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  • 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

    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 GTEx Consortium

    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
  • A molecular pore spans the double membrane of the coronavirus replication organelle.
    Science (IF 41.845) Pub Date : 2020-09-11
    Georg Wolff,Ronald W A L Limpens,Jessika C Zevenhoven-Dobbe,Ulrike Laugks,Shawn Zheng,Anja W M de Jong,Roman I Koning,David A Agard,Kay Grünewald,Abraham J Koster,Eric J Snijder,Montserrat Bárcena

    Coronavirus genome replication is associated with virus-induced cytosolic double-membrane vesicles, which may provide a tailored microenvironment for viral RNA synthesis in the infected cell. However, it is unclear how newly synthesized genomes and messenger RNAs can travel from these sealed replication compartments to the cytosol to ensure their translation and the assembly of progeny virions. In

    更新日期:2020-09-11
  • The impact of sex on gene expression across human tissues
    Science (IF 41.845) Pub Date : 2020-09-11
    Meritxell Oliva, Manuel Muñoz-Aguirre, Sarah Kim-Hellmuth, Valentin Wucher, Ariel D. H. Gewirtz, Daniel J. Cotter, Princy Parsana, Silva Kasela, Brunilda Balliu, Ana Viñuela, Stephane E. Castel, Pejman Mohammadi, François Aguet, Yuxin Zou, Ekaterina A. Khramtsova, Andrew D. Skol, Diego Garrido-Martín, Ferran Reverter, Andrew Brown, Patrick Evans, Eric R. Gamazon, Anthony Payne, Rodrigo Bonazzola, Alvaro

    Many complex human phenotypes exhibit sex-differentiated characteristics. However, the molecular mechanisms underlying these differences remain largely unknown. We generated a catalog of sex differences in gene expression and in the genetic regulation of gene expression across 44 human tissue sources surveyed by the Genotype-Tissue Expression project (GTEx, v8 release). We demonstrate that sex influences

    更新日期:2020-09-11
  • Transcriptomic signatures across human tissues identify functional rare genetic variation
    Science (IF 41.845) Pub Date : 2020-09-11
    Nicole M. Ferraro, Benjamin J. Strober, Jonah Einson, Nathan S. Abell, Francois Aguet, Alvaro N. Barbeira, Margot Brandt, Maja Bucan, Stephane E. Castel, Joe R. Davis, Emily Greenwald, Gaelen T. Hess, Austin T. Hilliard, Rachel L. Kember, Bence Kotis, YoSon Park, Gina Peloso, Shweta Ramdas, Alexandra J. Scott, Craig Smail, Emily K. Tsang, Seyedeh M. Zekavat, Marcello Ziosi, Aradhana, TOPMed Lipids

    Rare genetic variants are abundant across the human genome, and identifying their function and phenotypic impact is a major challenge. Measuring aberrant gene expression has aided in identifying functional, large-effect rare variants (RVs). Here, we expanded detection of genetically driven transcriptome abnormalities by analyzing gene expression, allele-specific expression, and alternative splicing

    更新日期:2020-09-11
  • Determinants of telomere length across human tissues
    Science (IF 41.845) Pub Date : 2020-09-11
    Kathryn Demanelis, Farzana Jasmine, Lin S. Chen, Meytal Chernoff, Lin Tong, Dayana Delgado, Chenan Zhang, Justin Shinkle, Mekala Sabarinathan, Hannah Lin, Eduardo Ramirez, Meritxell Oliva, Sarah Kim-Hellmuth, Barbara E. Stranger, Tsung-Po Lai, Abraham Aviv, Kristin G. Ardlie, François Aguet, Habibul Ahsan, GTEx Consortium*, Jennifer A. Doherty, Muhammad G. Kibriya, Brandon L. Pierce

    Telomere shortening is a hallmark of aging. Telomere length (TL) in blood cells has been studied extensively as a biomarker of human aging and disease; however, little is known regarding variability in TL in nonblood, disease-relevant tissue types. Here, we characterize variability in TLs from 6391 tissue samples, representing >20 tissue types and 952 individuals from the Genotype-Tissue Expression

    更新日期:2020-09-11
  • Cell type–specific genetic regulation of gene expression across human tissues
    Science (IF 41.845) Pub Date : 2020-09-11
    Sarah Kim-Hellmuth, François Aguet, Meritxell Oliva, Manuel Muñoz-Aguirre, Silva Kasela, Valentin Wucher, Stephane E. Castel, Andrew R. Hamel, Ana Viñuela, Amy L. Roberts, Serghei Mangul, Xiaoquan Wen, Gao Wang, Alvaro N. Barbeira, Diego Garrido-Martín, Brian B. Nadel, Yuxin Zou, Rodrigo Bonazzola, Jie Quan, Andrew Brown, Angel Martinez-Perez, José Manuel Soria, GTEx Consortium§, Gad Getz, Emmanouil

    The Genotype-Tissue Expression (GTEx) project has identified expression and splicing quantitative trait loci in cis (QTLs) for the majority of genes across a wide range of human tissues. However, the functional characterization of these QTLs has been limited by the heterogeneous cellular composition of GTEx tissue samples. We mapped interactions between computational estimates of cell type abundance

    更新日期:2020-09-11
  • The emergence of SARS-CoV-2 in Europe and North America
    Science (IF 41.845) Pub Date : 2020-09-11
    Michael Worobey, Jonathan Pekar, Brendan B. Larsen, Martha I. Nelson, Verity Hill, Jeffrey B. Joy, Andrew Rambaut, Marc A. Suchard, Joel O. Wertheim, Philippe Lemey

    Accurate understanding of the global spread of emerging viruses is critically important for public health responses and for anticipating and preventing future outbreaks. Here, we elucidate when, where and how the earliest sustained SARS-CoV-2 transmission networks became established in Europe and North America. Our results suggest that rapid early interventions successfully prevented early introductions

    更新日期:2020-09-11
  • Thermosensitive crystallization–boosted liquid thermocells for low-grade heat harvesting
    Science (IF 41.845) Pub Date : 2020-09-10
    Boyang Yu, Jiangjiang Duan, Hengjiang Cong, Wenke Xie, Rong Liu, Xinyan Zhuang, Hui Wang, Bei Qi, Ming Xu, Zhong Lin Wang, Jun Zhou

    Low-grade heat (below 373 K) is abundant and ubiquitous, but mostly wasted due to the lack of cost-effective recovery technologies. The liquid-state thermocell (LTC), an inexpensive and scalable thermoelectric device, may be commercially viable for harvesting low-grade heat energy if its Carnot-relative efficiency (ηr) reaches ~5%, which is a challenging metric to achieve experimentally. We used a

    更新日期:2020-09-11
  • Structural basis of nucleosome-dependent cGAS inhibition
    Science (IF 41.845) Pub Date : 2020-09-10
    Joshua A. Boyer, Cathy J. Spangler, Joshua D. Strauss, Andrew P. Cesmat, Pengda Liu, Robert K. McGinty, Qi Zhang

    Cyclic GMP-AMP synthase (cGAS) recognizes cytosolic foreign or damaged DNA to activate the innate immune response to infection, inflammatory diseases, and cancer. In contrast, cGAS reactivity against self-DNA in the nucleus is suppressed by chromatin tethering. We report a 3.3-angstrom-resolution cryo-electron microscopy structure of cGAS in complex with the nucleosome core particle. The structure

    更新日期:2020-09-11
  • Structural basis for the inhibition of cGAS by nucleosomes
    Science (IF 41.845) Pub Date : 2020-09-10
    Tomoya Kujirai, Christian Zierhut, Yoshimasa Takizawa, Ryan Kim, Lumi Negishi, Nobuki Uruma, Seiya Hirai, Hironori Funabiki, Hitoshi Kurumizaka

    The cyclic GMP-AMP synthase (cGAS) senses invasion of pathogenic DNA and stimulates inflammatory signaling, autophagy and apoptosis. Organization of host DNA into nucleosomes was proposed to limit cGAS autoinduction, but the underlying mechanism was unknown. Here, we report the structural basis for this inhibition. In the cryo-EM structure of the human cGAS-nucleosome core particle (NCP) complex, two

    更新日期:2020-09-11
  • Cryptic transmission of SARS-CoV-2 in Washington state
    Science (IF 41.845) Pub Date : 2020-09-10
    Trevor Bedford, Alexander L. Greninger, Pavitra Roychoudhury, Lea M. Starita, Michael Famulare, Meei-Li Huang, Arun Nalla, Gregory Pepper, Adam Reinhardt, Hong Xie, Lasata Shrestha, Truong N. Nguyen, Amanda Adler, Elisabeth Brandstetter, Shari Cho, Danielle Giroux, Peter D. Han, Kairsten Fay, Chris D. Frazar, Misja Ilcisin, Kirsten Lacombe, Jover Lee, Anahita Kiavand, Matthew Richardson, Thomas R.

    Following its emergence in Wuhan, China, in late November or early December 2019, the SARS-CoV-2 virus has rapidly spread globally. Genome sequencing of SARS-CoV-2 allows reconstruction of its transmission history, although this is contingent on sampling. We have analyzed 453 SARS-CoV-2 genomes collected between 20 February and 15 March 2020 from infected patients in Washington State, USA. We find

    更新日期:2020-09-11
  • De novo design of picomolar SARS-CoV-2 miniprotein inhibitors
    Science (IF 41.845) Pub Date : 2020-09-09
    Longxing Cao, Inna Goreshnik, Brian Coventry, James Brett Case, Lauren Miller, Lisa Kozodoy, Rita E. Chen, Lauren Carter, Alexandra C. Walls, Young-Jun Park, Eva-Maria Strauch, Lance Stewart, Michael S. Diamond, David Veesler, David Baker

    Targeting the interaction between the SARS-CoV-2 Spike protein and the human ACE2 receptor is a promising therapeutic strategy. We designed inhibitors using two de novo design approaches. Computer generated scaffolds were either built around an ACE2 helix that interacts with the Spike receptor binding domain (RBD), or docked against the RBD to identify new binding modes, and their amino acid sequences

    更新日期:2020-09-10
  • Regulation of sleep homeostasis mediator adenosine by basal forebrain glutamatergic neurons
    Science (IF 41.845) Pub Date : 2020-09-04
    Wanling Peng, Zhaofa Wu, Kun Song, Siyu Zhang, Yulong Li, Min Xu

    Sleep and wakefulness are homeostatically regulated by a variety of factors, including adenosine. However, how neural activity underlying the sleep-wake cycle controls adenosine release in the brain remains unclear. Using a newly developed genetically encoded adenosine sensor, we found an activity-dependent rapid increase in the concentration of extracellular adenosine in mouse basal forebrain (BF)

    更新日期:2020-09-05
  • Diversity and prosocial behavior
    Science (IF 41.845) Pub Date : 2020-09-04
    Delia Baldassarri, Maria Abascal

    Immigration and globalization have spurred interest in the effects of ethnic diversity in Western societies. Most scholars focus on whether diversity undermines trust, social capital, and collective goods provision. However, the type of prosociality that helps heterogeneous societies function is different from the in-group solidarity that glues homogeneous communities together. Social cohesion in multiethnic

    更新日期:2020-09-05
  • Can democracy work for the poor?
    Science (IF 41.845) Pub Date : 2020-09-04
    Rohini Pande

    Millions of the world’s poorest people now live in middle-income democracies that, in theory, could use their resources to end extreme poverty. However, citizens in those countries have not succeeded in using the vote to ensure adequate progressive redistribution. Interventions aiming to provide the economically vulnerable with needed resources must go beyond assisting them directly, they must also

    更新日期:2020-09-05
  • Democracy’s backsliding in the international environment
    Science (IF 41.845) Pub Date : 2020-09-04
    Susan D. Hyde

    If the end of the 20th century was defined by the relatively widespread acceptance of democracy, the second decade of the 21st century is marked by concerns about backsliding in new and established democracies alike and by a notable decline in foreign support for democracy around the world. As democracy’s global tailwinds shift to headwinds, scholars have an opportunity to better understand how experience

    更新日期:2020-09-05
  • False equivalencies: Online activism from left to right
    Science (IF 41.845) Pub Date : 2020-09-04
    Deen Freelon, Alice Marwick, Daniel Kreiss

    Digital media are critical for contemporary activism—even low-effort “clicktivism” is politically consequential and contributes to offline participation. We argue that in the United States and throughout the industrialized West, left- and right-wing activists use digital and legacy media differently to achieve political goals. Although left-wing actors operate primarily through “hashtag activism” and

    更新日期:2020-09-05
  • Systems biological assessment of immunity to mild versus severe COVID-19 infection in humans.
    Science (IF 41.845) Pub Date : 2020-09-04
    Prabhu S Arunachalam,Florian Wimmers,Chris Ka Pun Mok,Ranawaka A P M Perera,Madeleine Scott,Thomas Hagan,Natalia Sigal,Yupeng Feng,Laurel Bristow,Owen Tak-Yin Tsang,Dhananjay Wagh,John Coller,Kathryn L Pellegrini,Dmitri Kazmin,Ghina Alaaeddine,Wai Shing Leung,Jacky Man Chun Chan,Thomas Shiu Hong Chik,Chris Yau Chung Choi,Christopher Huerta,Michele Paine McCullough,Huibin Lv,Evan Anderson,Srilatha Edupuganti

    Coronavirus disease 2019 (COVID-19) represents a global crisis, yet major knowledge gaps remain about human immunity to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We analyzed immune responses in 76 COVID-19 patients and 69 healthy individuals from Hong Kong and Atlanta, Georgia, United States. In the peripheral blood mononuclear cells (PBMCs) of COVID-19 patients, we observed reduced

    更新日期:2020-09-05
  • Structure of a human 48S translational initiation complex
    Science (IF 41.845) Pub Date : 2020-09-04
    Jailson Brito Querido, Masaaki Sokabe, Sebastian Kraatz, Yuliya Gordiyenko, J. Mark Skehel, Christopher S. Fraser, V. Ramakrishnan

    A key step in translational initiation is the recruitment of the 43S preinitiation complex by the cap-binding complex [eukaryotic initiation factor 4F (eIF4F)] at the 5′ end of messenger RNA (mRNA) to form the 48S initiation complex (i.e., the 48S). The 48S then scans along the mRNA to locate a start codon. To understand the mechanisms involved, we used cryo–electron microscopy to determine the structure

    更新日期:2020-09-05
  • A defined structural unit enables de novo design of small-molecule–binding proteins
    Science (IF 41.845) Pub Date : 2020-09-04
    Nicholas F. Polizzi, William F. DeGrado

    The de novo design of proteins that bind highly functionalized small molecules represents a great challenge. To enable computational design of binders, we developed a unit of protein structure—a van der Mer (vdM)—that maps the backbone of each amino acid to statistically preferred positions of interacting chemical groups. Using vdMs, we designed six de novo proteins to bind the drug apixaban; two bound

    更新日期:2020-09-05
  • A triple-star system with a misaligned and warped circumstellar disk shaped by disk tearing
    Science (IF 41.845) Pub Date : 2020-09-04
    Stefan Kraus, Alexander Kreplin, Alison K. Young, Matthew R. Bate, John D. Monnier, Tim J. Harries, Henning Avenhaus, Jacques Kluska, Anna S. E. Laws, Evan A. Rich, Matthew Willson, Alicia N. Aarnio, Fred C. Adams, Sean M. Andrews, Narsireddy Anugu, Jaehan Bae, Theo ten Brummelaar, Nuria Calvet, Michel Curé, Claire L. Davies, Jacob Ennis, Catherine Espaillat, Tyler Gardner, Lee Hartmann, Sasha Hinkley

    Young stars are surrounded by a circumstellar disk of gas and dust, within which planet formation can occur. Gravitational forces in multiple star systems can disrupt the disk. Theoretical models predict that if the disk is misaligned with the orbital plane of the stars, the disk should warp and break into precessing rings, a phenomenon known as disk tearing. We present observations of the triple-star

    更新日期:2020-09-05
  • Proton-electron mass ratio from laser spectroscopy of HD+ at the part-per-trillion level.
    Science (IF 41.845) Pub Date : 2020-09-04
    Sayan Patra,M Germann,J-Ph Karr,M Haidar,L Hilico,V I Korobov,F M J Cozijn,K S E Eikema,W Ubachs,J C J Koelemeij

    Recent mass measurements of light atomic nuclei in Penning traps have indicated possible inconsistencies in closely related physical constants such as the proton-electron and deuteron-proton mass ratios. These quantities also influence the predicted vibrational spectrum of the deuterated molecular hydrogen ion (HD+) in its electronic ground state. We used Doppler-free two-photon laser spectroscopy

    更新日期:2020-09-05
  • Predicting temperature mortality and selection in natural Drosophila populations
    Science (IF 41.845) Pub Date : 2020-09-04
    Enrico L. Rezende, Francisco Bozinovic, András Szilágyi, Mauro Santos

    Average and extreme temperatures will increase in the near future, but how such shifts will affect mortality in natural populations is still unclear. We used a dynamic model to predict mortality under variable temperatures on the basis of heat tolerance laboratory measurements. Theoretical lethal temperatures for 11 Drosophila species under different warming conditions were virtually indistinguishable

    更新日期:2020-09-05
  • Plants sustain the terrestrial silicon cycle during ecosystem retrogression
    Science (IF 41.845) Pub Date : 2020-09-04
    F. de Tombeur, B. L. Turner, E. Laliberté, H. Lambers, G. Mahy, M.-P. Faucon, G. Zemunik, J.-T. Cornelis

    The biogeochemical silicon cycle influences global primary productivity and carbon cycling, yet changes in silicon sources and cycling during long-term development of terrestrial ecosystems remain poorly understood. Here, we show that terrestrial silicon cycling shifts from pedological to biological control during long-term ecosystem development along 2-million-year soil chronosequences in Western

    更新日期:2020-09-05
  • Structural basis for translational shutdown and immune evasion by the Nsp1 protein of SARS-CoV-2.
    Science (IF 41.845) Pub Date : 2020-09-04
    Matthias Thoms,Robert Buschauer,Michael Ameismeier,Lennart Koepke,Timo Denk,Maximilian Hirschenberger,Hanna Kratzat,Manuel Hayn,Timur Mackens-Kiani,Jingdong Cheng,Jan H Straub,Christina M Stürzel,Thomas Fröhlich,Otto Berninghausen,Thomas Becker,Frank Kirchhoff,Konstantin M J Sparrer,Roland Beckmann

    Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the current coronavirus disease 2019 (COVID-19) pandemic. A major virulence factor of SARS-CoVs is the nonstructural protein 1 (Nsp1), which suppresses host gene expression by ribosome association. Here, we show that Nsp1 from SARS-CoV-2 binds to the 40S ribosomal subunit, resulting in shutdown of messenger RNA (mRNA)

    更新日期:2020-09-05
  • Evolution and epidemic spread of SARS-CoV-2 in Brazil.
    Science (IF 41.845) Pub Date : 2020-09-04
    Darlan S Candido,Ingra M Claro,Jaqueline G de Jesus,William M Souza,Filipe R R Moreira,Simon Dellicour,Thomas A Mellan,Louis du Plessis,Rafael H M Pereira,Flavia C S Sales,Erika R Manuli,Julien Thézé,Luiz Almeida,Mariane T Menezes,Carolina M Voloch,Marcilio J Fumagalli,Thaís M Coletti,Camila A M da Silva,Mariana S Ramundo,Mariene R Amorim,Henrique H Hoeltgebaum,Swapnil Mishra,Mandev S Gill,Luiz M Carvalho

    Brazil currently has one of the fastest-growing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) epidemics in the world. Because of limited available data, assessments of the impact of nonpharmaceutical interventions (NPIs) on this virus spread remain challenging. Using a mobility-driven transmission model, we show that NPIs reduced the reproduction number from >3 to 1 to 1.6 in São Paulo

    更新日期:2020-09-05
  • Engineering human ACE2 to optimize binding to the spike protein of SARS coronavirus 2.
    Science (IF 41.845) Pub Date : 2020-09-04
    Kui K Chan,Danielle Dorosky,Preeti Sharma,Shawn A Abbasi,John M Dye,David M Kranz,Andrew S Herbert,Erik Procko

    The spike (S) protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) binds angiotensin-converting enzyme 2 (ACE2) on host cells to initiate entry, and soluble ACE2 is a therapeutic candidate that neutralizes infection by acting as a decoy. By using deep mutagenesis, mutations in ACE2 that increase S binding are found across the interaction surface, in the asparagine 90–glycosylation

    更新日期:2020-09-05
  • Changes in regeneration-responsive enhancers shape regenerative capacities in vertebrates
    Science (IF 41.845) Pub Date : 2020-09-04
    Wei Wang, Chi-Kuo Hu, An Zeng, Dana Alegre, Deqing Hu, Kirsten Gotting, Augusto Ortega Granillo, Yongfu Wang, Sofia Robb, Robert Schnittker, Shasha Zhang, Dillon Alegre, Hua Li, Eric Ross, Ning Zhang, Anne Brunet, Alejandro Sánchez Alvarado

    Vertebrates vary in their ability to regenerate, and the genetic mechanisms underlying such disparity remain elusive. Comparative epigenomic profiling and single-cell sequencing of two related teleost fish uncovered species-specific and evolutionarily conserved genomic responses to regeneration. The conserved response revealed several regeneration-responsive enhancers (RREs), including an element upstream

    更新日期:2020-09-05
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