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  •   Call for a framework for reporting evidence for life beyond Earth
    Nature (IF 49.962) Pub Date : 2021-10-27
    James Green, Tori Hoehler, Marc Neveu, Shawn Domagal-Goldman, Daniella Scalice, Mary Voytek

    Our generation could realistically be the one to discover evidence of life beyond Earth. With this privileged potential comes responsibility. The magnitude of the question of whether we are alone in the Universe, and the public interest therein, opens the possibility that results may be taken to imply more than the observations support, or than the observers intend. As life-detection objectives become

  •   Disease variant prediction with deep generative models of evolutionary data
    Nature (IF 49.962) Pub Date : 2021-10-27
    Jonathan Frazer, Pascal Notin, Mafalda Dias, Aidan Gomez, Joseph K. Min, Kelly Brock, Yarin Gal, Debora S. Marks

    Quantifying the pathogenicity of protein variants in human disease-related genes would have a marked effect on clinical decisions, yet the overwhelming majority (over 98%) of these variants still have unknown consequences1,2,3. In principle, computational methods could support the large-scale interpretation of genetic variants. However, state-of-the-art methods4,5,6,7,8,9,10 have relied on training

  •   Dispatched uses Na+ flux to power release of lipid-modified Hedgehog
    Nature (IF 49.962) Pub Date : 2021-10-27
    Qianqian Wang, Daniel E. Asarnow, Ke Ding, Randall K. Mann, Jason Hatakeyama, Yunxiao Zhang, Yong Ma, Yifan Cheng, Philip A. Beachy

    The Dispatched protein, which is related to the NPC1 and PTCH1 cholesterol transporters1,2 and to H+-driven transporters of the RND family3,4, enables tissue-patterning activity of the lipid-modified Hedgehog protein by releasing it from tightly -localized sites of embryonic expression5,6,7,8,9,10. Here we determine a cryo-electron microscopy structure of the mouse protein Dispatched homologue 1 (DISP1)

  •   A human-specific modifier of cortical connectivity and circuit function
    Nature (IF 49.962) Pub Date : 2021-10-27
    Ewoud R. E. Schmidt, Hanzhi T. Zhao, Jung M. Park, Mario Dipoppa, Mauro M. Monsalve-Mercado, Jacob B. Dahan, Chris C. Rodgers, Amélie Lejeune, Elizabeth M. C. Hillman, Kenneth D. Miller, Randy M. Bruno, Franck Polleux

    The cognitive abilities that characterize humans are thought to emerge from unique features of the cortical circuit architecture of the human brain, which include increased cortico–cortical connectivity. However, the evolutionary origin of these changes in connectivity and how they affected cortical circuit function and behaviour are currently unknown. The human-specific gene duplication SRGAP2C emerged

  •   SLC25A39 is necessary for mitochondrial glutathione import in mammalian cells
    Nature (IF 49.962) Pub Date : 2021-10-27
    Ying Wang, Frederick S. Yen, Xiphias Ge Zhu, Rebecca C. Timson, Ross Weber, Changrui Xing, Yuyang Liu, Benjamin Allwein, Hanzhi Luo, Hsi-Wen Yeh, Søren Heissel, Gokhan Unlu, Eric R. Gamazon, Michael G. Kharas, Richard Hite, Kıvanç Birsoy

    Glutathione (GSH) is a small-molecule thiol that is abundant in all eukaryotes and has key roles in oxidative metabolism1. Mitochondria, as the major site of oxidative reactions, must maintain sufficient levels of GSH to perform protective and biosynthetic functions2. GSH is synthesized exclusively in the cytosol, yet the molecular machinery involved in mitochondrial GSH import remains unknown. Here

  •   Cell surface and intracellular auxin signalling for H+ fluxes in root growth
    Nature (IF 49.962) Pub Date : 2021-10-27
    Lanxin Li, Inge Verstraeten, Mark Roosjen, Koji Takahashi, Lesia Rodriguez, Jack Merrin, Jian Chen, Lana Shabala, Wouter Smet, Hong Ren, Steffen Vanneste, Sergey Shabala, Bert De Rybel, Dolf Weijers, Toshinori Kinoshita, William M. Gray, Jiří Friml

    Growth regulation tailors development in plants to their environment. A prominent example of this is the response to gravity, in which shoots bend up and roots bend down1. This paradox is based on opposite effects of the phytohormone auxin, which promotes cell expansion in shoots while inhibiting it in roots via a yet unknown cellular mechanism2. Here, by combining microfluidics, live imaging, genetic

  •   Early-life inflammation primes a T helper 2 cell–fibroblast niche in skin
    Nature (IF 49.962) Pub Date : 2021-10-27
    Ian C. Boothby, Maxime J. Kinet, Devi P. Boda, Elaine Y. Kwan, Sean Clancy, Jarish N. Cohen, Ireneusz Habrylo, Margaret M. Lowe, Mariela Pauli, Ashley E. Yates, Jamie D. Chan, Hobart W. Harris, Isaac M. Neuhaus, Timothy H. McCalmont, Ari B. Molofsky, Michael D. Rosenblum

    Inflammation early in life can prime the local immune milieu of peripheral tissues, which can cause lasting changes in immunological tone that confer disease protection or susceptibility1. The cellular and molecular mechanisms that prompt changes in immune tone in many nonlymphoid tissues remain largely unknown. Here we find that time-limited neonatal inflammation induced by a transient reduction in

  •   Strongly correlated excitonic insulator in atomic double layers
    Nature (IF 49.962) Pub Date : 2021-10-27
    Liguo Ma, Phuong X. Nguyen, Zefang Wang, Yongxin Zeng, Kenji Watanabe, Takashi Taniguchi, Allan H. MacDonald, Kin Fai Mak, Jie Shan

    Excitonic insulators (EIs) arise from the formation of bound electron–hole pairs (excitons)1,2 in semiconductors and provide a solid-state platform for quantum many-boson physics3,4,5,6,7,8. Strong exciton–exciton repulsion is expected to stabilize condensed superfluid and crystalline phases by suppressing both density and phase fluctuations8,9,10,11. Although spectroscopic signatures of EIs have been

  •   Global potential for harvesting drinking water from air using solar energy
    Nature (IF 49.962) Pub Date : 2021-10-27
    Jackson Lord, Ashley Thomas, Neil Treat, Matthew Forkin, Robert Bain, Pierre Dulac, Cyrus H. Behroozi, Tilek Mamutov, Jillia Fongheiser, Nicole Kobilansky, Shane Washburn, Claudia Truesdell, Clare Lee, Philipp H. Schmaelzle

    Access to safely managed drinking water (SMDW) remains a global challenge, and affects 2.2 billion people1,2. Solar-driven atmospheric water harvesting (AWH) devices with continuous cycling may accelerate progress by enabling decentralized extraction of water from air3,4,5,6, but low specific yields (SY) and low daytime relative humidity (RH) have raised questions about their performance (in litres

  •   A global inventory of photovoltaic solar energy generating units
    Nature (IF 49.962) Pub Date : 2021-10-27
    L. Kruitwagen, K. T. Story, J. Friedrich, L. Byers, S. Skillman, C. Hepburn

    Photovoltaic (PV) solar energy generating capacity has grown by 41 per cent per year since 20091. Energy system projections that mitigate climate change and aid universal energy access show a nearly ten-fold increase in PV solar energy generating capacity by 20402,3. Geospatial data describing the energy system are required to manage generation intermittency, mitigate climate change risks, and identify

  •   The orbitofrontal cortex maps future navigational goals
    Nature (IF 49.962) Pub Date : 2021-10-27
    Raunak Basu, Robert Gebauer, Tim Herfurth, Simon Kolb, Zahra Golipour, Tatjana Tchumatchenko, Hiroshi T. Ito

    Accurate navigation to a desired goal requires consecutive estimates of spatial relationships between the current position and future destination throughout the journey. Although neurons in the hippocampal formation can represent the position of an animal as well as its nearby trajectories1,2,3,4,5,6,7, their role in determining the destination of the animal has been questioned8,9. It is, thus, unclear

  •   TMK-based cell-surface auxin signalling activates cell-wall acidification
    Nature (IF 49.962) Pub Date : 2021-10-27
    Wenwei Lin, Xiang Zhou, Wenxin Tang, Koji Takahashi, Xue Pan, Jiawei Dai, Hong Ren, Xiaoyue Zhu, Songqin Pan, Haiyan Zheng, William M. Gray, Tongda Xu, Toshinori Kinoshita, Zhenbiao Yang

    The phytohormone auxin controls many processes in plants, at least in part through its regulation of cell expansion1. The acid growth hypothesis has been proposed to explain auxin-stimulated cell expansion for five decades, but the mechanism that underlies auxin-induced cell-wall acidification is poorly characterized. Auxin induces the phosphorylation and activation of the plasma membrane H+-ATPase

  •   A solar C/O and sub-solar metallicity in a hot Jupiter atmosphere
    Nature (IF 49.962) Pub Date : 2021-10-27
    Michael R. Line, Matteo Brogi, Jacob L. Bean, Siddharth Gandhi, Joseph Zalesky, Vivien Parmentier, Peter Smith, Gregory N. Mace, Megan Mansfield, Eliza M.-R. Kempton, Jonathan J. Fortney, Evgenya Shkolnik, Jennifer Patience, Emily Rauscher, Jean-Michel Désert, Joost P. Wardenier

    Measurements of the atmospheric carbon (C) and oxygen (O) relative to hydrogen (H) in hot Jupiters (relative to their host stars) provide insight into their formation location and subsequent orbital migration1,2. Hot Jupiters that form beyond the major volatile (H2O/CO/CO2) ice lines and subsequently migrate post disk-dissipation are predicted have atmospheric carbon-to-oxygen ratios (C/O) near 1 and

  •   Indo-Pacific Walker circulation drove Pleistocene African aridification
    Nature (IF 49.962) Pub Date : 2021-10-27
    H. J. L. van der Lubbe, I. R. Hall, S. Barker, S. R. Hemming, T. F. Baars, A. Starr, J. Just, B. C. Backeberg, J. C. A. Joordens

    Today, the eastern African hydroclimate is tightly linked to fluctuations in the zonal atmospheric Walker circulation1,2. A growing body of evidence indicates that this circulation shaped hydroclimatic conditions in the Indian Ocean region also on much longer, glacial–interglacial timescales3,4,5, following the development of Pacific Walker circulation around 2.2–2.0 million years ago (Ma)6,7. However

  •   Fossil evidence unveils an early Cambrian origin for Bryozoa
    Nature (IF 49.962) Pub Date : 2021-10-27
    Zhiliang Zhang, Zhifei Zhang, Junye Ma, Paul D. Taylor, Luke C. Strotz, Sarah M. Jacquet, Christian B. Skovsted, Feiyang Chen, Jian Han, Glenn A. Brock

    Bryozoans (also known as ectoprocts or moss animals) are aquatic, dominantly sessile, filter-feeding lophophorates that construct an organic or calcareous modular colonial (clonal) exoskeleton1,2,3. The presence of six major orders of bryozoans with advanced polymorphisms in lower Ordovician rocks strongly suggests a Cambrian origin for the largest and most diverse lophophorate phylum2,4,5,6,7,8. However

  •   Glycogen metabolism links glucose homeostasis to thermogenesis in adipocytes
    Nature (IF 49.962) Pub Date : 2021-10-27
    Omer Keinan, Joseph M. Valentine, Haopeng Xiao, Sushil K. Mahata, Shannon M. Reilly, Mohammad Abu-Odeh, Julia H. Deluca, Benyamin Dadpey, Leslie Cho, Austin Pan, Ruth T. Yu, Yang Dai, Christopher Liddle, Michael Downes, Ronald M. Evans, Aldons J. Lusis, Markku Laakso, Edward T. Chouchani, Mikael Ryde’n, Alan R. Saltiel

    Adipocytes increase energy expenditure in response to prolonged sympathetic activation via persistent expression of uncoupling protein 1 (UCP1)1,2. Here we report that the regulation of glycogen metabolism by catecholamines is critical for UCP1 expression. Chronic β-adrenergic activation leads to increased glycogen accumulation in adipocytes expressing UCP1. Adipocyte-specific deletion of a scaffolding

  •   Human neural tube morphogenesis in vitro by geometric constraints
    Nature (IF 49.962) Pub Date : 2021-10-27
    Eyal Karzbrun, Aimal H. Khankhel, Heitor C. Megale, Stella M. K. Glasauer, Yofiel Wyle, George Britton, Aryeh Warmflash, Kenneth S. Kosik, Eric D. Siggia, Boris I. Shraiman, Sebastian J. Streichan

    Understanding human organ formation is a scientific challenge with far-reaching medical implications1,2. Three-dimensional stem-cell cultures have provided insights into human cell differentiation3,4. However, current approaches use scaffold-free stem-cell aggregates, which develop non-reproducible tissue shapes and variable cell-fate patterns. This limits their capacity to recapitulate organ formation

  •   A synthetic antibiotic class overcoming bacterial multidrug resistance
    Nature (IF 49.962) Pub Date : 2021-10-27
    Matthew J. Mitcheltree, Amarnath Pisipati, Egor A. Syroegin, Katherine J. Silvestre, Dorota Klepacki, Jeremy D. Mason, Daniel W. Terwilliger, Giambattista Testolin, Aditya R. Pote, Kelvin J. Y. Wu, Richard Porter Ladley, Kelly Chatman, Alexander S. Mankin, Yury S. Polikanov, Andrew G. Myers

    The dearth of new medicines effective against antibiotic-resistant bacteria presents a growing global public health concern1. For more than five decades, the search for new antibiotics has relied heavily on the chemical modification of natural products (semisynthesis), a method ill-equipped to combat rapidly evolving resistance threats. Semisynthetic modifications are typically of limited scope within

  •   A Conserved Mechanism for Regulating Replisome Disassembly in Eukaryotes
    Nature (IF 49.962) Pub Date : 2021-10-26
    Michael Jenkyn-Bedford, Morgan L. Jones, Yasemin Baris, Karim P. M. Labib, Giuseppe Cannone, Joseph T. P. Yeeles, Tom D. Deegan

    Replisome disassembly is the final step of eukaryotic DNA replication, and is triggered by ubiquitylation of the CMG (Cdc45-MCM-GINS) replicative helicase1–3. Despite being driven by evolutionarily diverse E3 ubiquitin ligases in different eukaryotes (SCFDia2 in budding yeast1, CUL2LRR1 in metazoa4–7), replisome disassembly is governed by a common regulatory principle, whereby CMG ubiquitylation is

  •   Cryptic transmission of SARS-CoV-2 and the first COVID-19 wave
    Nature (IF 49.962) Pub Date : 2021-10-25
    Jessica T. Davis, Matteo Chinazzi, Nicola Perra, Kunpeng Mu, Ana Pastore y Piontti, Marco Ajelli, Natalie E. Dean, Corrado Gioannini, Maria Litvinova, Stefano Merler, Luca Rossi, Kaiyuan Sun, Xinyue Xiong, Ira M. Longini, M. Elizabeth Halloran, Cécile Viboud, Alessandro Vespignani

    Considerable uncertainty surrounds the timeline of introductions and onsets of local transmission of SARS-CoV-2 globally1–7. Although a limited number of SARS-CoV-2 introductions were reported in January and February 20208,9, the narrowness of the initial testing criteria, combined with a slow growth in testing capacity and porous travel screening10, left many countries vulnerable to unmitigated, cryptic

  •   Prestin’s conformational cycle underlies outer hair cell electromotility
    Nature (IF 49.962) Pub Date : 2021-10-25
    Navid Bavi, Michael David Clark, Gustavo F. Contreras, Rong Shen, Bharat G. Reddy, Wieslawa Milewski, Eduardo Perozo

    The voltage-dependent motor protein Prestin (SLC26A5) is responsible for the electromotive behavior of outer hair cells and underlies the cochlear amplifier1. Knock out or impairment of Prestin causes severe hearing loss2–5. Despite Prestin’s key role in hearing, the mechanism by which mammalian Prestin senses voltage and transduces it into cellular-scale movements (electromotility) is poorly understood

  •   Untimely TGFβ responses in COVID-19 limit antiviral functions of NK cells
    Nature (IF 49.962) Pub Date : 2021-10-25
    Mario Witkowski, Caroline Tizian, Marta Ferreira-Gomes, Daniela Niemeyer, Terry C. Jones, Frederik Heinrich, Stefan Frischbutter, Stefan Angermair, Thordis Hohnstein, Irene Mattiola, Philipp Nawrath, Sophie Mc Ewen, Silvia Zocche, Edoardo Viviano, Gitta Anne Heinz, Marcus Maurer, Uwe Kölsch, Robert Lorenz Chua, Tom Aschman, Christian Meisel, Josefine Radke, Birgit Sawitzki, Jobst Roehmel, Kristina

    SARS-CoV-2 is a single-stranded RNA virus that causes coronavirus disease 2019 (COVID-19). Given its acute and often self-limiting course, components of the innate immune system are likely central in controlling virus replication thereby determining clinical outcome. Natural killer (NK) cells are innate lymphocytes with notable activity against a broad range of viruses, including RNA viruses1,2. NK

  •   Immunogenicity and efficacy of heterologous ChadOx1/BNT162b2 vaccination
    Nature (IF 49.962) Pub Date : 2021-10-21
    Bruno Pozzetto, Vincent Legros, Sophia Djebali, Véronique Barateau, Nicolas Guibert, Marine Villard, Loïc Peyrot, Omran Allatif, Jean-Baptiste Fassier, Amélie Massardier-Pilonchéry, Karen Brengel-Pesce, Melyssa Yaugel-Novoa, Solène Denolly, Bertrand Boson, Thomas Bourlet, Antonin Bal, Martine Valette, Thibault Andrieu, Bruno Lina, François-Loïc Cosset, Stéphane Paul, Thierry Defrance, Jacqueline Marvel

    Following severe adverse reactions to the AstraZeneca ChAdOx1-S-nCoV-19 vaccine1,2, European health authorities have recommended that patients under the age of 55 who received one dose of ChAdOx1-S-nCoV-19 vaccine receive a second dose of Pfizer BNT162b2 vaccine as a booster. However, the effectiveness and the immunogenicity of this vaccination regimen have not been formally tested. Here, we show that

  •   Evidence for unconventional superconductivity in twisted bilayer graphene
    Nature (IF 49.962) Pub Date : 2021-10-20
    Myungchul Oh, Kevin P. Nuckolls, Dillon Wong, Ryan L. Lee, Xiaomeng Liu, Kenji Watanabe, Takashi Taniguchi, Ali Yazdani

    The emergence of superconductivity and correlated insulators in magic-angle twisted bilayer graphene (MATBG) has raised the intriguing possibility that its pairing mechanism is distinct from that of conventional superconductors1–4, as described by the Bardeen-Cooper-Schrieffer (BCS) theory. However, recent studies have shown that superconductivity persists even when Coulomb interactions are partially

  •   Evidence for European presence in the Americas in ad 1021
    Nature (IF 49.962) Pub Date : 2021-10-20
    Margot Kuitems, Birgitta L. Wallace, Charles Lindsay, Andrea Scifo, Petra Doeve, Kevin Jenkins, Susanne Lindauer, Pınar Erdil, Paul M. Ledger, Véronique Forbes, Caroline Vermeeren, Ronny Friedrich, Michael W. Dee

    Transatlantic exploration took place centuries before the crossing of Columbus. Physical evidence for early European presence in the Americas can be found in Newfoundland, Canada1,2. However, it has thus far not been possible to determine when this activity took place3,4,5. Here we provide evidence that the Vikings were present in Newfoundland in ad 1021. We overcome the imprecision of previous age

  •   Dexterous magnetic manipulation of conductive non-magnetic objects
    Nature (IF 49.962) Pub Date : 2021-10-20
    Lan N. Pham, Griffin F. Tabor, Ashkan Pourkand, Jacob L. B. Aman, Tucker Hermans, Jake J. Abbott

    Dexterous magnetic manipulation of ferromagnetic objects is well established, with three to six degrees of freedom possible depending on object geometry1. There are objects for which non-contact dexterous manipulation is desirable that do not contain an appreciable amount of ferromagnetic material but do contain electrically conductive material. Time-varying magnetic fields generate eddy currents in

  •   Ethics of DNA research on human remains: five globally applicable guidelines
    Nature (IF 49.962) Pub Date : 2021-10-20
    Songül Alpaslan-Roodenberg, David Anthony, Hiba Babiker, Eszter Bánffy, Thomas Booth, Patricia Capone, Arati Deshpande-Mukherjee, Stefanie Eisenmann, Lars Fehren-Schmitz, Michael Frachetti, Ricardo Fujita, Catherine J. Frieman, Qiaomei Fu, Victoria Gibbon, Wolfgang Haak, Mateja Hajdinjak, Kerstin P. Hofmann, Brian Holguin, Takeshi Inomata, Hideaki Kanzawa-Kiriyama, William Keegan, Janet Kelso, Johannes

    We are a group of archaeologists, anthropologists, curators and geneticists representing diverse global communities and 31 countries. All of us met in a virtual workshop dedicated to ethics in ancient DNA research held in November 2020. There was widespread agreement that globally applicable ethical guidelines are needed, but that recent recommendations grounded in discussion about research on human

  •   Copper-coordinated cellulose ion conductors for solid-state batteries
    Nature (IF 49.962) Pub Date : 2021-10-20
    Chunpeng Yang, Qisheng Wu, Weiqi Xie, Xin Zhang, Alexandra Brozena, Jin Zheng, Mounesha N. Garaga, Byung Hee Ko, Yimin Mao, Shuaiming He, Yue Gao, Pengbo Wang, Madhusudan Tyagi, Feng Jiao, Robert Briber, Paul Albertus, Chunsheng Wang, Steven Greenbaum, Yan-Yan Hu, Akira Isogai, Martin Winter, Kang Xu, Yue Qi, Liangbing Hu

    Although solid-state lithium (Li)-metal batteries promise both high energy density and safety, existing solid ion conductors fail to satisfy the rigorous requirements of battery operations. Inorganic ion conductors allow fast ion transport, but their rigid and brittle nature prevents good interfacial contact with electrodes. Conversely, polymer ion conductors that are Li-metal-stable usually provide

  •   Linking hippocampal multiplexed tuning, Hebbian plasticity and navigation
    Nature (IF 49.962) Pub Date : 2021-10-20
    Jason J. Moore, Jesse D. Cushman, Lavanya Acharya, Briana Popeney, Mayank R. Mehta

    Three major pillars of hippocampal function are spatial navigation1, Hebbian synaptic plasticity2 and spatial selectivity3. The hippocampus is also implicated in episodic memory4, but the precise link between these four functions is missing. Here we report the multiplexed selectivity of dorsal CA1 neurons while rats performed a virtual navigation task using only distal visual cues5, similar to the

  •   Shigella evades pyroptosis by arginine ADP-riboxanation of caspase-11
    Nature (IF 49.962) Pub Date : 2021-10-20
    Zilin Li, Wang Liu, Jiaqi Fu, Sen Cheng, Yue Xu, Zhiqiang Wang, Xiaofan Liu, Xuyan Shi, Yaxin Liu, Xiangbing Qi, Xiaoyun Liu, Jingjin Ding, Feng Shao

    Mouse caspase-11 and human caspase-4 and caspase-5 recognize cytosolic lipopolysaccharide (LPS) to induce pyroptosis by cleaving the pore-forming protein GSDMD1,2,3,4,5. This non-canonical inflammasome defends against Gram-negative bacteria6,7. Shigella flexneri, which causes bacillary dysentery, lives freely within the host cytosol where these caspases reside. However, the role of caspase-11-mediated

  •   Direct radiative effects of airborne microplastics
    Nature (IF 49.962) Pub Date : 2021-10-20
    Laura E. Revell, Peter Kuma, Eric C. Le Ru, Walter R. C. Somerville, Sally Gaw

    Microplastics are now recognized as widespread contaminants in the atmosphere, where, due to their small size and low density, they can be transported with winds around the Earth1,2,3,4,5,6,7,8,9,10,11,12,13,14,15,16,17,18,19,20,21,22,23,24,25. Atmospheric aerosols, such as mineral dust and other types of airborne particulate matter, influence Earth’s climate by absorbing and scattering radiation (direct

  •   Regulation of intestinal immunity and tissue repair by enteric glia
    Nature (IF 49.962) Pub Date : 2021-10-20
    Fränze Progatzky, Michael Shapiro, Song Hui Chng, Bethania Garcia-Cassani, Cajsa Helena Classon, Selin Sevgi, Anna Laddach, Ana Carina Bon-Frauches, Reena Lasrado, Maryam Rahim, Eleni-Maria Amaniti, Stefan Boeing, Kathleen Shah, Lewis J. Entwistle, Alejandro Suárez-Bonnet, Mark S. Wilson, Brigitta Stockinger, Vassilis Pachnis

    Tissue maintenance and repair depend on the integrated activity of multiple cell types1. Whereas the contributions of epithelial2,3, immune4,5 and stromal cells6,7 in intestinal tissue integrity are well understood, the role of intrinsic neuroglia networks remains largely unknown. Here we uncover important roles of enteric glial cells (EGCs) in intestinal homeostasis, immunity and tissue repair. We

  •   Low glycaemic diets alter lipid metabolism to influence tumour growth
    Nature (IF 49.962) Pub Date : 2021-10-20
    Evan C. Lien, Anna M. Westermark, Yin Zhang, Chen Yuan, Zhaoqi Li, Allison N. Lau, Kiera M. Sapp, Brian M. Wolpin, Matthew G. Vander Heiden

    Dietary interventions can change metabolite levels in the tumour microenvironment, which might then affect cancer cell metabolism to alter tumour growth1,2,3,4,5. Although caloric restriction (CR) and a ketogenic diet (KD) are often thought to limit tumour progression by lowering blood glucose and insulin levels6,7,8, we found that only CR inhibits the growth of select tumour allografts in mice, suggesting

  •   KDM5B promotes immune evasion by recruiting SETDB1 to silence retroelements
    Nature (IF 49.962) Pub Date : 2021-10-20
    Shang-Min Zhang, Wesley L. Cai, Xiaoni Liu, Durga Thakral, Jiesi Luo, Lok Hei Chan, Meaghan K. McGeary, Eric Song, Kim R. M. Blenman, Goran Micevic, Shlomit Jessel, Yangyi Zhang, Mingzhu Yin, Carmen J. Booth, Lucia B. Jilaveanu, William Damsky, Mario Sznol, Harriet M. Kluger, Akiko Iwasaki, Marcus W. Bosenberg, Qin Yan

    Tumours use various strategies to evade immune surveillance1,2. Immunotherapies targeting tumour immune evasion such as immune checkpoint blockade have shown considerable efficacy on multiple cancers3,4 but are ineffective for most patients due to primary or acquired resistance5,6,7. Recent studies showed that some epigenetic regulators suppress anti-tumour immunity2,8,9,10,11,12, suggesting that epigenetic

  •   Neural dynamics underlying birdsong practice and performance
    Nature (IF 49.962) Pub Date : 2021-10-20
    Jonnathan Singh Alvarado, Jack Goffinet, Valerie Michael, William Liberti, Jordan Hatfield, Timothy Gardner, John Pearson, Richard Mooney

    Musical and athletic skills are learned and maintained through intensive practice to enable precise and reliable performance for an audience. Consequently, understanding such complex behaviours requires insight into how the brain functions during both practice and performance. Male zebra finches learn to produce courtship songs that are more varied when alone and more stereotyped in the presence of

  •   The origins and spread of domestic horses from the Western Eurasian steppes
    Nature (IF 49.962) Pub Date : 2021-10-20
    Pablo Librado, Naveed Khan, Antoine Fages, Mariya A. Kusliy, Tomasz Suchan, Laure Tonasso-Calvière, Stéphanie Schiavinato, Duha Alioglu, Aurore Fromentier, Aude Perdereau, Jean-Marc Aury, Charleen Gaunitz, Lorelei Chauvey, Andaine Seguin-Orlando, Clio Der Sarkissian, John Southon, Beth Shapiro, Alexey A. Tishkin, Alexey A. Kovalev, Saleh Alquraishi, Ahmed H. Alfarhan, Khaled A. S. Al-Rasheid, Timo

    Domestication of horses fundamentally transformed long-range mobility and warfare1. However, modern domesticated breeds do not descend from the earliest domestic horse lineage associated with archaeological evidence of bridling, milking and corralling2,3,4 at Botai, Central Asia around 3500 bc3. Other longstanding candidate regions for horse domestication, such as Iberia5 and Anatolia6, have also recently been

  •   eccDNAs are apoptotic products with high innate immunostimulatory activity
    Nature (IF 49.962) Pub Date : 2021-10-20
    Yuangao Wang, Meng Wang, Mohamed Nadhir Djekidel, Huan Chen, Di Liu, Frederick W. Alt, Yi Zhang

    Extrachromosomal circular DNA elements (eccDNAs) have been described in the literature for several decades, and are known for their broad existence across different species1,2. However, their biogenesis and functions are largely unknown. By developing a new circular DNA enrichment method, here we purified and sequenced full-length eccDNAs with Nanopore sequencing. We found that eccDNAs map across the

  •   Hybrid immunity improves B cells and antibodies against SARS-CoV-2 variants
    Nature (IF 49.962) Pub Date : 2021-10-20
    Emanuele Andreano, Ida Paciello, Giulia Piccini, Noemi Manganaro, Piero Pileri, Inesa Hyseni, Margherita Leonardi, Elisa Pantano, Valentina Abbiento, Linda Benincasa, Ginevra Giglioli, Concetta De Santi, Massimiliano Fabbiani, Ilaria Rancan, Mario Tumbarello, Francesca Montagnani, Claudia Sala, Emanuele Montomoli, Rino Rappuoli

    The emergence of SARS-CoV-2 variants is jeopardizing the effectiveness of current vaccines and limiting the application of monoclonal antibody-based therapy for COVID-191,2. Here we analysed at single-cell level the memory B cells of five naive and five convalescent people vaccinated with the BNT162b2 mRNA vaccine to dissect the nature of the B cell and antibody response. Almost six-thousands cells

  •   Non-KREEP origin for Chang’E-5 basalts in the Procellarum KREEP Terrane
    Nature (IF 49.962) Pub Date : 2021-10-19
    Heng-Ci Tian, Hao Wang, Yi Chen, Wei Yang, Qin Zhou, Chi Zhang, Hong-Lei Lin, Chao Huang, Shi-Tou Wu, Li-Hui Jia, Lei Xu, Di Zhang, Xiao-Guang Li, Rui Chang, Yue-Heng Yang, Lie-Wen Xie, Dan-Ping Zhang, Guang-Liang Zhang, Sai-Hong Yang, Fu-Yuan Wu

    Mare volcanics on the Moon are the key record of thermo-chemical evolution throughout most of lunar history1–3. Young mare basalts, mainly distributed in a region rich in potassium, rare earth elements, and phosphorus (KREEP) in Oceanus Procellarum called the Procellarum KREEP Terrane (PKT)4, were thought to be formed from KREEP-rich sources at depth5–7. However, this hypothesis has never been tested

  •   A dry lunar mantle reservoir for young mare basalts of Chang’E-5
    Nature (IF 49.962) Pub Date : 2021-10-19
    Sen Hu, Huicun He, Jianglong Ji, Yangting Lin, Hejiu Hui, Mahesh Anand, Romain Tartèse, Yihong Yan, Jialong Hao, Ruiying Li, Lixin Gu, Qian Guo, Huaiyu He, Ziyuan Ouyang

    The distribution of water in the Moon’s interior carries implications for the origin of the Moon1, the crystallisation of the lunar magma ocean2, and the duration of lunar volcanism2. The Chang’E-5 (CE5) mission returned the youngest mare basalt samples, dated at 2.0 billion years ago (Ga)3, from the northwestern Procellarum KREEP Terrane (PKT), providing a probe into the spatiotemporal evolution of

  •   Two billion-year-old volcanism on the Moon from Chang’E-5 basalts
    Nature (IF 49.962) Pub Date : 2021-10-19
    Qiu-Li Li, Qin Zhou, Yu Liu, Zhiyong Xiao, Yangting Lin, Jin-Hua Li, Hong-Xia Ma, Guo-Qiang Tang, Shun Guo, Xu Tang, Jiang-Yan Yuan, Jiao Li, Fu-Yuan Wu, Ziyuan Ouyang, Chunlai Li, Xian-Hua Li

    The Moon has a magmatic and thermal history distinct from those of the terrestrial planets1. Radioisotope dating of lunar samples suggests that most lunar basaltic magmatism ceased by ca. 2.9–2.8 Ga (billion years ago)2,3, although younger basalts between 3 and 1 Ga have been suggested by crater-counting chronology, which has large uncertainties owing to the lack of returned samples for calibration4

  •   Exome sequencing and analysis of 454,787 UK Biobank participants
    Nature (IF 49.962) Pub Date : 2021-10-18
    Joshua D. Backman, Alexander H. Li, Anthony Marcketta, Dylan Sun, Joelle Mbatchou, Michael D. Kessler, Christian Benner, Daren Liu, Adam E. Locke, Suganthi Balasubramanian, Ashish Yadav, Nilanjana Banerjee, Christopher Gillies, Amy Damask, Simon Liu, Xiaodong Bai, Alicia Hawes, Evan Maxwell, Lauren Gurski, Kyoko Watanabe, Jack A. Kosmicki, Veera Rajagopal, Jason Mighty, Marcus Jones, Lyndon Mitnaul

    A major goal in human genetics is to use natural variation to understand the phenotypic consequences of altering each protein-coding gene in the genome. Here we used exome sequencing1 to explore protein altering variants and their consequences in 454,787 UK Biobank study participants2. We identified 12 million coding variants, including ~1 million loss-of-function and ~1.8 million deleterious missense

  •   Genomic reconstruction of the SARS-CoV-2 epidemic in England
    Nature (IF 49.962) Pub Date : 2021-10-14
    Harald S. Vöhringer, Theo Sanderson, Matthew Sinnott, Nicola De Maio, Thuy Nguyen, Richard Goater, Frank Schwach, Ian Harrison, Joel Hellewell, Cristina V. Ariani, Sonia Gonçalves, David K. Jackson, Ian Johnston, Alexander W. Jung, Callum Saint, John Sillitoe, Maria Suciu, Nick Goldman, Jasmina Panovska-Griffiths, Ewan Birney, Erik Volz, Sebastian Funk, Dominic Kwiatkowski, Meera Chand, Inigo Martincorena

    The evolution of the SARS-CoV-2 pandemic continuously produces new variants, which warrant timely epidemiological characterisation. Here we use the dense genomic surveillance generated by the COVID-19 Genomics UK Consortium to reconstruct the dynamics of 71 different lineages in each of 315 English local authorities between September 2020 and June 2021. This analysis reveals a series of sub-epidemics

  •   Observation of fractional edge excitations in nanographene spin chains
    Nature (IF 49.962) Pub Date : 2021-10-13
    Shantanu Mishra, Gonçalo Catarina, Fupeng Wu, Ricardo Ortiz, David Jacob, Kristjan Eimre, Ji Ma, Carlo A. Pignedoli, Xinliang Feng, Pascal Ruffieux, Joaquín Fernández-Rossier, Roman Fasel

    Fractionalization is a phenomenon in which strong interactions in a quantum system drive the emergence of excitations with quantum numbers that are absent in the building blocks. Outstanding examples are excitations with charge e/3 in the fractional quantum Hall effect1,2, solitons in one-dimensional conducting polymers3,4 and Majorana states in topological superconductors5. Fractionalization is also

  •   Convergent somatic mutations in metabolism genes in chronic liver disease
    Nature (IF 49.962) Pub Date : 2021-10-13
    Stanley W. K. Ng, Foad J. Rouhani, Simon F. Brunner, Natalia Brzozowska, Sarah J. Aitken, Ming Yang, Federico Abascal, Luiza Moore, Efterpi Nikitopoulou, Lia Chappell, Daniel Leongamornlert, Aleksandra Ivovic, Philip Robinson, Timothy Butler, Mathijs A. Sanders, Nicholas Williams, Tim H. H. Coorens, Jon Teague, Keiran Raine, Adam P. Butler, Yvette Hooks, Beverley Wilson, Natalie Birtchnell, Huw Naylor

    The progression of chronic liver disease to hepatocellular carcinoma is caused by the acquisition of somatic mutations that affect 20–30 cancer genes1,2,3,4,5,6,7,8. Burdens of somatic mutations are higher and clonal expansions larger in chronic liver disease9,10,11,12,13 than in normal liver13,14,15,16, which enables positive selection to shape the genomic landscape9,10,11,12,13. Here we analysed

  •   Oestrogen engages brain MC4R signalling to drive physical activity in female mice
    Nature (IF 49.962) Pub Date : 2021-10-13
    William C. Krause, Ruben Rodriguez, Bruno Gegenhuber, Navneet Matharu, Andreas N. Rodriguez, Adriana M. Padilla-Roger, Kenichi Toma, Candice B. Herber, Stephanie M. Correa, Xin Duan, Nadav Ahituv, Jessica Tollkuhn, Holly A. Ingraham

    Oestrogen depletion in rodents and humans leads to inactivity, fat accumulation and diabetes1,2, underscoring the conserved metabolic benefits of oestrogen that inevitably decrease with age. In rodents, the preovulatory surge in 17β-oestradiol (E2) temporarily increases energy expenditure to coordinate increased physical activity with peak sexual receptivity. Here we report that a subset of oestrogen-sensitive

  •   Day–night cloud asymmetry prevents early oceans on Venus but not on Earth
    Nature (IF 49.962) Pub Date : 2021-10-13
    Martin Turbet, Emeline Bolmont, Guillaume Chaverot, David Ehrenreich, Jérémy Leconte, Emmanuel Marcq

    Earth has had oceans for nearly four billion years1 and Mars had lakes and rivers 3.5–3.8 billion years ago2. However, it is still unknown whether water has ever condensed on the surface of Venus3,4 because the planet—now completely dry5—has undergone global resurfacing events that obscure most of its history6,7. The conditions required for water to have initially condensed on the surface of Solar

  •   A bimodal burst energy distribution of a repeating fast radio burst source
    Nature (IF 49.962) Pub Date : 2021-10-13
    D. Li, P. Wang, W. W. Zhu, B. Zhang, X. X. Zhang, R. Duan, Y. K. Zhang, Y. Feng, N. Y. Tang, S. Chatterjee, J. M. Cordes, M. Cruces, S. Dai, V. Gajjar, G. Hobbs, C. Jin, M. Kramer, D. R. Lorimer, C. C. Miao, C. H. Niu, J. R. Niu, Z. C. Pan, L. Qian, L. Spitler, D. Werthimer, G. Q. Zhang, F. Y. Wang, X. Y. Xie, Y. L. Yue, L. Zhang, Q. J. Zhi, Y. Zhu

    The event rate, energy distribution and time-domain behaviour of repeating fast radio bursts (FRBs) contain essential information regarding their physical nature and central engine, which are as yet unknown1,2. As the first precisely localized source, FRB 121102 (refs. 3,4,5) has been extensively observed and shows non-Poisson clustering of bursts over time and a power-law energy distribution6,7,8

  •   Mutant clones in normal epithelium outcompete and eliminate emerging tumours
    Nature (IF 49.962) Pub Date : 2021-10-13
    B. Colom, A. Herms, M. W. J. Hall, S. C. Dentro, C. King, R. K. Sood, M. P. Alcolea, G. Piedrafita, D. Fernandez-Antoran, S. H. Ong, J. C. Fowler, K. T. Mahbubani, K. Saeb-Parsy, M. Gerstung, B. A. Hall, P. H. Jones

    Human epithelial tissues accumulate cancer-driver mutations with age1,2,3,4,5,6,7,8,9, yet tumour formation remains rare. The positive selection of these mutations suggests that they alter the behaviour and fitness of proliferating cells10,11,12. Thus, normal adult tissues become a patchwork of mutant clones competing for space and survival, with the fittest clones expanding by eliminating their less

  •   An elastic metal–organic crystal with a densely catenated backbone
    Nature (IF 49.962) Pub Date : 2021-10-13
    Wenjing Meng, Shun Kondo, Takuji Ito, Kazuki Komatsu, Jenny Pirillo, Yuh Hijikata, Yuichi Ikuhara, Takuzo Aida, Hiroshi Sato

    What particular mechanical properties can be expected for materials composed of interlocked backbones has been a long-standing issue in materials science since the first reports on polycatenane and polyrotaxane in the 1970s1,2,3. Here we report a three-dimensional porous metal–organic crystal, which is exceptional in that its warps and wefts are connected only by catenation. This porous crystal is

  •   Structure of Venezuelan equine encephalitis virus with its receptor LDLRAD3
    Nature (IF 49.962) Pub Date : 2021-10-13
    Bingting Ma, Cuiqing Huang, Jun Ma, Ye Xiang, Xinzheng Zhang

    Venezuelan equine encephalitis virus (VEEV) is an enveloped RNA virus that causes encephalitis and potentially mortality in infected humans and equines1. At present, no vaccines or drugs are available that prevent or cure diseases caused by VEEV. Low-density lipoprotein receptor class A domain-containing 3 (LDLRAD3) was recently identified as a receptor for the entry of VEEV into host cells2. Here

  •   An endogenous opioid circuit determines state-dependent reward consumption
    Nature (IF 49.962) Pub Date : 2021-10-13
    Daniel C. Castro, Corinna S. Oswell, Eric T. Zhang, Christian E. Pedersen, Sean C. Piantadosi, Mark A. Rossi, Avery C. Hunker, Anthony Guglin, Jose A. Morón, Larry S. Zweifel, Garret D. Stuber, Michael R. Bruchas

    µ-Opioid peptide receptor (MOPR) stimulation alters respiration, analgesia and reward behaviour, and can induce substance abuse and overdose1,2,3. Despite its evident importance, the endogenous mechanisms for MOPR regulation of consummatory behaviour have remained unknown4. Here we report that endogenous MOPR regulation of reward consumption in mice acts through a specific dorsal raphe to nucleus accumbens

  •   A neuroanatomical basis for electroacupuncture to drive the vagal–adrenal axis
    Nature (IF 49.962) Pub Date : 2021-10-13
    Shenbin Liu, Zhifu Wang, Yangshuai Su, Lu Qi, Wei Yang, Mingzhou Fu, Xianghong Jing, Yanqing Wang, Qiufu Ma

    Somatosensory autonomic reflexes allow electroacupuncture stimulation (ES) to modulate body physiology at distant sites1,2,3,4,5,6 (for example, suppressing severe systemic inflammation6,7,8,9). Since the 1970s, an emerging organizational rule about these reflexes has been the presence of body-region specificity1,2,3,4,5,6. For example, ES at the hindlimb ST36 acupoint but not the abdominal ST25 acupoint

  •   Leprosy in wild chimpanzees
    Nature (IF 49.962) Pub Date : 2021-10-13
    Kimberley J. Hockings, Benjamin Mubemba, Charlotte Avanzi, Kamilla Pleh, Ariane Düx, Elena Bersacola, Joana Bessa, Marina Ramon, Sonja Metzger, Livia V. Patrono, Jenny E. Jaffe, Andrej Benjak, Camille Bonneaud, Philippe Busso, Emmanuel Couacy-Hymann, Moussa Gado, Sebastien Gagneux, Roch C. Johnson, Mamoudou Kodio, Joshua Lynton-Jenkins, Irina Morozova, Kerstin Mätz-Rensing, Aissa Regalla, Abílio R

    Humans are considered as the main host for Mycobacterium leprae1, the aetiological agent of leprosy, but spillover has occurred to other mammals that are now maintenance hosts, such as nine-banded armadillos and red squirrels2,3. Although naturally acquired leprosy has also been described in captive nonhuman primates4,5,6,7, the exact origins of infection remain unclear. Here we describe leprosy-like

  •   A Jovian analogue orbiting a white dwarf star
    Nature (IF 49.962) Pub Date : 2021-10-13
    J. W. Blackman, J. P. Beaulieu, D. P. Bennett, C. Danielski, C. Alard, A. A. Cole, A. Vandorou, C. Ranc, S. K. Terry, A. Bhattacharya, I. Bond, E. Bachelet, D. Veras, N. Koshimoto, V. Batista, J. B. Marquette

    Studies1,2 have shown that the remnants of destroyed planets and debris-disk planetesimals can survive the volatile evolution of their host stars into white dwarfs3,4, but few intact planetary bodies around white dwarfs have been detected5,6,7,8. Simulations predict9,10,11 that planets in Jupiter-like orbits around stars of ≲8 M☉ (solar mass) avoid being destroyed by the strong tidal forces of their

  •   Structure of Venezuelan equine encephalitis virus in complex with the LDLRAD3 receptor
    Nature (IF 49.962) Pub Date : 2021-10-13
    Katherine Basore, Hongming Ma, Natasha M. Kafai, Samantha Mackin, Arthur S. Kim, Christopher A. Nelson, Michael S. Diamond, Daved H. Fremont

    LDLRAD3 is a recently defined attachment and entry receptor for Venezuelan equine encephalitis virus (VEEV)1, a New World alphavirus that causes severe neurological disease in humans. Here we present near-atomic-resolution cryo-electron microscopy reconstructions of VEEV virus-like particles alone and in a complex with the ectodomains of LDLRAD3. Domain 1 of LDLRAD3 is a low-density lipoprotein receptor

  •   Systems-level effects of allosteric perturbations to a model molecular switch
    Nature (IF 49.962) Pub Date : 2021-10-13
    Tina Perica, Christopher J. P. Mathy, Jiewei Xu, Gwendolyn Μ. Jang, Yang Zhang, Robyn Kaake, Noah Ollikainen, Hannes Braberg, Danielle L. Swaney, David G. Lambright, Mark J. S. Kelly, Nevan J. Krogan, Tanja Kortemme

    Molecular switch proteins whose cycling between states is controlled by opposing regulators1,2 are central to biological signal transduction. As switch proteins function within highly connected interaction networks3, the fundamental question arises of how functional specificity is achieved when different processes share common regulators. Here we show that functional specificity of the small GTPase

  •   Estimating a social cost of carbon for global energy consumption
    Nature (IF 49.962) Pub Date : 2021-10-13
    Ashwin Rode, Tamma Carleton, Michael Delgado, Michael Greenstone, Trevor Houser, Solomon Hsiang, Andrew Hultgren, Amir Jina, Robert E. Kopp, Kelly E. McCusker, Ishan Nath, James Rising, Jiacan Yuan

    Estimates of global economic damage caused by carbon dioxide (CO2) emissions can inform climate policy1,2,3. The social cost of carbon (SCC) quantifies these damages by characterizing how additional CO2 emissions today impact future economic outcomes through altering the climate4,5,6. Previous estimates have suggested that large, warming-driven increases in energy expenditures could dominate the SCC7

  •   Structural basis of cytokine-mediated activation of ALK family receptors
    Nature (IF 49.962) Pub Date : 2021-10-13
    Steven De Munck, Mathias Provost, Michiko Kurikawa, Ikuko Omori, Junko Mukohyama, Jan Felix, Yehudi Bloch, Omar Abdel-Wahab, J. Fernando Bazan, Akihide Yoshimi, Savvas N. Savvides

    Anaplastic lymphoma kinase (ALK)1 and the related leukocyte tyrosine kinase (LTK)2 are recently deorphanized receptor tyrosine kinases3. Together with their activating cytokines, ALKAL1 and ALKAL24,5,6 (also called FAM150A and FAM150B or AUGβ and AUGα, respectively), they are involved in neural development7, cancer7,8,9 and autoimmune diseases10. Furthermore, mammalian ALK recently emerged as a key

  •   The cellular environment shapes the nuclear pore complex architecture
    Nature (IF 49.962) Pub Date : 2021-10-13
    Anthony P. Schuller, Matthias Wojtynek, David Mankus, Meltem Tatli, Rafael Kronenberg-Tenga, Saroj G. Regmi, Phat V. Dip, Abigail K. R. Lytton-Jean, Edward J. Brignole, Mary Dasso, Karsten Weis, Ohad Medalia, Thomas U. Schwartz

    Nuclear pore complexes (NPCs) create large conduits for cargo transport between the nucleus and cytoplasm across the nuclear envelope (NE)1,2,3. These multi-megadalton structures are composed of about thirty different nucleoporins that are distributed in three main substructures (the inner, cytoplasmic and nucleoplasmic rings) around the central transport channel4,5,6. Here we use cryo-electron tomography

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