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Journal Cover Nature
  [SJR: 21.936]   [H-I: 948]   [3891 followers]  Follow
    
   Full-text available via subscription Subscription journal
   ISSN (Print) 0028-0836 - ISSN (Online) 1476-4687
   Published by NPG Homepage  [123 journals]
  • Effects of a ketamine metabolite on synaptic NMDAR function
    • Authors: Kanzo Suzuki, Elena Nosyreva, Kevin W. Hunt, Ege T. Kavalali, Lisa M. Monteggia
      Abstract: arising from P. Zanos et al. Nature533, 481–486 (2016); doi:10.1038/nature17998Clinical data have demonstrated rapid and sustained antidepressant effects of ketamine, a noncompetitive NMDAR (N-methyl-d-aspartate receptor) antagonist. Recently, Zanos et al. claimed that the
      Citation: Nature 546, 7659 (2017)
      PubDate: 2017-06-21
      DOI: 10.1038/nature22084
      Issue No: Vol. 546, No. 7659 (2017)
       
  • Zanos et al. reply
    • Authors: Panos Zanos, Ruin Moaddel, Patrick J. Morris, Polymnia Georgiou, Jonathan Fischell, Greg I. Elmer, Manickavasagom Alkondon, Peixiong Yuan, Heather J. Pribut, Nagendra S. Singh, Katina S. S. Dossou, Yuhong Fang, Xi-Ping Huang, Cheryl L. Mayo, Edson X. Albuquerque, Scott M. Thompson, Craig J. Thomas, Carlos A. Zarate, Todd D. Gould
      Abstract: Replying to K. Suzuki et al. Nature546, http://dx.doi.org/10.1038/nature22084 (2017)In the accompanying Comment, Suzuki et al. confirmed our previous findings that the ketamine metabolite (2R,6R)-hydroxynorketamine (HNK) does not functionally inhibit the NMDAR at
      Citation: Nature 546, 7659 (2017)
      PubDate: 2017-06-21
      DOI: 10.1038/nature22085
      Issue No: Vol. 546, No. 7659 (2017)
       
  • Don’t let Europe’s open-science dream drift
    • Pages: 451 - 451
      Abstract: Now that the major players have agreed to the giant European Open Science Cloud, it’s time to get the project moving.
      Citation: Nature 546, 7659 (2017)
      PubDate: 2017-06-20
      DOI: 10.1038/546451a
      Issue No: Vol. 546, No. 7659 (2017)
       
  • Heatwaves to soar above the hot air of climate politics
    • Pages: 452 - 452
      Abstract: Future generations will fear, rather than fend for, the global environment.
      Citation: Nature 546, 7659 (2017)
      PubDate: 2017-06-20
      DOI: 10.1038/546452a
      Issue No: Vol. 546, No. 7659 (2017)
       
  • A year on, Brexit brings lessons in uncertainty
    • Authors: Jane Green
      Pages: 453 - 453
      Abstract: It is more important to understand the electorate than to make predictions about the outcome of elections, says Jane Green.
      Citation: Nature 546, 7659 (2017)
      PubDate: 2017-06-20
      DOI: 10.1038/546453a
      Issue No: Vol. 546, No. 7659 (2017)
       
  • Macron consolidates electoral victory
    • Authors: Declan Butler
      Pages: 459 - 460
      Abstract: The party of France’s recently elected president won an absolute majority in its first general elections, with an agenda that included strong support for research.
      Citation: Nature 546, 7659 (2017)
      PubDate: 2017-06-19
      DOI: 10.1038/549459a
      Issue No: Vol. 546, No. 7659 (2017)
       
  • Ancient oak's youthful genome surprises biologists
    • Authors: Heidi Ledford
      Pages: 460 - 460
      Abstract: DNA of 234-year-old tree has few mutations, giving weight to idea that plants protect their stem cells.
      Citation: Nature 546, 7659 (2017)
      PubDate: 2017-06-19
      DOI: 10.1038/546460a
      Issue No: Vol. 546, No. 7659 (2017)
       
  • Teeth tell tale of hippo’s quick spread across Africa
    • Authors: Traci Watson
      Pages: 462 - 462
      Abstract: Fossils from ancient hippo ancestor suggest that grass helped the animals to conquer a continent.
      Citation: Nature 546, 7659 (2017)
      PubDate: 2017-06-20
      DOI: 10.1038/nature.2017.22168
      Issue No: Vol. 546, No. 7659 (2017)
       
  • New concerns raised over value of genome-wide disease studies
    • Authors: Ewen Callaway
      Pages: 463 - 463
      Abstract: Large analyses dredge up 'peripheral' genetic associations that offer little biological insight, researchers say.
      Citation: Nature 546, 7659 (2017)
      PubDate: 2017-06-15
      DOI: 10.1038/nature.2017.22152
      Issue No: Vol. 546, No. 7659 (2017)
       
  • China cracks down on fake peer reviews
    • Authors: David Cyranoski
      Pages: 464 - 464
      Abstract: Funding agencies announce harsh penalties and stronger policing efforts.
      Citation: Nature 546, 7659 (2017)
      PubDate: 2017-06-20
      DOI: 10.1038/546464a
      Issue No: Vol. 546, No. 7659 (2017)
       
  • Track batteries degrading in real time
    • Authors: Liqiang Mai, Mengyu Yan, Yunlong Zhao
      Pages: 469 - 470
      Abstract: Monitor deforming electrodes to speed development of renewable-energy storage, write Liqiang Mai, Mengyu Yan and Yunlong Zhao.
      Citation: Nature 546, 7659 (2017)
      PubDate: 2017-06-21
      DOI: 10.1038/546469a
      Issue No: Vol. 546, No. 7659 (2017)
       
  • Botany: He made plants a profession
    • Authors: Jim Endersby
      Pages: 472 - 473
      Abstract: Jim Endersby revisits the legacy of trailblazing botanist Joseph Dalton Hooker.
      Citation: Nature 546, 7659 (2017)
      PubDate: 2017-06-21
      DOI: 10.1038/546472a
      Issue No: Vol. 546, No. 7659 (2017)
       
  • Consent: Data-sharing for indigenous peoples
    • Authors: Emma Kowal, Bastien Llamas, Sarah Tishkoff
      Pages: 474 - 474
      Abstract: Broad-consent models for human studies, which leave decisions on data-sharing to the researchers, may not be appropriate for work with indigenous peoples. Making the sharing of data almost impossible is also problematic. Everyone stands to benefit from responsible data-sharing innovations that can be applied more
      Citation: Nature 546, 7659 (2017)
      PubDate: 2017-06-21
      DOI: 10.1038/546474a
      Issue No: Vol. 546, No. 7659 (2017)
       
  • Philosophy: Religion's openness towards science
    • Authors: Frank W. Nicholas
      Pages: 474 - 474
      Abstract: Your Editorial suggests that Pope Francis's meeting with patients and researchers is evidence of “a new openness [of religion] towards science”, in the spirit of his 2015 encyclical Laudato si' (Nature545, 265–266;10.1038/nature.2017.219852017). This is tempered
      Citation: Nature 546, 7659 (2017)
      PubDate: 2017-06-21
      DOI: 10.1038/546474b
      Issue No: Vol. 546, No. 7659 (2017)
       
  • Counterfeit drugs: Fight fake reagents with digital tools
    • Authors: Don Gunasekera
      Pages: 474 - 474
      Abstract: Digital technologies are emerging that could be used to stop the burgeoning market in fake research reagents that are contaminating global biomedical supply chains (see Nature545, 148–150;10.1038/545148a2017).The international counterfeit-drugs market is even more lucrative. Estimates of
      Citation: Nature 546, 7659 (2017)
      PubDate: 2017-06-21
      DOI: 10.1038/546474c
      Issue No: Vol. 546, No. 7659 (2017)
       
  • Ecology: Document India's floral biodiversity
    • Authors: Kamaljit S. Bawa, R. Ganesan
      Pages: 474 - 474
      Abstract: This month's bicentenary of the birth of Joseph Dalton Hooker, one of the great botanical explorers of the nineteenth century, is a good time to highlight the urgent need to document India's remarkable biodiversity for conservation purposes (see also J.EndersbyNature546, 472
      Citation: Nature 546, 7659 (2017)
      PubDate: 2017-06-21
      DOI: 10.1038/546474d
      Issue No: Vol. 546, No. 7659 (2017)
       
  • Correction
    • Pages: 474 - 474
      Abstract: The Spotlight article 'The genetic microscope' (Nature545, S25–S27; 2017) said that Orit Rozenblatt-Rosen was an associate director at the Klarman Cell Observatory. In fact, she is the scientific director there.
      Citation: Nature 546, 7659 (2017)
      PubDate: 2017-06-21
      DOI: 10.1038/546474e
      Issue No: Vol. 546, No. 7659 (2017)
       
  • Vision: These retinas are made for walkin'
    • Authors: Jonathan B. Demb, Damon A. Clark
      Pages: 476 - 477
      Abstract: Measurements of the activity of neurons called direction-selective ganglion cells in the mouse retina explain how visual motion encoded by the eye maps onto body movements such as walking. See Article p.492
      Citation: Nature 546, 7659 (2017)
      PubDate: 2017-06-07
      DOI: 10.1038/nature22505
      Issue No: Vol. 546, No. 7659 (2017)
       
  • Particle physics: No sign of asymmetry in the strong force
    • Authors: Alexandru Florin Dobrin
      Pages: 477 - 479
      Abstract: The strong force binds the constituents of nuclei together. Differences between the force's fundamental interactions and their mirror images were thought to have been observed in heavy-ion collisions, but new data challenge this picture.
      Citation: Nature 546, 7659 (2017)
      PubDate: 2017-06-14
      DOI: 10.1038/nature23086
      Issue No: Vol. 546, No. 7659 (2017)
       
  • 50 & 100 Years Ago
    • Pages: 478 - 478
      Abstract: 50 Years AgoIndividual plants of the amphibious buttercup species Ranunculus flabellaris Raf. are known to produce leaves of differing morphologies in response to different environments. Leaves produced in the aquatic phase are highly dissected, while terrestrially produced leaves are less dissected or simply
      Citation: Nature 546, 7659 (2017)
      PubDate: 2017-06-21
      DOI: 10.1038/546478a
      Issue No: Vol. 546, No. 7659 (2017)
       
  • Bacterial pathogens: A spoonful of sugar could be the medicine
    • Authors: Hea-Jin Jung, Eric G. Pamer
      Pages: 479 - 480
      Abstract: Pili are filamentous bacterial structures that promote adhesion to host cells. It emerges that a small molecule that inhibits this adhesion can prevent colonization of the mouse gut by a pathogenic bacterium. See Letter p.528
      Citation: Nature 546, 7659 (2017)
      PubDate: 2017-06-14
      DOI: 10.1038/nature23084
      Issue No: Vol. 546, No. 7659 (2017)
       
  • Genomics: The feline line
    • Authors: Luíseach Nic Eoin
      Pages: 480 - 480
      Abstract: A study of ancient cat DNA that uses samples from different times and from around the world provides insights into the spread and evolution of these enigmatic creatures. Writing in Nature Ecology & Evolution, Ottoni et al. report their investigation of more than
      Citation: Nature 546, 7659 (2017)
      PubDate: 2017-06-21
      DOI: 10.1038/546480a
      Issue No: Vol. 546, No. 7659 (2017)
       
  • Quantum physics: Interactions propel a magnetic dance
    • Authors: Lindsay J. LeBlanc
      Pages: 481 - 482
      Abstract: A combination of leading-edge techniques has enabled interaction-induced magnetic motion to be observed for pairs of ultracold atoms — a breakthrough in the development of models of complex quantum behaviour. See Letter p.519
      Citation: Nature 546, 7659 (2017)
      PubDate: 2017-06-21
      DOI: 10.1038/546481a
      Issue No: Vol. 546, No. 7659 (2017)
       
  • Neuroinflammation: Synapses pruned in lupus
    • Authors: Sarah McGlasson, David Hunt
      Pages: 482 - 483
      Abstract: Lupus is an autoimmune disease that can cause brain dysfunction. Studies in mouse models of lupus find that interferon proteins can cause the brain's immune cells to trim the synaptic connections between neurons. See Letter p.539
      Citation: Nature 546, 7659 (2017)
      PubDate: 2017-06-14
      DOI: 10.1038/nature23087
      Issue No: Vol. 546, No. 7659 (2017)
       
  • Climate science: Clouds unfazed by haze
    • Authors: Bjorn Stevens
      Pages: 483 - 484
      Abstract: The extent to which aerosols affect climate is highly uncertain. Observations of clouds interacting with aerosols from a volcanic eruption suggest that the effect is much smaller than was once feared. See Article p.485
      Citation: Nature 546, 7659 (2017)
      PubDate: 2017-06-21
      DOI: 10.1038/546483a
      Issue No: Vol. 546, No. 7659 (2017)
       
  • Strong constraints on aerosol–cloud interactions from volcanic
           eruptions
    • Authors: Florent F. Malavelle, Jim M. Haywood, Andy Jones, Andrew Gettelman, Lieven Clarisse, Sophie Bauduin, Richard P. Allan, Inger Helene H. Karset, Jón Egill Kristjánsson, Lazaros Oreopoulos, Nayeong Cho, Dongmin Lee, Nicolas Bellouin, Olivier Boucher, Daniel P. Grosvenor, Ken S. Carslaw, Sandip Dhomse, Graham W. Mann, Anja Schmidt, Hugh Coe, Margaret E. Hartley, Mohit Dalvi, Adrian A. Hill, Ben T. Johnson, Colin E. Johnson, Jeff R. Knight, Fiona M. O’Connor, Daniel G. Partridge, Philip Stier, Gunnar Myhre, Steven Platnick, Graeme L. Stephens, Hanii Takahashi, Thorvaldur Thordarson
      Pages: 485 - 491
      Abstract: Aerosols have a potentially large effect on climate, particularly through their interactions with clouds, but the magnitude of this effect is highly uncertain. Large volcanic eruptions produce sulfur dioxide, which in turn produces aerosols; these eruptions thus represent a natural experiment through which to quantify
      Citation: Nature 546, 7659 (2017)
      PubDate: 2017-06-22
      DOI: 10.1038/nature22974
      Issue No: Vol. 546, No. 7659 (2017)
       
  • A retinal code for motion along the gravitational and body axes
    • Authors: Shai Sabbah, John A. Gemmer, Ananya Bhatia-Lin, Gabrielle Manoff, Gabriel Castro, Jesse K. Siegel, Nathan Jeffery, David M. Berson
      Pages: 492 - 497
      Abstract: Self-motion triggers complementary visual and vestibular reflexes supporting image-stabilization and balance. Translation through space produces one global pattern of retinal image motion (optic flow), rotation another. We examined the direction preferences of direction-sensitive ganglion cells (DSGCs) in flattened mouse retinas in vitro. Here we
      Citation: Nature 546, 7659 (2017)
      PubDate: 2017-06-07
      DOI: 10.1038/nature22818
      Issue No: Vol. 546, No. 7659 (2017)
       
  • Exosomes facilitate therapeutic targeting of oncogenic KRAS in pancreatic
           cancer
    • Authors: Sushrut Kamerkar, Valerie S. LeBleu, Hikaru Sugimoto, Sujuan Yang, Carolina F. Ruivo, Sonia A. Melo, J. Jack Lee, Raghu Kalluri
      Pages: 498 - 503
      Abstract: The mutant form of the GTPase KRAS is a key driver of pancreatic cancer but remains a challenging therapeutic target. Exosomes are extracellular vesicles generated by all cells, and are naturally present in the blood. Here we show that enhanced retention of exosomes, compared to
      Citation: Nature 546, 7659 (2017)
      PubDate: 2017-06-07
      DOI: 10.1038/nature22341
      Issue No: Vol. 546, No. 7659 (2017)
       
  • Structure of the human multidrug transporter ABCG2
    • Authors: Nicholas M. I. Taylor, Ioannis Manolaridis, Scott M. Jackson, Julia Kowal, Henning Stahlberg, Kaspar P. Locher
      Pages: 504 - 509
      Abstract: ABCG2 is a constitutively expressed ATP-binding cassette (ABC) transporter that protects many tissues against xenobiotic molecules. Its activity affects the pharmacokinetics of commonly used drugs and limits the delivery of therapeutics into tumour cells, thus contributing to multidrug resistance. Here we present the structure of
      Citation: Nature 546, 7659 (2017)
      PubDate: 2017-05-29
      DOI: 10.1038/nature22345
      Issue No: Vol. 546, No. 7659 (2017)
       
  • A massive, dead disk galaxy in the early Universe
    • Authors: Sune Toft, Johannes Zabl, Johan Richard, Anna Gallazzi, Stefano Zibetti, Moire Prescott, Claudio Grillo, Allison W. S. Man, Nicholas Y. Lee, Carlos Gómez-Guijarro, Mikkel Stockmann, Georgios Magdis, Charles L. Steinhardt
      Pages: 510 - 513
      Abstract: At redshift z = 2, when the Universe was just three billion years old, half of the most massive galaxies were extremely compact and had already exhausted their fuel for star formation. It is believed that they were formed in intense nuclear starbursts and that they ultimately grew into the most massive local elliptical galaxies seen today, through mergers with minor companions, but validating this picture requires higher-resolution observations of their centres than is currently possible. Magnification from gravitational lensing offers an opportunity to resolve the inner regions of galaxies. Here we report an analysis of the stellar populations and kinematics of a lensed z = 2.1478 compact galaxy, which—surprisingly—turns out to be a fast-spinning, rotationally supported disk galaxy. Its stars must have formed in a disk, rather than in a merger-driven nuclear starburst. The galaxy was probably fed by streams of cold gas, which were able to penetrate the hot halo gas until they were cut off by shock heating from the dark matter halo. This result confirms previous indirect indications that the first galaxies to cease star formation must have gone through major changes not just in their structure, but also in their kinematics, to evolve into present-day elliptical galaxies.
      Citation: Nature 546, 7659 (2017)
      PubDate: 2017-06-21
      DOI: 10.1038/nature22388
      Issue No: Vol. 546, No. 7659 (2017)
       
  • A giant planet undergoing extreme-ultraviolet irradiation by its hot
           massive-star host
    • Authors: B. Scott Gaudi, Keivan G. Stassun, Karen A. Collins, Thomas G. Beatty, George Zhou, David W. Latham, Allyson Bieryla, Jason D. Eastman, Robert J. Siverd, Justin R. Crepp, Erica J. Gonzales, Daniel J. Stevens, Lars A. Buchhave, Joshua Pepper, Marshall C. Johnson, Knicole D. Colon, Eric L. N. Jensen, Joseph E. Rodriguez, Valerio Bozza, Sebastiano Calchi Novati, Giuseppe D’Ago, Mary T. Dumont, Tyler Ellis, Clement Gaillard, Hannah Jang-Condell, David H. Kasper, Akihiko Fukui, Joao Gregorio, Ayaka Ito, John F. Kielkopf, Mark Manner, Kyle Matt, Norio Narita, Thomas E. Oberst, Phillip A. Reed, Gaetano Scarpetta, Denice C. Stephens, Rex R. Yeigh, Roberto Zambelli, B. J. Fulton, Andrew W. Howard, David J. James, Matthew Penny, Daniel Bayliss, Ivan A. Curtis, D. L. DePoy, Gilbert A. Esquerdo, Andrew Gould, Michael D. Joner, Rudolf B. Kuhn, Jonathan Labadie-Bartz, Michael B. Lund, Jennifer L. Marshall, Kim K. McLeod, Richard W. Pogge, Howard Relles, Christopher Stockdale, T. G. Tan, Mark Trueblood, Patricia Trueblood
      Pages: 514 - 518
      Abstract: The amount of ultraviolet irradiation and ablation experienced by a planet depends strongly on the temperature of its host star. Of the thousands of extrasolar planets now known, only six have been found that transit hot, A-type stars (with temperatures of 7,300–10,000 kelvin), and no planets are known to transit the even hotter B-type stars. For example, WASP-33 is an A-type star with a temperature of about 7,430 kelvin, which hosts the hottest known transiting planet, WASP-33b (ref. 1); the planet is itself as hot as a red dwarf star of type M (ref. 2). WASP-33b displays a large heat differential between its dayside and nightside, and is highly inflated–traits that have been linked to high insolation. However, even at the temperature of its dayside, its atmosphere probably resembles the molecule-dominated atmospheres of other planets and, given the level of ultraviolet irradiation it experiences, its atmosphere is unlikely to be substantially ablated over the lifetime of its star. Here we report observations of the bright star HD 195689 (also known as KELT-9), which reveal a close-in (orbital period of about 1.48 days) transiting giant planet, KELT-9b. At approximately 10,170 kelvin, the host star is at the dividing line between stars of type A and B, and we measure the dayside temperature of KELT-9b to be about 4,600 kelvin. This is as hot as stars of stellar type K4 (ref. 5). The molecules in K stars are entirely dissociated, and so the primary sources of opacity in the dayside atmosphere of KELT-9b are probably atomic metals. Furthermore, KELT-9b receives 700 times more extreme-ultraviolet radiation (that is, with wavelengths shorter than 91.2 nanometres) than WASP-33b, leading to a predicted range of mass-loss rates that could leave the planet largely stripped of its envelope during the main-sequence lifetime of the host star.
      Citation: Nature 546, 7659 (2017)
      PubDate: 2017-06-05
      DOI: 10.1038/nature22392
      Issue No: Vol. 546, No. 7659 (2017)
       
  • Microscopy of the interacting Harper–Hofstadter model in the
           two-body limit
    • Authors: M. Eric Tai, Alexander Lukin, Matthew Rispoli, Robert Schittko, Tim Menke, Dan Borgnia, Philipp M. Preiss, Fabian Grusdt, Adam M. Kaufman, Markus Greiner
      Pages: 519 - 523
      Abstract: The interplay between magnetic fields and interacting particles can lead to exotic phases of matter that exhibit topological order and high degrees of spatial entanglement. Although these phases were discovered in a solid-state setting, recent innovations in systems of ultracold neutral atoms—uncharged atoms that do not naturally experience a Lorentz force—allow the synthesis of artificial magnetic, or gauge, fields. This experimental platform holds promise for exploring exotic physics in fractional quantum Hall systems, owing to the microscopic control and precision that is achievable in cold-atom systems. However, so far these experiments have mostly explored the regime of weak interactions, which precludes access to correlated many-body states. Here, through microscopic atomic control and detection, we demonstrate the controlled incorporation of strong interactions into a two-body system with a chiral band structure. We observe and explain the way in which interparticle interactions induce chirality in the propagation dynamics of particles in a ladder-like, real-space lattice governed by the interacting Harper–Hofstadter model, which describes lattice-confined, coherently mobile particles in the presence of a magnetic field. We use a bottom-up strategy to prepare interacting chiral quantum states, thus circumventing the challenges of a top-down approach that begins with a many-body system, the size of which can hinder the preparation of controlled states. Our experimental platform combines all of the necessary components for investigating highly entangled topological states, and our observations provide a benchmark for future experiments in the fractional quantum Hall regime.
      Citation: Nature 546, 7659 (2017)
      PubDate: 2017-06-21
      DOI: 10.1038/nature22811
      Issue No: Vol. 546, No. 7659 (2017)
       
  • Improved maize reference genome with single-molecule technologies
    • Authors: Yinping Jiao, Paul Peluso, Jinghua Shi, Tiffany Liang, Michelle C. Stitzer, Bo Wang, Michael S. Campbell, Joshua C. Stein, Xuehong Wei, Chen-Shan Chin, Katherine Guill, Michael Regulski, Sunita Kumari, Andrew Olson, Jonathan Gent, Kevin L. Schneider, Thomas K. Wolfgruber, Michael R. May, Nathan M. Springer, Eric Antoniou, W. Richard McCombie, Gernot G. Presting, Michael McMullen, Jeffrey Ross-Ibarra, R. Kelly Dawe, Alex Hastie, David R. Rank, Doreen Ware
      Pages: 524 - 527
      Abstract: Complete and accurate reference genomes and annotations provide fundamental tools for characterization of genetic and functional variation. These resources facilitate the determination of biological processes and support translation of research findings into improved and sustainable agricultural technologies. Many reference genomes for crop plants have been generated over the past decade, but these genomes are often fragmented and missing complex repeat regions. Here we report the assembly and annotation of a reference genome of maize, a genetic and agricultural model species, using single-molecule real-time sequencing and high-resolution optical mapping. Relative to the previous reference genome, our assembly features a 52-fold increase in contig length and notable improvements in the assembly of intergenic spaces and centromeres. Characterization of the repetitive portion of the genome revealed more than 130,000 intact transposable elements, allowing us to identify transposable element lineage expansions that are unique to maize. Gene annotations were updated using 111,000 full-length transcripts obtained by single-molecule real-time sequencing. In addition, comparative optical mapping of two other inbred maize lines revealed a prevalence of deletions in regions of low gene density and maize lineage-specific genes.
      Citation: Nature 546, 7659 (2017)
      PubDate: 2017-06-12
      DOI: 10.1038/nature22971
      Issue No: Vol. 546, No. 7659 (2017)
       
  • Selective depletion of uropathogenic E. coli from the gut by a FimH
           antagonist
    • Authors: Caitlin N. Spaulding, Roger D. Klein, Ségolène Ruer, Andrew L. Kau, Henry L. Schreiber, Zachary T. Cusumano, Karen W. Dodson, Jerome S. Pinkner, Daved H. Fremont, James W. Janetka, Han Remaut, Jeffrey I. Gordon, Scott J. Hultgren
      Pages: 528 - 532
      Abstract: Urinary tract infections (UTIs) caused by uropathogenic Escherichia coli (UPEC) affect 150 million people annually. Despite effective antibiotic therapy, 30–50% of patients experience recurrent UTIs. In addition, the growing prevalence of UPEC that are resistant to last-line antibiotic treatments, and more recently to carbapenems and colistin, make UTI a prime example of the antibiotic-resistance crisis and emphasize the need for new approaches to treat and prevent bacterial infections. UPEC strains establish reservoirs in the gut from which they are shed in the faeces, and can colonize the periurethral area or vagina and subsequently ascend through the urethra to the urinary tract, where they cause UTIs. UPEC isolates encode up to 16 distinct chaperone-usher pathway pili, and each pilus type may enable colonization of a habitat in the host or environment. For example, the type 1 pilus adhesin FimH binds mannose on the bladder surface, and mediates colonization of the bladder. However, little is known about the mechanisms underlying UPEC persistence in the gut. Here, using a mouse model, we show that F17-like and type 1 pili promote intestinal colonization and show distinct binding to epithelial cells distributed along colonic crypts. Phylogenomic and structural analyses reveal that F17-like pili are closely related to pilus types carried by intestinal pathogens, but are restricted to extra-intestinal pathogenic E. coli. Moreover, we show that targeting FimH with M4284, a high-affinity inhibitory mannoside, reduces intestinal colonization of genetically diverse UPEC isolates, while simultaneously treating UTI, without notably disrupting the structural configuration of the gut microbiota. By selectively depleting intestinal UPEC reservoirs, mannosides could markedly reduce the rate of UTIs and recurrent UTIs.
      Citation: Nature 546, 7659 (2017)
      PubDate: 2017-06-14
      DOI: 10.1038/nature22972
      Issue No: Vol. 546, No. 7659 (2017)
       
  • Multilineage communication regulates human liver bud development from
           pluripotency
    • Authors: J. Gray Camp, Keisuke Sekine, Tobias Gerber, Henry Loeffler-Wirth, Hans Binder, Malgorzata Gac, Sabina Kanton, Jorge Kageyama, Georg Damm, Daniel Seehofer, Lenka Belicova, Marc Bickle, Rico Barsacchi, Ryo Okuda, Emi Yoshizawa, Masaki Kimura, Hiroaki Ayabe, Hideki Taniguchi, Takanori Takebe, Barbara Treutlein
      Pages: 533 - 538
      Abstract: Conventional two-dimensional differentiation from pluripotency fails to recapitulate cell interactions occurring during organogenesis. Three-dimensional organoids generate complex organ-like tissues; however, it is unclear how heterotypic interactions affect lineage identity. Here we use single-cell RNA sequencing to reconstruct hepatocyte-like lineage progression from pluripotency in two-dimensional culture. We then derive three-dimensional liver bud organoids by reconstituting hepatic, stromal, and endothelial interactions, and deconstruct heterogeneity during liver bud development. We find that liver bud hepatoblasts diverge from the two-dimensional lineage, and express epithelial migration signatures characteristic of organ budding. We benchmark three-dimensional liver buds against fetal and adult human liver single-cell RNA sequencing data, and find a striking correspondence between the three-dimensional liver bud and fetal liver cells. We use a receptor–ligand pairing analysis and a high-throughput inhibitor assay to interrogate signalling in liver buds, and show that vascular endothelial growth factor (VEGF) crosstalk potentiates endothelial network formation and hepatoblast differentiation. Our molecular dissection reveals interlineage communication regulating organoid development, and illuminates previously inaccessible aspects of human liver development.
      Citation: Nature 546, 7659 (2017)
      PubDate: 2017-06-14
      DOI: 10.1038/nature22796
      Issue No: Vol. 546, No. 7659 (2017)
       
  • Microglia-dependent synapse loss in type I interferon-mediated lupus
    • Authors: Allison R. Bialas, Jessy Presumey, Abhishek Das, Cees E. van der Poel, Peter H. Lapchak, Luka Mesin, Gabriel Victora, George C. Tsokos, Christian Mawrin, Ronald Herbst, Michael C. Carroll
      Pages: 539 - 543
      Abstract: Systemic lupus erythematosus (SLE) is an incurable autoimmune disease characterized by autoantibody deposition in tissues such as kidney, skin and lungs. Notably, up to 75% of patients with SLE experience neuropsychiatric symptoms that range from anxiety, depression and cognitive impairment to seizures and, in rare cases, psychosis—collectively this is referred to as central nervous system (CNS) lupus. In some cases, certain autoantibodies, such as anti-NMDAR or anti-phospholipid antibodies, promote CNS lupus. However, in most patients, the mechanisms that underlie these symptoms are unknown. CNS lupus typically presents at lupus diagnosis or within the first year, suggesting that early factors contributing to peripheral autoimmunity may promote CNS lupus symptoms. Here we report behavioural phenotypes and synapse loss in lupus-prone mice that are prevented by blocking type I interferon (IFN) signalling. Furthermore, we show that type I IFN stimulates microglia to become reactive and engulf neuronal and synaptic material in lupus-prone mice. These findings and our observation of increased type I IFN signalling in post-mortem hippocampal brain sections from patients with SLE may instruct the evaluation of ongoing clinical trials of anifrolumab, a type I IFN-receptor antagonist. Moreover, identification of IFN-driven microglia-dependent synapse loss, along with microglia transcriptome data, connects CNS lupus with other CNS diseases and provides an explanation for the neurological symptoms observed in some patients with SLE.
      Citation: Nature 546, 7659 (2017)
      PubDate: 2017-06-14
      DOI: 10.1038/nature22821
      Issue No: Vol. 546, No. 7659 (2017)
       
  • Histone deacetylase 3 prepares brown adipose tissue for acute thermogenic
           challenge
    • Authors: Matthew J. Emmett, Hee-Woong Lim, Jennifer Jager, Hannah J. Richter, Marine Adlanmerini, Lindsey C. Peed, Erika R. Briggs, David J. Steger, Tao Ma, Carrie A. Sims, Joseph A. Baur, Liming Pei, Kyoung-Jae Won, Patrick Seale, Zachary Gerhart-Hines, Mitchell A. Lazar
      Pages: 544 - 548
      Abstract: Brown adipose tissue is a thermogenic organ that dissipates chemical energy as heat to protect animals against hypothermia and to counteract metabolic disease. However, the transcriptional mechanisms that determine the thermogenic capacity of brown adipose tissue before environmental cold are unknown. Here we show that histone deacetylase 3 (HDAC3) is required to activate brown adipose tissue enhancers to ensure thermogenic aptitude. Mice with brown adipose tissue-specific genetic ablation of HDAC3 become severely hypothermic and succumb to acute cold exposure. Uncoupling protein 1 (UCP1) is nearly absent in brown adipose tissue lacking HDAC3, and there is also marked downregulation of mitochondrial oxidative phosphorylation genes resulting in diminished mitochondrial respiration. Remarkably, although HDAC3 acts canonically as a transcriptional corepressor, it functions as a coactivator of oestrogen-related receptor α (ERRα) in brown adipose tissue. HDAC3 coactivation of ERRα is mediated by deacetylation of PGC-1α and is required for the transcription of Ucp1, Ppargc1a (encoding PGC-1α), and oxidative phosphorylation genes. Importantly, HDAC3 promotes the basal transcription of these genes independently of adrenergic stimulation. Thus, HDAC3 uniquely primes Ucp1 and the thermogenic transcriptional program to maintain a critical capacity for thermogenesis in brown adipose tissue that can be rapidly engaged upon exposure to dangerously cold temperature.
      Citation: Nature 546, 7659 (2017)
      PubDate: 2017-06-14
      DOI: 10.1038/nature22819
      Issue No: Vol. 546, No. 7659 (2017)
       
  • BAP1 regulates IP3R3-mediated Ca2+ flux to mitochondria suppressing cell
           transformation
    • Authors: Angela Bononi, Carlotta Giorgi, Simone Patergnani, David Larson, Kaitlyn Verbruggen, Mika Tanji, Laura Pellegrini, Valentina Signorato, Federica Olivetto, Sandra Pastorino, Masaki Nasu, Andrea Napolitano, Giovanni Gaudino, Paul Morris, Greg Sakamoto, Laura K. Ferris, Alberto Danese, Andrea Raimondi, Carlo Tacchetti, Shafi Kuchay, Harvey I. Pass, El Bachir Affar, Haining Yang, Paolo Pinton, Michele Carbone
      Pages: 549 - 553
      Abstract: BRCA1-associated protein 1 (BAP1) is a potent tumour suppressor gene that modulates environmental carcinogenesis. All carriers of inherited heterozygous germline BAP1-inactivating mutations (BAP1+/−) developed one and often several BAP1−/− malignancies in their lifetime, mostly malignant mesothelioma, uveal melanoma, and so on. Moreover, BAP1-acquired biallelic mutations are frequent in human cancers. BAP1 tumour suppressor activity has been attributed to its nuclear localization, where it helps to maintain genome integrity. The possible activity of BAP1 in the cytoplasm is unknown. Cells with reduced levels of BAP1 exhibit chromosomal abnormalities and decreased DNA repair by homologous recombination, indicating that BAP1 dosage is critical. Cells with extensive DNA damage should die and not grow into malignancies. Here we discover that BAP1 localizes at the endoplasmic reticulum. Here, it binds, deubiquitylates, and stabilizes type 3 inositol-1,4,5-trisphosphate receptor (IP3R3), modulating calcium (Ca2+) release from the endoplasmic reticulum into the cytosol and mitochondria, promoting apoptosis. Reduced levels of BAP1 in BAP1+/− carriers cause reduction both of IP3R3 levels and of Ca2+ flux, preventing BAP1+/− cells that accumulate DNA damage from executing apoptosis. A higher fraction of cells exposed to either ionizing or ultraviolet radiation, or to asbestos, survive genotoxic stress, resulting in a higher rate of cellular transformation. We propose that the high incidence of cancers in BAP1+/− carriers results from the combined reduced nuclear and cytoplasmic activities of BAP1. Our data provide a mechanistic rationale for the powerful ability of BAP1 to regulate gene–environment interaction in human carcinogenesis.
      Citation: Nature 546, 7659 (2017)
      PubDate: 2017-06-14
      DOI: 10.1038/nature22798
      Issue No: Vol. 546, No. 7659 (2017)
       
  • PTEN counteracts FBXL2 to promote IP3R3- and Ca2+-mediated apoptosis
           limiting tumour growth
    • Authors: Shafi Kuchay, Carlotta Giorgi, Daniele Simoneschi, Julia Pagan, Sonia Missiroli, Anita Saraf, Laurence Florens, Michael P. Washburn, Ana Collazo-Lorduy, Mireia Castillo-Martin, Carlos Cordon-Cardo, Said M. Sebti, Paolo Pinton, Michele Pagano
      Pages: 554 - 558
      Abstract: In response to environmental cues that promote IP3 (inositol 1,4,5-trisphosphate) generation, IP3 receptors (IP3Rs) located on the endoplasmic reticulum allow the ‘quasisynaptical’ feeding of calcium to the mitochondria to promote oxidative phosphorylation. However, persistent Ca2+ release results in mitochondrial Ca2+ overload and consequent apoptosis. Among the three mammalian IP3Rs, IP3R3 appears to be the major player in Ca2+-dependent apoptosis. Here we show that the F-box protein FBXL2 (the receptor subunit of one of 69 human SCF (SKP1, CUL1, F-box protein) ubiquitin ligase complexes) binds IP3R3 and targets it for ubiquitin-, p97- and proteasome-mediated degradation to limit Ca2+ influx into mitochondria. FBXL2-knockdown cells and FBXL2-insensitive IP3R3 mutant knock-in clones display increased cytosolic Ca2+ release from the endoplasmic reticulum and sensitization to Ca2+-dependent apoptotic stimuli. The phosphatase and tensin homologue (PTEN) gene is frequently mutated or lost in human tumours and syndromes that predispose individuals to cancer. We found that PTEN competes with FBXL2 for IP3R3 binding, and the FBXL2-dependent degradation of IP3R3 is accelerated in Pten−/− mouse embryonic fibroblasts and PTEN-null cancer cells. Reconstitution of PTEN-null cells with either wild-type PTEN or a catalytically dead mutant stabilizes IP3R3 and induces persistent Ca2+ mobilization and apoptosis. IP3R3 and PTEN protein levels directly correlate in human prostate cancer. Both in cell culture and xenograft models, a non-degradable IP3R3 mutant sensitizes tumour cells with low or no PTEN expression to photodynamic therapy, which is based on the ability of photosensitizer drugs to cause Ca2+-dependent cytotoxicity after irradiation with visible light. Similarly, disruption of FBXL2 localization with GGTi-2418, a geranylgeranyl transferase inhibitor, sensitizes xenotransplanted tumours to photodynamic therapy. In summary, we identify a novel molecular mechanism that limits mitochondrial Ca2+ overload to prevent cell death. Notably, we provide proof-of-principle that inhibiting IP3R3 degradation in PTEN-deregulated cancers represents a valid therapeutic strategy.
      Citation: Nature 546, 7659 (2017)
      PubDate: 2017-06-14
      DOI: 10.1038/nature22965
      Issue No: Vol. 546, No. 7659 (2017)
       
  • Structure of the Cpf1 endonuclease R-loop complex after target DNA
           cleavage
    • Authors: Stefano Stella, Pablo Alcón, Guillermo Montoya
      Pages: 559 - 563
      Abstract: Cpf1 is an RNA-guided endonuclease that is emerging as a powerful genome-editing tool. Here we provide insight into its DNA-targeting mechanism by determining the structure of Francisella novicida Cpf1 with the triple-stranded R-loop generated after DNA cleavage. The structure reveals the machinery involved in DNA unwinding to form a CRISPR RNA (crRNA)–DNA hybrid and a displaced DNA strand. The protospacer adjacent motif (PAM) is recognized by the PAM-interacting domain. The loop-lysine helix–loop motif in this domain contains three conserved lysine residues that are inserted in a dentate manner into the double-stranded DNA. Unzipping of the double-stranded DNA occurs in a cleft arranged by acidic and hydrophobic residues facilitating the crRNA–DNA hybrid formation. The PAM single-stranded DNA is funnelled towards the nuclease site through a mixed hydrophobic and basic cavity. In this catalytic conformation, the PAM-interacting domain and the helix–loop–helix motif in the REC1 domain adopt a ‘rail’ shape and ‘flap-on’ conformations, respectively, channelling the PAM strand into the cavity. A steric barrier between the RuvC-II and REC1 domains forms the ‘septum’, separating the displaced PAM strand and the crRNA–DNA hybrid, avoiding DNA re-annealing. Mutations in key residues reveal a mechanism linking the PAM and DNA nuclease sites. Analysis of the Cpf1 structures proposes a singular working model of RNA-guided DNA cleavage, suggesting new avenues for redesign of Cpf1.
      Citation: Nature 546, 7659 (2017)
      PubDate: 2017-05-31
      DOI: 10.1038/nature22398
      Issue No: Vol. 546, No. 7659 (2017)
       
  • Addendum: The antibody aducanumab reduces Aβ plaques in
           Alzheimer’s disease
    • Authors: Jeff Sevigny, Ping Chiao, Thierry Bussière, Paul H. Weinreb, Leslie Williams, Marcel Maier, Robert Dunstan, Stephen Salloway, Tianle Chen, Yan Ling, John O’Gorman, Fang Qian, Mahin Arastu, Mingwei Li, Sowmya Chollate, Melanie S. Brennan, Omar Quintero-Monzon, Robert H. Scannevin, H. Moore Arnold, Thomas Engber, Kenneth Rhodes, James Ferrero, Yaming Hang, Alvydas Mikulskis, Jan Grimm, Christoph Hock, Roger M. Nitsch, Alfred Sandrock
      Pages: 564 - 564
      Abstract: Nature537, 50–56 (2016); doi:10.1038/nature19323Figure 1 of our original Article illustrated that treatment with aducanumab reduced human brain amyloid-β plaques in a dose-dependent fashion as measured by florbetapir positron emission tomography (PET) imaging. The figure gave the
      Citation: Nature 546, 7659 (2017)
      PubDate: 2017-06-21
      DOI: 10.1038/nature22809
      Issue No: Vol. 546, No. 7659 (2017)
       
  • Sustainability: A greener culture
    • Authors: Julia Rosen
      Pages: 565 - 567
      Abstract: Creative minds are shrinking research's big carbon footprint.
      Citation: Nature 546, 7659 (2017)
      PubDate: 2017-06-21
      DOI: 10.1038/nj7659-565a
      Issue No: Vol. 546, No. 7659 (2017)
       
  • Women in science: Finding consensus
    • Pages: 567 - 567
      Abstract: Gender shapes US university officials' take on ways to recruit and retain women in STEM.
      Citation: Nature 546, 7659 (2017)
      PubDate: 2017-06-21
      DOI: 10.1038/nj7659-567a
      Issue No: Vol. 546, No. 7659 (2017)
       
  • Memories to come
    • Authors: Paul Alex Gray
      Pages: 570 - 570
      Abstract: Is this the real life'
      Citation: Nature 546, 7659 (2017)
      PubDate: 2017-06-21
      DOI: 10.1038/546570a
      Issue No: Vol. 546, No. 7659 (2017)
       
  • Protect funding for US earthquake early-warning system
    • Pages: 451 - 452
      Abstract: Donald Trump’s proposed cuts to ShakeAlert puts the west coast at risk.
      Citation: Nature 546, 7659 (2017)
      DOI: 10.1038/nature.2017.22162
      Issue No: Vol. 546, No. 7659
       
  • SEVEN DAYS
    • Pages: 456 - 457
      Abstract: The week in science: 16–22 June 2017.
      Citation: Nature 546, 7659 (2017)
      DOI: 10.1038/546456a
      Issue No: Vol. 546, No. 7659
       
  • China’s genomics giant to make stock-market debut
    • Authors: David Cyranoski
      Pages: 461 - 461
      Abstract: Once the world's biggest DNA sequencer for research, BGI is now looking to medical applications to boost profits.
      Citation: Nature 546, 7659 (2017)
      DOI: 10.1038/546461
      Issue No: Vol. 546, No. 7659
       
  • How sea-floor sensors could save the world from natural disasters
    • Authors: Alexandra Witze
      Pages: 466 - 468
      Abstract: Geophysicists are racing to monitor underwater faults in Earth’s crust so they can provide warning of the next big earthquake and tsunami.
      Citation: Nature 546, 7659 (2017)
      DOI: 10.1038/546466a
      Issue No: Vol. 546, No. 7659
       
 
 
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