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  • Archaeology: Inequality has deep roots in Eurasia
    Nature (IF 40.137) Pub Date : 2017-11-15
    Michelle Elliott

    A study of 64 archaeological sites across four continents shows that the growth of agricultural and political systems provoked economic disparities, more so in Eurasia than in North America.

    更新日期:2017-11-17
  • Cancer immunotherapy: The dark side of PD-1 receptor inhibition
    Nature (IF 40.137) Pub Date : 2017-11-15
    Aya Ludin, Leonard I. Zon

    Inhibiting the protein PD-1 can activate T cells that trigger immune responses against tumour cells. But it emerges that, in mice, this immunotherapy exacerbates a cancer that involves the T cells themselves.

    更新日期:2017-11-17
  • Microbiota: A high-pressure situation for bacteria
    Nature (IF 40.137) Pub Date : 2017-11-15
    David A. Relman

    Analyses in mice suggest that dietary salt increases blood pressure partly by affecting some of the microbes that inhabit the gut. The implications of this work for hypertension warrant further study in humans.

    更新日期:2017-11-17
  • Visualization of chemical modifications in the human 80S ribosome structure
    Nature (IF 40.137) Pub Date : 2017-11-15
    S. Kundhavai Natchiar, Alexander G. Myasnikov, Hanna Kratzat, Isabelle Hazemann, Bruno P. Klaholz

    A high-resolution structure of the human ribosome determined by cryo-electron microscopy visualizes numerous RNA modifications that are concentrated at functional sites with an extended shell, and suggests the possibility of designing more specific ribosome-targeting drugs.

    更新日期:2017-11-17
  • Salt-responsive gut commensal modulates TH17 axis and disease
    Nature (IF 40.137) Pub Date : 2017-11-15
    Nicola Wilck, Mariana G. Matus, Sean M. Kearney, Scott W. Olesen, Kristoffer Forslund, Hendrik Bartolomaeus, Stefanie Haase, Anja Mähler, András Balogh, Lajos Markó, Olga Vvedenskaya, Friedrich H. Kleiner, Dmitry Tsvetkov, Lars Klug, Paul I. Costea, Shinichi Sunagawa, Lisa Maier, Natalia Rakova, Valentin Schatz, Patrick Neubert, Christian Frätzer, Alexander Krannich, Maik Gollasch, Diana A. Grohme, Beatriz F. Côrte-Real, Roman G. Gerlach, Marijana Basic, Athanasios Typas, Chuan Wu, Jens M. Titze, Jonathan Jantsch, Michael Boschmann, Ralf Dechend, Markus Kleinewietfeld, Stefan Kempa, Peer Bork, Ralf A. Linker, Eric J. Alm, Dominik N. Müller

    High salt intake changed the gut microbiome and increased TH17 cell numbers in mice, and reduced intestinal survival of Lactobacillus species, increased the number of TH17 cells and increased blood pressure in humans.

    更新日期:2017-11-17
  • Greater post-Neolithic wealth disparities in Eurasia than in North America and Mesoamerica
    Nature (IF 40.137) Pub Date : 2017-11-15
    Timothy A. Kohler, Michael E. Smith, Amy Bogaard, Gary M. Feinman, Christian E. Peterson, Alleen Betzenhauser, Matthew Pailes, Elizabeth C. Stone, Anna Marie Prentiss, Timothy J. Dennehy, Laura J. Ellyson, Linda M. Nicholas, Ronald K. Faulseit, Amy Styring, Jade Whitlam, Mattia Fochesato, Thomas A. Foor, Samuel Bowles

    How wealth is distributed among households provides insight into the fundamental characters of societies and the opportunities they afford for social mobility. However, economic inequality has been hard to study in ancient societies for which we do not have written records, which adds to the challenge of placing current wealth disparities into a long-term perspective. Although various archaeological proxies for wealth, such as burial goods or exotic or expensive-to-manufacture goods in household assemblages, have been proposed, the first is not clearly connected with households, and the second is confounded by abandonment mode and other factors. As a result, numerous questions remain concerning the growth of wealth disparities, including their connection to the development of domesticated plants and animals and to increases in sociopolitical scale. Here we show that wealth disparities generally increased with the domestication of plants and animals and with increased sociopolitical scale, using Gini coefficients computed over the single consistent proxy of house-size distributions. However, unexpected differences in the responses of societies to these factors in North America and Mesoamerica, and in Eurasia, became evident after the end of the Neolithic period. We argue that the generally higher wealth disparities identified in post-Neolithic Eurasia were initially due to the greater availability of large mammals that could be domesticated, because they allowed more profitable agricultural extensification, and also eventually led to the development of a mounted warrior elite able to expand polities (political units that cohere via identity, ability to mobilize resources, or governance) to sizes that were not possible in North America and Mesoamerica before the arrival of Europeans. We anticipate that this analysis will stimulate other work to enlarge this sample to include societies in South America, Africa, South Asia and Oceania that were under-sampled or not included in this study.

    更新日期:2017-11-17
  • Genome sequence of the progenitor of the wheat D genome Aegilops tauschii
    Nature (IF 40.137) Pub Date : 2017-11-15
    Ming-Cheng Luo, Yong Q. Gu, Daniela Puiu, Hao Wang, Sven O. Twardziok, Karin R. Deal, Naxin Huo, Tingting Zhu, Le Wang, Yi Wang, Patrick E. McGuire, Shuyang Liu, Hai Long, Ramesh K. Ramasamy, Juan C. Rodriguez, Sonny L. Van, Luxia Yuan, Zhenzhong Wang, Zhiqiang Xia, Lichan Xiao, Olin D. Anderson, Shuhong Ouyang, Yong Liang, Aleksey V. Zimin, Geo Pertea, Peng Qi, Jeffrey L. Bennetzen, Xiongtao Dai, Matthew W. Dawson, Hans-Georg Müller, Karl Kugler, Lorena Rivarola-Duarte, Manuel Spannagl, Klaus F. X. Mayer, Fu-Hao Lu, Michael W. Bevan, Philippe Leroy, Pingchuan Li, Frank M. You, Qixin Sun, Zhiyong Liu, Eric Lyons, Thomas Wicker, Steven L. Salzberg, Katrien M. Devos, Jan Dvořák

    Aegilops tauschii is the diploid progenitor of the D genome of hexaploid wheat (Triticum aestivum, genomes AABBDD) and an important genetic resource for wheat. The large size and highly repetitive nature of the Ae. tauschii genome has until now precluded the development of a reference-quality genome sequence. Here we use an array of advanced technologies, including ordered-clone genome sequencing, whole-genome shotgun sequencing, and BioNano optical genome mapping, to generate a reference-quality genome sequence for Ae. tauschii ssp. strangulata accession AL8/78, which is closely related to the wheat D genome. We show that compared to other sequenced plant genomes, including a much larger conifer genome, the Ae. tauschii genome contains unprecedented amounts of very similar repeated sequences. Our genome comparisons reveal that the Ae. tauschii genome has a greater number of dispersed duplicated genes than other sequenced genomes and its chromosomes have been structurally evolving an order of magnitude faster than those of other grass genomes. The decay of colinearity with other grass genomes correlates with recombination rates along chromosomes. We propose that the vast amounts of very similar repeated sequences cause frequent errors in recombination and lead to gene duplications and structural chromosome changes that drive fast genome evolution.

    更新日期:2017-11-17
  • Structural basis of nucleotide sugar transport across the Golgi membrane
    Nature (IF 40.137) Pub Date : 2017-11-15
    Joanne L. Parker, Simon Newstead

    Glycosylation is a fundamental cellular process that, in eukaryotes, occurs in the lumen of both the Golgi apparatus and the endoplasmic reticulum. Nucleotide sugar transporters (NSTs) are an essential component of the glycosylation pathway, providing the diverse range of substrates required for the glycosyltransferases. NSTs are linked to several developmental and immune disorders in humans, and in pathogenic microbes they have an important role in virulence. How NSTs recognize and transport activated monosaccharides, however, is currently unclear. Here we present the crystal structure of an NST, the GDP–mannose transporter Vrg4, in both the substrate-free and the bound states. A hitherto unobserved requirement of short-chain lipids in activating the transporter supports a model for regulation within the highly dynamic membranes of the Golgi apparatus. Our results provide a structural basis for understanding nucleotide sugar recognition, and provide insights into the transport and regulatory mechanism of this family of intracellular transporters.

    更新日期:2017-11-17
  • Quantitative microbiome profiling links gut community variation to microbial load
    Nature (IF 40.137) Pub Date : 2017-11-15
    Doris Vandeputte, Gunter Kathagen, Kevin D’hoe, Sara Vieira-Silva, Mireia Valles-Colomer, João Sabino, Jun Wang, Raul Y. Tito, Lindsey De Commer, Youssef Darzi, Séverine Vermeire, Gwen Falony, Jeroen Raes

    Current sequencing-based analyses of faecal microbiota quantify microbial taxa and metabolic pathways as fractions of the sample sequence library generated by each analysis. Although these relative approaches permit detection of disease-associated microbiome variation, they are limited in their ability to reveal the interplay between microbiota and host health. Comparative analyses of relative microbiome data cannot provide information about the extent or directionality of changes in taxa abundance or metabolic potential. If microbial load varies substantially between samples, relative profiling will hamper attempts to link microbiome features to quantitative data such as physiological parameters or metabolite concentrations. Saliently, relative approaches ignore the possibility that altered overall microbiota abundance itself could be a key identifier of a disease-associated ecosystem configuration. To enable genuine characterization of host–microbiota interactions, microbiome research must exchange ratios for counts. Here we build a workflow for the quantitative microbiome profiling of faecal material, through parallelization of amplicon sequencing and flow cytometric enumeration of microbial cells. We observe up to tenfold differences in the microbial loads of healthy individuals and relate this variation to enterotype differentiation. We show how microbial abundances underpin both microbiota variation between individuals and covariation with host phenotype. Quantitative profiling bypasses compositionality effects in the reconstruction of gut microbiota interaction networks and reveals that the taxonomic trade-off between Bacteroides and Prevotella is an artefact of relative microbiome analyses. Finally, we identify microbial load as a key driver of observed microbiota alterations in a cohort of patients with Crohn’s disease, here associated with a low-cell-count Bacteroides enterotype (as defined through relative profiling).

    更新日期:2017-11-17
  • PD-1 is a haploinsufficient suppressor of T cell lymphomagenesis
    Nature (IF 40.137) Pub Date : 2017-11-15
    Tim Wartewig, Zsuzsanna Kurgyis, Selina Keppler, Konstanze Pechloff, Erik Hameister, Rupert Öllinger, Roman Maresch, Thorsten Buch, Katja Steiger, Christof Winter, Roland Rad, Jürgen Ruland

    T cell non-Hodgkin lymphomas are a heterogeneous group of highly aggressive malignancies with poor clinical outcomes. T cell lymphomas originate from peripheral T cells and are frequently characterized by genetic gain-of-function variants in T cell receptor (TCR) signalling molecules. Although these oncogenic alterations are thought to drive TCR pathways to induce chronic proliferation and cell survival programmes, it remains unclear whether T cells contain tumour suppressors that can counteract these events. Here we show that the acute enforcement of oncogenic TCR signalling in lymphocytes in a mouse model of human T cell lymphoma drives the strong expansion of these cells in vivo. However, this response is short-lived and robustly counteracted by cell-intrinsic mechanisms. A subsequent genome-wide in vivo screen using T cell-specific transposon mutagenesis identified PDCD1, which encodes the inhibitory receptor programmed death-1 (PD-1), as a master gene that suppresses oncogenic T cell signalling. Mono- and bi-allelic deletions of PDCD1 are also recurrently observed in human T cell lymphomas with frequencies that can exceed 30%, indicating high clinical relevance. Mechanistically, the activity of PD-1 enhances levels of the tumour suppressor PTEN and attenuates signalling by the kinases AKT and PKC in pre-malignant cells. By contrast, a homo- or heterozygous deletion of PD-1 allows unrestricted T cell growth after an oncogenic insult and leads to the rapid development of highly aggressive lymphomas in vivo that are readily transplantable to recipients. Thus, the inhibitory PD-1 receptor is a potent haploinsufficient tumour suppressor in T cell lymphomas that is frequently altered in human disease. These findings extend the known physiological functions of PD-1 beyond the prevention of immunopathology after antigen-induced T cell activation, and have implications for T cell lymphoma therapies and for current strategies that target PD-1 in the broader context of immuno-oncology.

    更新日期:2017-11-17
  • A Jurassic gliding euharamiyidan mammal with an ear of five auditory bones
    Nature (IF 40.137) Pub Date : 2017-11-13
    Gang Han, Fangyuan Mao, Shundong Bi, Yuanqing Wang, Jin Meng

    The fossil of a gliding mammal from the Jurassic period sheds light on both the evolution of gliding and the development of the middle ear, as it has a previously unseen five-ossicle auditory system.

    更新日期:2017-11-17
  • Solar abundance ratios of the iron-peak elements in the Perseus cluster
    Nature (IF 40.137) Pub Date : 2017-11-13

    The metal abundance of the hot plasma that permeates galaxy clusters represents the accumulation of heavy elements produced by billions of supernovae. Therefore, X-ray spectroscopy of the intracluster medium provides an opportunity to investigate the nature of supernova explosions integrated over cosmic time. In particular, the abundance of the iron-peak elements (chromium, manganese, iron and nickel) is key to understanding how the progenitors of typical type Ia supernovae evolve and explode. Recent X-ray studies of the intracluster medium found that the abundance ratios of these elements differ substantially from those seen in the Sun, suggesting differences between the nature of type Ia supernovae in the clusters and in the Milky Way. However, because the K-shell transition lines of chromium and manganese are weak and those of iron and nickel are very close in photon energy, high-resolution spectroscopy is required for an accurate determination of the abundances of these elements. Here we report observations of the Perseus cluster, with statistically significant detections of the resonance emission from chromium, manganese and nickel. Our measurements, combined with the latest atomic models, reveal that these elements have near-solar abundance ratios with respect to iron, in contrast to previous claims. Comparison between our results and modern nucleosynthesis calculations disfavours the hypothesis that type Ia supernova progenitors are exclusively white dwarfs with masses well below the Chandrasekhar limit (about 1.4 times the mass of the Sun). The observed abundance pattern of the iron-peak elements can be explained by taking into account a combination of near- and sub-Chandrasekhar-mass type Ia supernova systems, adding to the mounting evidence that both progenitor types make a substantial contribution to cosmic chemical enrichment.

    更新日期:2017-11-17
  • Graduate students face alarming tax hike
    Nature (IF 40.137) Pub Date : 

    Adding to PhD students’ woes will undermine US research and economy.

    更新日期:2017-11-16
  • Chemists get faster on the draw
    Nature (IF 40.137) Pub Date : 

    A Nature journals guide to drawing the structures of molecules should aid expert and casual chemists alike.

    更新日期:2017-11-16
  • How China could make the most of its beamlines
    Nature (IF 40.137) Pub Date : 

    More international collaboration could build capacity at big physics facilities especially in the south.

    更新日期:2017-11-16
  • Immunization needs a technology boost
    Nature (IF 40.137) Pub Date : 
    Seth Berkley

    Tracking who receives vaccines is essential, but will be impossible without innovations in digital technologies, says Seth Berkley.

    更新日期:2017-11-16
  • New Delhi smog, death-sentence appeal and a porpoise setback
    Nature (IF 40.137) Pub Date : 

    The week in science: 11–16 November 2017.

    更新日期:2017-11-16
  • Archaeologists say human-evolution study used stolen bone
    Nature (IF 40.137) Pub Date : 2017-11-13
    Ewen Callaway

    Bizarre tale of theft and suspicious packages casts doubt on claims for early-human occupation in northern Europe.

    更新日期:2017-11-16
  • Lab mice's ancestral ‘Eve’ gets her genome sequenced
    Nature (IF 40.137) Pub Date : 2017-11-13
    Sara Reardon

    Effort aims to help scientists understand how generations of inbreeding have altered the genetics of research rodents.

    更新日期:2017-11-16
  • UK government appoints next chief scientific adviser
    Nature (IF 40.137) Pub Date : 2017-11-08
    Elizabeth Gibney

    A former pharmaceutical boss will help navigate the UK’s exit from the European Union.

    更新日期:2017-11-16
  • Puerto Rico struggles to assess hurricane’s health effects
    Nature (IF 40.137) Pub Date : 2017-11-15
    Sara Reardon

    While dealing with their own losses, public-health researchers are regrouping to study the aftermath of Hurricane Maria.

    更新日期:2017-11-16
  • World’s carbon emissions set to spike by 2% in 2017
    Nature (IF 40.137) Pub Date : 2017-11-13
    Jeff Tollefson

    Increased coal use in China appears to be driving the first increase in global greenhouse-gas output since 2014.

    更新日期:2017-11-16
  • China fires up next-generation neutron-science facility
    Nature (IF 40.137) Pub Date : 2017-11-14
    David Cyranoski

    Beam generator puts country in elite company for doing experiments in materials science and other fields.

    更新日期:2017-11-16
  • Biology’s beloved amphibian — the axolotl — is racing towards extinction
    Nature (IF 40.137) Pub Date : 
    Erik Vance

    Although abundant in captivity, the salamander has nearly disappeared from its natural habitat, and that’s a problem.

    更新日期:2017-11-16
  • Chemists can help to solve the air-pollution health crisis
    Nature (IF 40.137) Pub Date : 
    Jos Lelieveld, Ulrich Pöschl

    Learning more about how pollutants enter and damage the body would reduce disease and deaths, say Jos Lelieveld and Ulrich Pöschl.

    更新日期:2017-11-16
  • Boycott products from states with dirty energy
    Nature (IF 40.137) Pub Date : 
    Christopher Kennedy

    Consumer pressure could encourage regions to switch from fossil fuels to cleaner sources of electricity, argues Christopher Kennedy.

    更新日期:2017-11-16
  • Bioethics: Justice in genomics
    Nature (IF 40.137) Pub Date : 2017-11-15
    Rosario Isasi

    Rosario Isasi examines a study on the societal impact of grand sequencing projects.

    更新日期:2017-11-16
  • Economics: How science got a golden ticket
    Nature (IF 40.137) Pub Date : 2017-11-15
    Ehsan Masood

    Ehsan Masood hails an account of the mixed implications of governments valuing research as an investment.

    更新日期:2017-11-16
  • Computer science: Visionary of virtual reality
    Nature (IF 40.137) Pub Date : 2017-11-15
    Aldo Faisal

    Aldo Faisal explores the immersive journey of technology pioneer Jaron Lanier.

    更新日期:2017-11-16
  • Survival stories: science endures
    Nature (IF 40.137) Pub Date : 2017-11-15
    Virginia Gewin

    Scientists hit hard by powerful hurricanes in 2017 share tips for weathering future disasters.

    更新日期:2017-11-16
  • Turning point: Gourmet investigator
    Nature (IF 40.137) Pub Date : 2017-11-15
    Virginia Gewin

    Cross-cultural chef-turned-scientist cooks up recipe for diversity outreach.

    更新日期:2017-11-16
  • Those who favour fire
    Nature (IF 40.137) Pub Date : 
    CB Droege

    A final farewell.

    更新日期:2017-11-16
  • Planetary science: Haze cools Pluto's atmosphere
    Nature (IF 40.137) Pub Date : 2017-11-15
    Robert A. West

    Modelling suggests that Pluto's atmospheric temperature is regulated by haze, unlike the other planetary bodies in the Solar System. The finding has implications for our understanding of exoplanetary atmospheres. See Letter p.352

    更新日期:2017-11-16
  • Microbiology: Bacteria disarm host-defence proteins
    Nature (IF 40.137) Pub Date : 2017-10-25
    John D. MacMicking

    Infection with Shigella flexneri bacteria is a major cause of infant death. It emerges that S. flexneri evades intracellular defences by releasing a protein that triggers the destruction of members of a key family of host enzymes. See Letter p.378

    更新日期:2017-11-16
  • 50 & 100 Years Ago
    Nature (IF 40.137) Pub Date : 2017-11-15

    50 Years AgoLast week's first Saturn V flight (called Apollo 4) may have helped NASA to catch up on the lagging timetable for landing two Americans on the Moon by 1970. By combining in one flight the first operational tests of several important components,

    更新日期:2017-11-16
  • Biogeochemistry: Ocean hotspots of nitrogen loss
    Nature (IF 40.137) Pub Date : 2017-11-15
    Katja Fennel

    Microbial activity in the sea results in a loss of bioavailable nitrogen. It emerges that the climate phenomenon called the El Niño–Southern Oscillation has a surprisingly large effect on the size of this loss.

    更新日期:2017-11-16
  • Gene therapy: Transgenic stem cells replace skin
    Nature (IF 40.137) Pub Date : 2017-11-08
    Mariaceleste Aragona, Cédric Blanpain

    The treatment of a patient affected by an incurable genetic skin disease demonstrates the efficacy, feasibility and safety of replacing almost the whole skin using genetically corrected stem cells. See Letter p.327

    更新日期:2017-11-16
  • Geophysics: The buoyancy of Earth's deep mantle
    Nature (IF 40.137) Pub Date : 2017-11-15
    Barbara Romanowicz

    The physical nature of two regions called large low-shear-velocity provinces at the base of Earth's mantle is uncertain. A measurement of their density has implications for our understanding of mantle dynamics. See Article p.321

    更新日期:2017-11-16
  • Ecology: The effect of conservation spending
    Nature (IF 40.137) Pub Date : 2017-10-25
    Hugh P. Possingham, Leah R. Gerber

    Statistical analysis of data on threatened species provides a model that can predict how rates of investment in conservation affect biodiversity under changing human population levels and agricultural and economic conditions. See Letter p.364

    更新日期:2017-11-16
  • Influenza: A broadly protective antibody
    Nature (IF 40.137) Pub Date : 2017-11-15
    Peter Palese

    A single antibody uses multiple antiviral mechanisms to block the replication of influenza B viruses in mice and ferrets. The development could inform research into improved flu vaccines.

    更新日期:2017-11-16
  • Progress in and promise of bacterial quorum sensing research
    Nature (IF 40.137) Pub Date : 2017-11-15
    Marvin Whiteley, Stephen P. Diggle, E. Peter Greenberg

    This Review highlights how we can build upon the relatively new and rapidly developing field of research into bacterial quorum sensing (QS). We now have a depth of knowledge about how bacteria use QS signals to communicate with each other and to coordinate their activities.

    更新日期:2017-11-16
  • Tidal tomography constrains Earth’s deep-mantle buoyancy
    Nature (IF 40.137) Pub Date : 2017-11-15
    Harriet C. P. Lau, Jerry X. Mitrovica, James L. Davis, Jeroen Tromp, Hsin-Ying Yang, David Al-Attar

    Earth’s body tide—also known as the solid Earth tide, the displacement of the solid Earth’s surface caused by gravitational forces from the Moon and the Sun—is sensitive to the density of the two Large Low Shear Velocity Provinces (LLSVPs) beneath Africa and the Pacific. These

    更新日期:2017-11-16
  • Regeneration of the entire human epidermis using transgenic stem cells
    Nature (IF 40.137) Pub Date : 2017-11-08
    Tobias Hirsch, Tobias Rothoeft, Norbert Teig, Johann W. Bauer, Graziella Pellegrini, Laura De Rosa, Davide Scaglione, Julia Reichelt, Alfred Klausegger, Daniela Kneisz, Oriana Romano, Alessia Secone Seconetti, Roberta Contin, Elena Enzo, Irena Jurman, Sonia Carulli, Frank Jacobsen, Thomas Luecke, Marcus Lehnhardt, Meike Fischer, Maximilian Kueckelhaus, Daniela Quaglino, Michele Morgante, Silvio Bicciato, Sergio Bondanza, Michele De Luca

    Junctional epidermolysis bullosa (JEB) is a severe and often lethal genetic disease caused by mutations in genes encoding the basement membrane component laminin-332. Surviving patients with JEB develop chronic wounds to the skin and mucosa, which impair their quality of life and lead to skin

    更新日期:2017-11-16
  • A single-cell survey of the small intestinal epithelium
    Nature (IF 40.137) Pub Date : 2017-11-08
    Adam L. Haber, Moshe Biton, Noga Rogel, Rebecca H. Herbst, Karthik Shekhar, Christopher Smillie, Grace Burgin, Toni M. Delorey, Michael R. Howitt, Yarden Katz, Itay Tirosh, Semir Beyaz, Danielle Dionne, Mei Zhang, Raktima Raychowdhury, Wendy S. Garrett, Orit Rozenblatt-Rosen, Hai Ning Shi, Omer Yilmaz, Ramnik J. Xavier, Aviv Regev

    Intestinal epithelial cells absorb nutrients, respond to microbes, function as a barrier and help to coordinate immune responses. Here we report profiling of 53,193 individual epithelial cells from the small intestine and organoids of mice, which enabled the identification and characterization of previously unknown subtypes

    更新日期:2017-11-16
  • Inflammation-induced IgA+ cells dismantle anti-liver cancer immunity
    Nature (IF 40.137) Pub Date : 2017-11-08
    Shabnam Shalapour, Xue-Jia Lin, Ingmar N. Bastian, John Brain, Alastair D. Burt, Alexander A. Aksenov, Alison F. Vrbanac, Weihua Li, Andres Perkins, Takaji Matsutani, Zhenyu Zhong, Debanjan Dhar, Jose A. Navas-Molina, Jun Xu, Rohit Loomba, Michael Downes, Ruth T. Yu, Ronald M. Evans, Pieter C. Dorrestein, Rob Knight, Christopher Benner, Quentin M. Anstee, Michael Karin

    The role of adaptive immunity in early cancer development is controversial. Here we show that chronic inflammation and fibrosis in humans and mice with non-alcoholic fatty liver disease is accompanied by accumulation of liver-resident immunoglobulin-A-producing (IgA+) cells. These cells also express programmed death

    更新日期:2017-11-16
  • Dynamics of P-type ATPase transport revealed by single-molecule FRET
    Nature (IF 40.137) Pub Date : 2017-11-08
    Mateusz Dyla, Daniel S. Terry, Magnus Kjaergaard, Thomas L.-M. Sørensen, Jacob Lauwring Andersen, Jens Peter Andersen, Charlotte Rohde Knudsen, Roger B. Altman, Poul Nissen, Scott C. Blanchard

    Phosphorylation-type (P-type) ATPases are ubiquitous primary transporters that pump cations across cell membranes through the formation and breakdown of a phosphoenzyme intermediate. Structural investigations suggest that the transport mechanism is defined by conformational changes in the cytoplasmic domains of the protein that are allosterically coupled

    更新日期:2017-11-16
  • Haze heats Pluto’s atmosphere yet explains its cold temperature
    Nature (IF 40.137) Pub Date : 2017-11-15
    Xi Zhang, Darrell F. Strobel, Hiroshi Imanaka

    Pluto’s atmosphere is cold and hazy. Recent observations have shown it to be much colder than predicted theoretically, suggesting an unknown cooling mechanism. Atmospheric gas molecules, particularly water vapour, have been proposed as a coolant; however, because Pluto’s thermal structure is expected to be in radiative–conductive equilibrium, the required water vapour would need to be supersaturated by many orders of magnitude under thermodynamic equilibrium conditions. Here we report that atmospheric hazes, rather than gases, can explain Pluto’s temperature profile. We find that haze particles have substantially larger solar heating and thermal cooling rates than gas molecules, dominating the atmospheric radiative balance from the ground to an altitude of 700 kilometres, above which heat conduction maintains an isothermal atmosphere. We conclude that Pluto’s atmosphere is unique among Solar System planetary atmospheres, as its radiative energy equilibrium is controlled primarily by haze particles instead of gas molecules. We predict that Pluto is therefore several orders of magnitude brighter at mid-infrared wavelengths than previously thought—a brightness that could be detected by future telescopes.

    更新日期:2017-11-16
  • Collective emission of matter-wave jets from driven Bose–Einstein condensates
    Nature (IF 40.137) Pub Date : 2017-11-06
    Logan W. Clark, Anita Gaj, Lei Feng, Cheng Chin

    Scattering is used to probe matter and its interactions in all areas of physics. In ultracold atomic gases, control over pairwise interactions enables us to investigate scattering in quantum many-body systems. Previous experiments on colliding Bose–Einstein condensates have revealed matter–wave interference, haloes of scattered atoms, four-wave mixing and correlations between counter-propagating pairs. However, a regime with strong stimulation of spontaneous collisions analogous to superradiance has proved elusive. In this regime, the collisions rapidly produce highly correlated states with macroscopic population. Here we find that runaway stimulated collisions in Bose–Einstein condensates with periodically modulated interaction strength cause the collective emission of matter-wave jets that resemble fireworks. Jets appear only above a threshold modulation amplitude and their correlations are invariant even when the number of ejected atoms grows exponentially. Hence, we show that the structures and atom occupancies of the jets stem from the quantum fluctuations of the condensate. Our findings demonstrate the conditions required for runaway stimulated collisions and reveal the quantum nature of matter-wave emission.

    更新日期:2017-11-16
  • Granular materials flow like complex fluids
    Nature (IF 40.137) Pub Date : 2017-11-01
    Binquan Kou, Yixin Cao, Jindong Li, Chengjie Xia, Zhifeng Li, Haipeng Dong, Ang Zhang, Jie Zhang, Walter Kob, Yujie Wang

    Granular materials such as sand, powders and foams are ubiquitous in daily life and in industrial and geotechnical applications. These disordered systems form stable structures when unperturbed, but in the presence of external influences such as tapping or shear they ‘relax’, becoming fluid in nature. It is often assumed that the relaxation dynamics of granular systems is similar to that of thermal glass-forming systems. However, so far it has not been possible to determine experimentally the dynamic properties of three-dimensional granular systems at the particle level. This lack of experimental data, combined with the fact that the motion of granular particles involves friction (whereas the motion of particles in thermal glass-forming systems does not), means that an accurate description of the relaxation dynamics of granular materials is lacking. Here we use X-ray tomography to determine the microscale relaxation dynamics of hard granular ellipsoids subject to an oscillatory shear. We find that the distribution of the displacements of the ellipsoids is well described by a Gumbel law (which is similar to a Gaussian distribution for small displacements but has a heavier tail for larger displacements), with a shape parameter that is independent of the amplitude of the shear strain and of the time. Despite this universality, the mean squared displacement of an individual ellipsoid follows a power law as a function of time, with an exponent that does depend on the strain amplitude and time. We argue that these results are related to microscale relaxation mechanisms that involve friction and memory effects (whereby the motion of an ellipsoid at a given point in time depends on its previous motion). Our observations demonstrate that, at the particle level, the dynamic behaviour of granular systems is qualitatively different from that of thermal glass-forming systems, and is instead more similar to that of complex fluids. We conclude that granular materials can relax even when the driving strain is weak.

    更新日期:2017-11-16
  • Reductions in global biodiversity loss predicted from conservation spending
    Nature (IF 40.137) Pub Date : 2017-10-25
    Anthony Waldron, Daniel C. Miller, Dave Redding, Arne Mooers, Tyler S. Kuhn, Nate Nibbelink, J. Timmons Roberts, Joseph A. Tobias, John L. Gittleman

    Halting global biodiversity loss is central to the Convention on Biological Diversity and United Nations Sustainable Development Goals, but success to date has been very limited. A critical determinant of success in achieving these goals is the financing that is committed to maintaining biodiversity; however, financing decisions are hindered by considerable uncertainty over the likely impact of any conservation investment. For greater effectiveness, we need an evidence-based model that shows how conservation spending quantitatively reduces the rate of biodiversity loss. Here we demonstrate such a model, and empirically quantify how conservation investment between 1996 and 2008 reduced biodiversity loss in 109 countries (signatories to the Convention on Biological Diversity and Sustainable Development Goals), by a median average of 29% per country. We also show that biodiversity changes in signatory countries can be predicted with high accuracy, using a dual model that balances the effects of conservation investment against those of economic, agricultural and population growth (human development pressures). Decision-makers can use this model to forecast the improvement that any proposed biodiversity budget would achieve under various scenarios of human development pressure, and then compare these forecasts to any chosen policy target. We find that the impact of spending decreases as human development pressures grow, which implies that funding may need to increase over time. The model offers a flexible tool for balancing the Sustainable Development Goals of human development and maintaining biodiversity, by predicting the dynamic changes in conservation finance that will be needed as human development proceeds.

    更新日期:2017-11-16
  • Parallel palaeogenomic transects reveal complex genetic history of early European farmers
    Nature (IF 40.137) Pub Date : 2017-11-08
    Mark Lipson, Anna Szécsényi-Nagy, Swapan Mallick, Annamária Pósa, Balázs Stégmár, Victoria Keerl, Nadin Rohland, Kristin Stewardson, Matthew Ferry, Megan Michel, Jonas Oppenheimer, Nasreen Broomandkhoshbacht, Eadaoin Harney, Susanne Nordenfelt, Bastien Llamas, Balázs Gusztáv Mende, Kitti Köhler, Krisztián Oross, Mária Bondár, Tibor Marton, Anett Osztás, János Jakucs, Tibor Paluch, Ferenc Horváth, Piroska Csengeri, Judit Koós, Katalin Sebők, Alexandra Anders, Pál Raczky, Judit Regenye, Judit P. Barna, Szilvia Fábián, Gábor Serlegi, Zoltán Toldi, Emese Gyöngyvér Nagy, János Dani, Erika Molnár, György Pálfi, László Márk, Béla Melegh, Zsolt Bánfai, László Domboróczki, Javier Fernández-Eraso, José Antonio Mujika-Alustiza, Carmen Alonso Fernández, Javier Jiménez Echevarría, Ruth Bollongino, Jörg Orschiedt, Kerstin Schierhold, Harald Meller, Alan Cooper, Joachim Burger, Eszter Bánffy, Kurt W. Alt, Carles Lalueza-Fox, Wolfgang Haak, David Reich

    Ancient DNA studies have established that Neolithic European populations were descended from Anatolian migrants who received a limited amount of admixture from resident hunter-gatherers. Many open questions remain, however, about the spatial and temporal dynamics of population interactions and admixture during the Neolithic period. Here we investigate the population dynamics of Neolithization across Europe using a high-resolution genome-wide ancient DNA dataset with a total of 180 samples, of which 130 are newly reported here, from the Neolithic and Chalcolithic periods of Hungary (6000–2900 bc, n = 100), Germany (5500–3000 bc, n = 42) and Spain (5500–2200 bc, n = 38). We find that genetic diversity was shaped predominantly by local processes, with varied sources and proportions of hunter-gatherer ancestry among the three regions and through time. Admixture between groups with different ancestry profiles was pervasive and resulted in observable population transformation across almost all cultural transitions. Our results shed new light on the ways in which gene flow reshaped European populations throughout the Neolithic period and demonstrate the potential of time-series-based sampling and modelling approaches to elucidate multiple dimensions of historical population interactions.

    更新日期:2017-11-16
  • Locomotor speed control circuits in the caudal brainstem
    Nature (IF 40.137) Pub Date : 2017-10-23
    Paolo Capelli, Chiara Pivetta, Maria Soledad Esposito, Silvia Arber

    Locomotion is a universal behaviour that provides animals with the ability to move between places. Classical experiments have used electrical microstimulation to identify brain regions that promote locomotion, but the identity of neurons that act as key intermediaries between higher motor planning centres and executive circuits in the spinal cord has remained controversial. Here we show that the mouse caudal brainstem encompasses functionally heterogeneous neuronal subpopulations that have differential effects on locomotion. These subpopulations are distinguishable by location, neurotransmitter identity and connectivity. Notably, glutamatergic neurons within the lateral paragigantocellular nucleus (LPGi), a small subregion in the caudal brainstem, are essential to support high-speed locomotion, and can positively tune locomotor speed through inputs from glutamatergic neurons of the upstream midbrain locomotor region. By contrast, glycinergic inhibitory neurons can induce different forms of behavioural arrest mapping onto distinct caudal brainstem regions. Anatomically, descending pathways of glutamatergic and glycinergic LPGi subpopulations communicate with distinct effector circuits in the spinal cord. Our results reveal that behaviourally opposing locomotor functions in the caudal brainstem were historically masked by the unexposed diversity of intermingled neuronal subpopulations. We demonstrate how specific brainstem neuron populations represent essential substrates to implement key parameters in the execution of motor programs.

    更新日期:2017-11-16
  • Ubiquitination and degradation of GBPs by a Shigella effector to suppress host defence
    Nature (IF 40.137) Pub Date : 2017-10-11
    Peng Li, Wei Jiang, Qin Yu, Wang Liu, Ping Zhou, Jun Li, Junjie Xu, Bo Xu, Fengchao Wang, Feng Shao

    Interferon-inducible guanylate-binding proteins (GBPs) mediate cell-autonomous antimicrobial defences. Shigella flexneri, a Gram-negative cytoplasmic free-living bacterium that causes bacillary dysentery, encodes a repertoire of highly similar type III secretion system effectors called invasion plasmid antigen Hs (IpaHs). IpaHs represent a large family of bacterial ubiquitin-ligases, but their function is poorly understood. Here we show that S. flexneri infection induces rapid proteasomal degradation of human guanylate binding protein-1 (hGBP1). We performed a transposon screen to identify a mutation in the S. flexneri gene ipaH9.8 that prevented hGBP1 degradation. IpaH9.8 targets hGBP1 for degradation via Lys48-linked ubiquitination. IpaH9.8 targets multiple GBPs in the cytoplasm independently of their nucleotide-bound states and their differential function in antibacterial defence, promoting S. flexneri replication and resulting in the death of infected mice. In the absence of IpaH9.8, or when binding of GBPs to IpaH9.8 was disrupted, GBPs such as hGBP1 and mouse GBP2 (mGBP2) translocated to intracellular S. flexneri and inhibited bacterial replication. Like wild-type mice, mutant mice deficient in GBP1–3, 5 and 7 succumbed to S. flexneri infection, but unlike wild-type mice, mice deficient in these GBPs were also susceptible to S. flexneri lacking ipaH9.8. The mode of IpaH9.8 action highlights the functional importance of GBPs in antibacterial defences. IpaH9.8 and S. flexneri provide a unique system for dissecting GBP-mediated immunity.

    更新日期:2017-11-16
  • BCAT1 restricts αKG levels in AML stem cells leading to IDHmut-like DNA hypermethylation
    Nature (IF 40.137) Pub Date : 2017-11-08
    Simon Raffel, Mattia Falcone, Niclas Kneisel, Jenny Hansson, Wei Wang, Christoph Lutz, Lars Bullinger, Gernot Poschet, Yannic Nonnenmacher, Andrea Barnert, Carsten Bahr, Petra Zeisberger, Adriana Przybylla, Markus Sohn, Martje Tönjes, Ayelet Erez, Lital Adler, Patrizia Jensen, Claudia Scholl, Stefan Fröhling, Sibylle Cocciardi, Patrick Wuchter, Christian Thiede, Anne Flörcken, Jörg Westermann, Gerhard Ehninger, Peter Lichter, Karsten Hiller, Rüdiger Hell, Carl Herrmann, Anthony D. Ho, Jeroen Krijgsveld, Bernhard Radlwimmer, Andreas Trumpp

    The branched-chain amino acid (BCAA) pathway and high levels of BCAA transaminase 1 (BCAT1) have recently been associated with aggressiveness in several cancer entities. However, the mechanistic role of BCAT1 in this process remains largely uncertain. Here, by performing high-resolution proteomic analysis of human acute myeloid leukaemia (AML) stem-cell and non-stem-cell populations, we find the BCAA pathway enriched and BCAT1 protein and transcripts overexpressed in leukaemia stem cells. We show that BCAT1, which transfers α-amino groups from BCAAs to α-ketoglutarate (αKG), is a critical regulator of intracellular αKG homeostasis. Further to its role in the tricarboxylic acid cycle, αKG is an essential cofactor for αKG-dependent dioxygenases such as Egl-9 family hypoxia inducible factor 1 (EGLN1) and the ten-eleven translocation (TET) family of DNA demethylases. Knockdown of BCAT1 in leukaemia cells caused accumulation of αKG, leading to EGLN1-mediated HIF1α protein degradation. This resulted in a growth and survival defect and abrogated leukaemia-initiating potential. By contrast, overexpression of BCAT1 in leukaemia cells decreased intracellular αKG levels and caused DNA hypermethylation through altered TET activity. AML with high levels of BCAT1 (BCAT1high) displayed a DNA hypermethylation phenotype similar to cases carrying a mutant isocitrate dehydrogenase (IDHmut), in which TET2 is inhibited by the oncometabolite 2-hydroxyglutarate. High levels of BCAT1 strongly correlate with shorter overall survival in IDHWTTET2WT, but not IDHmut or TET2mut AML. Gene sets characteristic for IDHmut AML were enriched in samples from patients with an IDHWTTET2WTBCAT1high status. BCAT1high AML showed robust enrichment for leukaemia stem-cell signatures, and paired sample analysis showed a significant increase in BCAT1 levels upon disease relapse. In summary, by limiting intracellular αKG, BCAT1 links BCAA catabolism to HIF1α stability and regulation of the epigenomic landscape, mimicking the effects of IDH mutations. Our results suggest the BCAA–BCAT1–αKG pathway as a therapeutic target to compromise leukaemia stem-cell function in patients with IDHWTTET2WT AML.

    更新日期:2017-11-16
  • A ubiquitin-dependent signalling axis specific for ALKBH-mediated DNA dealkylation repair
    Nature (IF 40.137) Pub Date : 2017-11-08
    Joshua R. Brickner, Jennifer M. Soll, Patrick M. Lombardi, Cathrine B. Vågbø, Miranda C. Mudge, Clement Oyeniran, Renana Rabe, Jessica Jackson, Meagan E. Sullender, Elyse Blazosky, Andrea K. Byrum, Yu Zhao, Mark A. Corbett, Jozef Gécz, Michael Field, Alessandro Vindigni, Geir Slupphaug, Cynthia Wolberger, Nima Mosammaparast

    DNA repair is essential to prevent the cytotoxic or mutagenic effects of various types of DNA lesions, which are sensed by distinct pathways to recruit repair factors specific to the damage type. Although biochemical mechanisms for repairing several forms of genomic insults are well understood, the upstream signalling pathways that trigger repair are established for only certain types of damage, such as double-stranded breaks and interstrand crosslinks. Understanding the upstream signalling events that mediate recognition and repair of DNA alkylation damage is particularly important, since alkylation chemotherapy is one of the most widely used systemic modalities for cancer treatment and because environmental chemicals may trigger DNA alkylation. Here we demonstrate that human cells have a previously unrecognized signalling mechanism for sensing damage induced by alkylation. We find that the alkylation repair complex ASCC (activating signal cointegrator complex) relocalizes to distinct nuclear foci specifically upon exposure of cells to alkylating agents. These foci associate with alkylated nucleotides, and coincide spatially with elongating RNA polymerase II and splicing components. Proper recruitment of the repair complex requires recognition of K63-linked polyubiquitin by the CUE (coupling of ubiquitin conjugation to ER degradation) domain of the subunit ASCC2. Loss of this subunit impedes alkylation adduct repair kinetics and increases sensitivity to alkylating agents, but not other forms of DNA damage. We identify RING finger protein 113A (RNF113A) as the E3 ligase responsible for upstream ubiquitin signalling in the ASCC pathway. Cells from patients with X-linked trichothiodystrophy, which harbour a mutation in RNF113A, are defective in ASCC foci formation and are hypersensitive to alkylating agents. Together, our work reveals a previously unrecognized ubiquitin-dependent pathway induced specifically to repair alkylation damage, shedding light on the molecular mechanism of X-linked trichothiodystrophy.

    更新日期:2017-11-16
  • Structure and assembly of the Ebola virus nucleocapsid
    Nature (IF 40.137) Pub Date : 2017-11-08
    William Wan, Larissa Kolesnikova, Mairi Clarke, Alexander Koehler, Takeshi Noda, Stephan Becker, John A. G. Briggs

    Ebola and Marburg viruses are filoviruses: filamentous, enveloped viruses that cause haemorrhagic fever. Filoviruses are within the order Mononegavirales, which also includes rabies virus, measles virus, and respiratory syncytial virus. Mononegaviruses have non-segmented, single-stranded negative-sense RNA genomes that are encapsidated by nucleoprotein and other viral proteins to form a helical nucleocapsid. The nucleocapsid acts as a scaffold for virus assembly and as a template for genome transcription and replication. Insights into nucleoprotein–nucleoprotein interactions have been derived from structural studies of oligomerized, RNA-encapsidating nucleoprotein, and cryo-electron microscopy of nucleocapsid or nucleocapsid-like structures. There have been no high-resolution reconstructions of complete mononegavirus nucleocapsids. Here we apply cryo-electron tomography and subtomogram averaging to determine the structure of Ebola virus nucleocapsid within intact viruses and recombinant nucleocapsid-like assemblies. These structures reveal the identity and arrangement of the nucleocapsid components, and suggest that the formation of an extended α-helix from the disordered carboxy-terminal region of nucleoprotein-core links nucleoprotein oligomerization, nucleocapsid condensation, RNA encapsidation, and accessory protein recruitment.

    更新日期:2017-11-16
  • Corrigendum: Superparamagnetic enhancement of thermoelectric performance
    Nature (IF 40.137) Pub Date : 2017-11-08
    Wenyu Zhao, Zhiyuan Liu, Zhigang Sun, Qingjie Zhang, Ping Wei, Xin Mu, Hongyu Zhou, Cuncheng Li, Shifang Ma, Danqi He, Pengxia Ji, Wanting Zhu, Xiaolei Nie, Xianli Su, Xinfeng Tang, Baogen Shen, Xiaoli Dong, Jihui Yang, Yong Liu, Jing Shi

    Nature549, 247–251 (2017); doi:10.1038/nature23667In the Methods subsection ‘Measure the Hall coefficient’ of this Letter, the equation μH = neσ should read μH = σ/(ne). This error has been corrected online.

    更新日期:2017-11-16
  • Erratum: Non-homeostatic body weight regulation through a brainstem-restricted receptor for GDF15
    Nature (IF 40.137) Pub Date : 2017-11-08
    Jer-Yuan Hsu, Suzanne Crawley, Michael Chen, Dina A. Ayupova, Darrin A. Lindhout, Jared Higbee, Alan Kutach, William Joo, Zhengyu Gao, Diana Fu, Carmen To, Kalyani Mondal, Betty Li, Avantika Kekatpure, Marilyn Wang, Teresa Laird, Geoffrey Horner, Jackie Chan, Michele McEntee, Manuel Lopez, Damodharan Lakshminarasimhan, Andre White, Sheng-Ping Wang, Jun Yao, Junming Yie, Hugo Matern, Mark Solloway, Raj Haldankar, Thomas Parsons, Jie Tang, Wenyan D. Shen, Yu Alice Chen, Hui Tian, Bernard B. Allan

    Nature550, 255–259 (2017); doi:10.1038/nature24042Owing to an error during the production process, in Fig. 2c of this Letter, all four groups of mice were incorrectly labelled as ‘WT’ (wild type), but the two groups on the left

    更新日期:2017-11-16
  • Corrigendum: High-throughput discovery of novel developmental phenotypes
    Nature (IF 40.137) Pub Date : 2017-11-08
    Mary E. Dickinson, Ann M. Flenniken, Xiao Ji, Lydia Teboul, Michael D. Wong, Jacqueline K. White, Terrence F. Meehan, Wolfgang J. Weninger, Henrik Westerberg, Hibret Adissu, Candice N. Baker, Lynette Bower, James M. Brown, L. Brianna Caddle, Francesco Chiani, Dave Clary, James Cleak, Mark J. Daly, James M. Denegre, Brendan Doe, Mary E. Dolan, Sarah M. Edie Helmut Fuchs, Valerie Gailus-Durner, Antonella Galli, Alessia Gambadoro, Juan Gallegos, Shiying Guo, Neil R. Horner, Chih-Wei Hsu, Sara J. Johnson, Sowmya Kalaga, Lance C. Keith, Louise Lanoue, Thomas N. Lawson, Monkol Lek, Manuel Mark, Susan Marschall, Jeremy Mason, Melissa L. McElwee, Susan Newbigging Lauryl M. J. Nutter, Kevin A. Peterson, Ramiro Ramirez-Solis, Douglas J. Rowland, Edward Ryder, Kaitlin E. Samocha, John R. Seavitt, Mohammed Selloum, Zsombor Szoke-Kovacs, Masaru Tamura, Amanda G. Trainor, Ilinca Tudose, Shigeharu Wakana, Jonathan Warren, Olivia Wendling, David B. West, Leeyean Wong, Atsushi Yoshiki, Wolfga..

    Nature537, 508–514 (2016); doi:10.1038/nature19356In this Article, the author Wolfgang Wurst was erroneously omitted from the author list. They are associated with the affiliations: HelmholtzZentrum Munich, Institute of Developmental Genetics, 85764 Munich-Neuherberg, Germany; Technical University of Munich,

    更新日期:2017-11-16
  • Skin regeneration with insights
    Nature (IF 40.137) Pub Date : 2017-11-08

    A feat in stem-cell therapy highlights what can be achieved when basic and clinical research combine to advance biological understanding and treatment.

    更新日期:2017-11-09
Some contents have been Reproduced with permission of the American Chemical Society.
Some contents have been Reproduced by permission of The Royal Society of Chemistry.
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