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  • Warming impairs trophic transfer efficiency in a long-term field experiment
    Nature (IF 42.778) Pub Date : 2021-03-01
    Diego R. Barneche; Chris J. Hulatt; Matteo Dossena; Daniel Padfield; Guy Woodward; Mark Trimmer; Gabriel Yvon-Durocher

    In natural ecosystems, the efficiency of energy transfer from resources to consumers determines the biomass structure of food webs. As a general rule, about 10% of the energy produced in one trophic level makes it up to the next1–3. Recent theory suggests this energy transfer could be further constrained if rising temperatures increase metabolic growth costs4, although experimental confirmation in

  • SARS-CoV-2 spike D614G change enhances replication and transmission
    Nature (IF 42.778) Pub Date : 2021-02-26
    Bin Zhou; Tran Thi Nhu Thao; Donata Hoffmann; Adriano Taddeo; Nadine Ebert; Fabien Labroussaa; Anne Pohlmann; Jacqueline King; Silvio Steiner; Jenna N. Kelly; Jasmine Portmann; Nico Joel Halwe; Lorenz Ulrich; Bettina Salome Trüeb; Xiaoyu Fan; Bernd Hoffmann; Li Wang; Lisa Thomann; Xudong Lin; Hanspeter Stalder; Berta Pozzi; Simone de Brot; Nannan Jiang; Dan Cui; Jaber Hossain; Malania Wilson; Matthew

    During the evolution of SARS-CoV-2 in humans a D614G substitution in the spike (S) protein emerged and became the predominant circulating variant (S-614G) of the COVID-19 pandemic1. However, whether the increasing prevalence of the S-614G variant represents a fitness advantage that improves replication and/or transmission in humans or is merely due to founder effects remains elusive. Here, we generated

  • Deterministic multi-qubit entanglement in a quantum network
    Nature (IF 42.778) Pub Date : 2021-02-24
    Youpeng Zhong; Hung-Shen Chang; Audrey Bienfait; Étienne Dumur; Ming-Han Chou; Christopher R. Conner; Joel Grebel; Rhys G. Povey; Haoxiong Yan; David I. Schuster; Andrew N. Cleland

    The generation of high-fidelity distributed multi-qubit entanglement is a challenging task for large-scale quantum communication and computational networks1,2,3,4. The deterministic entanglement of two remote qubits has recently been demonstrated with both photons5,6,7,8,9,10 and phonons11. However, the deterministic generation and transmission of multi-qubit entanglement has not been demonstrated

  • A mechanosensitive peri-arteriolar niche for osteogenesis and lymphopoiesis
    Nature (IF 42.778) Pub Date : 2021-02-24
    Bo Shen; Alpaslan Tasdogan; Jessalyn M. Ubellacker; Jingzhu Zhang; Elena D. Nosyreva; Liming Du; Malea M. Murphy; Shuiqing Hu; Yating Yi; Nergis Kara; Xin Liu; Shay Guela; Yuemeng Jia; Vijayashree Ramesh; Claire Embree; Evann C. Mitchell; Yunduo C. Zhao; Lining A. Ju; Zhao Hu; Genevieve M. Crane; Zhiyu Zhao; Ruhma Syeda; Sean J. Morrison

    Stromal cells in adult bone marrow that express leptin receptor (LEPR) are a critical source of growth factors, including stem cell factor (SCF), for the maintenance of haematopoietic stem cells and early restricted progenitors1,2,3,4,5,6. LEPR+ cells are heterogeneous, including skeletal stem cells and osteogenic and adipogenic progenitors7,8,9,10,11,12, although few markers have been available to

  • Reset of hippocampal–prefrontal circuitry facilitates learning
    Nature (IF 42.778) Pub Date : 2021-02-24
    Alan J. Park; Alexander Z. Harris; Kelly M. Martyniuk; Chia-Yuan Chang; Atheir I. Abbas; Daniel C. Lowes; Christoph Kellendonk; Joseph A. Gogos; Joshua A. Gordon

    The ability to rapidly adapt to novel situations is essential for survival, and this flexibility is impaired in many neuropsychiatric disorders1. Thus, understanding whether and how novelty prepares, or primes, brain circuitry to facilitate cognitive flexibility has important translational relevance. Exposure to novelty recruits the hippocampus and medial prefrontal cortex (mPFC)2 and may prime hi

  • Multi-kingdom ecological drivers of microbiota assembly in preterm infants
    Nature (IF 42.778) Pub Date : 2021-02-24
    Chitong Rao; Katharine Z. Coyte; Wayne Bainter; Raif S. Geha; Camilia R. Martin; Seth Rakoff-Nahoum

    The gut microbiota of preterm infants develops predictably1,2,3,4,5,6,7, with pioneer species colonizing the gut after birth, followed by an ordered succession of microorganisms. The gut microbiota is vital to the health of preterm infants8,9, but the forces that shape these predictable dynamics of microbiome assembly are unknown. The environment, the host and interactions between microorganisms all

  • A multi-scale brain map derived from whole-brain volumetric reconstructions
    Nature (IF 42.778) Pub Date : 2021-02-24
    Christopher A. Brittin; Steven J. Cook; David H. Hall; Scott W. Emmons; Netta Cohen

    Animal nervous system organization is crucial for all body functions and its disruption can lead to severe cognitive and behavioural impairment1. This organization relies on features across scales—from the localization of synapses at the nanoscale, through neurons, which possess intricate neuronal morphologies that underpin circuit organization, to stereotyped connections between different regions

  • Spatiotemporal dissection of the cell cycle with single-cell proteogenomics
    Nature (IF 42.778) Pub Date : 2021-02-24
    Diana Mahdessian; Anthony J. Cesnik; Christian Gnann; Frida Danielsson; Lovisa Stenström; Muhammad Arif; Cheng Zhang; Trang Le; Fredric Johansson; Rutger Shutten; Anna Bäckström; Ulrika Axelsson; Peter Thul; Nathan H. Cho; Oana Carja; Mathias Uhlén; Adil Mardinoglu; Charlotte Stadler; Cecilia Lindskog; Burcu Ayoglu; Manuel D. Leonetti; Fredrik Pontén; Devin P. Sullivan; Emma Lundberg

    The cell cycle, over which cells grow and divide, is a fundamental process of life. Its dysregulation has devastating consequences, including cancer1,2,3. The cell cycle is driven by precise regulation of proteins in time and space, which creates variability between individual proliferating cells. To our knowledge, no systematic investigations of such cell-to-cell proteomic variability exist. Here

  • Sulfur sequestration promotes multicellularity during nutrient limitation
    Nature (IF 42.778) Pub Date : 2021-02-24
    Beth Kelly; Gustavo E. Carrizo; Joy Edwards-Hicks; David E. Sanin; Michal A. Stanczak; Chantal Priesnitz; Lea J. Flachsmann; Jonathan D. Curtis; Gerhard Mittler; Yaarub Musa; Thomas Becker; Joerg M. Buescher; Erika L. Pearce

    The behaviour of Dictyostelium discoideum depends on nutrients1. When sufficient food is present these amoebae exist in a unicellular state, but upon starvation they aggregate into a multicellular organism2,3. This biology makes D. discoideum an ideal model for investigating how fundamental metabolism commands cell differentiation and function. Here we show that reactive oxygen species—generated as

  • An organoid-based organ-repurposing approach to treat short bowel syndrome
    Nature (IF 42.778) Pub Date : 2021-02-24
    Shinya Sugimoto; Eiji Kobayashi; Masayuki Fujii; Yuki Ohta; Kazuya Arai; Mami Matano; Keiko Ishikawa; Kentaro Miyamoto; Kohta Toshimitsu; Sirirat Takahashi; Kosaku Nanki; Yoji Hakamata; Takanori Kanai; Toshiro Sato

    The small intestine is the main organ for nutrient absorption, and its extensive resection leads to malabsorption and wasting conditions referred to as short bowel syndrome (SBS). Organoid technology enables an efficient expansion of intestinal epithelium tissue in vitro1, but reconstruction of the whole small intestine, including the complex lymphovascular system, has remained challenging2. Here we

  • Lipid signalling enforces functional specialization of T reg cells in tumours
    Nature (IF 42.778) Pub Date : 2021-02-24
    Seon Ah Lim; Jun Wei; Thanh-Long M. Nguyen; Hao Shi; Wei Su; Gustavo Palacios; Yogesh Dhungana; Nicole M. Chapman; Lingyun Long; Jordy Saravia; Peter Vogel; Hongbo Chi

    Regulatory T cells (Treg cells) are essential for immune tolerance1, but also drive immunosuppression in the tumour microenvironment2. Therapeutic targeting of Treg cells in cancer will therefore require the identification of context-specific mechanisms that affect their function. Here we show that inhibiting lipid synthesis and metabolic signalling that are dependent on sterol-regulatory-element-binding

  • The asymmetry of antimatter in the proton
    Nature (IF 42.778) Pub Date : 2021-02-24
    J. Dove; B. Kerns; R. E. McClellan; S. Miyasaka; D. H. Morton; K. Nagai; S. Prasad; F. Sanftl; M. B. C. Scott; A. S. Tadepalli; C. A. Aidala; J. Arrington; C. Ayuso; C. L. Barker; C. N. Brown; W. C. Chang; A. Chen; D. C. Christian; B. P. Dannowitz; M. Daugherity; M. Diefenthaler; L. El Fassi; D. F. Geesaman; R. Gilman; Y. Goto; L. Guo; R. Guo; T. J. Hague; R. J. Holt; D. Isenhower; E. R. Kinney; N

    The fundamental building blocks of the proton—quarks and gluons—have been known for decades. However, we still have an incomplete theoretical and experimental understanding of how these particles and their dynamics give rise to the quantum bound state of the proton and its physical properties, such as its spin1. The two up quarks and the single down quark that comprise the proton in the simplest picture

  • Genomic Insights into the Formation of Human Populations in East Asia
    Nature (IF 42.778) Pub Date : 2021-02-22
    Chuan-Chao Wang; Hui-Yuan Yeh; Alexander N. Popov; Hu-Qin Zhang; Hirofumi Matsumura; Kendra Sirak; Olivia Cheronet; Alexey Kovalev; Nadin Rohland; Alexander M. Kim; Swapan Mallick; Rebecca Bernardos; Dashtseveg Tumen; Jing Zhao; Yi-Chang Liu; Jiun-Yu Liu; Matthew Mah; Ke Wang; Zhao Zhang; Nicole Adamski; Nasreen Broomandkhoshbacht; Kimberly Callan; Francesca Candilio; Kellie Sara Duffett Carlson; Brendan

    The deep population history of East Asia remains poorly understood due to a lack of ancient DNA data and sparse sampling of present-day people1,2. We report genome-wide data from 166 East Asians dating to 6000 BCE – 1000 CE and 46 present-day groups. Hunter-gatherers from Japan, the Amur River Basin, and people of Neolithic and Iron Age Taiwan and the Tibetan plateau are linked by a deeply-splitting

  • Closed-loop recycling of polyethylene-like materials
    Nature (IF 42.778) Pub Date : 2021-02-17
    Manuel Häußler; Marcel Eck; Dario Rothauer; Stefan Mecking

    Plastics are key components of almost any technology today. Although their production consumes substantial feedstock resources, plastics are largely disposed of after their service life. In terms of a circular economy1,2,3,4,5,6,7,8, reuse of post-consumer sorted polymers (‘mechanical recycling’) is hampered by deterioration of materials performance9,10. Chemical recycling1,11 via depolymerization

  • High-resolution X-ray luminescence extension imaging
    Nature (IF 42.778) Pub Date : 2021-02-17
    Xiangyu Ou; Xian Qin; Bolong Huang; Jie Zan; Qinxia Wu; Zhongzhu Hong; Lili Xie; Hongyu Bian; Zhigao Yi; Xiaofeng Chen; Yiming Wu; Xiaorong Song; Juan Li; Qiushui Chen; Huanghao Yang; Xiaogang Liu

    Current X-ray imaging technologies involving flat-panel detectors have difficulty in imaging three-dimensional objects because fabrication of large-area, flexible, silicon-based photodetectors on highly curved surfaces remains a challenge1,2,3. Here we demonstrate ultralong-lived X-ray trapping for flat-panel-free, high-resolution, three-dimensional imaging using a series of solution-processable, lanthanide-doped

  • Structure and inhibition mechanism of the human citrate transporter NaCT
    Nature (IF 42.778) Pub Date : 2021-02-17
    David B. Sauer; Jinmei Song; Bing Wang; Jacob K. Hilton; Nathan K. Karpowich; Joseph A. Mindell; William J. Rice; Da-Neng Wang

    Citrate is best known as an intermediate in the tricarboxylic acid cycle of the cell. In addition to this essential role in energy metabolism, the tricarboxylate anion also acts as both a precursor and a regulator of fatty acid synthesis1,2,3. Thus, the rate of fatty acid synthesis correlates directly with the cytosolic concentration of citrate4,5. Liver cells import citrate through the sodium-dependent

  • Creatine kinase B controls futile creatine cycling in thermogenic fat
    Nature (IF 42.778) Pub Date : 2021-02-17
    Janane F. Rahbani; Anna Roesler; Mohammed F. Hussain; Bozena Samborska; Christien B. Dykstra; Linus Tsai; Mark P. Jedrychowski; Laurent Vergnes; Karen Reue; Bruce M. Spiegelman; Lawrence Kazak

    Obesity increases the risk of mortality because of metabolic sequelae such as type 2 diabetes and cardiovascular disease1. Thermogenesis by adipocytes can counteract obesity and metabolic diseases2,3. In thermogenic fat, creatine liberates a molar excess of mitochondrial ADP—purportedly via a phosphorylation cycle4—to drive thermogenic respiration. However, the proteins that control this futile creatine

  • Loop extrusion as a mechanism for formation of DNA damage repair foci
    Nature (IF 42.778) Pub Date : 2021-02-17
    Coline Arnould; Vincent Rocher; Anne-Laure Finoux; Thomas Clouaire; Kevin Li; Felix Zhou; Pierre Caron; Philippe. E. Mangeot; Emiliano P. Ricci; Raphaël Mourad; James E. Haber; Daan Noordermeer; Gaëlle Legube

    The repair of DNA double-strand breaks (DSBs) is essential for safeguarding genome integrity. When a DSB forms, the PI3K-related ATM kinase rapidly triggers the establishment of megabase-sized, chromatin domains decorated with phosphorylated histone H2AX (γH2AX), which act as seeds for the formation of DNA-damage response foci1. It is unclear how these foci are rapidly assembled to establish a ‘repair-prone’

  • Localization of lattice dynamics in low-angle twisted bilayer graphene
    Nature (IF 42.778) Pub Date : 2021-02-17
    Andreij C. Gadelha; Douglas A. A. Ohlberg; Cassiano Rabelo; Eliel G. S. Neto; Thiago L. Vasconcelos; João L. Campos; Jessica S. Lemos; Vinícius Ornelas; Daniel Miranda; Rafael Nadas; Fabiano C. Santana; Kenji Watanabe; Takashi Taniguchi; Benoit van Troeye; Michael Lamparski; Vincent Meunier; Viet-Hung Nguyen; Dawid Paszko; Jean-Christophe Charlier; Leonardo C. Campos; Luiz G. Cançado; Gilberto Medeiros-Ribeiro;

    Twisted bilayer graphene is created by slightly rotating the two crystal networks in bilayer graphene with respect to each other. For small twist angles, the material undergoes a self-organized lattice reconstruction, leading to the formation of a periodically repeated domain1,2,3. The resulting superlattice modulates the vibrational3,4 and electronic5,6 structures within the material, leading to changes

  • Glutamate transporters have a chloride channel with two hydrophobic gates
    Nature (IF 42.778) Pub Date : 2021-02-17
    Ichia Chen; Shashank Pant; Qianyi Wu; Rosemary J. Cater; Meghna Sobti; Robert J. Vandenberg; Alastair G. Stewart; Emad Tajkhorshid; Josep Font; Renae M. Ryan

    Glutamate is the most abundant excitatory neurotransmitter in the central nervous system, and its precise control is vital to maintain normal brain function and to prevent excitotoxicity1. The removal of extracellular glutamate is achieved by plasma-membrane-bound transporters, which couple glutamate transport to sodium, potassium and pH gradients using an elevator mechanism2,3,4,5. Glutamate transporters

  • Coherent X-ray−optical control of nuclear excitons
    Nature (IF 42.778) Pub Date : 2021-02-17
    Kilian P. Heeg; Andreas Kaldun; Cornelius Strohm; Christian Ott; Rajagopalan Subramanian; Dominik Lentrodt; Johann Haber; Hans-Christian Wille; Stephan Goerttler; Rudolf Rüffer; Christoph H. Keitel; Ralf Röhlsberger; Thomas Pfeifer; Jörg Evers

    Coherent control of quantum dynamics is key to a multitude of fundamental studies and applications1. In the visible or longer-wavelength domains, near-resonant light fields have become the primary tool with which to control electron dynamics2. Recently, coherent control in the extreme-ultraviolet range was demonstrated3, with a few-attosecond temporal resolution of the phase control. At hard-X-ray

  • Million-year-old DNA sheds light on the genomic history of mammoths
    Nature (IF 42.778) Pub Date : 2021-02-17
    Tom van der Valk; Patrícia Pečnerová; David Díez-del-Molino; Anders Bergström; Jonas Oppenheimer; Stefanie Hartmann; Georgios Xenikoudakis; Jessica A. Thomas; Marianne Dehasque; Ekin Sağlıcan; Fatma Rabia Fidan; Ian Barnes; Shanlin Liu; Mehmet Somel; Peter D. Heintzman; Pavel Nikolskiy; Beth Shapiro; Pontus Skoglund; Michael Hofreiter; Adrian M. Lister; Anders Götherström; Love Dalén

    Temporal genomic data hold great potential for studying evolutionary processes such as speciation. However, sampling across speciation events would, in many cases, require genomic time series that stretch well back into the Early Pleistocene subepoch. Although theoretical models suggest that DNA should survive on this timescale1, the oldest genomic data recovered so far are from a horse specimen dated

  • Affinity-coupled CCL22 promotes positive selection in germinal centres
    Nature (IF 42.778) Pub Date : 2021-02-17
    Bo Liu; Yihan Lin; Jiacong Yan; Jiacheng Yao; Dan Liu; Weiwei Ma; Jianbin Wang; Wanli Liu; Chengshuo Wang; Luo Zhang; Hai Qi

    Antibody affinity maturation depends on positive selection in germinal centres (GCs) of rare B cell clones that acquire higher-affinity B cell receptors via somatic hypermutation, present more antigen to follicular helper T (TFH) cells and, consequently, receive more contact-dependent T cell help1. As these GC B cells and TFH cells do not maintain long-lasting contacts in the chaotic GC environment2

  • Self-similar mesocrystals form via interface-driven nucleation and assembly
    Nature (IF 42.778) Pub Date : 2021-02-17
    Guomin Zhu; Maria L. Sushko; John S. Loring; Benjamin A. Legg; Miao Song; Jennifer A. Soltis; Xiaopeng Huang; Kevin M. Rosso; James J. De Yoreo

    Crystallization by particle attachment (CPA) is a frequently occurring mechanism of colloidal crystallization that results in hierarchical morphologies1,2,3,4. CPA has been exploited to create nanomaterials with unusual properties4,5,6 and is implicated in the development of complex mineral textures1,7. Oriented attachment7,8—a form of CPA in which particles align along specific crystallographic directions—produces

  • CTLA-4 blockade drives loss of T reg stability in glycolysis-low tumours
    Nature (IF 42.778) Pub Date : 2021-02-15
    Roberta Zappasodi; Inna Serganova; Ivan J. Cohen; Masatomo Maeda; Masahiro Shindo; Yasin Senbabaoglu; McLane J. Watson; Avigdor Leftin; Rachana Maniyar; Svena Verma; Matthew Lubin; Myat Ko; Mayuresh M. Mane; Hong Zhong; Cailian Liu; Arnab Ghosh; Mohsen Abu-Akeel; Ellen Ackerstaff; Jason A. Koutcher; Ping-Chih Ho; Greg M. Delgoffe; Ronald Blasberg; Jedd D. Wolchok; Taha Merghoub

    Limiting the metabolic competition in the tumor microenvironment (TME) may increase the effectiveness of immunotherapy. Because of its critical role in glucose metabolism of activated T cells, CD28 signaling has been proposed as a T-cell metabolic biosensor1. Conversely, CTLA-4 engagement has been shown to down-regulate T-cell glycolysis1. Here, we investigated the impact of CTLA-4 blockade on the

  • Metabolic support of tumour-infiltrating regulatory T cells by lactic acid
    Nature (IF 42.778) Pub Date : 2021-02-15
    McLane J. Watson; Paolo D. A. Vignali; Steven J. Mullett; Abigail E. Overacre-Delgoffe; Ronal M. Peralta; Stephanie Grebinoski; Ashley V. Menk; Natalie L. Rittenhouse; Kristin DePeaux; Ryan D. Whetstone; Dario A. A. Vignali; Timothy W. Hand; Amanda C. Poholek; Brett M. Morrison; Jeffrey D. Rothstein; Stacy G. Wendell; Greg M. Delgoffe

    Regulatory T (Treg) cells, although vital for immune homeostasis, also represent a major barrier to anti-cancer immunity, as the tumour microenvironment (TME) promotes the recruitment, differentiation and activity of these cells1,2. Tumour cells show deregulated metabolism, leading to a metabolite-depleted, hypoxic and acidic TME3, which places infiltrating effector T cells in competition with the

  • mRNA vaccine-elicited antibodies to SARS-CoV-2 and circulating variants
    Nature (IF 42.778) Pub Date : 2021-02-10
    Zijun Wang; Fabian Schmidt; Yiska Weisblum; Frauke Muecksch; Christopher O. Barnes; Shlomo Finkin; Dennis Schaefer-Babajew; Melissa Cipolla; Christian Gaebler; Jenna A. Lieberman; Thiago Y. Oliveira; Zhi Yang; Morgan E. Abernathy; Kathryn E. Huey-Tubman; Arlene Hurley; Martina Turroja; Kamille A. West; Kristie Gordon; Katrina G. Millard; Victor Ramos; Justin Da Silva; Jianliang Xu; Robert A. Colbert;

    Here we report on the antibody and memory B cell responses in a cohort of 20 volunteers who received either the Moderna (mRNA-1273) or Pfizer-BioNTech (BNT162b2) vaccines1–4. Eight weeks after the second vaccine injection volunteers showed high levels of IgM, and IgG anti-SARS-CoV-2 spike protein (S) and receptor binding domain (RBD) binding titers. Moreover, the plasma neutralizing activity, and the

  • Macrophages provide a transient muscle stem cell niche via NAMPT secretion
    Nature (IF 42.778) Pub Date : 2021-02-10
    Dhanushika Ratnayake; Phong D. Nguyen; Fernando J. Rossello; Verena C. Wimmer; Jean L. Tan; Laura A. Galvis; Ziad Julier; Alasdair J. Wood; Thomas Boudier; Abdulsalam I. Isiaku; Silke Berger; Viola Oorschot; Carmen Sonntag; Kelly L. Rogers; Christophe Marcelle; Graham J. Lieschke; Mikaël M. Martino; Jeroen Bakkers; Peter D. Currie

    Skeletal muscle regenerates through the activation of resident stem cells. Termed satellite cells, these normally quiescent cells are induced to proliferate by wound-derived signals1. Identifying the source and nature of these cues has been hampered by an inability to visualize the complex cell interactions that occur within the wound. Here we use muscle injury models in zebrafish to systematically

  • Thermally reconfigurable monoclinic nematic colloidal fluids
    Nature (IF 42.778) Pub Date : 2021-02-10
    Haridas Mundoor; Jin-Sheng Wu; Henricus H. Wensink; Ivan I. Smalyukh

    Fundamental relationships are believed to exist between the symmetries of building blocks and the condensed matter phases that they form1. For example, constituent molecular and colloidal rods and disks impart their uniaxial symmetry onto nematic liquid crystals, such as those used in displays1,2. Low-symmetry organizations could form in mixtures of rods and disks3,4,5, but entropy tends to phase-separate

  • A decline in emissions of CFC-11 and related chemicals from eastern China
    Nature (IF 42.778) Pub Date : 2021-02-10
    Sunyoung Park; Luke M. Western; Takuya Saito; Alison L. Redington; Stephan Henne; Xuekun Fang; Ronald G. Prinn; Alistair J. Manning; Stephen A. Montzka; Paul J. Fraser; Anita L. Ganesan; Christina M. Harth; Jooil Kim; Paul B. Krummel; Qing Liang; Jens Mühle; Simon O’Doherty; Hyeri Park; Mi-Kyung Park; Stefan Reimann; Peter K. Salameh; Ray F. Weiss; Matthew Rigby

    Emissions of ozone-depleting substances, including trichlorofluoromethane (CFC-11), have decreased since the mid-1980s in response to the Montreal Protocol1,2. In recent years, an unexpected increase in CFC-11 emissions beginning in 2013 has been reported, with much of the global rise attributed to emissions from eastern China3,4. Here we use high-frequency atmospheric mole fraction observations from

  • A decline in global CFC-11 emissions during 2018−2019
    Nature (IF 42.778) Pub Date : 2021-02-10
    Stephen A. Montzka; Geoffrey S. Dutton; Robert W. Portmann; Martyn P. Chipperfield; Sean Davis; Wuhu Feng; Alistair J. Manning; Eric Ray; Matthew Rigby; Bradley D. Hall; Carolina Siso; J. David Nance; Paul B. Krummel; Jens Mühle; Dickon Young; Simon O’Doherty; Peter K. Salameh; Christina M. Harth; Ronald G. Prinn; Ray F. Weiss; James W. Elkins; Helen Walter-Terrinoni; Christina Theodoridi

    The atmospheric concentration of trichlorofluoromethane (CFC-11) has been in decline since the production of ozone-depleting substances was phased out under the Montreal Protocol1,2. Since 2013, the concentration decline of CFC-11 slowed unexpectedly owing to increasing emissions, probably from unreported production, which, if sustained, would delay the recovery of the stratospheric ozone layer1,2

  • Origins of modern human ancestry
    Nature (IF 42.778) Pub Date : 2021-02-10
    Anders Bergström; Chris Stringer; Mateja Hajdinjak; Eleanor M. L. Scerri; Pontus Skoglund

    New finds in the palaeoanthropological and genomic records have changed our view of the origins of modern human ancestry. Here we review our current understanding of how the ancestry of modern humans around the globe can be traced into the deep past, and which ancestors it passes through during our journey back in time. We identify three key phases that are surrounded by major questions, and which

  • A universal 3D imaging sensor on a silicon photonics platform
    Nature (IF 42.778) Pub Date : 2021-02-10
    Christopher Rogers; Alexander Y. Piggott; David J. Thomson; Robert F. Wiser; Ion E. Opris; Steven A. Fortune; Andrew J. Compston; Alexander Gondarenko; Fanfan Meng; Xia Chen; Graham T. Reed; Remus Nicolaescu

    Accurate three-dimensional (3D) imaging is essential for machines to map and interact with the physical world1,2. Although numerous 3D imaging technologies exist, each addressing niche applications with varying degrees of success, none has achieved the breadth of applicability and impact that digital image sensors have in the two-dimensional imaging world3,4,5,6,7,8,9,10. A large-scale two-dimensional

  • Protecting a bosonic qubit with autonomous quantum error correction
    Nature (IF 42.778) Pub Date : 2021-02-10
    Jeffrey M. Gertler; Brian Baker; Juliang Li; Shruti Shirol; Jens Koch; Chen Wang

    To build a universal quantum computer from fragile physical qubits, effective implementation of quantum error correction (QEC)1 is an essential requirement and a central challenge. Existing demonstrations of QEC are based on an active schedule of error-syndrome measurements and adaptive recovery operations2,3,4,5,6,7 that are hardware intensive and prone to introducing and propagating errors. In principle

  • A quantum enhanced search for dark matter axions
    Nature (IF 42.778) Pub Date : 2021-02-10
    K. M. Backes; D. A. Palken; S. Al Kenany; B. M. Brubaker; S. B. Cahn; A. Droster; Gene C. Hilton; Sumita Ghosh; H. Jackson; S. K. Lamoreaux; A. F. Leder; K. W. Lehnert; S. M. Lewis; M. Malnou; R. H. Maruyama; N. M. Rapidis; M. Simanovskaia; Sukhman Singh; D. H. Speller; I. Urdinaran; Leila R. Vale; E. C. van Assendelft; K. van Bibber; H. Wang

    The manipulation of quantum states of light1 holds the potential to enhance searches for fundamental physics. Only recently has the maturation of quantum squeezing technology coincided with the emergence of fundamental physics searches that are limited by quantum uncertainty2,3. In particular, the quantum chromodynamics axion provides a possible solution to two of the greatest outstanding problems

  • Cooperative epithelial phagocytosis enables error correction in the early embryo
    Nature (IF 42.778) Pub Date : 2021-02-10
    Esteban Hoijman; Hanna-Maria Häkkinen; Queralt Tolosa-Ramon; Senda Jiménez-Delgado; Chris Wyatt; Marta Miret-Cuesta; Manuel Irimia; Andrew Callan-Jones; Stefan Wieser; Verena Ruprecht

    Errors in early embryogenesis are a cause of sporadic cell death and developmental failure1,2. Phagocytic activity has a central role in scavenging apoptotic cells in differentiated tissues3,4,5,6. However, how apoptotic cells are cleared in the blastula embryo in the absence of specialized immune cells remains unknown. Here we show that the surface epithelium of zebrafish and mouse embryos, which

  • Sequencing of 53,831 diverse genomes from the NHLBI TOPMed Program
    Nature (IF 42.778) Pub Date : 2021-02-10
    Daniel Taliun; Daniel N. Harris; Michael D. Kessler; Jedidiah Carlson; Zachary A. Szpiech; Raul Torres; Sarah A. Gagliano Taliun; André Corvelo; Stephanie M. Gogarten; Hyun Min Kang; Achilleas N. Pitsillides; Jonathon LeFaive; Seung-been Lee; Xiaowen Tian; Brian L. Browning; Sayantan Das; Anne-Katrin Emde; Wayne E. Clarke; Douglas P. Loesch; Amol C. Shetty; Thomas W. Blackwell; Albert V. Smith; Quenna

    The Trans-Omics for Precision Medicine (TOPMed) programme seeks to elucidate the genetic architecture and biology of heart, lung, blood and sleep disorders, with the ultimate goal of improving diagnosis, treatment and prevention of these diseases. The initial phases of the programme focused on whole-genome sequencing of individuals with rich phenotypic data and diverse backgrounds. Here we describe

  • Visualization of the mechanosensitive ion channel MscS under membrane tension
    Nature (IF 42.778) Pub Date : 2021-02-10
    Yixiao Zhang; Csaba Daday; Ruo-Xu Gu; Charles D. Cox; Boris Martinac; Bert L. de Groot; Thomas Walz

    Mechanosensitive channels sense mechanical forces in cell membranes and underlie many biological sensing processes1,2,3. However, how exactly they sense mechanical force remains under investigation4. The bacterial mechanosensitive channel of small conductance, MscS, is one of the most extensively studied mechanosensitive channels4,5,6,7,8, but how it is regulated by membrane tension remains unclear

  • The kinetic landscape of an RNA-binding protein in cells
    Nature (IF 42.778) Pub Date : 2021-02-10
    Deepak Sharma; Leah L. Zagore; Matthew M. Brister; Xuan Ye; Carlos E. Crespo-Hernández; Donny D. Licatalosi; Eckhard Jankowsky

    Gene expression in higher eukaryotic cells orchestrates interactions between thousands of RNA-binding proteins (RBPs) and tens of thousands of RNAs1. The kinetics by which RBPs bind to and dissociate from their RNA sites are critical for the coordination of cellular RNA–protein interactions2. However, these kinetic parameters have not been experimentally measured in cells. Here we show that time-resolved

  • Non-coding deletions identify Maenli lncRNA as a limb-specific En1 regulator
    Nature (IF 42.778) Pub Date : 2021-02-10
    Lila Allou; Sara Balzano; Andreas Magg; Mathieu Quinodoz; Beryl Royer-Bertrand; Robert Schöpflin; Wing-Lee Chan; Carlos E. Speck-Martins; Daniel Rocha Carvalho; Luciano Farage; Charles Marques Lourenço; Regina Albuquerque; Srilakshmi Rajagopal; Sheela Nampoothiri; Belinda Campos-Xavier; Carole Chiesa; Florence Niel-Bütschi; Lars Wittler; Bernd Timmermann; Malte Spielmann; Michael I. Robson; Alessa

    Long non-coding RNAs (lncRNAs) can be important components in gene-regulatory networks1, but the exact nature and extent of their involvement in human Mendelian disease is largely unknown. Here we show that genetic ablation of a lncRNA locus on human chromosome 2 causes a severe congenital limb malformation. We identified homozygous 27–63-kilobase deletions located 300 kilobases upstream of the engrailed-1

  • Facile route to bulk ultrafine-grain steels for high strength and ductility
    Nature (IF 42.778) Pub Date : 2021-02-10
    Junheng Gao; Suihe Jiang; Huairuo Zhang; Yuhe Huang; Dikai Guan; Yidong Xu; Shaokang Guan; Leonid A. Bendersky; Albert V. Davydov; Yuan Wu; Huihui Zhu; Yandong Wang; Zhaoping Lu; W. Mark Rainforth

    Steels with sub-micrometre grain sizes usually possess high toughness and strength, which makes them promising for lightweighting technologies and energy-saving strategies. So far, the industrial fabrication of ultrafine-grained (UFG) alloys, which generally relies on the manipulation of diffusional phase transformation, has been limited to steels with austenite-to-ferrite transformation1,2,3. Moreover

  • SARS-CoV-2 infection is effectively treated and prevented by EIDD-2801
    Nature (IF 42.778) Pub Date : 2021-02-09
    Angela Wahl; Lisa E. Gralinski; Claire E. Johnson; Wenbo Yao; Martina Kovarova; Kenneth H. Dinnon; Hongwei Liu; Victoria J. Madden; Halina M. Krzystek; Chandrav De; Kristen K. White; Kendra Gully; Alexandra Schäfer; Tanzila Zaman; Sarah R. Leist; Paul O. Grant; Gregory R. Bluemling; Alexander A. Kolykhalov; Michael G. Natchus; Frederic B. Askin; George Painter; Edward P. Browne; Corbin D. Jones; Raymond

    All known recently emerged human coronaviruses probably originated in bats1. Here we used a single experimental platform based on human lung-only mice (LoM) to demonstrate efficient in vivo replication of all recently emerged human coronaviruses (SARS-CoV, MERS-CoV and SARS-CoV-2) and two highly relevant endogenous pre-pandemic SARS-like bat coronaviruses. Virus replication in this model occurs in

  • SARS-CoV-2 evolution during treatment of chronic infection
    Nature (IF 42.778) Pub Date : 2021-02-05
    Steven A. Kemp; Dami A. Collier; Rawlings P. Datir; Isabella A. T. M. Ferreira; Salma Gayed; Aminu Jahun; Myra Hosmillo; Chloe Rees-Spear; Petra Mlcochova; Ines Ushiro Lumb; David J. Roberts; Anita Chandra; Nigel Temperton; Katherine Sharrocks; Elizabeth Blane; Yorgo Modis; Kendra Leigh; John Briggs; Marit van Gils; Kenneth G. C. Smith; John R. Bradley; Chris Smith; Rainer Doffinger; Lourdes Ceron-Gutierrez;

    SARS-CoV-2 Spike protein is critical for virus infection via engagement of ACE21, and is a major antibody target. Here we report chronic SARS-CoV-2 with reduced sensitivity to neutralising antibodies in an immune suppressed individual treated with convalescent plasma, generating whole genome ultradeep sequences over 23 time points spanning 101 days. Little change was observed in the overall viral population

  • Viscoelastic control of spatiotemporal order in bacterial active matter
    Nature (IF 42.778) Pub Date : 2021-02-03
    Song Liu; Suraj Shankar; M. Cristina Marchetti; Yilin Wu

    Active matter consists of units that generate mechanical work by consuming energy1. Examples include living systems (such as assemblies of bacteria2,3,4,5 and biological tissues6,7), biopolymers driven by molecular motors8,9,10,11 and suspensions of synthetic self-propelled particles12,13,14. A central goal is to understand and control the self-organization of active assemblies in space and time. Most

  • Bayesian reaction optimization as a tool for chemical synthesis
    Nature (IF 42.778) Pub Date : 2021-02-03
    Benjamin J. Shields; Jason Stevens; Jun Li; Marvin Parasram; Farhan Damani; Jesus I. Martinez Alvarado; Jacob M. Janey; Ryan P. Adams; Abigail G. Doyle

    Reaction optimization is fundamental to synthetic chemistry, from optimizing the yield of industrial processes to selecting conditions for the preparation of medicinal candidates1. Likewise, parameter optimization is omnipresent in artificial intelligence, from tuning virtual personal assistants to training social media and product recommendation systems2. Owing to the high cost associated with carrying

  • Elevated NSD3 histone methylation activity drives squamous cell lung cancer
    Nature (IF 42.778) Pub Date : 2021-02-03
    Gang Yuan; Natasha M. Flores; Simone Hausmann; Shane M. Lofgren; Vladlena Kharchenko; Maria Angulo-Ibanez; Deepanwita Sengupta; Xiaoyin Lu; Iwona Czaban; Dulat Azhibek; Silvestre Vicent; Wolfgang Fischle; Mariusz Jaremko; Bingliang Fang; Ignacio I. Wistuba; Katrin F. Chua; Jack A. Roth; John D. Minna; Ning-Yi Shao; Łukasz Jaremko; Pawel K. Mazur; Or Gozani

    Amplification of chromosomal region 8p11–12 is a common genetic alteration that has been implicated in the aetiology of lung squamous cell carcinoma (LUSC)1,2,3. The FGFR1 gene is the main candidate driver of tumorigenesis within this region4. However, clinical trials evaluating FGFR1 inhibition as a targeted therapy have been unsuccessful5. Here we identify the histone H3 lysine 36 (H3K36) methyltransferase

  • A gene–environment-induced epigenetic program initiates tumorigenesis
    Nature (IF 42.778) Pub Date : 2021-02-03
    Direna Alonso-Curbelo; Yu-Jui Ho; Cassandra Burdziak; Jesper L. V. Maag; John P. Morris; Rohit Chandwani; Hsuan-An Chen; Kaloyan M. Tsanov; Francisco M. Barriga; Wei Luan; Nilgun Tasdemir; Geulah Livshits; Elham Azizi; Jaeyoung Chun; John E. Wilkinson; Linas Mazutis; Steven D. Leach; Richard Koche; Dana Pe’er; Scott W. Lowe

    Tissue damage increases the risk of cancer through poorly understood mechanisms1. In mouse models of pancreatic cancer, pancreatitis associated with tissue injury collaborates with activating mutations in the Kras oncogene to markedly accelerate the formation of early neoplastic lesions and, ultimately, adenocarcinoma2,3. Here, by integrating genomics, single-cell chromatin assays and spatiotemporally

  • Ubiquitin ligation to F-box protein targets by SCF–RBR E3–E3 super-assembly
    Nature (IF 42.778) Pub Date : 2021-02-03
    Daniel Horn-Ghetko; David T. Krist; J. Rajan Prabu; Kheewoong Baek; Monique P. C. Mulder; Maren Klügel; Daniel C. Scott; Huib Ovaa; Gary Kleiger; Brenda A. Schulman

    E3 ligases are typically classified by hallmark domains such as RING and RBR, which are thought to specify unique catalytic mechanisms of ubiquitin transfer to recruited substrates1,2. However, rather than functioning individually, many neddylated cullin–RING E3 ligases (CRLs) and RBR-type E3 ligases in the ARIH family—which together account for nearly half of all ubiquitin ligases in humans—form E3–E3

  • Skin-resident innate lymphoid cells converge on a pathogenic effector state
    Nature (IF 42.778) Pub Date : 2021-02-03
    Piotr Bielecki; Samantha J. Riesenfeld; Jan-Christian Hütter; Elena Torlai Triglia; Monika S. Kowalczyk; Roberto R. Ricardo-Gonzalez; Mi Lian; Maria C. Amezcua Vesely; Lina Kroehling; Hao Xu; Michal Slyper; Christoph Muus; Leif S. Ludwig; Elena Christian; Liming Tao; Amanda J. Kedaigle; Holly R. Steach; Autumn G. York; Mathias H. Skadow; Parastou Yaghoubi; Danielle Dionne; Abigail Jarret; Heather M

    Tissue-resident innate lymphoid cells (ILCs) help sustain barrier function and respond to local signals. ILCs are traditionally classified as ILC1, ILC2 or ILC3 on the basis of their expression of specific transcription factors and cytokines1. In the skin, disease-specific production of ILC3-associated cytokines interleukin (IL)-17 and IL-22 in response to IL-23 signalling contributes to dermal inflammation

  • Molecular basis for control of antibiotic production by a bacterial hormone
    Nature (IF 42.778) Pub Date : 2021-02-03
    Shanshan Zhou; Hussain Bhukya; Nicolas Malet; Peter J. Harrison; Dean Rea; Matthew J. Belousoff; Hariprasad Venugopal; Paulina K. Sydor; Kathryn M. Styles; Lijiang Song; Max J. Cryle; Lona M. Alkhalaf; Vilmos Fülöp; Gregory L. Challis; Christophe Corre

    Actinobacteria produce numerous antibiotics and other specialized metabolites that have important applications in medicine and agriculture1. Diffusible hormones frequently control the production of such metabolites by binding TetR family transcriptional repressors (TFTRs), but the molecular basis for this remains unclear2. The production of methylenomycin antibiotics in Streptomyces coelicolor A3(2)

  • Regulatory genomic circuitry of human disease loci by integrative epigenomics
    Nature (IF 42.778) Pub Date : 2021-02-03
    Carles A. Boix; Benjamin T. James; Yongjin P. Park; Wouter Meuleman; Manolis Kellis

    Annotating the molecular basis of human disease remains an unsolved challenge, as 93% of disease loci are non-coding and gene-regulatory annotations are highly incomplete1,2,3. Here we present EpiMap, a compendium comprising 10,000 epigenomic maps across 800 samples, which we used to define chromatin states, high-resolution enhancers, enhancer modules, upstream regulators and downstream target genes

  • Immunogenic BNT162b vaccines protect rhesus macaques from SARS-CoV-2
    Nature (IF 42.778) Pub Date : 2021-02-01
    Annette B. Vogel; Isis Kanevsky; Ye Che; Kena A. Swanson; Alexander Muik; Mathias Vormehr; Lena M. Kranz; Kerstin C. Walzer; Stephanie Hein; Alptekin Güler; Jakob Loschko; Mohan S. Maddur; Ayuko Ota-Setlik; Kristin Tompkins; Journey Cole; Bonny G. Lui; Thomas Ziegenhals; Arianne Plaschke; David Eisel; Sarah C. Dany; Stephanie Fesser; Stephanie Erbar; Ferdia Bates; Diana Schneider; Bernadette Jesionek;

    A safe and effective vaccine against COVID-19 is urgently needed in quantities sufficient to immunise large populations. We report the preclinical development of two BNT162b vaccine candidates, which contain lipid-nanoparticle (LNP) formulated nucleoside-modified mRNA encoding SARS-CoV-2 spike glycoprotein-derived immunogens. BNT162b1 encodes a soluble, secreted, trimerised receptor-binding domain

  • Tunable strongly coupled superconductivity in magic-angle twisted trilayer graphene
    Nature (IF 42.778) Pub Date : 2021-02-01
    Jeong Min Park; Yuan Cao; Kenji Watanabe; Takashi Taniguchi; Pablo Jarillo-Herrero

    Moiré superlattices1,2 have recently emerged as a platform upon which correlated physics and superconductivity can be studied with unprecedented tunability3,4,5,6. Although correlated effects have been observed in several other moiré systems7,8,9,10,11,12,13,14,15,16,17, magic-angle twisted bilayer graphene remains the only one in which robust superconductivity has been reproducibly measured4,5,6.

  • Cell Competition Constitutes a Barrier for Interspecies Chimerism
    Nature (IF 42.778) Pub Date : 2021-01-28
    Canbin Zheng; Yingying Hu; Masahiro Sakurai; Carlos A. Pinzon-Arteaga; Jie Li; Yulei Wei; Daiji Okamura; Benjamin Ravaux; Haley Rose Barlow; Leqian Yu; Hai-Xi Sun; Elizabeth H. Chen; Ying Gu; Jun Wu

    Cell competition entails a conserved fitness-sensing process during which fitter cells eliminate neighboring less-fit but viable cells1. Cell competition has been proposed as a surveillance mechanism to ensure normal development and tissue homeostasis, and has also been suggested to act as a barrier to interspecies chimerism2. To date, however, cell competition has not been studied in an interspecies

  • Genomic mechanisms of climate adaptation in polyploid bioenergy switchgrass
    Nature (IF 42.778) Pub Date : 2021-01-27
    John T. Lovell; Alice H. MacQueen; Sujan Mamidi; Jason Bonnette; Jerry Jenkins; Joseph D. Napier; Avinash Sreedasyam; Adam Healey; Adam Session; Shengqiang Shu; Kerrie Barry; Stacy Bonos; LoriBeth Boston; Christopher Daum; Shweta Deshpande; Aren Ewing; Paul P. Grabowski; Taslima Haque; Melanie Harrison; Jiming Jiang; Dave Kudrna; Anna Lipzen; Thomas H. Pendergast; Chris Plott; Peng Qi; Christopher

    Long-term climate change and periodic environmental extremes threaten food and fuel security1 and global crop productivity2,3,4. Although molecular and adaptive breeding strategies can buffer the effects of climatic stress and improve crop resilience5, these approaches require sufficient knowledge of the genes that underlie productivity and adaptation6—knowledge that has been limited to a small number

  • De novo design of modular and tunable protein biosensors
    Nature (IF 42.778) Pub Date : 2021-01-27
    Alfredo Quijano-Rubio; Hsien-Wei Yeh; Jooyoung Park; Hansol Lee; Robert A. Langan; Scott E. Boyken; Marc J. Lajoie; Longxing Cao; Cameron M. Chow; Marcos C. Miranda; Jimin Wi; Hyo Jeong Hong; Lance Stewart; Byung-Ha Oh; David Baker

    Naturally occurring protein switches have been repurposed for developing novel biosensors and reporters for cellular and clinical applications1, but the number of such switches is limited, and engineering them is often challenging as each is different. Here, we show that a very general class of protein-based biosensors can be created by inverting the flow of information through de novo designed protein

  • A monotreme-like auditory apparatus in a Middle Jurassic haramiyidan
    Nature (IF 42.778) Pub Date : 2021-01-27
    Junyou Wang; John R. Wible; Bin Guo; Sarah L. Shelley; Han Hu; Shundong Bi

    Among extant vertebrates, mammals are distinguished by having a chain of three auditory ossicles (the malleus, incus and stapes) that transduce sound waves and promote an increased range of audible—especially high—frequencies1. By contrast, the homologous bones in early fossil mammals and relatives also functioned in chewing through their bony attachments to the lower jaw2. Recent discoveries of well-preserved

  • A growth-factor-activated lysosomal K + channel regulates Parkinson’s pathology
    Nature (IF 42.778) Pub Date : 2021-01-27
    Jinhong Wie; Zhenjiang Liu; Haikun Song; Thomas F. Tropea; Lu Yang; Huanhuan Wang; Yuling Liang; Chunlei Cang; Kimberly Aranda; Joey Lohmann; Jing Yang; Boxun Lu; Alice S. Chen-Plotkin; Kelvin C. Luk; Dejian Ren

    Lysosomes have fundamental physiological roles and have previously been implicated in Parkinson’s disease1,2,3,4,5. However, how extracellular growth factors communicate with intracellular organelles to control lysosomal function is not well understood. Here we report a lysosomal K+ channel complex that is activated by growth factors and gated by protein kinase B (AKT) that we term lysoKGF. LysoKGF

  • Systematic analysis of binding of transcription factors to noncoding variants
    Nature (IF 42.778) Pub Date : 2021-01-27
    Jian Yan; Yunjiang Qiu; André M. Ribeiro dos Santos; Yimeng Yin; Yang E. Li; Nick Vinckier; Naoki Nariai; Paola Benaglio; Anugraha Raman; Xiaoyu Li; Shicai Fan; Joshua Chiou; Fulin Chen; Kelly A. Frazer; Kyle J. Gaulton; Maike Sander; Jussi Taipale; Bing Ren

    Many sequence variants have been linked to complex human traits and diseases1, but deciphering their biological functions remains challenging, as most of them reside in noncoding DNA. Here we have systematically assessed the binding of 270 human transcription factors to 95,886 noncoding variants in the human genome using an ultra-high-throughput multiplex protein–DNA binding assay, termed single-nucleotide

  • Inceptor counteracts insulin signalling in β-cells to control glycaemia
    Nature (IF 42.778) Pub Date : 2021-01-27
    Ansarullah; Chirag Jain; Fataneh Fathi Far; Sarah Homberg; Katharina Wißmiller; Felizitas Gräfin von Hahn; Aurelia Raducanu; Silvia Schirge; Michael Sterr; Sara Bilekova; Johanna Siehler; Julius Wiener; Lena Oppenländer; Amir Morshedi; Aimée Bastidas-Ponce; Gustav Collden; Martin Irmler; Johannes Beckers; Annette Feuchtinger; Michal Grzybek; Christin Ahlbrecht; Regina Feederle; Oliver Plettenburg;

    Resistance to insulin and insulin-like growth factor 1 (IGF1) in pancreatic β-cells causes overt diabetes in mice; thus, therapies that sensitize β-cells to insulin may protect patients with diabetes against β-cell failure1,2,3. Here we identify an inhibitor of insulin receptor (INSR) and IGF1 receptor (IGF1R) signalling in mouse β-cells, which we name the insulin inhibitory receptor (inceptor; encoded

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