feature is very near the Pluto–Charon tidal axis. Here we report that the location of Sputnik Planitia is the natural consequence of the sequestration of volatile ices within the basin and the resulting reorientation (true polar wander) of Pluto. Loading of volatile ices within a basin the size of Sputnik Planitia can substantially alter Pluto’s inertia tensor, resulting in a reorientation of the dwarf planet of around 60 degrees with respect to the rotational and tidal axes. The combination of this reorientation, loading and global expansion due to the freezing of a possible subsurface ocean generates stresses within the planet’s lithosphere, resulting in a global network of extensional faults that closely replicate the observed fault networks on Pluto. Sputnik Planitia probably formed northwest of its present location, and was loaded with volatiles over million-year timescales as a result of volatile transport cycles on Pluto. Pluto’s past, present and future orientation is controlled by feedbacks between volatile sublimation and condensation, changing insolation conditions and Pluto’s interior structure.
      Citation: Nature 540, 7631 (2016)
      PubDate: 2016-11-16
      DOI: 10.1038/nature20120
      Issue No: Vol. 540, No. 7631 (2016)
       
  • Reorientation of Sputnik Planitia implies a subsurface ocean on Pluto
    • Authors: F. Nimmo, D. P. Hamilton, W. B. McKinnon, P. M. Schenk, R. P. Binzel, C. J. Bierson, R. A. Beyer, J. M. Moore, S. A. Stern, H. A. Weaver, C. B. Olkin, L. A. Young, K. E. Smith
      Pages: 94 - 96
      Abstract: The deep nitrogen-covered basin on Pluto, informally named Sputnik Planitia, is located very close to the longitude of Pluto’s tidal axis and may be an impact feature, by analogy with other large basins in the Solar System. Reorientation of Sputnik Planitia arising from tidal and rotational torques can explain the basin’s present-day location, but requires the feature to be a positive gravity anomaly, despite its negative topography. Here we argue that if Sputnik Planitia did indeed form as a result of an impact and if Pluto possesses a subsurface ocean, the required positive gravity anomaly would naturally result because of shell thinning and ocean uplift, followed by later modest nitrogen deposition. Without a subsurface ocean, a positive gravity anomaly requires an implausibly thick nitrogen layer (exceeding 40 kilometres). To prolong the lifetime of such a subsurface ocean to the present day and to maintain ocean uplift, a rigid, conductive water-ice shell is required. Because nitrogen deposition is latitude-dependent, nitrogen loading and reorientation may have exhibited complex feedbacks.
      Citation: Nature 540, 7631 (2016)
      PubDate: 2016-11-16
      DOI: 10.1038/nature20148
      Issue No: Vol. 540, No. 7631 (2016)
       
  • The rapid formation of Sputnik Planitia early in Pluto’s history
    • Authors: Douglas P. Hamilton, S. A. Stern, J. M. Moore, L. A. Young
      Pages: 97 - 99
      Abstract: Pluto’s Sputnik Planitia is a bright, roughly circular feature that resembles a polar ice cap. It is approximately 1,000 kilometres across and is centred on a latitude of 25 degrees north and a longitude of 175 degrees, almost directly opposite the side of Pluto that always faces Charon as a result of tidal locking. One explanation for its location includes the formation of a basin in a giant impact, with subsequent upwelling of a dense interior ocean. Once the basin was established, ice would naturally have accumulated there. Then, provided that the basin was a positive gravity anomaly (with or without the ocean), true polar wander could have moved the feature towards the Pluto–Charon tidal axis, on the far side of Pluto from Charon. Here we report modelling that shows that ice quickly accumulates on Pluto near latitudes of 30 degrees north and south, even in the absence of a basin, because, averaged over its orbital period, those are Pluto’s coldest regions. Within a million years of Charon’s formation, ice deposits on Pluto concentrate into a single cap centred near a latitude of 30 degrees, owing to the runaway albedo effect. This accumulation of ice causes a positive gravity signature that locks, as Pluto’s rotation slows, to a longitude directly opposite Charon. Once locked, Charon raises a permanent tidal bulge on Pluto, which greatly enhances the gravity signature of the ice cap. Meanwhile, the weight of the ice in Sputnik Planitia causes the crust under it to slump, creating its own basin (as has happened on Earth in Greenland). Even if the feature is now a modest negative gravity anomaly, it remains locked in place because of the permanent tidal bulge raised by Charon. Any movement of the feature away from 30 degrees latitude is countered by the preferential recondensation of ices near the coldest extremities of the cap. Therefore, our modelling suggests that Sputnik Planitia formed shortly after Charon did and has been stable, albeit gradually losing volume, over the age of the Solar System.
      Citation: Nature 540, 7631 (2016)
      PubDate: 2016-11-30
      DOI: 10.1038/nature20586
      Issue No: Vol. 540, No. 7631 (2016)
       
  • Ghost imaging with atoms
    • Authors: R. I. Khakimov, B. M. Henson, D. K. Shin, S. S. Hodgman, R. G. Dall, K. G. H. Baldwin, A. G. Truscott
      Pages: 100 - 103
      Abstract: Ghost imaging is a counter-intuitive phenomenon—first realized in quantum optics—that enables the image of a two-dimensional object (mask) to be reconstructed using the spatio-temporal properties of a beam of particles with which it never interacts. Typically, two beams of correlated photons are used: one passes through the mask to a single-pixel (bucket) detector while the spatial profile of the other is measured by a high-resolution (multi-pixel) detector. The second beam never interacts with the mask. Neither detector can reconstruct the mask independently, but temporal cross-correlation between the two beams can be used to recover a ‘ghost’ image. Here we report the realization of ghost imaging using massive particles instead of photons. In our experiment, the two beams are formed by correlated pairs of ultracold, metastable helium atoms, which originate from s-wave scattering of two colliding Bose–Einstein condensates. We use higher-order Kapitza–Dirac scattering to generate a large number of correlated atom pairs, enabling the creation of a clear ghost image with submillimetre resolution. Future extensions of our technique could lead to the realization of ghost interference, and enable tests of Einstein–Podolsky–Rosen entanglement and Bell’s inequalities with atoms.
      Citation: Nature 540, 7631 (2016)
      PubDate: 2016-11-30
      DOI: 10.1038/nature20154
      Issue No: Vol. 540, No. 7631 (2016)
       
  • Quantifying global soil carbon losses in response to warming
    • Authors: T. W. Crowther, K. E. O. Todd-Brown, C. W. Rowe, W. R. Wieder, J. C. Carey, M. B. Machmuller, B. L. Snoek, S. Fang, G. Zhou, S. D. Allison, J. M. Blair, S. D. Bridgham, A. J. Burton, Y. Carrillo, P. B. Reich, J. S. Clark, A. T. Classen, F. A. Dijkstra, B. Elberling, B. A. Emmett, M. Estiarte, S. D. Frey, J. Guo, J. Harte, L. Jiang, B. R. Johnson, G. Kröel-Dulay, K. S. Larsen, H. Laudon, J. M. Lavallee, Y. Luo, M. Lupascu, L. N. Ma, S. Marhan, A. Michelsen, J. Mohan, S. Niu, E. Pendall, J. Peñuelas, L. Pfeifer-Meister, C. Poll, S. Reinsch, L. L. Reynolds, I. K. Schmidt, S. Sistla, N. W. Sokol, P. H. Templer, K. K. Treseder, J. M. Welker, M. A. Bradford
      Pages: 104 - 108
      Abstract: The majority of the Earth’s terrestrial carbon is stored in the soil. If anthropogenic warming stimulates the loss of this carbon to the atmosphere, it could drive further planetary warming. Despite evidence that warming enhances carbon fluxes to and from the soil, the net global balance between these responses remains uncertain. Here we present a comprehensive analysis of warming-induced changes in soil carbon stocks by assembling data from 49 field experiments located across North America, Europe and Asia. We find that the effects of warming are contingent on the size of the initial soil carbon stock, with considerable losses occurring in high-latitude areas. By extrapolating this empirical relationship to the global scale, we provide estimates of soil carbon sensitivity to warming that may help to constrain Earth system model projections. Our empirical relationship suggests that global soil carbon stocks in the upper soil horizons will fall by 30 ± 30 petagrams of carbon to 203 ± 161 petagrams of carbon under one degree of warming, depending on the rate at which the effects of warming are realized. Under the conservative assumption that the response of soil carbon to warming occurs within a year, a business-as-usual climate scenario would drive the loss of 55 ± 50 petagrams of carbon from the upper soil horizons by 2050. This value is around 12–17 per cent of the expected anthropogenic emissions over this period. Despite the considerable uncertainty in our estimates, the direction of the global soil carbon response is consistent across all scenarios. This provides strong empirical support for the idea that rising temperatures will stimulate the net loss of soil carbon to the atmosphere, driving a positive land carbon–climate feedback that could accelerate climate change.
      Citation: Nature 540, 7631 (2016)
      PubDate: 2016-11-30
      DOI: 10.1038/nature20150
      Issue No: Vol. 540, No. 7631 (2016)
       
  • Unexpected diversity in socially synchronized rhythms of shorebirds
    • Authors: Martin Bulla, Mihai Valcu, Adriaan M. Dokter, Alexei G. Dondua, András Kosztolányi, Anne L. Rutten, Barbara Helm, Brett K. Sandercock, Bruce Casler, Bruno J. Ens, Caleb S. Spiegel, Chris J. Hassell, Clemens Küpper, Clive Minton, Daniel Burgas, David B. Lank, David C. Payer, Egor Y. Loktionov, Erica Nol, Eunbi Kwon, Fletcher Smith, H. River Gates, Hana Vitnerová, Hanna Prüter, James A. Johnson, James J. H. St Clair, Jean-François Lamarre, Jennie Rausch, Jeroen Reneerkens, Jesse R. Conklin, Joanna Burger, Joe Liebezeit, Joël Bêty, Jonathan T. Coleman, Jordi Figuerola, Jos C. E. W. Hooijmeijer, José A. Alves, Joseph A. M. Smith, Karel Weidinger, Kari Koivula, Ken Gosbell, Klaus-Michael Exo, Larry Niles, Laura Koloski, Laura McKinnon, Libor Praus, Marcel Klaassen, Marie-Andrée Giroux, Martin Sládeček, Megan L. Boldenow, Michael I. Goldstein, Miroslav Šálek, Nathan Senner, Nelli Rönkä, Nicolas Lecomte, Olivier Gilg, Orsolya Vincze, Oscar W. Johnson, Paul A. Smith, Paul F. Woodard, Pavel S. Tomkovich, Phil F. Battley, Rebecca Bentzen, Richard B. Lanctot, Ron Porter, Sarah T. Saalfeld, Scott Freeman, Stephen C. Brown, Stephen Yezerinac, Tamás Székely, Tomás Montalvo, Theunis Piersma, Vanessa Loverti, Veli-Matti Pakanen, Wim Tijsen, Bart Kempenaers
      Pages: 109 - 113
      Abstract: The behavioural rhythms of organisms are thought to be under strong selection, influenced by the rhythmicity of the environment. Such behavioural rhythms are well studied in isolated individuals under laboratory conditions, but free-living individuals have to temporally synchronize their activities with those of others, including potential mates, competitors, prey and predators. Individuals can temporally segregate their daily activities (for example, prey avoiding predators, subordinates avoiding dominants) or synchronize their activities (for example, group foraging, communal defence, pairs reproducing or caring for offspring). The behavioural rhythms that emerge from such social synchronization and the underlying evolutionary and ecological drivers that shape them remain poorly understood. Here we investigate these rhythms in the context of biparental care, a particularly sensitive phase of social synchronization where pair members potentially compromise their individual rhythms. Using data from 729 nests of 91 populations of 32 biparentally incubating shorebird species, where parents synchronize to achieve continuous coverage of developing eggs, we report remarkable within- and between-species diversity in incubation rhythms. Between species, the median length of one parent’s incubation bout varied from 1–19 h, whereas period length—the time in which a parent’s probability to incubate cycles once between its highest and lowest value—varied from 6–43 h. The length of incubation bouts was unrelated to variables reflecting energetic demands, but species relying on crypsis (the ability to avoid detection by other animals) had longer incubation bouts than those that are readily visible or who actively protect their nest against predators. Rhythms entrainable to the 24-h light–dark cycle were less prevalent at high latitudes and absent in 18 species. Our results indicate that even under similar environmental conditions and despite 24-h environmental cues, social synchronization can generate far more diverse behavioural rhythms than expected from studies of individuals in captivity. The risk of predation, not the risk of starvation, may be a key factor underlying the diversity in these rhythms.
      Citation: Nature 540, 7631 (2016)
      PubDate: 2016-11-23
      DOI: 10.1038/nature20563
      Issue No: Vol. 540, No. 7631 (2016)
       
  • Genomic evolution and chemoresistance in germ-cell tumours
    • Authors: Amaro Taylor-Weiner, Travis Zack, Elizabeth O’Donnell, Jennifer L. Guerriero, Brandon Bernard, Anita Reddy, G. Celine Han, Saud AlDubayan, Ali Amin-Mansour, Steven E. Schumacher, Kevin Litchfield, Clare Turnbull, Stacey Gabriel, Rameen Beroukhim, Gad Getz, Scott L. Carter, Michelle S. Hirsch, Anthony Letai, Christopher Sweeney, Eliezer M Van Allen
      Pages: 114 - 118
      Abstract: Germ-cell tumours (GCTs) are derived from germ cells and occur most frequently in the testes. GCTs are histologically heterogeneous and distinctly curable with chemotherapy. Gains of chromosome arm 12p and aneuploidy are nearly universal in GCTs, but specific somatic genomic features driving tumour initiation, chemosensitivity and progression are incompletely characterized. Here, using clinical whole-exome and transcriptome sequencing of precursor, primary (testicular and mediastinal) and chemoresistant metastatic human GCTs, we show that the primary somatic feature of GCTs is highly recurrent chromosome arm level amplifications and reciprocal deletions (reciprocal loss of heterozygosity), variations that are significantly enriched in GCTs compared to 19 other cancer types. These tumours also acquire KRAS mutations during the development from precursor to primary disease, and primary testicular GCTs (TGCTs) are uniformly wild type for TP53. In addition, by functional measurement of apoptotic signalling (BH3 profiling) of fresh tumour and adjacent tissue, we find that primary TGCTs have high mitochondrial priming that facilitates chemotherapy-induced apoptosis. Finally, by phylogenetic analysis of serial TGCTs that emerge with chemotherapy resistance, we show how TGCTs gain additional reciprocal loss of heterozygosity and that this is associated with loss of pluripotency markers (NANOG and POU5F1) in chemoresistant teratomas or transformed carcinomas. Our results demonstrate the distinct genomic features underlying the origins of this disease and associated with the chemosensitivity phenotype, as well as the rare progression to chemoresistance. These results identify the convergence of cancer genomics, mitochondrial priming and GCT evolution, and may provide insights into chemosensitivity and resistance in other cancers.
      Citation: Nature 540, 7631 (2016)
      PubDate: 2016-11-30
      DOI: 10.1038/nature20596
      Issue No: Vol. 540, No. 7631 (2016)
       
  • Inhibition of mTOR induces a paused pluripotent state
    • Authors: Aydan Bulut-Karslioglu, Steffen Biechele, Hu Jin, Trisha A. Macrae, Miroslav Hejna, Marina Gertsenstein, Jun S. Song, Miguel Ramalho-Santos
      Pages: 119 - 123
      Abstract: Cultured pluripotent stem cells are a cornerstone of regenerative medicine owing to their ability to give rise to all cell types of the body. Although pluripotent stem cells can be propagated indefinitely in vitro, pluripotency is paradoxically a transient state in vivo, lasting 2–3 days around the time of blastocyst implantation. The exception to this rule is embryonic diapause, a reversible state of suspended development triggered by unfavourable conditions. Diapause is a physiological reproductive strategy widely employed across the animal kingdom, including in mammals, but its regulation remains poorly understood. Here we report that the partial inhibition of mechanistic target of rapamycin (mTOR), a major nutrient sensor and promoter of growth, induces reversible pausing of mouse blastocyst development and allows their prolonged culture ex vivo. Paused blastocysts remain pluripotent and competent—able to give rise to embryonic stem (ES) cells and live, fertile mice. We show that both naturally diapaused blastocysts in vivo and paused blastocysts ex vivo display pronounced reductions in mTOR activity, translation, histone modifications associated with gene activity and transcription. Pausing can be induced directly in cultured ES cells and sustained for weeks without appreciable cell death or deviations from cell cycle distributions. We show that paused ES cells display a remarkable global suppression of transcription, maintain a gene expression signature of diapaused blastocysts and remain pluripotent. These results uncover a new pluripotent stem cell state corresponding to the epiblast of the diapaused blastocyst and indicate that mTOR regulates developmental timing at the peri-implantation stage. Our findings have implications in the fields of assisted reproduction, regenerative medicine, cancer, metabolic disorders and ageing.
      Citation: Nature 540, 7631 (2016)
      PubDate: 2016-11-23
      DOI: 10.1038/nature20578
      Issue No: Vol. 540, No. 7631 (2016)
       
  • RIPK1 counteracts ZBP1-mediated necroptosis to inhibit inflammation
    • Authors: Juan Lin, Snehlata Kumari, Chun Kim, Trieu-My Van, Laurens Wachsmuth, Apostolos Polykratis, Manolis Pasparakis
      Pages: 124 - 128
      Abstract: Receptor-interacting protein kinase 1 (RIPK1) regulates cell death and inflammation through kinase-dependent and -independent functions. RIPK1 kinase activity induces caspase-8-dependent apoptosis and RIPK3 and mixed lineage kinase like (MLKL)-dependent necroptosis. In addition, RIPK1 inhibits apoptosis and necroptosis through kinase-independent functions, which are important for late embryonic development and the prevention of inflammation in epithelial barriers. The mechanism by which RIPK1 counteracts RIPK3–MLKL-mediated necroptosis has remained unknown. Here we show that RIPK1 prevents skin inflammation by inhibiting activation of RIPK3–MLKL-dependent necroptosis mediated by Z-DNA binding protein 1 (ZBP1, also known as DAI or DLM1). ZBP1 deficiency inhibited keratinocyte necroptosis and skin inflammation in mice with epidermis-specific RIPK1 knockout. Moreover, mutation of the conserved RIP homotypic interaction motif (RHIM) of endogenous mouse RIPK1 (RIPK1mRHIM) caused perinatal lethality that was prevented by RIPK3, MLKL or ZBP1 deficiency. Furthermore, mice expressing only RIPK1mRHIM in keratinocytes developed skin inflammation that was abrogated by MLKL or ZBP1 deficiency. Mechanistically, ZBP1 interacted strongly with phosphorylated RIPK3 in cells expressing RIPK1mRHIM, suggesting that the RIPK1 RHIM prevents ZBP1 from binding and activating RIPK3. Collectively, these results show that RIPK1 prevents perinatal death as well as skin inflammation in adult mice by inhibiting ZBP1-induced necroptosis. Furthermore, these findings identify ZBP1 as a critical mediator of inflammation beyond its previously known role in antiviral defence and suggest that ZBP1 might be implicated in the pathogenesis of necroptosis-associated inflammatory diseases.
      Citation: Nature 540, 7631 (2016)
      PubDate: 2016-11-07
      DOI: 10.1038/nature20558
      Issue No: Vol. 540, No. 7631 (2016)
       
  • RIPK1 inhibits ZBP1-driven necroptosis during development
    • Authors: Kim Newton, Katherine E. Wickliffe, Allie Maltzman, Debra L. Dugger, Andreas Strasser, Victoria C. Pham, Jennie R. Lill, Merone Roose-Girma, Søren Warming, Margaret Solon, Hai Ngu, Joshua D. Webster, Vishva M. Dixit
      Pages: 129 - 133
      Abstract: Receptor-interacting protein kinase 1 (RIPK1) promotes cell survival—mice lacking RIPK1 die perinatally, exhibiting aberrant caspase-8-dependent apoptosis and mixed lineage kinase-like (MLKL)-dependent necroptosis. However, mice expressing catalytically inactive RIPK1 are viable, and an ill-defined pro-survival function for the RIPK1 scaffold has therefore been proposed. Here we show that the RIP homotypic interaction motif (RHIM) in RIPK1 prevents the RHIM-containing adaptor protein ZBP1 (Z-DNA binding protein 1; also known as DAI or DLM1) from activating RIPK3 upstream of MLKL. Ripk1RHIM/RHIM mice that expressed mutant RIPK1 with critical RHIM residues IQIG mutated to AAAA died around birth and exhibited RIPK3 autophosphorylation on Thr231 and Ser232, which is a hallmark of necroptosis, in the skin and thymus. Blocking necroptosis with catalytically inactive RIPK3(D161N), RHIM mutant RIPK3, RIPK3 deficiency, or MLKL deficiency prevented lethality in Ripk1RHIM/RHIM mice. Loss of ZBP1, which engages RIPK3 in response to certain viruses but previously had no defined role in development, also prevented perinatal lethality in Ripk1RHIM/RHIM mice. Consistent with the RHIM of RIPK1 functioning as a brake that prevents ZBP1 from engaging the RIPK3 RHIM, ZBP1 interacted with RIPK3 in Ripk1RHIM/RHIMMlkl−/− macrophages, but not in wild-type, Mlkl−/− or Ripk1RHIM/RHIMRipk3RHIM/RHIM macrophages. Collectively, these findings indicate that the RHIM of RIPK1 is critical for preventing ZBP1/RIPK3/MLKL-dependent necroptosis during development.
      Citation: Nature 540, 7631 (2016)
      PubDate: 2016-11-07
      DOI: 10.1038/nature20559
      Issue No: Vol. 540, No. 7631 (2016)
       
  • The SND proteins constitute an alternative targeting route to the
           endoplasmic reticulum
    • Authors: Naama Aviram, Tslil Ast, Elizabeth A. Costa, Eric C. Arakel, Silvia G. Chuartzman, Calvin H. Jan, Sarah Haßdenteufel, Johanna Dudek, Martin Jung, Stefan Schorr, Richard Zimmermann, Blanche Schwappach, Jonathan S. Weissman, Maya Schuldiner
      Pages: 134 - 138
      Abstract: In eukaryotes, up to one-third of cellular proteins are targeted to the endoplasmic reticulum, where they undergo folding, processing, sorting and trafficking to subsequent endomembrane compartments. Targeting to the endoplasmic reticulum has been shown to occur co-translationally by the signal recognition particle (SRP) pathway or post-translationally by the mammalian transmembrane recognition complex of 40 kDa (TRC40) and homologous yeast guided entry of tail-anchored proteins (GET) pathways. Despite the range of proteins that can be catered for by these two pathways, many proteins are still known to be independent of both SRP and GET, so there seems to be a critical need for an additional dedicated pathway for endoplasmic reticulum relay. We set out to uncover additional targeting proteins using unbiased high-content screening approaches. To this end, we performed a systematic visual screen using the yeast Saccharomyces cerevisiae, and uncovered three uncharacterized proteins whose loss affected targeting. We suggest that these proteins work together and demonstrate that they function in parallel with SRP and GET to target a broad range of substrates to the endoplasmic reticulum. The three proteins, which we name Snd1, Snd2 and Snd3 (for SRP-independent targeting), can synthetically compensate for the loss of both the SRP and GET pathways, and act as a backup targeting system. This explains why it has previously been difficult to demonstrate complete loss of targeting for some substrates. Our discovery thus puts in place an essential piece of the endoplasmic reticulum targeting puzzle, highlighting how the targeting apparatus of the eukaryotic cell is robust, interlinked and flexible.
      Citation: Nature 540, 7631 (2016)
      PubDate: 2016-11-30
      DOI: 10.1038/nature20169
      Issue No: Vol. 540, No. 7631 (2016)
       
  • Multiple dynamin family members collaborate to drive mitochondrial
           division
    • Authors: Jason E. Lee, Laura M. Westrate, Haoxi Wu, Cynthia Page, Gia K. Voeltz
      Pages: 139 - 143
      Abstract: Mitochondria cannot be generated de novo; they must grow, replicate their genome, and divide in order to be inherited by each daughter cell during mitosis. Mitochondrial division is a structural challenge that requires the substantial remodelling of membrane morphology. Although division factors differ across organisms, the need for multiple constriction steps and a dynamin-related protein (Drp1, Dnm1 in yeast) has been conserved. In mammalian cells, mitochondrial division has been shown to proceed with at least two sequential constriction steps: the endoplasmic reticulum and actin must first collaborate to generate constrictions suitable for Drp1 assembly on the mitochondrial outer membrane; Drp1 then further constricts membranes until mitochondrial fission occurs. In vitro experiments, however, indicate that Drp1 does not have the dynamic range to complete membrane fission. In contrast to Drp1, the neuron-specific classical dynamin dynamin-1 (Dyn1) has been shown to assemble on narrower lipid profiles and facilitate spontaneous membrane fission upon GTP hydrolysis. Here we report that the ubiquitously expressed classical dynamin-2 (Dyn2) is a fundamental component of the mitochondrial division machinery. A combination of live-cell and electron microscopy in three different mammalian cell lines reveals that Dyn2 works in concert with Drp1 to orchestrate sequential constriction events that build up to division. Our work underscores the biophysical limitations of Drp1 and positions Dyn2, which has intrinsic membrane fission properties, at the final step of mitochondrial division.
      Citation: Nature 540, 7631 (2016)
      PubDate: 2016-10-31
      DOI: 10.1038/nature20555
      Issue No: Vol. 540, No. 7631 (2016)
       
  • In vivo genome editing via CRISPR/Cas9 mediated homology-independent
           targeted integration
    • Authors: Keiichiro Suzuki, Yuji Tsunekawa, Reyna Hernandez-Benitez, Jun Wu, Jie Zhu, Euiseok J. Kim, Fumiyuki Hatanaka, Mako Yamamoto, Toshikazu Araoka, Zhe Li, Masakazu Kurita, Tomoaki Hishida, Mo Li, Emi Aizawa, Shicheng Guo, Song Chen, April Goebl, Rupa Devi Soligalla, Jing Qu, Tingshuai Jiang, Xin Fu, Maryam Jafari, Concepcion Rodriguez Esteban, W. Travis Berggren, Jeronimo Lajara, Estrella Nuñez-Delicado, Pedro Guillen, Josep M. Campistol, Fumio Matsuzaki, Guang-Hui Liu, Pierre Magistretti, Kun Zhang, Edward M. Callaway, Kang Zhang, Juan Carlos Izpisua Belmonte
      Pages: 144 - 149
      Abstract: Targeted genome editing via engineered nucleases is an exciting area of biomedical research and holds potential for clinical applications. Despite rapid advances in the field, in vivo targeted transgene integration is still infeasible because current tools are inefficient, especially for non-dividing cells, which compose most adult tissues. This poses a barrier for uncovering fundamental biological principles and developing treatments for a broad range of genetic disorders. Based on clustered regularly interspaced short palindromic repeat/Cas9 (CRISPR/Cas9) technology, here we devise a homology-independent targeted integration (HITI) strategy, which allows for robust DNA knock-in in both dividing and non-dividing cells in vitro and, more importantly, in vivo (for example, in neurons of postnatal mammals). As a proof of concept of its therapeutic potential, we demonstrate the efficacy of HITI in improving visual function using a rat model of the retinal degeneration condition retinitis pigmentosa. The HITI method presented here establishes new avenues for basic research and targeted gene therapies.
      Citation: Nature 540, 7631 (2016)
      PubDate: 2016-11-16
      DOI: 10.1038/nature20565
      Issue No: Vol. 540, No. 7631 (2016)
       
  • Corrigendum: Design of a hyperstable 60-subunit protein icosahedron
    • Authors: Yang Hsia, Jacob B. Bale, Shane Gonen, Dan Shi, William Sheffler, Kimberly K. Fong, Una Nattermann, Chunfu Xu, Po-Ssu Huang, Rashmi Ravichandran, Sue Yi, Trisha N. Davis, Tamir Gonen, Neil P. King, David Baker
      Pages: 150 - 150
      Abstract: Nature535, 136–139 (2016); doi:10.1038/nature18010In this Letter, the 60-subunit protein assembly presented more strongly resembles a wireframe dodecahedron than an icosahedron. We thank the reader who drew this to our attention and we agree that all instances
      Citation: Nature 540, 7631 (2016)
      PubDate: 2016-10-19
      DOI: 10.1038/nature20108
      Issue No: Vol. 540, No. 7631 (2016)
       
  • Corrigendum: Fumarate is an epigenetic modifier that elicits
           epithelial-to-mesenchymal transition
    • Authors: Marco Sciacovelli, Emanuel Gonçalves, Timothy Isaac Johnson, Vincent Roberto Zecchini, Ana Sofia Henriques da Costa, Edoardo Gaude, Alizee Vercauteren Drubbel, Sebastian Julian Theobald, Sandra Riekje Abbo, Maxine Gia Binh Tran, Vinothini Rajeeve, Simone Cardaci, Sarah Foster, Haiyang Yun, Pedro Cutillas, Anne Warren, Vincent Gnanapragasam, Eyal Gottlieb, Kristian Franze, Brian Huntly, Eamonn Richard Maher, Patrick Henry Maxwell, Julio Saez-Rodriguez, Christian Frezza
      Pages: 150 - 150
      Abstract: Nature537, 544–547 (2016); doi:10.1038/nature19353In this Letter, the ArrayExpress accession number provided for the gene expression data for Sdhb-deficient cells should have been ‘ E-MTAB-4349’, rather than the Affymetrix GeneChip platform accession ‘A-AFFY-130’; this has been
      Citation: Nature 540, 7631 (2016)
      PubDate: 2016-10-19
      DOI: 10.1038/nature20144
      Issue No: Vol. 540, No. 7631 (2016)
       
  • Erratum: Pancreatic stellate cells support tumour metabolism through
           autophagic alanine secretion
    • Authors: Cristovão M. Sousa, Douglas E. Biancur, Xiaoxu Wang, Christopher J. Halbrook, Mara H. Sherman, Li Zhang, Daniel Kremer, Rosa F. Hwang, Agnes K. Witkiewicz, Haoqiang Ying, John M. Asara, Ronald M. Evans, Lewis C. Cantley, Costas A. Lyssiotis, Alec C. Kimmelman
      Pages: 150 - 150
      Abstract: Nature536, 479–483 (2016); doi:10.1038/nature19084In this Letter, during the production process, one of the images in Fig. 3a was inadvertently labelled with the incorrect PDAC cell line name. The second picture from the left should have been
      Citation: Nature 540, 7631 (2016)
      PubDate: 2016-10-05
      DOI: 10.1038/nature19851
      Issue No: Vol. 540, No. 7631 (2016)
       
  • Erratum: Pore-forming activity and structural autoinhibition of the
           gasdermin family
    • Authors: Jingjin Ding, Kun Wang, Wang Liu, Yang She, Qi Sun, Jianjin Shi, Hanzi Sun, Da-Cheng Wang, Feng Shao
      Pages: 150 - 150
      Abstract: Nature535, 111–116 (2016); doi:10.1038/nature18590In this Article, owing to a typesetter error the ‘received date’ was incorrectly shown as ‘6 March 2015’ instead of ‘6 March 2016’; this has been corrected in the online versions of the
      Citation: Nature 540, 7631 (2016)
      PubDate: 2016-10-05
      DOI: 10.1038/nature20106
      Issue No: Vol. 540, No. 7631 (2016)
       
  • The first fragmented church of entropy
    • Authors: Steven Fischer
      Pages: 162 - 162
      Abstract: Order from chaos.
      Citation: Nature 540, 7631 (2016)
      PubDate: 2016-11-30
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      Issue No: Vol. 540, No. 7631 (2016)
       
  • Multiple sclerosis
    • Multiple sclerosis

      Nature. doi:10.1038/540S1a

      Author: Brian Owens

      Nature2016-11-30
      DOI: 10.1038/540S1a
       
  • Biology: A degenerative affliction
    • Authors: Charles Schmidt
      Abstract: Multiple sclerosis often strikes between the ages of 20 and 40, when people are entering the workforce and raising families.
      Citation: Nature
      PubDate: 2016-11-30
      DOI: 10.1038/540S2a
       
  • Aetiology: Neighbourhood watch
    • Authors: Carolyn Brown
      Abstract: Emerging evidence points to a viral infection, low levels of vitamin D and genetics as culprits in multiple sclerosis, but how they combine to cause the disease is unclear.
      Citation: Nature
      PubDate: 2016-11-30
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  • Therapies: Progressive steps
    • Authors: Elie Dolgin
      Abstract: New drugs are beginning to show promise for people with one of the less common, and harder to treat, forms of multiple sclerosis.
      Citation: Nature
      PubDate: 2016-11-30
      DOI: 10.1038/540S7a
       
  • Perspective: Who dares, wins
    • Authors: Bibi Bielekova
      Abstract: It is time for a bolder approach to developing drugs for progressive multiple sclerosis, says Bibi Bielekova.
      Citation: Nature
      PubDate: 2016-11-30
      DOI: 10.1038/540S10a
       
  • Stem cells: Stemming the tide
    • Authors: Asher Mullard
      Abstract: Could a high-risk treatment play a part in tackling multiple sclerosis?
      Citation: Nature
      PubDate: 2016-11-30
      DOI: 10.1038/540S11a
       
  • Diet: Changing the recipe
    • Authors: Sujata Gupta
      Abstract: Dietary changes may be able to alleviate the symptoms of multiple sclerosis, but testing the effects of diet will need a different protocol to the one used for drugs.
      Citation: Nature
      PubDate: 2016-11-30
      DOI: 10.1038/540S13a
       
  • Human behaviour: Find your voice
    • Authors: Julia Rosen
      Pages: 157 - 159
      Abstract: Technology and practice can help shy and introverted researchers to succeed when reticence is risky.
      Citation: Nature (2016)
      PubDate: 2016-11-30
      DOI: 10.1038/nj7631-157a
       
  • Gender: Co-author differences
    • Pages: 159 - 159
      Abstract: Women have fewer co-authors than men over the course of their careers.
      Citation: Nature (2016)
      PubDate: 2016-11-30
      DOI: 10.1038/nj7631-159a
       
  • Income: UK pay gap
    • Pages: 159 - 159
      Abstract: The pay gap between men and women in UK science is narrowing.
      Citation: Nature (2016)
      PubDate: 2016-11-30
      DOI: 10.1038/nj7631-159b
       
  • Can old computers bring Palestinians and Israelis together?
    • Authors: Josie Glausiusz
      Pages: 22 - 25
      Abstract: Some of the most toxic refuse from modern society ends up in poor communities. Researchers are helping one area in the Middle East clean up its electronic-waste problem.
      Citation: Nature 540, 7631 (2016)
      DOI: 10.1038/540022a
      Issue No: Vol. 540, No. 7631
       
  • Stem cells and interspecies chimaeras
    • Authors: Jun Wu, Henry T. Greely, Rudolf Jaenisch, Hiromitsu Nakauchi, Janet Rossant, Juan Carlos Izpisua Belmonte
      Pages: 51 - 59
      Abstract: Chimaeras are both monsters of the ancient imagination and a long-established research tool. Recent advances, particularly those dealing with the identification and generation of various kinds of stem cells, have broadened the repertoire and utility of mammalian interspecies chimaeras and carved out new paths towards
      Citation: Nature 540, 7631 (2016)
      DOI: 10.1038/nature20573
      Issue No: Vol. 540, No. 7631
       
  • Organization and functions of mGlu and GABAB receptor complexes
    • Authors: Jean-Philippe Pin, Bernhard Bettler
      Pages: 60 - 68
      Abstract: The neurotransmitters glutamate and γ-aminobutyric acid (GABA) transmit synaptic signals by activating fast-acting ligand-gated ion channels and more slowly acting G-protein-coupled receptors (GPCRs). The GPCRs for these neurotransmitters, metabotropic glutamate (mGlu) and GABAB receptors, are atypical GPCRs with a large extracellular domain and
      Citation: Nature 540, 7631 (2016)
      DOI: 10.1038/nature20566
      Issue No: Vol. 540, No. 7631
       
 
 
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