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  • Inborn errors of type I IFN immunity in patients with life-threatening COVID-19
    Science (IF 41.845) Pub Date : 2020-09-25
    Qian Zhang, Paul Bastard, Zhiyong Liu, Jérémie Le Pen, Marcela Moncada-Velez, Jie Chen, Masato Ogishi, Ira K. D. Sabli, Stephanie Hodeib, Cecilia Korol, Jérémie Rosain, Kaya Bilguvar, Junqiang Ye, Alexandre Bolze, Benedetta Bigio, Rui Yang, Andrés Augusto Arias, Qinhua Zhou, Yu Zhang, Fanny Onodi, Sarantis Korniotis, Léa Karpf, Quentin Philippot, Marwa Chbihi, Lucie Bonnet-Madin, Karim Dorgham, Nikaïa

    Clinical outcome upon infection with SARS-CoV-2 ranges from silent infection to lethal COVID-19. We have found an enrichment in rare variants predicted to be loss-of-function (LOF) at the 13 human loci known to govern TLR3- and IRF7-dependent type I interferon (IFN) immunity to influenza virus, in 659 patients with life-threatening COVID-19 pneumonia, relative to 534 subjects with asymptomatic or benign

    更新日期:2020-09-26
  • Distinct conformational states of SARS-CoV-2 spike protein.
    Science (IF 41.845) Pub Date : 2020-09-25
    Yongfei Cai,Jun Zhang,Tianshu Xiao,Hanqin Peng,Sarah M Sterling,Richard M Walsh,Shaun Rawson,Sophia Rits-Volloch,Bing Chen

    Intervention strategies are urgently needed to control the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. The trimeric viral spike (S) protein catalyzes fusion between viral and target cell membranes to initiate infection. Here, we report two cryo–electron microscopy structures derived from a preparation of the full-length S protein, representing its prefusion (2.9-angstrom

    更新日期:2020-09-25
  • Rotational resonances in the H2CO roaming reaction are revealed by detailed correlations.
    Science (IF 41.845) Pub Date : 2020-09-25
    Mitchell S Quinn,Klaas Nauta,Meredith J T Jordan,Joel M Bowman,Paul L Houston,Scott H Kable

    Since its discovery 16 years ago, roaming has become a ubiquitous mechanism in molecular photochemistry. Its general features are now understood, but little detail is known about how the potential energy surface (PES) determines reaction outcomes. We performed detailed experiments on formaldehyde (H2CO) photodissociation and determined fully correlated quantum state distributions of the molecular hydrogen

    更新日期:2020-09-25
  • Inducing metallicity in graphene nanoribbons via zero-mode superlattices
    Science (IF 41.845) Pub Date : 2020-09-25
    Daniel J. Rizzo, Gregory Veber, Jingwei Jiang, Ryan McCurdy, Ting Cao, Christopher Bronner, Ting Chen, Steven G. Louie, Felix R. Fischer, Michael F. Crommie

    The design and fabrication of robust metallic states in graphene nanoribbons (GNRs) are challenging because lateral quantum confinement and many-electron interactions induce electronic band gaps when graphene is patterned at nanometer length scales. Recent developments in bottom-up synthesis have enabled the design and characterization of atomically precise GNRs, but strategies for realizing GNR metallicity

    更新日期:2020-09-25
  • Adaptation of SARS-CoV-2 in BALB/c mice for testing vaccine efficacy.
    Science (IF 41.845) Pub Date : 2020-09-25
    Hongjing Gu,Qi Chen,Guan Yang,Lei He,Hang Fan,Yong-Qiang Deng,Yanxiao Wang,Yue Teng,Zhongpeng Zhao,Yujun Cui,Yuchang Li,Xiao-Feng Li,Jiangfan Li,Na-Na Zhang,Xiaolan Yang,Shaolong Chen,Yan Guo,Guangyu Zhao,Xiliang Wang,De-Yan Luo,Hui Wang,Xiao Yang,Yan Li,Gencheng Han,Yuxian He,Xiaojun Zhou,Shusheng Geng,Xiaoli Sheng,Shibo Jiang,Shihui Sun,Cheng-Feng Qin,Yusen Zhou

    The ongoing coronavirus disease 2019 (COVID-19) pandemic has prioritized the development of small-animal models for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We adapted a clinical isolate of SARS-CoV-2 by serial passaging in the respiratory tract of aged BALB/c mice. The resulting mouse-adapted strain at passage 6 (called MASCp6) showed increased infectivity in mouse lung and led

    更新日期:2020-09-25
  • The immunogenetics of sexual parasitism.
    Science (IF 41.845) Pub Date : 2020-09-25
    Jeremy B Swann,Stephen J Holland,Malte Petersen,Theodore W Pietsch,Thomas Boehm

    Sexual parasitism has evolved as a distinctive mode of reproduction among deep-sea anglerfishes. The permanent attachment of males to host females observed in these species represents a form of anatomical joining, which is otherwise unknown in nature. Pronounced modifications to immune facilities are associated with this reproductive trait. The genomes of species with temporarily attaching males lack

    更新日期:2020-09-25
  • Stable perovskite solar cells with efficiency exceeding 24.8% and 0.3-V voltage loss
    Science (IF 41.845) Pub Date : 2020-09-25
    Mingyu Jeong, In Woo Choi, Eun Min Go, Yongjoon Cho, Minjin Kim, Byongkyu Lee, Seonghun Jeong, Yimhyun Jo, Hye Won Choi, Jiyun Lee, Jin-Hyuk Bae, Sang Kyu Kwak, Dong Suk Kim, Changduk Yang

    Further improvement and stabilization of perovskite solar cell (PSC) performance are essential to achieve the commercial viability of next-generation photovoltaics. Considering the benefits of fluorination to conjugated materials for energy levels, hydrophobicity, and noncovalent interactions, two fluorinated isomeric analogs of the well-known hole-transporting material (HTM) Spiro-OMeTAD are developed

    更新日期:2020-09-25
  • High-impact marine heatwaves attributable to human-induced global warming
    Science (IF 41.845) Pub Date : 2020-09-25
    Charlotte Laufkötter, Jakob Zscheischler, Thomas L. Frölicher

    Marine heatwaves (MHWs)—periods of extremely high ocean temperatures in specific regions—have occurred in all of Earth’s ocean basins over the past two decades, with severe negative impacts on marine organisms and ecosystems. However, for most individual MHWs, it is unclear to what extent they have been altered by human-induced climate change. We show that the occurrence probabilities of the duration

    更新日期:2020-09-25
  • A neural correlate of sensory consciousness in a corvid bird
    Science (IF 41.845) Pub Date : 2020-09-25
    Andreas Nieder, Lysann Wagener, Paul Rinnert

    Subjective experiences that can be consciously accessed and reported are associated with the cerebral cortex. Whether sensory consciousness can also arise from differently organized brains that lack a layered cerebral cortex, such as the bird brain, remains unknown. We show that single-neuron responses in the pallial endbrain of crows performing a visual detection task correlate with the birds’ perception

    更新日期:2020-09-25
  • Photon-recoil imaging: Expanding the view of nonlinear x-ray physics
    Science (IF 41.845) Pub Date : 2020-09-25
    U. Eichmann, H. Rottke, S. Meise, J.-E. Rubensson, J. Söderström, M. Agåker, C. Såthe, M. Meyer, T. M. Baumann, R. Boll, A. De Fanis, P. Grychtol, M. Ilchen, T. Mazza, J. Montano, V. Music, Y. Ovcharenko, D. E. Rivas, S. Serkez, R. Wagner, S. Eisebitt

    Addressing the ultrafast coherent evolution of electronic wave functions has long been a goal of nonlinear x-ray physics. A first step toward this goal is the investigation of stimulated x-ray Raman scattering (SXRS) using intense pulses from an x-ray free-electron laser. Earlier SXRS experiments relied on signal amplification during pulse propagation through dense resonant media. By contrast, our

    更新日期:2020-09-25
  • Succination inactivates gasdermin D and blocks pyroptosis.
    Science (IF 41.845) Pub Date : 2020-09-25
    Fiachra Humphries,Liraz Shmuel-Galia,Natalia Ketelut-Carneiro,Sheng Li,Bingwei Wang,Venkatesh V Nemmara,Ruth Wilson,Zhaozhao Jiang,Farnaz Khalighinejad,Khaja Muneeruddin,Scott A Shaffer,Ranjan Dutta,Carolina Ionete,Scott Pesiridis,Shuo Yang,Paul R Thompson,Katherine A Fitzgerald

    Activated macrophages undergo a metabolic switch to aerobic glycolysis, accumulating Krebs’ cycle intermediates that alter transcription of immune response genes. We extended these observations by defining fumarate as an inhibitor of pyroptotic cell death. We found that dimethyl fumarate (DMF) delivered to cells or endogenous fumarate reacts with gasdermin D (GSDMD) at critical cysteine residues to

    更新日期:2020-09-25
  • Designed protein logic to target cells with precise combinations of surface antigens.
    Science (IF 41.845) Pub Date : 2020-09-25
    Marc J Lajoie,Scott E Boyken,Alexander I Salter,Jilliane Bruffey,Anusha Rajan,Robert A Langan,Audrey Olshefsky,Vishaka Muhunthan,Matthew J Bick,Mesfin Gewe,Alfredo Quijano-Rubio,JayLee Johnson,Garreck Lenz,Alisha Nguyen,Suzie Pun,Colin E Correnti,Stanley R Riddell,David Baker

    Precise cell targeting is challenging because most mammalian cell types lack a single surface marker that distinguishes them from other cells. A solution would be to target cells using specific combinations of proteins present on their surfaces. In this study, we design colocalization-dependent protein switches (Co-LOCKR) that perform AND, OR, and NOT Boolean logic operations. These switches activate

    更新日期:2020-09-25
  • A single-cell RNA-seq atlas of Schistosoma mansoni identifies a key regulator of blood feeding
    Science (IF 41.845) Pub Date : 2020-09-25
    George Wendt, Lu Zhao, Rui Chen, Chenxi Liu, Anthony J. O’Donoghue, Conor R. Caffrey, Michael L. Reese, James J. Collins

    Schistosomiasis is a neglected tropical disease that infects 240 million people. With no vaccines and only one drug available, new therapeutic targets are needed. The causative agents, schistosomes, are intravascular flatworm parasites that feed on blood and lay eggs, resulting in pathology. The function of the parasite’s various tissues in successful parasitism are poorly understood, hindering identification

    更新日期:2020-09-25
  • Large-scale RNAi screening uncovers therapeutic targets in the parasite Schistosoma mansoni
    Science (IF 41.845) Pub Date : 2020-09-25
    Jipeng Wang, Carlos Paz, Gilda Padalino, Avril Coghlan, Zhigang Lu, Irina Gradinaru, Julie N. R. Collins, Matthew Berriman, Karl F. Hoffmann, James J. Collins

    Schistosome parasites kill 250,000 people every year. Treatment of schistosomiasis relies on the drug praziquantel. Unfortunately, a scarcity of molecular tools has hindered the discovery of new drug targets. Here, we describe a large-scale RNA interference (RNAi) screen in adult Schistosoma mansoni that examined the function of 2216 genes. We identified 261 genes with phenotypes affecting neuromuscular

    更新日期:2020-09-25
  • The evolutionary history of Neanderthal and Denisovan Y chromosomes
    Science (IF 41.845) Pub Date : 2020-09-25
    Martin Petr, Mateja Hajdinjak, Qiaomei Fu, Elena Essel, Hélène Rougier, Isabelle Crevecoeur, Patrick Semal, Liubov V. Golovanova, Vladimir B. Doronichev, Carles Lalueza-Fox, Marco de la Rasilla, Antonio Rosas, Michael V. Shunkov, Maxim B. Kozlikin, Anatoli P. Derevianko, Benjamin Vernot, Matthias Meyer, Janet Kelso

    Ancient DNA has provided new insights into many aspects of human history. However, we lack comprehensive studies of the Y chromosomes of Denisovans and Neanderthals because the majority of specimens that have been sequenced to sufficient coverage are female. Sequencing Y chromosomes from two Denisovans and three Neanderthals shows that the Y chromosomes of Denisovans split around 700 thousand years

    更新日期:2020-09-25
  • Synthetic connectivity, emergence, and self-regeneration in the network of prebiotic chemistry
    Science (IF 41.845) Pub Date : 2020-09-25
    Agnieszka Wołos, Rafał Roszak, Anna Żądło-Dobrowolska, Wiktor Beker, Barbara Mikulak-Klucznik, Grzegorz Spólnik, Mirosław Dygas, Sara Szymkuć, Bartosz A. Grzybowski

    The challenge of prebiotic chemistry is to trace the syntheses of life’s key building blocks from a handful of primordial substrates. Here we report a forward-synthesis algorithm that generates a full network of prebiotic chemical reactions accessible from these substrates under generally accepted conditions. This network contains both reported and previously unidentified routes to biotic targets,

    更新日期:2020-09-25
  • The science and medicine of human immunology
    Science (IF 41.845) Pub Date : 2020-09-25
    Bali Pulendran, Mark M. Davis

    Although the development of effective vaccines has saved countless lives from infectious diseases, the basic workings of the human immune system are complex and have required the development of animal models, such as inbred mice, to define mechanisms of immunity. More recently, new strategies and technologies have been developed to directly explore the human immune system with unprecedented precision

    更新日期:2020-09-25
  • A cortex-like canonical circuit in the avian forebrain
    Science (IF 41.845) Pub Date : 2020-09-25
    Martin Stacho, Christina Herold, Noemi Rook, Hermann Wagner, Markus Axer, Katrin Amunts, Onur Güntürkün

    Although the avian pallium seems to lack an organization akin to that of the cerebral cortex, birds exhibit extraordinary cognitive skills that are comparable to those of mammals. We analyzed the fiber architecture of the avian pallium with three-dimensional polarized light imaging and subsequently reconstructed local and associative pallial circuits with tracing techniques. We discovered an iteratively

    更新日期:2020-09-25
  • The endoplasmic reticulum P5A-ATPase is a transmembrane helix dislocase
    Science (IF 41.845) Pub Date : 2020-09-25
    Michael J. McKenna, Sue Im Sim, Alban Ordureau, Lianjie Wei, J. Wade Harper, Sichen Shao, Eunyong Park

    Organelle identity depends on protein composition. How mistargeted proteins are selectively recognized and removed from organelles is incompletely understood. Here, we found that the orphan P5A–adenosine triphosphatase (ATPase) transporter ATP13A1 (Spf1 in yeast) directly interacted with the transmembrane segment (TM) of mitochondrial tail–anchored proteins. P5A-ATPase activity mediated the extraction

    更新日期:2020-09-25
  • Ultrapotent human antibodies protect against SARS-CoV-2 challenge via multiple mechanisms
    Science (IF 41.845) Pub Date : 2020-09-24
    M. Alejandra Tortorici, Martina Beltramello, Florian A. Lempp, Dora Pinto, Ha V. Dang, Laura E. Rosen, Matthew McCallum, John Bowen, Andrea Minola, Stefano Jaconi, Fabrizia Zatta, Anna De Marco, Barbara Guarino, Siro Bianchi, Elvin J. Lauron, Heather Tucker, Jiayi Zhou, Alessia Peter, Colin Havenar-Daughton, Jason A. Wojcechowskyj, James Brett Case, Rita E. Chen, Hannah Kaiser, Martin Montiel-Ruiz

    Efficient therapeutic options are needed to control the spread of SARS-CoV-2 that has caused more than 922,000 fatalities as of September 13th, 2020. We report the isolation and characterization of two ultrapotent SARS-CoV-2 human neutralizing antibodies (S2E12 and S2M11) that protect hamsters against SARS-CoV-2 challenge. Cryo-electron microscopy structures show that S2E12 and S2M11 competitively

    更新日期:2020-09-25
  • Singing in a silent spring: Birds respond to a half-century soundscape reversion during the COVID-19 shutdown
    Science (IF 41.845) Pub Date : 2020-09-24
    Elizabeth P. Derryberry, Jennifer N. Phillips, Graham E. Derryberry, Michael J. Blum, David Luther

    Actions taken to control the coronavirus disease 2019 (COVID-19) pandemic have conspicuously reduced motor vehicle traffic, potentially alleviating auditory pressures on animals that rely on sound for survival and reproduction. Here we evaluate whether a common songbird responsively exploited newly emptied acoustic space by comparing soundscapes and songs across the San Francisco Bay Area prior to

    更新日期:2020-09-25
  • Auto-antibodies against type I IFNs in patients with life-threatening COVID-19
    Science (IF 41.845) Pub Date : 2020-09-24
    Paul Bastard, Lindsey B. Rosen, Qian Zhang, Eleftherios Michailidis, Hans-Heinrich Hoffmann, Yu Zhang, Karim Dorgham, Quentin Philippot, Jérémie Rosain, Vivien Béziat, Jérémy Manry, Elana Shaw, Liis Haljasmägi, Pärt Peterson, Lazaro Lorenzo, Lucy Bizien, Sophie Trouillet-Assant, Kerry Dobbs, Adriana Almeida de Jesus, Alexandre Belot, Anne Kallaste, Emilie Catherinot, Yacine Tandjaoui-Lambiotte, Jeremie

    Interindividual clinical variability in the course of SARS-CoV-2 infection is immense. We report that at least 101 of 987 patients with life-threatening COVID-19 pneumonia had neutralizing IgG auto-Abs against IFN-ω (13 patients), the 13 types of IFN-α (36), or both (52), at the onset of critical disease; a few also had auto-Abs against the other three type I IFNs. The auto-Abs neutralize the ability

    更新日期:2020-09-25
  • Long-term collapse in fruit availability threatens Central African forest megafauna
    Science (IF 41.845) Pub Date : 2020-09-24
    Emma R. Bush, Robin C. Whytock, Laila Bahaa-el-din, Stéphanie Bourgeois, Nils Bunnefeld, Anabelle W. Cardoso, Jean Thoussaint Dikangadissi, Pacôme Dimbonda, Edmond Dimoto, Josué Edzang Ndong, Kathryn J. Jeffery, David Lehmann, Loïc Makaga, Brice Momboua, Ludovic R. W. Momont, Caroline E. G. Tutin, Lee J. T. White, Alden Whittaker, Katharine Abernethy

    Afrotropical forests host many of the world’s remaining megafauna, but even here they are confined to areas where direct human influences are low. We use a rare long-term dataset of tree reproduction and a photographic database of forest elephants to assess food availability and body condition of an emblematic megafauna species at Lopé National Park, Gabon. We show an 81% decline in fruiting over a

    更新日期:2020-09-25
  • The coupling mechanism of mammalian respiratory complex I
    Science (IF 41.845) Pub Date : 2020-09-24
    Domen Kampjut, Leonid A. Sazanov

    Mitochondrial complex I couples NADH:ubiquinone oxidoreduction to proton pumping by an unknown mechanism. Here we present cryo-EM structures of ovine complex I in five different conditions, including turnover, at resolutions up to 2.3-2.5 Å. Resolved water molecules allowed us to experimentally define the proton translocation pathways. Quinone binds at three positions along the quinone cavity, as does

    更新日期:2020-09-25
  • Coherently forming a single molecule in an optical trap
    Science (IF 41.845) Pub Date : 2020-09-24
    Xiaodong He, Kunpeng Wang, Jun Zhuang, Peng Xu, Xiang Gao, Ruijun Guo, Cheng Sheng, Min Liu, Jin Wang, Jiaming Li, G. V. Shlyapnikov, Mingsheng Zhan

    Ultracold single molecules have wide-spread potential applications, such as ultracold chemistry, precision measurements, quantum simulation and computation. However due to difficulty in full control of a complex atom-molecule system, the coherent formation of single molecules remains a challenge. Here we report an alternative route to coherently bind two atoms into a weakly bound molecule at MHz levels

    更新日期:2020-09-25
  • Immune life history, vaccination, and the dynamics of SARS-CoV-2 over the next 5 years.
    Science (IF 41.845) Pub Date : 2020-09-21
    Chadi M Saad-Roy,Caroline E Wagner,Rachel E Baker,Sinead E Morris,Jeremy Farrar,Andrea L Graham,Simon A Levin,Michael J Mina,C Jessica E Metcalf,Bryan T Grenfell

    The future trajectory of the Covid-19 pandemic hinges on the dynamics of adaptive immunity against SARS-CoV2; however, salient features of the immune response elicited by natural infection or vaccination are still uncertain. We use simple epidemiological models to explore estimates for the magnitude and timing of future Covid-19 cases given different protective efficacy and duration of the adaptive

    更新日期:2020-09-22
  • Free fatty acid binding pocket in the locked structure of SARS-CoV-2 spike protein.
    Science (IF 41.845) Pub Date : 2020-09-21
    Christine Toelzer,Kapil Gupta,Sathish K N Yadav,Ufuk Borucu,Andrew D Davidson,Maia Kavanagh Williamson,Deborah K Shoemark,Frederic Garzoni,Oskar Staufer,Rachel Milligan,Julien Capin,Adrian J Mulholland,Joachim Spatz,Daniel Fitzgerald,Imre Berger,Christiane Schaffitzel

    COVID-19, caused by severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2), represents a global crisis. Key to SARS-CoV-2 therapeutic development is unraveling the mechanisms driving high infectivity, broad tissue tropism and severe pathology. Our 2.85 Å cryo-EM structure of SARS-CoV-2 spike (S) glycoprotein reveals that the receptor binding domains (RBDs) tightly bind the essential free fatty

    更新日期:2020-09-22
  • Species-specific segmentation clock periods are due to differential biochemical reaction speeds.
    Science (IF 41.845) Pub Date : 2020-09-18
    Mitsuhiro Matsuda,Hanako Hayashi,Jordi Garcia-Ojalvo,Kumiko Yoshioka-Kobayashi,Ryoichiro Kageyama,Yoshihiro Yamanaka,Makoto Ikeya,Junya Toguchida,Cantas Alev,Miki Ebisuya

    Although mechanisms of embryonic development are similar between mice and humans, the time scale is generally slower in humans. To investigate these interspecies differences in development, we recapitulate murine and human segmentation clocks that display 2- to 3-hour and 5- to 6-hour oscillation periods, respectively. Our interspecies genome-swapping analyses indicate that the period difference is

    更新日期:2020-09-17
  • Evaluating scenarios toward zero plastic pollution.
    Science (IF 41.845) Pub Date : 2020-09-18
    Winnie W Y Lau,Yonathan Shiran,Richard M Bailey,Ed Cook,Martin R Stuchtey,Julia Koskella,Costas A Velis,Linda Godfrey,Julien Boucher,Margaret B Murphy,Richard C Thompson,Emilia Jankowska,Arturo Castillo Castillo,Toby D Pilditch,Ben Dixon,Laura Koerselman,Edward Kosior,Enzo Favoino,Jutta Gutberlet,Sarah Baulch,Meera E Atreya,David Fischer,Kevin K He,Milan M Petit,U Rashid Sumaila,Emily Neil,Mark V Bernhofen

    Plastic pollution is a pervasive and growing problem. To estimate the effectiveness of interventions to reduce plastic pollution, we modeled stocks and flows of municipal solid waste and four sources of microplastics through the global plastic system for five scenarios between 2016 and 2040. Implementing all feasible interventions reduced plastic pollution by 40% from 2016 rates and 78% relative to

    更新日期:2020-09-17
  • Following the microscopic pathway to adsorption through chemisorption and physisorption wells.
    Science (IF 41.845) Pub Date : 2020-09-18
    Dmitriy Borodin,Igor Rahinov,Pranav R Shirhatti,Meng Huang,Alexander Kandratsenka,Daniel J Auerbach,Tianli Zhong,Hua Guo,Dirk Schwarzer,Theofanis N Kitsopoulos,Alec M Wodtke

    Adsorption involves molecules colliding at the surface of a solid and losing their incidence energy by traversing a dynamical pathway to equilibrium. The interactions responsible for energy loss generally include both chemical bond formation (chemisorption) and nonbonding interactions (physisorption). In this work, we present experiments that revealed a quantitative energy landscape and the microscopic

    更新日期:2020-09-17
  • Assessing the impact of coordinated COVID-19 exit strategies across Europe.
    Science (IF 41.845) Pub Date : 2020-09-18
    N W Ruktanonchai,J R Floyd,S Lai,C W Ruktanonchai,A Sadilek,P Rente-Lourenco,X Ben,A Carioli,J Gwinn,J E Steele,O Prosper,A Schneider,A Oplinger,P Eastham,A J Tatem

    As rates of new coronavirus disease 2019 (COVID-19) cases decline across Europe owing to nonpharmaceutical interventions such as social distancing policies and lockdown measures, countries require guidance on how to ease restrictions while minimizing the risk of resurgent outbreaks. We use mobility and case data to quantify how coordinated exit strategies could delay continental resurgence and limit

    更新日期:2020-09-17
  • 90S pre-ribosome transformation into the primordial 40S subunit.
    Science (IF 41.845) Pub Date : 2020-09-18
    Jingdong Cheng,Benjamin Lau,Giuseppe La Venuta,Michael Ameismeier,Otto Berninghausen,Ed Hurt,Roland Beckmann

    Production of small ribosomal subunits initially requires the formation of a 90S precursor followed by an enigmatic process of restructuring into the primordial pre-40S subunit. We elucidate this process by biochemical and cryo–electron microscopy analysis of intermediates along this pathway in yeast. First, the remodeling RNA helicase Dhr1 engages the 90S pre-ribosome, followed by Utp24 endonuclease–driven

    更新日期:2020-09-17
  • Cryo-EM structure of 90S small ribosomal subunit precursors in transition states.
    Science (IF 41.845) Pub Date : 2020-09-18
    Yifei Du,Weidong An,Xing Zhu,Qi Sun,Jia Qi,Keqiong Ye

    The 90S preribosome is a large, early assembly intermediate of small ribosomal subunits that undergoes structural changes to give a pre-40S ribosome. Here, we gained insight into this transition by determining cryo–electron microscopy structures of Saccharomyces cerevisiae intermediates in the path from the 90S to the pre-40S. The full transition is blocked by deletion of RNA helicase Dhr1. A series

    更新日期:2020-09-17
  • Microbiome-derived inosine modulates response to checkpoint inhibitor immunotherapy.
    Science (IF 41.845) Pub Date : 2020-09-18
    Lukas F Mager,Regula Burkhard,Nicola Pett,Noah C A Cooke,Kirsty Brown,Hena Ramay,Seungil Paik,John Stagg,Ryan A Groves,Marco Gallo,Ian A Lewis,Markus B Geuking,Kathy D McCoy

    Several species of intestinal bacteria have been associated with enhanced efficacy of checkpoint blockade immunotherapy, but the underlying mechanisms by which the microbiome enhances antitumor immunity are unclear. In this study, we isolated three bacterial species—Bifidobacterium pseudolongum, Lactobacillus johnsonii, and Olsenella species—that significantly enhanced efficacy of immune checkpoint

    更新日期:2020-09-17
  • Reversible structural transformations in supercooled liquid water from 135 to 245 K.
    Science (IF 41.845) Pub Date : 2020-09-18
    Loni Kringle,Wyatt A Thornley,Bruce D Kay,Greg A Kimmel

    A fundamental understanding of the unusual properties of water remains elusive because of the limited data at the temperatures and pressures needed to decide among competing theories. We investigated the structural transformations of transiently heated supercooled water films, which evolved for several nanoseconds per pulse during fast laser heating before quenching to 70 kelvin (K). Water’s structure

    更新日期:2020-09-17
  • Universal coherence protection in a solid-state spin qubit.
    Science (IF 41.845) Pub Date : 2020-09-18
    Kevin C Miao,Joseph P Blanton,Christopher P Anderson,Alexandre Bourassa,Alexander L Crook,Gary Wolfowicz,Hiroshi Abe,Takeshi Ohshima,David D Awschalom

    Decoherence limits the physical realization of qubits, and its mitigation is critical for the development of quantum science and technology. We construct a robust qubit embedded in a decoherence-protected subspace, obtained by applying microwave dressing to a clock transition of the ground-state electron spin of a silicon carbide divacancy defect. The qubit is universally protected from magnetic, electric

    更新日期:2020-09-17
  • (Sub)stellar companions shape the winds of evolved stars.
    Science (IF 41.845) Pub Date : 2020-09-18
    L Decin,M Montargès,A M S Richards,C A Gottlieb,W Homan,I McDonald,I El Mellah,T Danilovich,S H J Wallström,A Zijlstra,A Baudry,J Bolte,E Cannon,E De Beck,F De Ceuster,A de Koter,J De Ridder,S Etoka,D Gobrecht,M Gray,F Herpin,M Jeste,E Lagadec,P Kervella,T Khouri,K Menten,T J Millar,H S P Müller,J M C Plane,R Sahai,H Sana,M Van de Sande,L B F M Waters,K T Wong,J Yates

    Binary interactions dominate the evolution of massive stars, but their role is less clear for low- and intermediate-mass stars. The evolution of a spherical wind from an asymptotic giant branch (AGB) star into a nonspherical planetary nebula (PN) could be due to binary interactions. We observed a sample of AGB stars with the Atacama Large Millimeter/submillimeter Array (ALMA) and found that their winds

    更新日期:2020-09-17
  • Structure-based design of prefusion-stabilized SARS-CoV-2 spikes.
    Science (IF 41.845) Pub Date : 2020-09-18
    Ching-Lin Hsieh,Jory A Goldsmith,Jeffrey M Schaub,Andrea M DiVenere,Hung-Che Kuo,Kamyab Javanmardi,Kevin C Le,Daniel Wrapp,Alison G Lee,Yutong Liu,Chia-Wei Chou,Patrick O Byrne,Christy K Hjorth,Nicole V Johnson,John Ludes-Meyers,Annalee W Nguyen,Juyeon Park,Nianshuang Wang,Dzifa Amengor,Jason J Lavinder,Gregory C Ippolito,Jennifer A Maynard,Ilya J Finkelstein,Jason S McLellan

    The coronavirus disease 2019 (COVID-19) pandemic has led to accelerated efforts to develop therapeutics and vaccines. A key target of these efforts is the spike (S) protein, which is metastable and difficult to produce recombinantly. We characterized 100 structure-guided spike designs and identified 26 individual substitutions that increased protein yields and stability. Testing combinations of beneficial

    更新日期:2020-09-17
  • Structural basis for neutralization of SARS-CoV-2 and SARS-CoV by a potent therapeutic antibody.
    Science (IF 41.845) Pub Date : 2020-09-18
    Zhe Lv,Yong-Qiang Deng,Qing Ye,Lei Cao,Chun-Yun Sun,Changfa Fan,Weijin Huang,Shihui Sun,Yao Sun,Ling Zhu,Qi Chen,Nan Wang,Jianhui Nie,Zhen Cui,Dandan Zhu,Neil Shaw,Xiao-Feng Li,Qianqian Li,Liangzhi Xie,Youchun Wang,Zihe Rao,Cheng-Feng Qin,Xiangxi Wang

    The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in an unprecedented public health crisis. There are no approved vaccines or therapeutics for treating COVID-19. Here we report a humanized monoclonal antibody, H014, that efficiently neutralizes SARS-CoV-2 and SARS-CoV pseudoviruses as well as authentic SARS-CoV-2 at

    更新日期:2020-09-17
  • Seismic ocean thermometry.
    Science (IF 41.845) Pub Date : 2020-09-18
    Wenbo Wu,Zhongwen Zhan,Shirui Peng,Sidao Ni,Jörn Callies

    More than 90% of the energy trapped on Earth by increasingly abundant greenhouse gases is absorbed by the ocean. Monitoring the resulting ocean warming remains a challenging sampling problem. To complement existing point measurements, we introduce a method that infers basin-scale deep-ocean temperature changes from the travel times of sound waves that are generated by repeating earthquakes. A first

    更新日期:2020-09-17
  • Predicted growth in plastic waste exceeds efforts to mitigate plastic pollution.
    Science (IF 41.845) Pub Date : 2020-09-18
    Stephanie B Borrelle,Jeremy Ringma,Kara Lavender Law,Cole C Monnahan,Laurent Lebreton,Alexis McGivern,Erin Murphy,Jenna Jambeck,George H Leonard,Michelle A Hilleary,Marcus Eriksen,Hugh P Possingham,Hannah De Frond,Leah R Gerber,Beth Polidoro,Akbar Tahir,Miranda Bernard,Nicholas Mallos,Megan Barnes,Chelsea M Rochman

    Plastic pollution is a planetary threat, affecting nearly every marine and freshwater ecosystem globally. In response, multilevel mitigation strategies are being adopted but with a lack of quantitative assessment of how such strategies reduce plastic emissions. We assessed the impact of three broad management strategies, plastic waste reduction, waste management, and environmental recovery, at different

    更新日期:2020-09-17
  • Diet posttranslationally modifies the mouse gut microbial proteome to modulate renal function.
    Science (IF 41.845) Pub Date : 2020-09-18
    Lior Lobel,Y Grace Cao,Kathrin Fenn,Jonathan N Glickman,Wendy S Garrett

    Associations between chronic kidney disease (CKD) and the gut microbiota have been postulated, yet questions remain about the underlying mechanisms. In humans, dietary protein increases gut bacterial production of hydrogen sulfide (H2S), indole, and indoxyl sulfate. The latter are uremic toxins, and H2S has diverse physiological functions, some of which are mediated by posttranslational modification

    更新日期:2020-09-17
  • The ecological and evolutionary consequences of systemic racism in urban environments.
    Science (IF 41.845) Pub Date : 2020-09-18
    Christopher J Schell,Karen Dyson,Tracy L Fuentes,Simone Des Roches,Nyeema C Harris,Danica Sterud Miller,Cleo A Woelfle-Erskine,Max R Lambert

    Urban areas are dynamic ecological systems defined by interdependent biological, physical, and social components. The emergent structure and heterogeneity of urban landscapes drives biotic outcomes in these areas, and such spatial patterns are often attributed to the unequal stratification of wealth and power in human societies. Despite these patterns, few studies have effectively considered structural

    更新日期:2020-09-17
  • Species-specific pace of development is associated with differences in protein stability.
    Science (IF 41.845) Pub Date : 2020-09-18
    Teresa Rayon,Despina Stamataki,Ruben Perez-Carrasco,Lorena Garcia-Perez,Christopher Barrington,Manuela Melchionda,Katherine Exelby,Jorge Lazaro,Victor L J Tybulewicz,Elizabeth M C Fisher,James Briscoe

    Although many molecular mechanisms controlling developmental processes are evolutionarily conserved, the speed at which the embryo develops can vary substantially between species. For example, the same genetic program, comprising sequential changes in transcriptional states, governs the differentiation of motor neurons in mouse and human, but the tempo at which it operates differs between species.

    更新日期:2020-09-17
  • Looking at neurodevelopment through a big data lens.
    Science (IF 41.845) Pub Date : 2020-09-18
    James Briscoe,Oscar Marín

    The formation of the human brain, which contains nearly 100 billion neurons making an average of 1000 connections each, represents an astonishing feat of self-organization. Despite impressive progress, our understanding of how neurons form the nervous system and enable function is very fragmentary, especially for the human brain. New technologies that produce large volumes of high-resolution measurements—big

    更新日期:2020-09-17
  • HDAC6 mediates an aggresome-like mechanism for NLRP3 and pyrin inflammasome activation.
    Science (IF 41.845) Pub Date : 2020-09-18
    Venkat Giri Magupalli,Roberto Negro,Yuzi Tian,Arthur V Hauenstein,Giuseppe Di Caprio,Wesley Skillern,Qiufang Deng,Pontus Orning,Hasan B Alam,Zoltan Maliga,Humayun Sharif,Jun Jacob Hu,Charles L Evavold,Jonathan C Kagan,Florian I Schmidt,Katherine A Fitzgerald,Tom Kirchhausen,Yongqing Li,Hao Wu

    Inflammasomes are supramolecular complexes that play key roles in immune surveillance. This is accomplished by the activation of inflammatory caspases, which leads to the proteolytic maturation of interleukin 1β (IL-1β) and pyroptosis. Here, we show that nucleotide-binding domain, leucine-rich repeat, and pyrin domain–containing protein 3 (NLRP3)- and pyrin-mediated inflammasome assembly, caspase activation

    更新日期:2020-09-17
  • Vascular transcription factors guide plant epidermal responses to limiting phosphate conditions.
    Science (IF 41.845) Pub Date : 2020-09-17
    Jos R Wendrich,BaoJun Yang,Niels Vandamme,Kevin Verstaen,Wouter Smet,Celien Van de Velde,Max Minne,Brecht Wybouw,Eliana Mor,Helena E Arents,Jonah Nolf,Julie Van Duyse,Gert Van Isterdael,Steven Maere,Yvan Saeys,Bert De Rybel

    Optimal plant growth is hampered by deficiency of the essential macronutrient phosphate in most soils. Plant roots can, however, increase their root hair density to efficiently forage the soil for this immobile nutrient. By generating and exploiting a high-resolution single-cell gene expression atlas of Arabidopsis roots, we show an enrichment of TARGET OF MONOPTEROS 5 / LONESOME HIGHWAY (TMO5/LHW)

    更新日期:2020-09-17
  • The GTEx Consortium atlas of genetic regulatory effects across human tissues.
    Science (IF 41.845) Pub Date : 2020-09-11

    The Genotype-Tissue Expression (GTEx) project was established to characterize genetic effects on the transcriptome across human tissues and to link these regulatory mechanisms to trait and disease associations. Here, we present analyses of the version 8 data, examining 15,201 RNA-sequencing samples from 49 tissues of 838 postmortem donors. We comprehensively characterize genetic associations for gene

    更新日期:2020-09-11
  • Global quieting of high-frequency seismic noise due to COVID-19 pandemic lockdown measures.
    Science (IF 41.845) Pub Date : 2020-09-11
    Thomas Lecocq,Stephen P Hicks,Koen Van Noten,Kasper van Wijk,Paula Koelemeijer,Raphael S M De Plaen,Frédérick Massin,Gregor Hillers,Robert E Anthony,Maria-Theresia Apoloner,Mario Arroyo-Solórzano,Jelle D Assink,Pinar Büyükakpınar,Andrea Cannata,Flavio Cannavo,Sebastian Carrasco,Corentin Caudron,Esteban J Chaves,David G Cornwell,David Craig,Olivier F C den Ouden,Jordi Diaz,Stefanie Donner,Christos P

    Human activity causes vibrations that propagate into the ground as high-frequency seismic waves. Measures to mitigate the coronavirus disease 2019 (COVID-19) pandemic caused widespread changes in human activity, leading to a months-long reduction in seismic noise of up to 50%. The 2020 seismic noise quiet period is the longest and most prominent global anthropogenic seismic noise reduction on record

    更新日期:2020-09-11
  • Scale-free ferroelectricity induced by flat phonon bands in HfO2.
    Science (IF 41.845) Pub Date : 2020-09-11
    Hyun-Jae Lee,Minseong Lee,Kyoungjun Lee,Jinhyeong Jo,Hyemi Yang,Yungyeom Kim,Seung Chul Chae,Umesh Waghmare,Jun Hee Lee

    Discovery of robust yet reversibly switchable electric dipoles at reduced dimensions is critical to the advancement of nanoelectronics devices. Energy bands flat in momentum space generate robust localized states that are activated independently of each other. We determined that flat bands exist and induce robust yet independently switchable dipoles that exhibit a distinct ferroelectricity in hafnium

    更新日期:2020-09-11
  • An excess of small-scale gravitational lenses observed in galaxy clusters.
    Science (IF 41.845) Pub Date : 2020-09-11
    Massimo Meneghetti,Guido Davoli,Pietro Bergamini,Piero Rosati,Priyamvada Natarajan,Carlo Giocoli,Gabriel B Caminha,R Benton Metcalf,Elena Rasia,Stefano Borgani,Francesco Calura,Claudio Grillo,Amata Mercurio,Eros Vanzella

    Cold dark matter (CDM) constitutes most of the matter in the Universe. The interplay between dark and luminous matter in dense cosmic environments, such as galaxy clusters, is studied theoretically using cosmological simulations. Observations of gravitational lensing are used to characterize the properties of substructures—the small-scale distribution of dark matter—in clusters. We derive a metric

    更新日期:2020-09-11
  • Keystone predators govern the pathway and pace of climate impacts in a subarctic marine ecosystem.
    Science (IF 41.845) Pub Date : 2020-09-11
    Douglas B Rasher,Robert S Steneck,Jochen Halfar,Kristy J Kroeker,Justin B Ries,M Tim Tinker,Phoebe T W Chan,Jan Fietzke,Nicholas A Kamenos,Brenda H Konar,Jonathan S Lefcheck,Christopher J D Norley,Benjamin P Weitzman,Isaac T Westfield,James A Estes

    Predator loss and climate change are hallmarks of the Anthropocene yet their interactive effects are largely unknown. Here, we show that massive calcareous reefs, built slowly by the alga Clathromorphum nereostratum over centuries to millennia, are now declining because of the emerging interplay between these two processes. Such reefs, the structural base of Aleutian kelp forests, are rapidly eroding

    更新日期:2020-09-11
  • Structural basis of transcription-translation coupling and collision in bacteria.
    Science (IF 41.845) Pub Date : 2020-09-11
    Michael William Webster,Maria Takacs,Chengjin Zhu,Vita Vidmar,Ayesha Eduljee,Mo'men Abdelkareem,Albert Weixlbaumer

    Prokaryotic messenger RNAs (mRNAs) are translated as they are transcribed. The lead ribosome potentially contacts RNA polymerase (RNAP) and forms a supramolecular complex known as the expressome. The basis of expressome assembly and its consequences for transcription and translation are poorly understood. Here, we present a series of structures representing uncoupled, coupled, and collided expressome

    更新日期:2020-09-11
  • Structural basis of transcription-translation coupling.
    Science (IF 41.845) Pub Date : 2020-09-11
    Chengyuan Wang,Vadim Molodtsov,Emre Firlar,Jason T Kaelber,Gregor Blaha,Min Su,Richard H Ebright

    In bacteria, transcription and translation are coupled processes in which the movement of RNA polymerase (RNAP)–synthesizing messenger RNA (mRNA) is coordinated with the movement of the first ribosome-translating mRNA. Coupling is modulated by the transcription factors NusG (which is thought to bridge RNAP and the ribosome) and NusA. Here, we report cryo–electron microscopy structures of Escherichia

    更新日期:2020-09-11
  • Direct laser cooling of a symmetric top molecule.
    Science (IF 41.845) Pub Date : 2020-09-11
    Debayan Mitra,Nathaniel B Vilas,Christian Hallas,Loïc Anderegg,Benjamin L Augenbraun,Louis Baum,Calder Miller,Shivam Raval,John M Doyle

    Ultracold polyatomic molecules have potentially wide-ranging applications in quantum simulation and computation, particle physics, and quantum chemistry. For atoms and small molecules, direct laser cooling has proven to be a powerful tool for quantum science in the ultracold regime. However, the feasibility of laser-cooling larger, nonlinear polyatomic molecules has remained unknown because of their

    更新日期:2020-09-11
  • Self-limiting directional nanoparticle bonding governed by reaction stoichiometry.
    Science (IF 41.845) Pub Date : 2020-09-11
    Chenglin Yi,Hong Liu,Shaoyi Zhang,Yiqun Yang,Yan Zhang,Zhongyuan Lu,Eugenia Kumacheva,Zhihong Nie

    Nanoparticle clusters with molecular-like configurations are an emerging class of colloidal materials. Particles decorated with attractive surface patches acting as analogs of functional groups are used to assemble colloidal molecules (CMs); however, high-yield generation of patchy nanoparticles remains a challenge. We show that for nanoparticles capped with complementary reactive polymers, a stoichiometric

    更新日期:2020-09-11
  • Multiphase buffer theory explains contrasts in atmospheric aerosol acidity.
    Science (IF 41.845) Pub Date : 2020-09-11
    Guangjie Zheng,Hang Su,Siwen Wang,Meinrat O Andreae,Ulrich Pöschl,Yafang Cheng

    Aerosol acidity largely regulates the chemistry of atmospheric particles, and resolving the drivers of aerosol pH is key to understanding their environmental effects. We find that an individual buffering agent can adopt different buffer pH values in aerosols and that aerosol pH levels in populated continental regions are widely buffered by the conjugate acid-base pair NH4+/NH3 (ammonium/ammonia). We

    更新日期:2020-09-11
  • Long-term forest degradation surpasses deforestation in the Brazilian Amazon.
    Science (IF 41.845) Pub Date : 2020-09-11
    Eraldo Aparecido Trondoli Matricardi,David Lewis Skole,Olívia Bueno Costa,Marcos Antonio Pedlowski,Jay Howard Samek,Eder Pereira Miguel

    Although deforestation rates in the Brazilian Amazon are well known, the extent of the area affected by forest degradation is a notable data gap, with implications for conservation biology, carbon cycle science, and international policy. We generated a long-term spatially quantified assessment of forest degradation for the entire Brazilian Amazon from 1992 to 2014. We measured and mapped the full range

    更新日期:2020-09-11
  • An astronomically dated record of Earth's climate and its predictability over the last 66 million years.
    Science (IF 41.845) Pub Date : 2020-09-11
    Thomas Westerhold,Norbert Marwan,Anna Joy Drury,Diederik Liebrand,Claudia Agnini,Eleni Anagnostou,James S K Barnet,Steven M Bohaty,David De Vleeschouwer,Fabio Florindo,Thomas Frederichs,David A Hodell,Ann E Holbourn,Dick Kroon,Vittoria Lauretano,Kate Littler,Lucas J Lourens,Mitchell Lyle,Heiko Pälike,Ursula Röhl,Jun Tian,Roy H Wilkens,Paul A Wilson,James C Zachos

    Much of our understanding of Earth’s past climate comes from the measurement of oxygen and carbon isotope variations in deep-sea benthic foraminifera. Yet, long intervals in existing records lack the temporal resolution and age control needed to thoroughly categorize climate states of the Cenozoic era and to study their dynamics. Here, we present a new, highly resolved, astronomically dated, continuous

    更新日期:2020-09-11
  • The hepatocyte clock and feeding control chronophysiology of multiple liver cell types.
    Science (IF 41.845) Pub Date : 2020-09-11
    Dongyin Guan,Ying Xiong,Trang Minh Trinh,Yang Xiao,Wenxiang Hu,Chunjie Jiang,Pieterjan Dierickx,Cholsoon Jang,Joshua D Rabinowitz,Mitchell A Lazar

    Most cells of the body contain molecular clocks, but the requirement of peripheral clocks for rhythmicity and their effects on physiology are not well understood. We show that deletion of core clock components REV-ERBα and REV-ERBβ in adult mouse hepatocytes disrupts diurnal rhythms of a subset of liver genes and alters the diurnal rhythm of de novo lipogenesis. Liver function is also influenced by

    更新日期:2020-09-11
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