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Journal Cover   Nature
  [SJR: 21.323]   [H-I: 829]   [2766 followers]  Follow
    
   Full-text available via subscription Subscription journal
   ISSN (Print) 0028-0836 - ISSN (Online) 1476-4687
   Published by Nature Publishing Group Homepage  [110 journals]
  • Timeless advice
    • Pages: 381 - 382
      Abstract: The best guidance on how to get ahead in science stands the test of time.
      Citation: Nature 523, 7561 (2015)
      PubDate: 2015-07-22
      DOI: 10.1038/523381b
      Issue No: Vol. 523, No. 7561 (2015)
       
  • Prepare farms for the future
    • Pages: 381 - 381
      Abstract: Scientists must work closely with farmers to ensure that agriculture can stand up to the ravages of climate change.
      Citation: Nature 523, 7561 (2015)
      PubDate: 2015-07-21
      DOI: 10.1038/523381a
      Issue No: Vol. 523, No. 7561 (2015)
       
  • It’s good to talk
    • Pages: 382 - 382
      Abstract: Help for those struggling to reproduce results could be just a phone call away.
      Citation: Nature 523, 7561 (2015)
      PubDate: 2015-07-22
      DOI: 10.1038/523382a
      Issue No: Vol. 523, No. 7561 (2015)
       
  • Russia's crackdowns are jeopardizing its science
    • Authors: Fyodor Kondrashov
      Pages: 383 - 383
      Abstract: The escalating encroachment on democratic freedoms undermines the nation's claim of support for science, says Fyodor Kondrashov.
      Citation: Nature 523, 7561 (2015)
      PubDate: 2015-07-22
      DOI: 10.1038/523383a
      Issue No: Vol. 523, No. 7561 (2015)
       
  • Astronomy: Total eclipse of rare twin stars
    • Pages: 384 - 384
      Abstract: Amateur and professional astronomers have spotted a rare pair of stars in which one completely eclipses the other as they orbit each other.A team led by Heather Campbell at the University of Cambridge, UK, analysed data from the European Space Agency's Gaia satellite and
      Citation: Nature 523, 7561 (2015)
      PubDate: 2015-07-22
      DOI: 10.1038/523384d
      Issue No: Vol. 523, No. 7561 (2015)
       
  • The week in science: 17–23 July
    • Pages: 384 - 385
      Abstract: A pledge on fishing in Arctic high seas; global inequalities on mental health; and another ethics scandal at the University of Minnesota.
      Citation: Nature 523, 7561 (2015)
      PubDate: 2015-07-22
      DOI: 10.1038/523384a
      Issue No: Vol. 523, No. 7561 (2015)
       
  • Anthropology: Earliest signs of chicken husbandry
    • Pages: 384 - 384
      Abstract: Humans first used chickens for economic gain roughly 2,300 years ago in the Middle East, before Europeans began exploiting the bird.The chicken (Gallus gallus domesticus) was first domesticated in southeast Asia, but its dispersal from that region has been unclear. Lee Perry-Gal
      Citation: Nature 523, 7561 (2015)
      PubDate: 2015-07-22
      DOI: 10.1038/523384b
      Issue No: Vol. 523, No. 7561 (2015)
       
  • Stem cells: Heart cells come of age
    • Pages: 384 - 384
      Abstract: Human stem cells have been coaxed into forming heart progenitor cells that then develop into more-specialized heart cells.Researchers have struggled to turn stem cells into large pools of cardiac cells that would further divide. Christine Mummery at Leiden University Medical Center in the Netherlands
      Citation: Nature 523, 7561 (2015)
      PubDate: 2015-07-22
      DOI: 10.1038/523384c
      Issue No: Vol. 523, No. 7561 (2015)
       
  • Energy: Sun's heat could cut fossil-fuel use
    • Pages: 384 - 384
      Abstract: Integrating solar technologies into coal-fired power plants could ease the transition from fossil fuels to renewable energy sources.Vishwanath Haily Dalvi of the Institute of Chemical Technology in Mumbai, India, and his colleagues looked at solar thermal technology, which collects the Sun's energy as heat.
      Citation: Nature 523, 7561 (2015)
      PubDate: 2015-07-22
      DOI: 10.1038/523384a
      Issue No: Vol. 523, No. 7561 (2015)
       
  • Chemistry: Elusive molecule made in the lab
    • Pages: 385 - 385
      Abstract: An organic molecule first postulated a century ago has finally been created and characterized in the lab.Scientists first theorized the existence of ethylenedione in 1913, but it remained unobserved despite its simple chemical formula (OCCO). Andrei Sanov and his colleagues at the University of
      Citation: Nature 523, 7561 (2015)
      PubDate: 2015-07-22
      DOI: 10.1038/523385c
      Issue No: Vol. 523, No. 7561 (2015)
       
  • Neuroscience: 'Mini-brain' gives autism hints
    • Pages: 385 - 385
      Abstract: Researchers have cultured stem cells from people with autism spectrum disorder (ASD) to form brain-like structures in the lab, revealing errors in neuronal development.Flora Vaccarino of Yale University in New Haven, Connecticut, and her colleagues took skin cells from four people with ASD and
      Citation: Nature 523, 7561 (2015)
      PubDate: 2015-07-22
      DOI: 10.1038/523385d
      Issue No: Vol. 523, No. 7561 (2015)
       
  • Palaeontology: Oldest animal sperm spotted
    • Pages: 385 - 385
      Abstract: Cells preserved inside a 50-million-year-old fossilized worm cocoon represent the oldest animal sperm ever found.Because of their delicate nature, sperm cells are rarely found in fossils. But Benjamin Bomfleur at the Swedish Museum of Natural History in Stockholm and his colleagues spotted the sperm
      Citation: Nature 523, 7561 (2015)
      PubDate: 2015-07-22
      DOI: 10.1038/523385e
      Issue No: Vol. 523, No. 7561 (2015)
       
  • Evolution: Hands hold clues to primate evolution
    • Pages: 385 - 385
      Abstract: Human hand proportions are similar to those of some of our ancestors, suggesting that our hands did not evolve to serve the unique needs of modern humans.Sergio Almécija at George Washington University in Washington DC and his colleagues analysed hand-length proportions in humans, apes
      Citation: Nature 523, 7561 (2015)
      PubDate: 2015-07-22
      DOI: 10.1038/523385b
      Issue No: Vol. 523, No. 7561 (2015)
       
  • Materials: Nanocrystals seen in solution in 3D
    • Pages: 385 - 385
      Abstract: Researchers have determined the 3D structure of individual nanoparticles in a solution with near-atomic resolution.Paul Alivisatos at the University of California, Berkeley, and his colleagues used graphene (sheets of single carbon atoms) to protect a solution containing platinum nanocrystals from the vacuum conditions of
      Citation: Nature 523, 7561 (2015)
      PubDate: 2015-07-22
      DOI: 10.1038/523385a
      Issue No: Vol. 523, No. 7561 (2015)
       
  • Collaborate and listen to reproduce research
    • Authors: Chris Woolston
      Pages: 385 - 385
      Abstract: Better communication between labs may resolve many reproducibility problems, according to report.
      Citation: Nature 523, 7561 (2015)
      PubDate: 2015-07-16
      DOI: 10.1038/523385f
      Issue No: Vol. 523, No. 7561 (2015)
       
  • Vibrant Pluto stuns scientists
    • Authors: Alexandra Witze
      Pages: 389 - 390
      Abstract: Mission seeking clues to early Solar System finds a world made anew.
      Citation: Nature 523, 7561 (2015)
      PubDate: 2015-07-21
      DOI: 10.1038/523389a
      Issue No: Vol. 523, No. 7561 (2015)
       
  • US tailored-medicine project aims for ethnic balance
    • Authors: Sara Reardon
      Pages: 391 - 392
      Abstract: Massive study seeks to succeed where others failed, but faces tight deadline and questions about strategy.
      Citation: Nature 523, 7561 (2015)
      PubDate: 2015-07-21
      DOI: 10.1038/523391a
      Issue No: Vol. 523, No. 7561 (2015)
       
  • French teenager healthy 12 years after ceasing HIV treatment
    • Authors: Erika Check Hayden
      Pages: 391 - 392
      Abstract: Eighteen-year-old joins small group of patients who can control the virus after discontinuing drugs.
      Citation: Nature 523, 7561 (2015)
      PubDate: 2015-07-20
      DOI: 10.1038/nature.2015.17951
      Issue No: Vol. 523, No. 7561 (2015)
       
  • Search for extraterrestrial intelligence gets a $100-million boost
    • Authors: Zeeya Merali
      Pages: 392 - 393
      Abstract: Russian billionaire Yuri Milner announces most comprehensive hunt for alien life.
      Citation: Nature 523, 7561 (2015)
      PubDate: 2015-07-20
      DOI: 10.1038/nature.2015.18016
      Issue No: Vol. 523, No. 7561 (2015)
       
  • UK shifts its space-science strategy
    • Authors: Elizabeth Gibney
      Pages: 394 - 395
      Abstract: Research surrounding human spaceflight is booming.
      Citation: Nature 523, 7561 (2015)
      PubDate: 2015-07-22
      DOI: 10.1038/523394a
      Issue No: Vol. 523, No. 7561 (2015)
       
  • Iranian researchers welcome nuclear deal
    • Authors: Davide Castelvecchi
      Pages: 394 - 394
      Abstract: Lifted sanctions could boost international scientific collaboration.
      Citation: Nature 523, 7561 (2015)
      PubDate: 2015-07-15
      DOI: 10.1038/nature.2015.17984
      Issue No: Vol. 523, No. 7561 (2015)
       
  • Quest for climate-proof farms
    • Authors: Quirin Schiermeier
      Pages: 396 - 397
      Abstract: Climate change is a major threat to food production, so researchers are working with farmers to make agriculture more resilient.
      Citation: Nature 523, 7561 (2015)
      PubDate: 2015-07-21
      DOI: 10.1038/523396a
      Issue No: Vol. 523, No. 7561 (2015)
       
  • A cellular puzzle: The weird and wonderful architecture of RNA
    • Authors: Elie Dolgin
      Pages: 398 - 399
      Abstract: Cells contain an ocean of twisting and turning RNA molecules. Now researchers are working out the structures — and how important they could be.
      Citation: Nature 523, 7561 (2015)
      PubDate: 2015-07-22
      DOI: 10.1038/523398a
      Issue No: Vol. 523, No. 7561 (2015)
       
  • Conservation: Stop misuse of biodiversity offsets
    • Authors: Martine Maron, Ascelin Gordon, Brendan G. Mackey, Hugh P. Possingham, James E. M. Watson
      Pages: 401 - 403
      Abstract: Governments should not meet existing conservation targets using the compensation that developers pay for damaging biodiversity, say Martine Maron and colleagues.
      Citation: Nature 523, 7561 (2015)
      PubDate: 2015-07-22
      DOI: 10.1038/523401a
      Issue No: Vol. 523, No. 7561 (2015)
       
  • Environmental science: Agree on biodiversity metrics to track from space
    • Authors: Andrew K. Skidmore, Nathalie Pettorelli, Nicholas C. Coops, Gary N. Geller, Matthew Hansen, Richard Lucas, Caspar A. Mücher, Brian O'Connor, Marc Paganini, Henrique Miguel Pereira, Michael E. Schaepman, Woody Turner, Tiejun Wang, Martin Wegmann
      Pages: 403 - 405
      Abstract: Ecologists and space agencies must forge a global monitoring strategy, say Andrew K. Skidmore, Nathalie Pettorelli and colleagues.
      Citation: Nature 523, 7561 (2015)
      PubDate: 2015-07-22
      DOI: 10.1038/523403a
      Issue No: Vol. 523, No. 7561 (2015)
       
  • Mathematics: The mercurial mathematician
    • Authors: Michael Harris
      Pages: 406 - 407
      Abstract: Michael Harris relishes a biography of the playful, complicated group theorist John Horton Conway.
      Citation: Nature 523, 7561 (2015)
      PubDate: 2015-07-22
      DOI: 10.1038/523406a
      Issue No: Vol. 523, No. 7561 (2015)
       
  • Science fiction: Star-flight dreaming
    • Authors: Gregory Benford
      Pages: 407 - 407
      Abstract: Gregory Benford probes Kim Stanley Robinson's politics-drenched tale of interstellar travel.
      Citation: Nature 523, 7561 (2015)
      PubDate: 2015-07-22
      DOI: 10.1038/523407a
      Issue No: Vol. 523, No. 7561 (2015)
       
  • Experimental psychology: The anatomy of obedience
    • Authors: Brendan Maher
      Pages: 408 - 409
      Abstract: Brendan Maher reviews two films probing notorious US psychological experiments.
      Citation: Nature 523, 7561 (2015)
      PubDate: 2015-07-22
      DOI: 10.1038/523408a
      Issue No: Vol. 523, No. 7561 (2015)
       
  • Correction
    • Pages: 409 - 409
      Abstract: The review 'Space-rock alert' (Nature522, 418; 2015) gave an incorrect affiliation for Peter Jenniskens. He is at the SETI Institute in Mountain View, California.
      Citation: Nature 523, 7561 (2015)
      PubDate: 2015-07-22
      DOI: 10.1038/523409a
      Issue No: Vol. 523, No. 7561 (2015)
       
  • Hazardous products: Cut animal wastage in toxicology testing
    • Authors: Colin Berry
      Pages: 410 - 410
      Abstract: In my view, the questionable use of animals in toxicology studies for the regulation of devices, medicines and agrichemicals is more of a concern than the inappropriate use of animal models in research (see I. A. S.Olsson and N. H.FrancoNature523
      Citation: Nature 523, 7561 (2015)
      PubDate: 2015-07-22
      DOI: 10.1038/523410a
      Issue No: Vol. 523, No. 7561 (2015)
       
  • Trans-Pacific Partnership: Add conservation to US trade agreement
    • Authors: Maribel Rodriguez, Jacob Phelps
      Pages: 410 - 410
      Abstract: The US Senate last month fast-tracked negotiations for the Trans-Pacific Partnership (see go.nature.com/lt2eex), one of the largest free-trade agreements in history. We fear that this could inadvertently fuel the illegal wildlife trade unless strict precautionary measures are put in place.Last year saw vast
      Citation: Nature 523, 7561 (2015)
      PubDate: 2015-07-22
      DOI: 10.1038/523410b
      Issue No: Vol. 523, No. 7561 (2015)
       
  • Conservation management: Probe effects of krill fishing and climate
    • Authors: Tom Hart, Heather J. Lynch, Ron Naveen
      Pages: 410 - 410
      Abstract: Progress in establishing marine protected areas around East Antarctica and in the Ross Sea seems to have stalled, threatening to derail research and conservation in the region. We propose temporary, experimental closures of fisheries to help to disentangle the complex effects of human activities and
      Citation: Nature 523, 7561 (2015)
      PubDate: 2015-07-22
      DOI: 10.1038/523410c
      Issue No: Vol. 523, No. 7561 (2015)
       
  • Climate law: Dutch decision raises bar
    • Authors: Kai Purnhagen
      Pages: 410 - 410
      Abstract: A District Court in The Hague ruled last month that the government of the Netherlands must make more drastic cuts to its greenhouse-gas emissions (see Naturehttp://doi.org/559; 2015). Given that climate lawsuits are increasingly being brought against governments, other countries would do well
      Citation: Nature 523, 7561 (2015)
      PubDate: 2015-07-22
      DOI: 10.1038/523410d
      Issue No: Vol. 523, No. 7561 (2015)
       
  • Climate law: path paved for civil action
    • Authors: Yali Si, Herbert H. T. Prins
      Pages: 410 - 410
      Abstract: The Lancet Commission on Health and Climate Change last month concluded that climate change is a risk to public health (N.Wattset al. Lancethttp://doi.org/56b; 2015). In the same week, a Dutch court ordered the government of the Netherlands to
      Citation: Nature 523, 7561 (2015)
      PubDate: 2015-07-22
      DOI: 10.1038/523410e
      Issue No: Vol. 523, No. 7561 (2015)
       
  • Nanotechnology: Pathfinder for DNA constructs
    • Authors: Tim Liedl
      Pages: 412 - 413
      Abstract: Representations of 3D surfaces used in computer graphics have been adopted as templates in an efficient method for making nanoscale objects from DNA, lowering the barriers to applications of DNA nanotechnology. See Letter p.441
      Citation: Nature 523, 7561 (2015)
      PubDate: 2015-07-22
      DOI: 10.1038/523412a
      Issue No: Vol. 523, No. 7561 (2015)
       
  • Parasitology: CRISPR for Cryptosporidium
    • Authors: Stephen M. Beverley
      Pages: 413 - 414
      Abstract: Study of the diarrhoea-causing pathogen Cryptosporidium has been hindered by a lack of genetic-modification and culture tools. A description of genome editing and propagation methods for the parasite changes this picture. See Letter p.477
      Citation: Nature 523, 7561 (2015)
      PubDate: 2015-07-15
      DOI: 10.1038/nature14636
      Issue No: Vol. 523, No. 7561 (2015)
       
  • Genetics: Feedforward loop for diversity
    • Authors: Michael Lynch
      Pages: 414 - 416
      Abstract: DNA-sequence analysis suggests that genetic mutations arise at elevated rates in genomes harbouring high levels of heterozygosity — the state in which the two copies of a genetic region contain sequence differences. See Letter p.463
      Citation: Nature 523, 7561 (2015)
      PubDate: 2015-07-15
      DOI: 10.1038/nature14634
      Issue No: Vol. 523, No. 7561 (2015)
       
  • Computational imaging: Machine learning for 3D microscopy
    • Authors: Laura Waller, Lei Tian
      Pages: 416 - 417
      Abstract: Artificial neural networks have been combined with microscopy to visualize the 3D structure of biological cells. This could lead to solutions for difficult imaging problems, such as the multiple scattering of light.
      Citation: Nature 523, 7561 (2015)
      PubDate: 2015-07-22
      DOI: 10.1038/523416a
      Issue No: Vol. 523, No. 7561 (2015)
       
  • Organic chemistry: Natural polarity inverted
    • Authors: Fedor Romanov-Michailidis, Tomislav Rovis
      Pages: 417 - 418
      Abstract: The concept of umpolung describes the reversal of the naturally occurring electrostatic polarization of chemical groups. It has now been used to make single mirror-image isomers of nitrogen-containing molecules. See Letter p.445
      Citation: Nature 523, 7561 (2015)
      PubDate: 2015-07-22
      DOI: 10.1038/523417a
      Issue No: Vol. 523, No. 7561 (2015)
       
  • Speed cells in the medial entorhinal cortex
    • Authors: Emilio Kropff, James E. Carmichael, May-Britt Moser, Edvard I. Moser
      Pages: 419 - 424
      Abstract: Grid cells in the medial entorhinal cortex have spatial firing fields that repeat periodically in a hexagonal pattern. When animals move, activity is translated between grid cells in accordance with the animal’s displacement in the environment. For this translation to occur, grid cells must have
      Citation: Nature 523, 7561 (2015)
      PubDate: 2015-07-15
      DOI: 10.1038/nature14622
      Issue No: Vol. 523, No. 7561 (2015)
       
  • Crystal structures of a polypeptide processing and secretion transporter
    • Authors: David Yin-wei Lin, Shuo Huang, Jue Chen
      Pages: 425 - 430
      Abstract: Bacteria secrete peptides and proteins to communicate, to poison competitors, and to manipulate host cells. Among the various protein-translocation machineries, the peptidase-containing ATP-binding cassette transporters (PCATs) are appealingly simple. Each PCAT contains two peptidase domains that cleave the secretion signal from the substrate, two transmembrane
      Citation: Nature 523, 7561 (2015)
      PubDate: 2015-07-22
      DOI: 10.1038/nature14623
      Issue No: Vol. 523, No. 7561 (2015)
       
  • Antibody against early driver of neurodegeneration cis P-tau blocks brain
           injury and tauopathy
    • Authors: Asami Kondo, Koorosh Shahpasand, Rebekah Mannix, Jianhua Qiu, Juliet Moncaster, Chun-Hau Chen, Yandan Yao, Yu-Min Lin, Jane A. Driver, Yan Sun, Shuo Wei, Man-Li Luo, Onder Albayram, Pengyu Huang, Alexander Rotenberg, Akihide Ryo, Lee E. Goldstein, Alvaro Pascual-Leone, Ann C. McKee, William Meehan, Xiao Zhen Zhou, Kun Ping Lu
      Pages: 431 - 436
      Abstract: Traumatic brain injury (TBI), characterized by acute neurological dysfunction, is one of the best known environmental risk factors for chronic traumatic encephalopathy and Alzheimer’s disease, the defining pathologic features of which include tauopathy made of phosphorylated tau protein (P-tau). However, tauopathy has not been detected
      Citation: Nature 523, 7561 (2015)
      PubDate: 2015-07-15
      DOI: 10.1038/nature14658
      Issue No: Vol. 523, No. 7561 (2015)
       
  • Small-scale filament eruptions as the driver of X-ray jets in solar
           coronal holes
    • Authors: Alphonse C. Sterling, Ronald L. Moore, David A. Falconer, Mitzi Adams
      Pages: 437 - 440
      Abstract: Solar X-ray jets are thought to be made by a burst of reconnection of closed magnetic field at the base of a jet with ambient open field. In the accepted version of the ‘emerging-flux’ model, such a reconnection occurs at a plasma current sheet between the open field and the emerging closed field, and also forms a localized X-ray brightening that is usually observed at the edge of the jet’s base. Here we report high-resolution X-ray and extreme-ultraviolet observations of 20 randomly selected X-ray jets that form in coronal holes at the Sun’s poles. In each jet, contrary to the emerging-flux model, a miniature version of the filament eruptions that initiate coronal mass ejections drives the jet-producing reconnection. The X-ray bright point occurs by reconnection of the ‘legs’ of the minifilament-carrying erupting closed field, analogous to the formation of solar flares in larger-scale eruptions. Previous observations have found that some jets are driven by base-field eruptions, but only one such study, of only one jet, provisionally questioned the emerging-flux model. Our observations support the view that solar filament eruptions are formed by a fundamental explosive magnetic process that occurs on a vast range of scales, from the biggest mass ejections and flare eruptions down to X-ray jets, and perhaps even down to smaller jets that may power coronal heating. A similar scenario has previously been suggested, but was inferred from different observations and based on a different origin of the erupting minifilament.
      Citation: Nature 523, 7561 (2015)
      PubDate: 2015-07-06
      DOI: 10.1038/nature14556
      Issue No: Vol. 523, No. 7561 (2015)
       
  • DNA rendering of polyhedral meshes at the nanoscale
    • Authors: Erik Benson, Abdulmelik Mohammed, Johan Gardell, Sergej Masich, Eugen Czeizler, Pekka Orponen, Björn Högberg
      Pages: 441 - 444
      Abstract: It was suggested more than thirty years ago that Watson–Crick base pairing might be used for the rational design of nanometre-scale structures from nucleic acids. Since then, and especially since the introduction of the origami technique, DNA nanotechnology has enabled increasingly more complex structures. But although general approaches for creating DNA origami polygonal meshes and design software are available, there are still important constraints arising from DNA geometry and sense/antisense pairing, necessitating some manual adjustment during the design process. Here we present a general method of folding arbitrary polygonal digital meshes in DNA that readily produces structures that would be very difficult to realize using previous approaches. The design process is highly automated, using a routeing algorithm based on graph theory and a relaxation simulation that traces scaffold strands through the target structures. Moreover, unlike conventional origami designs built from close-packed helices, our structures have a more open conformation with one helix per edge and are therefore stable under the ionic conditions usually used in biological assays.
      Citation: Nature 523, 7561 (2015)
      PubDate: 2015-07-22
      DOI: 10.1038/nature14586
      Issue No: Vol. 523, No. 7561 (2015)
       
  • Catalytic asymmetric umpolung reactions of imines
    • Authors: Yongwei Wu, Lin Hu, Zhe Li, Li Deng
      Pages: 445 - 450
      Abstract: The carbon–nitrogen double bonds in imines are fundamentally important functional groups in organic chemistry. This is largely due to the fact that imines act as electrophiles towards carbon nucleophiles in reactions that form carbon–carbon bonds, thereby serving as one of the most widely used precursors for the formation of amines in both synthetic and biosynthetic settings. If the carbon atom of the imine could be rendered electron-rich, the imine could react as a nucleophile instead of as an electrophile. Such a reversal in the electronic characteristics of the imine functionality would facilitate the development of new chemical transformations that convert imines into amines via carbon–carbon bond-forming reactions with carbon electrophiles, thereby creating new opportunities for the efficient synthesis of amines. The development of asymmetric umpolung reactions of imines (in which the imines act as nucleophiles) remains uncharted territory, in spite of the far-reaching impact such reactions would have in organic synthesis. Here we report the discovery and development of new chiral phase-transfer catalysts that promote the highly efficient asymmetric umpolung reactions of imines with the carbon electrophile enals. These catalysts mediate the deprotonation of imines and direct the 2-azaallyl anions thus formed to react with enals in a highly chemoselective, regioselective, diastereoselective and enantioselective fashion. The reaction tolerates a broad range of imines and enals, and can be carried out in high yield with as little as 0.01 mole per cent catalyst with a moisture- and air-tolerant operational protocol. These umpolung reactions provide a conceptually new and practical approach to chiral amino compounds.
      Citation: Nature 523, 7561 (2015)
      PubDate: 2015-07-22
      DOI: 10.1038/nature14617
      Issue No: Vol. 523, No. 7561 (2015)
       
  • Statistical analysis of iron geochemical data suggests limited late
           Proterozoic oxygenation
    • Authors: Erik A. Sperling, Charles J. Wolock, Alex S. Morgan, Benjamin C. Gill, Marcus Kunzmann, Galen P. Halverson, Francis A. Macdonald, Andrew H. Knoll, David T. Johnston
      Pages: 451 - 454
      Abstract: Sedimentary rocks deposited across the Proterozoic–Phanerozoic transition record extreme climate fluctuations, a potential rise in atmospheric oxygen or re-organization of the seafloor redox landscape, and the initial diversification of animals. It is widely assumed that the inferred redox change facilitated the observed trends in biodiversity. Establishing this palaeoenvironmental context, however, requires that changes in marine redox structure be tracked by means of geochemical proxies and translated into estimates of atmospheric oxygen. Iron-based proxies are among the most effective tools for tracking the redox chemistry of ancient oceans. These proxies are inherently local, but have global implications when analysed collectively and statistically. Here we analyse about 4,700 iron-speciation measurements from shales 2,300 to 360 million years old. Our statistical analyses suggest that subsurface water masses in mid-Proterozoic oceans were predominantly anoxic and ferruginous (depleted in dissolved oxygen and iron-bearing), but with a tendency towards euxinia (sulfide-bearing) that is not observed in the Neoproterozoic era. Analyses further indicate that early animals did not experience appreciable benthic sulfide stress. Finally, unlike proxies based on redox-sensitive trace-metal abundances, iron geochemical data do not show a statistically significant change in oxygen content through the Ediacaran and Cambrian periods, sharply constraining the magnitude of the end-Proterozoic oxygen increase. Indeed, this re-analysis of trace-metal data is consistent with oxygenation continuing well into the Palaeozoic era. Therefore, if changing redox conditions facilitated animal diversification, it did so through a limited rise in oxygen past critical functional and ecological thresholds, as is seen in modern oxygen minimum zone benthic animal communities.
      Citation: Nature 523, 7561 (2015)
      PubDate: 2015-07-22
      DOI: 10.1038/nature14589
      Issue No: Vol. 523, No. 7561 (2015)
       
  • The ancestry and affiliations of Kennewick Man
    • Authors: Morten Rasmussen, Martin Sikora, Anders Albrechtsen, Thorfinn Sand Korneliussen, J. Víctor Moreno-Mayar, G. David Poznik, Christoph P. E. Zollikofer, Marcia S. Ponce de León, Morten E. Allentoft, Ida Moltke, Hákon Jónsson, Cristina Valdiosera, Ripan S. Malhi, Ludovic Orlando, Carlos D. Bustamante, Thomas W. Stafford, David J. Meltzer, Rasmus Nielsen, Eske Willerslev
      Pages: 455 - 458
      Abstract: Kennewick Man, referred to as the Ancient One by Native Americans, is a male human skeleton discovered in Washington state (USA) in 1996 and initially radiocarbon dated to 8,340–9,200 calibrated years before present (bp). His population affinities have been the subject of scientific debate and legal controversy. Based on an initial study of cranial morphology it was asserted that Kennewick Man was neither Native American nor closely related to the claimant Plateau tribes of the Pacific Northwest, who claimed ancestral relationship and requested repatriation under the Native American Graves Protection and Repatriation Act (NAGPRA). The morphological analysis was important to judicial decisions that Kennewick Man was not Native American and that therefore NAGPRA did not apply. Instead of repatriation, additional studies of the remains were permitted. Subsequent craniometric analysis affirmed Kennewick Man to be more closely related to circumpacific groups such as the Ainu and Polynesians than he is to modern Native Americans. In order to resolve Kennewick Man’s ancestry and affiliations, we have sequenced his genome to ∼1× coverage and compared it to worldwide genomic data including for the Ainu and Polynesians. We find that Kennewick Man is closer to modern Native Americans than to any other population worldwide. Among the Native American groups for whom genome-wide data are available for comparison, several seem to be descended from a population closely related to that of Kennewick Man, including the Confederated Tribes of the Colville Reservation (Colville), one of the five tribes claiming Kennewick Man. We revisit the cranial analyses and find that, as opposed to genome-wide comparisons, it is not possible on that basis to affiliate Kennewick Man to specific contemporary groups. We therefore conclude based on genetic comparisons that Kennewick Man shows continuity with Native North Americans over at least the last eight millennia.
      Citation: Nature 523, 7561 (2015)
      PubDate: 2015-06-18
      DOI: 10.1038/nature14625
      Issue No: Vol. 523, No. 7561 (2015)
       
  • Directional dominance on stature and cognition in diverse human
           populations
    • Authors: Peter K. Joshi, Tonu Esko, Hannele Mattsson, Niina Eklund, Ilaria Gandin, Teresa Nutile, Anne U. Jackson, Claudia Schurmann, Albert V. Smith, Weihua Zhang, Yukinori Okada, Alena Stančáková, Jessica D. Faul, Wei Zhao, Traci M. Bartz, Maria Pina Concas, Nora Franceschini, Stefan Enroth, Veronique Vitart, Stella Trompet, Xiuqing Guo, Daniel I. Chasman, Jeffrey R. O'Connel, Tanguy Corre, Suraj S. Nongmaithem, Yuning Chen, Massimo Mangino, Daniela Ruggiero, Michela Traglia, Aliki-Eleni Farmaki, Tim Kacprowski, Andrew Bjonnes, Ashley van der Spek, Ying Wu, Anil K. Giri, Lisa R. Yanek, Lihua Wang, Edith Hofer, Cornelius A. Rietveld, Olga McLeod, Marilyn C. Cornelis, Cristian Pattaro, Niek Verweij, Clemens Baumbach, Abdel Abdellaoui, Helen R. Warren, Dragana Vuckovic, Hao Mei, Claude Bouchard, John R. B. Perry, Stefania Cappellani, Saira S. Mirza, Miles C. Benton, Ulrich Broeckel, Sarah E. Medland, Penelope A. Lind, Giovanni Malerba, Alexander Drong, Loic Yengo, Lawrence F. Bielak, Degui Zhi, Peter J. van der Most, Daniel Shriner, Reedik Mägi, Gibran Hemani, Tugce Karaderi, Zhaoming Wang, Tian Liu, Ilja Demuth, Jing Hua Zhao, Weihua Meng, Lazaros Lataniotis, Sander W. van der Laan, Jonathan P. Bradfield, Andrew R. Wood, Amelie Bonnefond, Tarunveer S. Ahluwalia, Leanne M. Hall, Erika Salvi, Seyhan Yazar, Lisbeth Carstensen, Hugoline G. de Haan, Mark Abney, Uzma Afzal, Matthew A. Allison, Najaf Amin, Folkert W. Asselbergs, Stephan J. L. Bakker, R. Graham Barr, Sebastian E. Baumeister, Daniel J. Benjamin, Sven Bergmann, Eric Boerwinkle, Erwin P. Bottinger, Archie Campbell, Aravinda Chakravarti, Yingleong Chan, Stephen J. Chanock, Constance Chen, Y.-D. Ida Chen, Francis S. Collins, John Connell, Adolfo Correa, L. Adrienne Cupples, George Davey Smith, Gail Davies, Marcus Dörr, Georg Ehret, Stephen B. Ellis, Bjarke Feenstra, Mary F. Feitosa, Ian Ford, Caroline S. Fox, Timothy M. Frayling, Nele Friedrich, Frank Geller, Generation Scotland, Irina Gillham-Nasenya, Omri Gottesman, Misa Graff, Francine Grodstein, Charles Gu, Chris Haley, Christopher J. Hammond, Sarah E. Harris, Tamara B. Harris, Nicholas D. Hastie, Nancy L. Heard-Costa, Kauko Heikkilä, Lynne J. Hocking, Georg Homuth, Jouke-Jan Hottenga, Jinyan Huang, Jennifer E. Huffman, Pirro G. Hysi, M. Arfan Ikram, Erik Ingelsson, Anni Joensuu, Åsa Johansson, Pekka Jousilahti, J. Wouter Jukema, Mika Kähönen, Yoichiro Kamatani, Stavroula Kanoni, Shona M. Kerr, Nazir M. Khan, Philipp Koellinger, Heikki A. Koistinen, Manraj K. Kooner, Michiaki Kubo, Johanna Kuusisto, Jari Lahti, Lenore J. Launer, Rodney A. Lea, Benjamin Lehne, Terho Lehtimäki, David C.M. Liewald, Lars Lind, Marie Loh, Marja-Liisa Lokki, Stephanie J. London, Stephanie J. Loomis, Anu Loukola, Yingchang Lu, Thomas Lumley, Annamari Lundqvist, Satu Männistö, Pedro Marques-Vidal, Corrado Masciullo, Angela Matchan, Rasika A. Mathias, Koichi Matsuda, James B. Meigs, Christa Meisinger, Thomas Meitinger, Cristina Menni, Frank D. Mentch, Evelin Mihailov, Lili Milani, May E. Montasser, Grant W. Montgomery, Alanna Morrison, Richard H. Myers, Rajiv Nadukuru, Pau Navarro, Mari Nelis, Markku S. Nieminen, Ilja M. Nolte, George T. O'Connor, Adesola Ogunniyi, Sandosh Padmanabhan, Walter R. Palmas, James S. Pankow, Inga Patarcic, Francesca Pavani, Patricia A. Peyser, Kirsi Pietilainen, Neil Poulter, Inga Prokopenko, Sarju Ralhan, Paul Redmond, Stephen S. Rich, Harri Rissanen, Antonietta Robino, Lynda M. Rose, Richard Rose, Cinzia Sala, Babatunde Salako, Veikko Salomaa, Antti-Pekka Sarin, Richa Saxena, Helena Schmidt, Laura J. Scott, William R. Scott, Bengt Sennblad, Sudha Seshadri, Peter Sever, Smeeta Shrestha, Blair H. Smith, Jennifer A. Smith, Nicole Soranzo, Nona Sotoodehnia, Lorraine Southam, Alice V. Stanton, Maria G. Stathopoulou, Konstantin Strauch, Rona J. Strawbridge, Matthew J. Suderman, Nikhil Tandon, Sian-Tsun Tang, Kent D. Taylor, Bamidele O. Tayo, Anna Maria Töglhofer, Maciej Tomaszewski, Natalia Tšernikova, Jaakko Tuomilehto, Andre G. Uitterlinden, Dhananjay Vaidya, Astrid van Hylckama Vlieg, Jessica van Setten, Tuula Vasankari, Sailaja Vedantam, Efthymia Vlachopoulou, Diego Vozzi, Eero Vuoksimaa, Melanie Waldenberger, Erin B. Ware, William Wentworth-Shields, John B. Whitfield, Sarah Wild, Gonneke Willemsen, Chittaranjan S. Yajnik, Jie Yao, Gianluigi Zaza, Xiaofeng Zhu, Rany M. Salem, Mads Melbye, Hans Bisgaard, Nilesh J. Samani, Daniele Cusi, David A. Mackey, Richard S. Cooper, Philippe Froguel, Gerard Pasterkamp, Struan F.A. Grant, Hakon Hakonarson, Luigi Ferrucci, Robert A. Scott, Andrew D. Morris, Colin N. A. Palmer, George Dedoussis, Panos Deloukas, Lars Bertram, Ulman Lindenberger, Sonja I. Berndt, Cecilia M. Lindgren, Nicholas J. Timpson, Anke Tönjes, Patricia B. Munroe, Thorkild I. A. Sørensen, Charles N. Rotimi, Donna K. Arnett, Albertine J. Oldehinkel, Sharon L. R. Kardia, Beverley Balkau, Giovanni Gambaro, Andrew P. Morris, Johan G. Eriksson, Margie J. Wright, Nicholas G. Martin, Steven C. Hunt, John M. Starr, Ian J. Deary, Lyn R. Griffiths, Henning Tiemeier, Nicola Pirastu, Jaakko Kaprio, Nicholas J. Wareham, Louis Pérusse, James G. Wilson, Giorgia Girotto, Mark J. Caulfield, Olli Raitakari, Dorret I. Boomsma, Christian Gieger, Pim van der Harst, Andrew A. Hicks, Peter Kraft, Juha Sinisalo, Paul Knekt, Magnus Johannesson, Patrik K. E. Magnusson, Anders Hamsten, Reinhold Schmidt, Ingrid B. Borecki, Erkki Vartiainen, Diane M. Becker, Dwaipayan Bharadwaj, Karen L. Mohlke, Michael Boehnke, Cornelia M. van Duijn, Dharambir K. Sanghera, Alexander Teumer, Eleftheria Zeggini, Andres Metspalu, Paolo Gasparini, Sheila Ulivi, Carole Ober, Daniela Toniolo, Igor Rudan, David J. Porteous, Marina Ciullo, Tim D. Spector, Caroline Hayward, Josée Dupuis, Ruth J. F. Loos, Alan F. Wright, Giriraj R. Chandak, Peter Vollenweider, Alan R. Shuldiner, Paul M. Ridker, Jerome I. Rotter, Naveed Sattar, Ulf Gyllensten, Kari E. North, Mario Pirastu, Bruce M. Psaty, David R. Weir, Markku Laakso, Vilmundur Gudnason, Atsushi Takahashi, John C. Chambers, Jaspal S. Kooner, David P. Strachan, Harry Campbell, Joel N. Hirschhorn, Markus Perola, Ozren Polašek, James F. Wilson
      Pages: 459 - 462
      Abstract: Homozygosity has long been associated with rare, often devastating, Mendelian disorders, and Darwin was one of the first to recognize that inbreeding reduces evolutionary fitness. However, the effect of the more distant parental relatedness that is common in modern human populations is less well understood. Genomic data now allow us to investigate the effects of homozygosity on traits of public health importance by observing contiguous homozygous segments (runs of homozygosity), which are inferred to be homozygous along their complete length. Given the low levels of genome-wide homozygosity prevalent in most human populations, information is required on very large numbers of people to provide sufficient power. Here we use runs of homozygosity to study 16 health-related quantitative traits in 354,224 individuals from 102 cohorts, and find statistically significant associations between summed runs of homozygosity and four complex traits: height, forced expiratory lung volume in one second, general cognitive ability and educational attainment (P < 1 × 10−300, 2.1 × 10−6, 2.5 × 10−10 and 1.8 × 10−10, respectively). In each case, increased homozygosity was associated with decreased trait value, equivalent to the offspring of first cousins being 1.2 cm shorter and having 10 months’ less education. Similar effect sizes were found across four continental groups and populations with different degrees of genome-wide homozygosity, providing evidence that homozygosity, rather than confounding, directly contributes to phenotypic variance. Contrary to earlier reports in substantially smaller samples, no evidence was seen of an influence of genome-wide homozygosity on blood pressure and low density lipoprotein cholesterol, or ten other cardio-metabolic traits. Since directional dominance is predicted for traits under directional evolutionary selection, this study provides evidence that increased stature and cognitive function have been positively selected in human evolution, whereas many important risk factors for late-onset complex diseases may not have been.
      Citation: Nature 523, 7561 (2015)
      PubDate: 2015-07-01
      DOI: 10.1038/nature14618
      Issue No: Vol. 523, No. 7561 (2015)
       
  • Parent–progeny sequencing indicates higher mutation rates in
           heterozygotes
    • Authors: Sihai Yang, Long Wang, Ju Huang, Xiaohui Zhang, Yang Yuan, Jian-Qun Chen, Laurence D. Hurst, Dacheng Tian
      Pages: 463 - 467
      Abstract: Mutation rates vary within genomes, but the causes of this remain unclear. As many prior inferences rely on methods that assume an absence of selection, potentially leading to artefactual results, we call mutation events directly using a parent–offspring sequencing strategy focusing on Arabidopsis and using rice and honey bee for replication. Here we show that mutation rates are higher in heterozygotes and in proximity to crossover events. A correlation between recombination rate and intraspecific diversity is in part owing to a higher mutation rate in domains of high recombination/diversity. Implicating diversity per se as a cause, we find an ∼3.5-fold higher mutation rate in heterozygotes than in homozygotes, with mutations occurring in closer proximity to heterozygous sites than expected by chance. In a genome that is a patchwork of heterozygous and homozygous domains, mutations occur disproportionately more often in the heterozygous domains. If segregating mutations predispose to a higher local mutation rate, clusters of genes dominantly under purifying selection (more commonly homozygous) and under balancing selection (more commonly heterozygous), might have low and high mutation rates, respectively. Our results are consistent with this, there being a ten times higher mutation rate in pathogen resistance genes, expected to be under positive or balancing selection. Consequently, we do not necessarily need to evoke extremely weak selection on the mutation rate to explain why mutational hot and cold spots might correspond to regions under positive/balancing and purifying selection, respectively.
      Citation: Nature 523, 7561 (2015)
      PubDate: 2015-07-15
      DOI: 10.1038/nature14649
      Issue No: Vol. 523, No. 7561 (2015)
       
  • Epoxyeicosatrienoic acids enhance embryonic haematopoiesis and adult
           marrow engraftment
    • Authors: Pulin Li, Jamie L. Lahvic, Vera Binder, Emily K. Pugach, Elizabeth B. Riley, Owen J. Tamplin, Dipak Panigrahy, Teresa V. Bowman, Francesca G. Barrett, Garrett C. Heffner, Shannon McKinney-Freeman, Thorsten M. Schlaeger, George Q. Daley, Darryl C. Zeldin, Leonard I. Zon
      Pages: 468 - 471
      Abstract: Haematopoietic stem and progenitor cell (HSPC) transplant is a widely used treatment for life-threatening conditions such as leukaemia; however, the molecular mechanisms regulating HSPC engraftment of the recipient niche remain incompletely understood. Here we develop a competitive HSPC transplant method in adult zebrafish, using in vivo imaging as a non-invasive readout. We use this system to conduct a chemical screen, and identify epoxyeicosatrienoic acids (EETs) as a family of lipids that enhance HSPC engraftment. The pro-haematopoietic effects of EETs were conserved in the developing zebrafish embryo, where 11,12-EET promoted HSPC specification by activating a unique activator protein 1 (AP-1) and runx1 transcription program autonomous to the haemogenic endothelium. This effect required the activation of the phosphatidylinositol-3-OH kinase (PI(3)K) pathway, specifically PI(3)Kγ. In adult HSPCs, 11,12-EET induced transcriptional programs, including AP-1 activation, which modulate several cellular processes, such as migration, to promote engraftment. Furthermore, we demonstrate that the EET effects on enhancing HSPC homing and engraftment are conserved in mammals. Our study establishes a new method to explore the molecular mechanisms of HSPC engraftment, and discovers a previously unrecognized, evolutionarily conserved pathway regulating multiple haematopoietic generation and regeneration processes. EETs may have clinical application in marrow or cord blood transplantation.
      Citation: Nature 523, 7561 (2015)
      PubDate: 2015-07-22
      DOI: 10.1038/nature14569
      Issue No: Vol. 523, No. 7561 (2015)
       
  • Redox rhythm reinforces the circadian clock to gate immune response
    • Authors: Mian Zhou, Wei Wang, Sargis Karapetyan, Musoki Mwimba, Jorge Marqués, Nicolas E. Buchler, Xinnian Dong
      Pages: 472 - 476
      Abstract: Recent studies have shown that in addition to the transcriptional circadian clock, many organisms, including Arabidopsis, have a circadian redox rhythm driven by the organism’s metabolic activities. It has been hypothesized that the redox rhythm is linked to the circadian clock, but the mechanism and the biological significance of this link have only begun to be investigated. Here we report that the master immune regulator NPR1 (non-expressor of pathogenesis-related gene 1) of Arabidopsis is a sensor of the plant’s redox state and regulates transcription of core circadian clock genes even in the absence of pathogen challenge. Surprisingly, acute perturbation in the redox status triggered by the immune signal salicylic acid does not compromise the circadian clock but rather leads to its reinforcement. Mathematical modelling and subsequent experiments show that NPR1 reinforces the circadian clock without changing the period by regulating both the morning and the evening clock genes. This balanced network architecture helps plants gate their immune responses towards the morning and minimize costs on growth at night. Our study demonstrates how a sensitive redox rhythm interacts with a robust circadian clock to ensure proper responsiveness to environmental stimuli without compromising fitness of the organism.
      Citation: Nature 523, 7561 (2015)
      PubDate: 2015-06-22
      DOI: 10.1038/nature14449
      Issue No: Vol. 523, No. 7561 (2015)
       
  • Genetic modification of the diarrhoeal pathogen Cryptosporidium parvum
    • Authors: Sumiti Vinayak, Mattie C. Pawlowic, Adam Sateriale, Carrie F. Brooks, Caleb J. Studstill, Yael Bar-Peled, Michael J. Cipriano, Boris Striepen
      Pages: 477 - 480
      Abstract: Recent studies into the global causes of severe diarrhoea in young children have identified the protozoan parasite Cryptosporidium as the second most important diarrhoeal pathogen after rotavirus. Diarrhoeal disease is estimated to be responsible for 10.5% of overall child mortality. Cryptosporidium is also an opportunistic pathogen in the contexts of human immunodeficiency virus (HIV)-caused AIDS and organ transplantation. There is no vaccine and only a single approved drug that provides no benefit for those in gravest danger: malnourished children and immunocompromised patients. Cryptosporidiosis drug and vaccine development is limited by the poor tractability of the parasite, which includes a lack of systems for continuous culture, facile animal models, and molecular genetic tools. Here we describe an experimental framework to genetically modify this important human pathogen. We established and optimized transfection of C. parvum sporozoites in tissue culture. To isolate stable transgenics we developed a mouse model that delivers sporozoites directly into the intestine, a Cryptosporidium clustered regularly interspaced short palindromic repeat (CRISPR)/Cas9 system, and in vivo selection for aminoglycoside resistance. We derived reporter parasites suitable for in vitro and in vivo drug screening, and we evaluated the basis of drug susceptibility by gene knockout. We anticipate that the ability to genetically engineer this parasite will be transformative for Cryptosporidium research. Genetic reporters will provide quantitative correlates for disease, cure and protection, and the role of parasite genes in these processes is now open to rigorous investigation.
      Citation: Nature 523, 7561 (2015)
      PubDate: 2015-07-15
      DOI: 10.1038/nature14651
      Issue No: Vol. 523, No. 7561 (2015)
       
  • Engineered CRISPR-Cas9 nucleases with altered PAM specificities
    • Authors: Benjamin P. Kleinstiver, Michelle S. Prew, Shengdar Q. Tsai, Ved V. Topkar, Nhu T. Nguyen, Zongli Zheng, Andrew P. W. Gonzales, Zhuyun Li, Randall T. Peterson, Jing-Ruey Joanna Yeh, Martin J. Aryee, J. Keith Joung
      Pages: 481 - 485
      Abstract: Although CRISPR-Cas9 nucleases are widely used for genome editing, the range of sequences that Cas9 can recognize is constrained by the need for a specific protospacer adjacent motif (PAM). As a result, it can often be difficult to target double-stranded breaks (DSBs) with the precision that is necessary for various genome-editing applications. The ability to engineer Cas9 derivatives with purposefully altered PAM specificities would address this limitation. Here we show that the commonly used Streptococcus pyogenes Cas9 (SpCas9) can be modified to recognize alternative PAM sequences using structural information, bacterial selection-based directed evolution, and combinatorial design. These altered PAM specificity variants enable robust editing of endogenous gene sites in zebrafish and human cells not currently targetable by wild-type SpCas9, and their genome-wide specificities are comparable to wild-type SpCas9 as judged by GUIDE-seq analysis. In addition, we identify and characterize another SpCas9 variant that exhibits improved specificity in human cells, possessing better discrimination against off-target sites with non-canonical NAG and NGA PAMs and/or mismatched spacers. We also find that two smaller-size Cas9 orthologues, Streptococcus thermophilus Cas9 (St1Cas9) and Staphylococcus aureus Cas9 (SaCas9), function efficiently in the bacterial selection systems and in human cells, suggesting that our engineering strategies could be extended to Cas9s from other species. Our findings provide broadly useful SpCas9 variants and, more importantly, establish the feasibility of engineering a wide range of Cas9s with altered and improved PAM specificities.
      Citation: Nature 523, 7561 (2015)
      PubDate: 2015-06-22
      DOI: 10.1038/nature14592
      Issue No: Vol. 523, No. 7561 (2015)
       
  • Single-cell chromatin accessibility reveals principles of regulatory
           variation
    • Authors: Jason D. Buenrostro, Beijing Wu, Ulrike M. Litzenburger, Dave Ruff, Michael L. Gonzales, Michael P. Snyder, Howard Y. Chang, William J. Greenleaf
      Pages: 486 - 490
      Abstract: Cell-to-cell variation is a universal feature of life that affects a wide range of biological phenomena, from developmental plasticity to tumour heterogeneity. Although recent advances have improved our ability to document cellular phenotypic variation, the fundamental mechanisms that generate variability from identical DNA sequences remain elusive. Here we reveal the landscape and principles of mammalian DNA regulatory variation by developing a robust method for mapping the accessible genome of individual cells by assay for transposase-accessible chromatin using sequencing (ATAC-seq) integrated into a programmable microfluidics platform. Single-cell ATAC-seq (scATAC-seq) maps from hundreds of single cells in aggregate closely resemble accessibility profiles from tens of millions of cells and provide insights into cell-to-cell variation. Accessibility variance is systematically associated with specific trans-factors and cis-elements, and we discover combinations of trans-factors associated with either induction or suppression of cell-to-cell variability. We further identify sets of trans-factors associated with cell-type-specific accessibility variance across eight cell types. Targeted perturbations of cell cycle or transcription factor signalling evoke stimulus-specific changes in this observed variability. The pattern of accessibility variation in cis across the genome recapitulates chromosome compartmentsde novo, linking single-cell accessibility variation to three-dimensional genome organization. Single-cell analysis of DNA accessibility provides new insight into cellular variation of the ‘regulome’.
      Citation: Nature 523, 7561 (2015)
      PubDate: 2015-06-17
      DOI: 10.1038/nature14590
      Issue No: Vol. 523, No. 7561 (2015)
       
  • Career advancement: Insider knowledge
    • Authors: Chris Woolston
      Pages: 491 - 493
      Abstract: Junior researchers have a lot to learn, but talking to others about their experiences will help to avert nasty surprises.
      Citation: Nature 523, 7561 (2015)
      PubDate: 2015-07-22
      DOI: 10.1038/nj7561-491a
      Issue No: Vol. 523, No. 7561 (2015)
       
  • Turning point: Mike Runge
    • Authors: Virginia Gewin
      Pages: 493 - 493
      Abstract: Designing a way to save the polar bear means learning to disagree respectfully.
      Citation: Nature 523, 7561 (2015)
      PubDate: 2015-07-22
      DOI: 10.1038/nj7561-493a
      Issue No: Vol. 523, No. 7561 (2015)
       
  • The memory of trees
    • Authors: Lynette Mejía
      Pages: 496 - 496
      Abstract: An unnatural request.
      Citation: Nature 523, 7561 (2015)
      PubDate: 2015-07-22
      DOI: 10.1038/523496a
      Issue No: Vol. 523, No. 7561 (2015)
       
 
 
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