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  • Selective and cross-reactive SARS-CoV-2 T cell epitopes in unexposed humans
    Science (IF 41.845) Pub Date : 2020-08-04
    Jose Mateus, Alba Grifoni, Alison Tarke, John Sidney, Sydney I. Ramirez, Jennifer M. Dan, Zoe C. Burger, Stephen A. Rawlings, Davey M. Smith, Elizabeth Phillips, Simon Mallal, Marshall Lammers, Paul Rubiro, Lorenzo Quiambao, Aaron Sutherland, Esther Dawen Yu, Ricardo da Silva Antunes, Jason Greenbaum, April Frazier, Alena J. Markmann, Lakshmanane Premkumar, Aravinda de Silva, Bjoern Peters, Shane Crotty

    Many unknowns exist about human immune responses to the SARS-CoV-2 virus. SARS-CoV-2 reactive CD4+ T cells have been reported in unexposed individuals, suggesting pre-existing cross-reactive T cell memory in 20-50% of people. However, the source of those T cells has been speculative. Using human blood samples derived before the SARS-CoV-2 virus was discovered in 2019, we mapped 142 T cell epitopes

    更新日期:2020-08-05
  • Engineering human ACE2 to optimize binding to the spike protein of SARS coronavirus 2
    Science (IF 41.845) Pub Date : 2020-08-04
    Kui K. Chan, Danielle Dorosky, Preeti Sharma, Shawn A. Abbasi, John M. Dye, David M. Kranz, Andrew S. Herbert, Erik Procko

    The spike protein S of SARS coronavirus 2 (SARS-CoV-2) binds ACE2 on host cells to initiate entry, and soluble ACE2 is a therapeutic candidate that neutralizes infection by acting as a decoy. Using deep mutagenesis, mutations in ACE2 that increase S binding are found across the interaction surface, in the N90-glycosylation motif and at buried sites. The mutational landscape provides a blueprint for

    更新日期:2020-08-05
  • ANGEL2 is a member of the CCR4 family of deadenylases with 2′,3′-cyclic phosphatase activity
    Science (IF 41.845) Pub Date : 2020-07-31
    Paola H. Pinto, Alena Kroupova, Alexander Schleiffer, Karl Mechtler, Martin Jinek, Stefan Weitzer, Javier Martinez

    RNA molecules are frequently modified with a terminal 2′,3′-cyclic phosphate group as a result of endonuclease cleavage, exonuclease trimming, or de novo synthesis. During pre-transfer RNA (tRNA) and unconventional messenger RNA (mRNA) splicing, 2′,3′-cyclic phosphates are substrates of the tRNA ligase complex, and their removal is critical for recycling of tRNAs upon ribosome stalling. We identified

    更新日期:2020-07-31
  • Human fetal microglia acquire homeostatic immune-sensing properties early in development
    Science (IF 41.845) Pub Date : 2020-07-31
    L. Kracht, M. Borggrewe, S. Eskandar, N. Brouwer, S. M. Chuva de Sousa Lopes, J. D. Laman, S. A. Scherjon, J. R. Prins, S. M. Kooistra, B. J. L. Eggen

    Microglia, immune cells of the central nervous system (CNS), are important for tissue development and maintenance and are implicated in CNS disease, but we lack understanding of human fetal microglia development. Single-cell gene expression and bulk chromatin profiles of microglia at 9 to 18 gestational weeks (GWs) of human fetal development were generated. Microglia were heterogeneous at all studied

    更新日期:2020-07-31
  • Boosted molecular mobility during common chemical reactions
    Science (IF 41.845) Pub Date : 2020-07-31
    Huan Wang, Myeonggon Park, Ruoyu Dong, Junyoung Kim, Yoon-Kyoung Cho, Tsvi Tlusty, Steve Granick

    Mobility of reactants and nearby solvent is more rapid than Brownian diffusion during several common chemical reactions when the energy release rate exceeds a threshold. Screening a family of 15 organic chemical reactions, we demonstrate the largest boost for catalyzed bimolecular reactions, click chemistry, ring-opening metathesis polymerization, and Sonogashira coupling. Boosted diffusion is also

    更新日期:2020-07-31
  • Exceptional plasticity in the bulk single-crystalline van der Waals semiconductor InSe
    Science (IF 41.845) Pub Date : 2020-07-31
    Tian-Ran Wei, Min Jin, Yuecun Wang, Hongyi Chen, Zhiqiang Gao, Kunpeng Zhao, Pengfei Qiu, Zhiwei Shan, Jun Jiang, Rongbin Li, Lidong Chen, Jian He, Xun Shi

    Inorganic semiconductors are vital for a number of critical applications but are almost universally brittle. Here, we report the superplastic deformability of indium selenide (InSe). Bulk single-crystalline InSe can be compressed by orders of magnitude and morphed into a Möbius strip or a simple origami at room temperature. The exceptional plasticity of this two-dimensional van der Waals inorganic

    更新日期:2020-07-31
  • Human-specific ARHGAP11B increases size and folding of primate neocortex in the fetal marmoset.
    Science (IF 41.845) Pub Date : 2020-07-31
    Michael Heide,Christiane Haffner,Ayako Murayama,Yoko Kurotaki,Haruka Shinohara,Hideyuki Okano,Erika Sasaki,Wieland B Huttner

    The neocortex has expanded during mammalian evolution. Overexpression studies in developing mouse and ferret neocortex have implicated the human-specific gene ARHGAP11B in neocortical expansion, but the relevance for primate evolution has been unclear. Here, we provide functional evidence that ARHGAP11B causes expansion of the primate neocortex. ARHGAP11B expressed in fetal neocortex of the common

    更新日期:2020-07-31
  • Cooling and entangling ultracold atoms in optical lattices.
    Science (IF 41.845) Pub Date : 2020-07-31
    Bing Yang,Hui Sun,Chun-Jiong Huang,Han-Yi Wang,Youjin Deng,Han-Ning Dai,Zhen-Sheng Yuan,Jian-Wei Pan

    Scalable, coherent many-body systems can enable the realization of previously unexplored quantum phases and have the potential to exponentially speed up information processing. Thermal fluctuations are negligible and quantum effects govern the behavior of such systems with extremely low temperature. We report the cooling of a quantum simulator with 10,000 atoms and mass production of high-fidelity

    更新日期:2020-07-31
  • In-cell architecture of an actively transcribing-translating expressome
    Science (IF 41.845) Pub Date : 2020-07-31
    Francis J. O’Reilly, Liang Xue, Andrea Graziadei, Ludwig Sinn, Swantje Lenz, Dimitry Tegunov, Cedric Blötz, Neil Singh, Wim J. H. Hagen, Patrick Cramer, Jörg Stülke, Julia Mahamid, Juri Rappsilber

    Structural biology studies performed inside cells can capture molecular machines in action within their native context. In this work, we developed an integrative in-cell structural approach using the genome-reduced human pathogen Mycoplasma pneumoniae. We combined whole-cell cross-linking mass spectrometry, cellular cryo–electron tomography, and integrative modeling to determine an in-cell architecture

    更新日期:2020-07-31
  • Direct reversible decarboxylation from stable organic acids in dimethylformamide solution.
    Science (IF 41.845) Pub Date : 2020-07-31
    Duanyang Kong,Patrick J Moon,Erica K J Lui,Odey Bsharat,Rylan J Lundgren

    Many classical and emerging methodologies in organic chemistry rely on carbon dioxide (CO2) extrusion to generate reactive intermediates for bond-forming events. Synthetic reactions that involve the microscopic reverse—the carboxylation of reactive intermediates—have conventionally been undertaken using very different conditions. We report that chemically stable C(sp3) carboxylates, such as arylacetic

    更新日期:2020-07-31
  • Allele-specific open chromatin in human iPSC neurons elucidates functional disease variants
    Science (IF 41.845) Pub Date : 2020-07-31
    Siwei Zhang, Hanwen Zhang, Yifan Zhou, Min Qiao, Siming Zhao, Alena Kozlova, Jianxin Shi, Alan R. Sanders, Gao Wang, Kaixuan Luo, Subhajit Sengupta, Siobhan West, Sheng Qian, Michael Streit, Dimitrios Avramopoulos, Chad A. Cowan, Mengjie Chen, Zhiping P. Pang, Pablo V. Gejman, Xin He, Jubao Duan

    Most neuropsychiatric disease risk variants are in noncoding sequences and lack functional interpretation. Because regulatory sequences often reside in open chromatin, we reasoned that neuropsychiatric disease risk variants may affect chromatin accessibility during neurodevelopment. Using human induced pluripotent stem cell (iPSC)–derived neurons that model developing brains, we identified thousands

    更新日期:2020-07-31
  • DNA capture by a CRISPR-Cas9–guided adenine base editor
    Science (IF 41.845) Pub Date : 2020-07-31
    Audrone Lapinaite, Gavin J. Knott, Cody M. Palumbo, Enrique Lin-Shiao, Michelle F. Richter, Kevin T. Zhao, Peter A. Beal, David R. Liu, Jennifer A. Doudna

    CRISPR-Cas–guided base editors convert A•T to G•C, or C•G to T•A, in cellular DNA for precision genome editing. To understand the molecular basis for DNA adenosine deamination by adenine base editors (ABEs), we determined a 3.2-angstrom resolution cryo–electron microscopy structure of ABE8e in a substrate-bound state in which the deaminase domain engages DNA exposed within the CRISPR-Cas9 R-loop complex

    更新日期:2020-07-31
  • Rational synthesis of atomically precise graphene nanoribbons directly on metal oxide surfaces
    Science (IF 41.845) Pub Date : 2020-07-31
    Marek Kolmer, Ann-Kristin Steiner, Irena Izydorczyk, Wonhee Ko, Mads Engelund, Marek Szymonski, An-Ping Li, Konstantin Amsharov

    Atomically precise graphene nanoribbons (GNRs) attract great interest because of their highly tunable electronic, optical, and transport properties. However, on-surface synthesis of GNRs is typically based on metal surface–assisted chemical reactions, where metallic substrates strongly screen their designer electronic properties and limit further applications. Here, we present an on-surface synthesis

    更新日期:2020-07-31
  • Disparities in PM2.5 air pollution in the United States
    Science (IF 41.845) Pub Date : 2020-07-31
    Jonathan Colmer, Ian Hardman, Jay Shimshack, John Voorheis

    Air pollution at any given time is unequally distributed across locations. Average concentrations of fine particulate matter smaller than 2.5 micrometers in diameter (PM2.5) have fallen over time. However, we do not know how the spatial distribution of PM2.5 has evolved. Here, we provide early evidence. We combine 36 years of PM2.5 concentrations measured over ~8.6 million grid cells with geographic

    更新日期:2020-07-31
  • Ancient orogenic and monsoon-driven assembly of the world’s richest temperate alpine flora
    Science (IF 41.845) Pub Date : 2020-07-31
    Wen-Na Ding, Richard H. Ree, Robert A. Spicer, Yao-Wu Xing

    Understanding how alpine biotas formed in response to historical environmental change may improve our ability to predict and mitigate the threats to alpine species posed by global warming. In the world’s richest temperate alpine flora, that of the Tibet-Himalaya-Hengduan region, phylogenetic reconstructions of biome and geographic range evolution show that extant lineages emerged by the early Oligocene

    更新日期:2020-07-31
  • Genomic surveillance reveals multiple introductions of SARS-CoV-2 into Northern California.
    Science (IF 41.845) Pub Date : 2020-07-31
    Xianding Deng,Wei Gu,Scot Federman,Louis du Plessis,Oliver G Pybus,Nuno Faria,Candace Wang,Guixia Yu,Brian Bushnell,Chao-Yang Pan,Hugo Guevara,Alicia Sotomayor-Gonzalez,Kelsey Zorn,Allan Gopez,Venice Servellita,Elaine Hsu,Steve Miller,Trevor Bedford,Alexander L Greninger,Pavitra Roychoudhury,Lea M Starita,Michael Famulare,Helen Y Chu,Jay Shendure,Keith R Jerome,Catie Anderson,Karthik Gangavarapu,Mark

    The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread globally, with >365,000 cases in California as of 17 July 2020. We investigated the genomic epidemiology of SARS-CoV-2 in Northern California from late January to mid-March 2020, using samples from 36 patients spanning nine counties and the Grand Princess cruise ship. Phylogenetic

    更新日期:2020-07-31
  • A physics-based method that can predict imminent large solar flares
    Science (IF 41.845) Pub Date : 2020-07-31
    Kanya Kusano, Tomoya Iju, Yumi Bamba, Satoshi Inoue

    Solar flares are highly energetic events in the Sun’s corona that affect Earth’s space weather. The mechanism that drives the onset of solar flares is unknown, hampering efforts to forecast them, which mostly rely on empirical methods. We present the κ-scheme, a physics-based model to predict large solar flares through a critical condition of magnetohydrodynamic instability, triggered by magnetic reconnection

    更新日期:2020-07-31
  • The function of the thymus and its impact on modern medicine
    Science (IF 41.845) Pub Date : 2020-07-31
    Jacques F. A. P. Miller

    The lymphoid system is intimately involved in immunological processes. The small lymphocyte that circulates through blood into lymphoid tissues, then through the lymph and back to the blood through the thoracic duct, is able to initiate immune responses after appropriate stimulation by antigen. However, the lymphocytes found in the thymus are deficient in this ability despite the fact that the thymus

    更新日期:2020-07-31
  • Structural insights into differences in G protein activation by family A and family B GPCRs
    Science (IF 41.845) Pub Date : 2020-07-31
    Daniel Hilger, Kaavya Krishna Kumar, Hongli Hu, Mie Fabricius Pedersen, Evan S. O’Brien, Lise Giehm, Christine Jennings, Gözde Eskici, Asuka Inoue, Michael Lerch, Jesper Mosolff Mathiesen, Georgios Skiniotis, Brian K. Kobilka

    Family B heterotrimeric guanine nucleotide–binding protein (G protein)–coupled receptors (GPCRs) play important roles in carbohydrate metabolism. Recent structures of family B GPCR-Gs protein complexes reveal a disruption in the α-helix of transmembrane segment 6 (TM6) not observed in family A GPCRs. To investigate the functional impact of this structural difference, we compared the structure and function

    更新日期:2020-07-31
  • The immunogenetics of sexual parasitism
    Science (IF 41.845) Pub Date : 2020-07-30
    Jeremy B. Swann, Stephen J. Holland, Malte Petersen, Theodore W. Pietsch, Thomas Boehm

    Sexual parasitism has evolved as a unique 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. Striking modifications to immune facilities are associated with this reproductive trait. The genomes of species with temporarily attaching males lack functional

    更新日期:2020-07-31
  • Adaptation of SARS-CoV-2 in BALB/c mice for testing vaccine efficacy
    Science (IF 41.845) Pub Date : 2020-07-30
    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 COVID-19 pandemic has prioritized the development of small animal models for SARS-CoV-2. Herein, 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 (termed MASCp6) showed increased infectivity in mouse lung, and led to interstitial pneumonia and inflammatory responses in both young

    更新日期:2020-07-31
  • Julich-Brain: A 3D probabilistic atlas of the human brain’s cytoarchitecture
    Science (IF 41.845) Pub Date : 2020-07-30
    Katrin Amunts, Hartmut Mohlberg, Sebastian Bludau, Karl Zilles

    Cytoarchitecture is a basic principle of microstructural brain parcellation. Here we introduce Julich-Brain, a 3D atlas containing cytoarchitectonic maps of cortical areas and subcortical nuclei. The atlas is probabilistic to consider variations between individual brains. Building such an atlas was highly data- and labor-intensive and required to develop nested, interdependent workflows for detecting

    更新日期:2020-07-31
  • The hepatocyte clock and feeding control chronophysiology of multiple liver cell types
    Science (IF 41.845) Pub Date : 2020-07-30
    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. Here we show that deletion of core clock components REV-ERBα and β in adult mouse hepatocytes disrupted diurnal rhythms of a subset of liver genes and altered the diurnal rhythm of de novo lipogenesis. Liver function is also influenced

    更新日期:2020-07-31
  • Proton-electron mass ratio from laser spectroscopy of HD+ at the part-per-trillion level
    Science (IF 41.845) Pub Date : 2020-07-30
    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 like the proton-electron and deuteron-proton mass ratios. These quantities also influence the predicted vibrational spectrum of the deuterated molecular hydrogen ion in its electronic ground state. We measure the frequency of the v = 0→9 overtone transition

    更新日期:2020-07-31
  • Diverse variola virus (smallpox) strains were widespread in northern Europe in the Viking Age
    Science (IF 41.845) Pub Date : 2020-07-24
    Barbara Mühlemann, Lasse Vinner, Ashot Margaryan, Helene Wilhelmson, Constanza de la Fuente Castro, Morten E. Allentoft, Peter de Barros Damgaard, Anders Johannes Hansen, Sofie Holtsmark Nielsen, Lisa Mariann Strand, Jan Bill, Alexandra Buzhilova, Tamara Pushkina, Ceri Falys, Valeri Khartanovich, Vyacheslav Moiseyev, Marie Louise Schjellerup Jørkov, Palle Østergaard Sørensen, Yvonne Magnusson, Ingrid

    Smallpox, one of the most devastating human diseases, killed between 300 million and 500 million people in the 20th century alone. We recovered viral sequences from 13 northern European individuals, including 11 dated to ~600–1050 CE, overlapping the Viking Age, and reconstructed near-complete variola virus genomes for four of them. The samples predate the earliest confirmed smallpox cases by ~1000

    更新日期:2020-07-24
  • Simultaneous cross-evaluation of heterogeneous E. coli datasets via mechanistic simulation
    Science (IF 41.845) Pub Date : 2020-07-24
    Derek N. Macklin, Travis A. Ahn-Horst, Heejo Choi, Nicholas A. Ruggero, Javier Carrera, John C. Mason, Gwanggyu Sun, Eran Agmon, Mialy M. DeFelice, Inbal Maayan, Keara Lane, Ryan K. Spangler, Taryn E. Gillies, Morgan L. Paull, Sajia Akhter, Samuel R. Bray, Daniel S. Weaver, Ingrid M. Keseler, Peter D. Karp, Jerry H. Morrison, Markus W. Covert

    The extensive heterogeneity of biological data poses challenges to analysis and interpretation. Construction of a large-scale mechanistic model of Escherichia coli enabled us to integrate and cross-evaluate a massive, heterogeneous dataset based on measurements reported by various groups over decades. We identified inconsistencies with functional consequences across the data, including that the total

    更新日期:2020-07-24
  • Cell growth dilutes the cell cycle inhibitor Rb to trigger cell division
    Science (IF 41.845) Pub Date : 2020-07-24
    Evgeny Zatulovskiy, Shuyuan Zhang, Daniel F. Berenson, Benjamin R. Topacio, Jan M. Skotheim

    Cell size is fundamental to cell physiology. For example, cell size determines the spatial scale of organelles and intracellular transport and thereby affects biosynthesis. Although some genes that affect mammalian cell size have been identified, the molecular mechanisms through which cell growth drives cell division have remained elusive. We show that cell growth during the G1 phase of the cell division

    更新日期:2020-07-24
  • Large-scale mutation in the evolution of a gene complex for cryptic coloration
    Science (IF 41.845) Pub Date : 2020-07-24
    Romain Villoutreix, Clarissa F. de Carvalho, Víctor Soria-Carrasco, Dorothea Lindtke, Marisol De-la-Mora, Moritz Muschick, Jeffrey L. Feder, Thomas L. Parchman, Zach Gompert, Patrik Nosil

    The types of mutations affecting adaptation in the wild are only beginning to be understood. In particular, whether structural changes shape adaptation by suppressing recombination or by creating new mutations is unresolved. Here, we show that multiple linked but recombining loci underlie cryptic color morphs of Timema chumash stick insects. In a related species, these loci are found in a region of

    更新日期:2020-07-24
  • Genomic insights into the early peopling of the Caribbean.
    Science (IF 41.845) Pub Date : 2020-07-24
    Kathrin Nägele,Cosimo Posth,Miren Iraeta Orbegozo,Yadira Chinique de Armas,Silvia Teresita Hernández Godoy,Ulises M González Herrera,Maria A Nieves-Colón,Marcela Sandoval-Velasco,Dorothea Mylopotamitaki,Rita Radzeviciute,Jason Laffoon,William J Pestle,Jazmin Ramos-Madrigal,Thiseas C Lamnidis,William C Schaffer,Robert S Carr,Jane S Day,Carlos Arredondo Antúnez,Armando Rangel Rivero,Antonio J Martínez-Fuentes

    The Caribbean was one of the last regions of the Americas to be settled by humans, but where they came from and how and when they reached the islands remain unclear. We generated genome-wide data for 93 ancient Caribbean islanders dating between 3200 and 400 calibrated years before the present and found evidence of at least three separate dispersals into the region, including two early dispersals into

    更新日期:2020-07-24
  • Itaconate is an effector of a Rab GTPase cell-autonomous host defense pathway against Salmonella
    Science (IF 41.845) Pub Date : 2020-07-24
    Meixin Chen, Hui Sun, Maikel Boot, Lin Shao, Shu-Jung Chang, Weiwei Wang, Tukiet T. Lam, Maria Lara-Tejero, E. Hesper Rego, Jorge E. Galán

    The guanosine triphosphatase (GTPase) Rab32 coordinates a cell-intrinsic host defense mechanism that restricts the replication of intravacuolar pathogens such as Salmonella. Here, we show that this mechanism requires aconitate decarboxylase 1 (IRG1), which synthesizes itaconate, a metabolite with antimicrobial activity. We find that Rab32 interacts with IRG1 on Salmonella infection and facilitates

    更新日期:2020-07-24
  • Anomalous absorption of electromagnetic waves by 2D transition metal carbonitride Ti3CNTx (MXene)
    Science (IF 41.845) Pub Date : 2020-07-24
    Aamir Iqbal, Faisal Shahzad, Kanit Hantanasirisakul, Myung-Ki Kim, Jisung Kwon, Junpyo Hong, Hyerim Kim, Daesin Kim, Yury Gogotsi, Chong Min Koo

    Lightweight, ultrathin, and flexible electromagnetic interference (EMI) shielding materials are needed to protect electronic circuits and portable telecommunication devices and to eliminate cross-talk between devices and device components. Here, we show that a two-dimensional (2D) transition metal carbonitride, Ti3CNTx MXene, with a moderate electrical conductivity, provides a higher shielding effectiveness

    更新日期:2020-07-24
  • An evolution-based model for designing chorismate mutase enzymes
    Science (IF 41.845) Pub Date : 2020-07-24
    William P. Russ, Matteo Figliuzzi, Christian Stocker, Pierre Barrat-Charlaix, Michael Socolich, Peter Kast, Donald Hilvert, Remi Monasson, Simona Cocco, Martin Weigt, Rama Ranganathan

    The rational design of enzymes is an important goal for both fundamental and practical reasons. Here, we describe a process to learn the constraints for specifying proteins purely from evolutionary sequence data, design and build libraries of synthetic genes, and test them for activity in vivo using a quantitative complementation assay. For chorismate mutase, a key enzyme in the biosynthesis of aromatic

    更新日期:2020-07-24
  • Remote structuring of near-field landscapes
    Science (IF 41.845) Pub Date : 2020-07-24
    Vincent Ginis, Marco Piccardo, Michele Tamagnone, Jinsheng Lu, Min Qiu, Simon Kheifets, Federico Capasso

    The electromagnetic near field enables subwavelength applications such as near-field microscopy and nanoparticle manipulation. Present methods to structure the near field rely on optical antenna theory, involving nanostructures that locally convert propagating waves into confined near-field patterns. We developed a theory of remote rather than local near-field shaping, based on cascaded mode conversion

    更新日期:2020-07-24
  • Structural basis for membrane insertion by the human ER membrane protein complex.
    Science (IF 41.845) Pub Date : 2020-07-24
    Tino Pleiner,Giovani Pinton Tomaleri,Kurt Januszyk,Alison J Inglis,Masami Hazu,Rebecca M Voorhees

    A defining step in the biogenesis of a membrane protein is the insertion of its hydrophobic transmembrane helices into the lipid bilayer. The nine-subunit endoplasmic reticulum (ER) membrane protein complex (EMC) is a conserved co- and posttranslational insertase at the ER. We determined the structure of the human EMC in a lipid nanodisc to an overall resolution of 3.4 angstroms by cryo–electron microscopy

    更新日期:2020-07-24
  • Ultrahigh-strength and ductile superlattice alloys with nanoscale disordered interfaces
    Science (IF 41.845) Pub Date : 2020-07-24
    T. Yang, Y. L. Zhao, W. P. Li, C. Y. Yu, J. H. Luan, D. Y. Lin, L. Fan, Z. B. Jiao, W. H. Liu, X. J. Liu, J. J. Kai, J. C. Huang, C. T. Liu

    Alloys that have high strengths at high temperatures are crucial for a variety of important industries including aerospace. Alloys with ordered superlattice structures are attractive for this purpose but generally suffer from poor ductility and rapid grain coarsening. We discovered that nanoscale disordered interfaces can effectively overcome these problems. Interfacial disordering is driven by multielement

    更新日期:2020-07-24
  • Determining plasmonic hot-carrier energy distributions via single-molecule transport measurements.
    Science (IF 41.845) Pub Date : 2020-07-24
    Harsha Reddy,Kun Wang,Zhaxylyk Kudyshev,Linxiao Zhu,Shen Yan,Andrea Vezzoli,Simon J Higgins,Vikram Gavini,Alexandra Boltasseva,Pramod Reddy,Vladimir M Shalaev,Edgar Meyhofer

    Hot carriers in plasmonic nanostructures, generated via plasmon decay, play key roles in applications such as photocatalysis and in photodetectors that circumvent bandgap limitations. However, direct experimental quantification of steady-state energy distributions of hot carriers in nanostructures has so far been lacking. We present transport measurements from single-molecule junctions, created by

    更新日期:2020-07-24
  • The impact of COVID-19 and strategies for mitigation and suppression in low- and middle-income countries.
    Science (IF 41.845) Pub Date : 2020-07-24
    Patrick G T Walker,Charles Whittaker,Oliver J Watson,Marc Baguelin,Peter Winskill,Arran Hamlet,Bimandra A Djafaara,Zulma Cucunubá,Daniela Olivera Mesa,Will Green,Hayley Thompson,Shevanthi Nayagam,Kylie E C Ainslie,Sangeeta Bhatia,Samir Bhatt,Adhiratha Boonyasiri,Olivia Boyd,Nicholas F Brazeau,Lorenzo Cattarino,Gina Cuomo-Dannenburg,Amy Dighe,Christl A Donnelly,Ilaria Dorigatti,Sabine L van Elsland

    The ongoing coronavirus disease 2019 (COVID-19) pandemic poses a severe threat to public health worldwide. We combine data on demography, contact patterns, disease severity, and health care capacity and quality to understand its impact and inform strategies for its control. Younger populations in lower-income countries may reduce overall risk, but limited health system capacity coupled with closer

    更新日期:2020-07-24
  • The activities of drug inactive ingredients on biological targets
    Science (IF 41.845) Pub Date : 2020-07-24
    Joshua Pottel, Duncan Armstrong, Ling Zou, Alexander Fekete, Xi-Ping Huang, Hayarpi Torosyan, Dallas Bednarczyk, Steven Whitebread, Barun Bhhatarai, Guiqing Liang, Hong Jin, S. Nassir Ghaemi, Samuel Slocum, Katalin V. Lukacs, John J. Irwin, Ellen L. Berg, Kathleen M. Giacomini, Bryan L. Roth, Brian K. Shoichet, Laszlo Urban

    Excipients, considered “inactive ingredients,” are a major component of formulated drugs and play key roles in their pharmacokinetics. Despite their pervasiveness, whether they are active on any targets has not been systematically explored. We computed the likelihood that approved excipients would bind to molecular targets. Testing in vitro revealed 25 excipient activities, ranging from low-nanomolar

    更新日期:2020-07-24
  • Chaperone-mediated autophagy regulates the pluripotency of embryonic stem cells
    Science (IF 41.845) Pub Date : 2020-07-24
    Yi Xu, Yang Zhang, Juan C. García-Cañaveras, Lili Guo, Mengyuan Kan, Sixiang Yu, Ian A. Blair, Joshua D. Rabinowitz, Xiaolu Yang

    Embryonic stem cells can propagate indefinitely in a pluripotent state, able to differentiate into all types of specialized cells when restored to the embryo. What sustains their pluripotency during propagation remains unclear. Here, we show that core pluripotency factors OCT4 and SOX2 suppress chaperone-mediated autophagy (CMA), a selective form of autophagy, until the initiation of differentiation

    更新日期:2020-07-24
  • Cooperative carbon capture and steam regeneration with tetraamine-appended metal–organic frameworks
    Science (IF 41.845) Pub Date : 2020-07-24
    Eugene J. Kim, Rebecca L. Siegelman, Henry Z. H. Jiang, Alexander C. Forse, Jung-Hoon Lee, Jeffrey D. Martell, Phillip J. Milner, Joseph M. Falkowski, Jeffrey B. Neaton, Jeffrey A. Reimer, Simon C. Weston, Jeffrey R. Long

    Natural gas has become the dominant source of electricity in the United States, and technologies capable of efficiently removing carbon dioxide (CO2) from the flue emissions of natural gas–fired power plants could reduce their carbon intensity. However, given the low partial pressure of CO2 in the flue stream, separation of CO2 is particularly challenging. Taking inspiration from the crystal structures

    更新日期:2020-07-24
  • Evaluating scenarios toward zero plastic pollution
    Science (IF 41.845) Pub Date : 2020-07-23
    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

    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:2020-07-24
  • Structural basis for neutralization of SARS-CoV-2 and SARS-CoV by a potent therapeutic antibody
    Science (IF 41.845) Pub Date : 2020-07-23
    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 COVID-19 pandemic caused by the SARS-CoV-2 virus has resulted in an unprecedented public health crisis. There are no approved vaccines or therapeutics for treating COVID-19. Here we reported a humanized monoclonal antibody, H014, efficiently neutralizes SARS-CoV-2 and SARS-CoV pseudoviruses as well as authentic SARS-CoV-2 at nM level by engaging the S receptor binding domain (RBD). Importantly

    更新日期:2020-07-24
  • Structure-based design of prefusion-stabilized SARS-CoV-2 spikes
    Science (IF 41.845) Pub Date : 2020-07-23
    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

    The 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. Here, we characterized 100 structure-guided spike designs and identified 26 individual substitutions that increased protein yields and stability. Testing combinations of beneficial substitutions

    更新日期:2020-07-24
  • Evolution and epidemic spread of SARS-CoV-2 in Brazil
    Science (IF 41.845) Pub Date : 2020-07-23
    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

    Brazil currently has one of the fastest growing SARS-CoV-2 epidemics in the world. Owing to limited available data, assessments of the impact of non-pharmaceutical interventions (NPIs) on virus spread remain challenging. Using a mobility-driven transmission model, we show that NPIs reduced the reproduction number from >3 to 1–1.6 in São Paulo and Rio de Janeiro. Sequencing of 427 new genomes and analysis

    更新日期:2020-07-24
  • Global quieting of high-frequency seismic noise due to COVID-19 pandemic lockdown measures
    Science (IF 41.845) Pub Date : 2020-07-23
    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

    Human activity causes vibrations that propagate into the ground as high-frequency seismic waves. Measures to mitigate the 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. While the reduction is strongest

    更新日期:2020-07-24
  • Serial interval of SARS-CoV-2 was shortened over time by nonpharmaceutical interventions
    Science (IF 41.845) Pub Date : 2020-07-21
    Sheikh Taslim Ali, Lin Wang, Eric H. Y. Lau, Xiao-Ke Xu, Zhanwei Du, Ye Wu, Gabriel M. Leung, Benjamin J. Cowling

    Studies of novel coronavirus disease (COVID-19) have reported varying estimates of epidemiological parameters including serial interval distributions, i.e., the time between illness onset in successive cases in a transmission chain, and reproduction numbers. By compiling a line-list database of transmission pairs in mainland China, we show that mean serial intervals of COVID-19 have shortened substantially

    更新日期:2020-07-22
  • Distinct conformational states of SARS-CoV-2 spike protein
    Science (IF 41.845) Pub Date : 2020-07-21
    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 SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) pandemic. The trimeric viral spike (S) protein catalyzes fusion between viral and target cell membranes to initiate infection. Here we report two cryo-EM structures, derived from a preparation of the full-length S protein, representing its prefusion (2.9Å resolution) and postfusion

    更新日期:2020-07-22
  • Assessing the impact of coordinated COVID-19 exit strategies across Europe
    Science (IF 41.845) Pub Date : 2020-07-17
    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 COVID-19 cases decline across Europe due to non-pharmaceutical interventions such as social distancing policies and lockdown measures, countries require guidance on how to ease restrictions while minimizing the risk of resurgent outbreaks. Here, we use mobility and case data to quantify how coordinated exit strategies could delay continental resurgence and limit community transmission

    更新日期:2020-07-18
  • Structural basis for translational shutdown and immune evasion by the Nsp1 protein of SARS-CoV-2
    Science (IF 41.845) Pub Date : 2020-07-17
    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

    SARS-CoV-2 is the causative agent of the current 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 mRNA translation both in vitro and in cells. Structural analysis by cryo-electron microscopy

    更新日期:2020-07-18
  • Population genetics of the coral Acropora millepora: Toward genomic prediction of bleaching
    Science (IF 41.845) Pub Date : 2020-07-17
    Zachary L. Fuller, Veronique J. L. Mocellin, Luke A. Morris, Neal Cantin, Jihanne Shepherd, Luke Sarre, Julie Peng, Yi Liao, Joseph Pickrell, Peter Andolfatto, Mikhail Matz, Line K. Bay, Molly Przeworski

    Although reef-building corals are declining worldwide, responses to bleaching vary within and across species and are partly heritable. Toward predicting bleaching response from genomic data, we generated a chromosome-scale genome assembly for the coral Acropora millepora. We obtained whole-genome sequences for 237 phenotyped samples collected at 12 reefs along the Great Barrier Reef, among which we

    更新日期:2020-07-17
  • Optical frequency combs: Coherently uniting the electromagnetic spectrum
    Science (IF 41.845) Pub Date : 2020-07-17
    Scott A. Diddams, Kerry Vahala, Thomas Udem

    Optical frequency combs were introduced around 20 years ago as a laser technology that could synthesize and count the ultrafast rate of the oscillating cycles of light. Functioning in a manner analogous to a clockwork of gears, the frequency comb phase-coherently upconverts a radio frequency signal by a factor of ≈105 to provide a vast array of evenly spaced optical frequencies, which is the comb for

    更新日期:2020-07-17
  • Tumor-initiating cells establish an IL-33–TGF-β niche signaling loop to promote cancer progression
    Science (IF 41.845) Pub Date : 2020-07-17
    Sachiko Taniguchi, Ajit Elhance, Avery Van Duzer, Sushil Kumar, Justin J. Leitenberger, Naoki Oshimori

    Targeting the cross-talk between tumor-initiating cells (TICs) and the niche microenvironment is an attractive avenue for cancer therapy. We show here, using a mouse model of squamous cell carcinoma, that TICs play a crucial role in creating a niche microenvironment that is required for tumor progression and drug resistance. Antioxidant activity in TICs, mediated by the transcription factor NRF2, facilitates

    更新日期:2020-07-17
  • CRISPR-CasΦ from huge phages is a hypercompact genome editor
    Science (IF 41.845) Pub Date : 2020-07-17
    Patrick Pausch, Basem Al-Shayeb, Ezra Bisom-Rapp, Connor A. Tsuchida, Zheng Li, Brady F. Cress, Gavin J. Knott, Steven E. Jacobsen, Jillian F. Banfield, Jennifer A. Doudna

    CRISPR-Cas systems are found widely in prokaryotes, where they provide adaptive immunity against virus infection and plasmid transformation. We describe a minimal functional CRISPR-Cas system, comprising a single ~70-kilodalton protein, CasΦ, and a CRISPR array, encoded exclusively in the genomes of huge bacteriophages. CasΦ uses a single active site for both CRISPR RNA (crRNA) processing and crRNA-guided

    更新日期:2020-07-17
  • Site-specific glycan analysis of the SARS-CoV-2 spike.
    Science (IF 41.845) Pub Date : 2020-07-17
    Yasunori Watanabe,Joel D Allen,Daniel Wrapp,Jason S McLellan,Max Crispin

    The emergence of the betacoronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19), represents a considerable threat to global human health. Vaccine development is focused on the principal target of the humoral immune response, the spike (S) glycoprotein, which mediates cell entry and membrane fusion. The SARS-CoV-2 S gene

    更新日期:2020-07-17
  • A programmable fate decision landscape underlies single-cell aging in yeast
    Science (IF 41.845) Pub Date : 2020-07-17
    Yang Li, Yanfei Jiang, Julie Paxman, Richard O’Laughlin, Stephen Klepin, Yuelian Zhu, Lorraine Pillus, Lev S. Tsimring, Jeff Hasty, Nan Hao

    Chromatin instability and mitochondrial decline are conserved processes that contribute to cellular aging. Although both processes have been explored individually in the context of their distinct signaling pathways, the mechanism that determines which process dominates during aging of individual cells is unknown. We show that interactions between the chromatin silencing and mitochondrial pathways lead

    更新日期:2020-07-17
  • Autoreactivity in naïve human fetal B cells is associated with commensal bacteria recognition
    Science (IF 41.845) Pub Date : 2020-07-17
    Jeff W. Chen, Tyler A. Rice, Jason M. Bannock, Agata A. Bielecka, Juliet D. Strauss, Jason R. Catanzaro, Haowei Wang, Laurence C. Menard, Jennifer H. Anolik, Noah W. Palm, Eric Meffre

    Restricted V(D)J recombination during fetal development was postulated to limit antibody repertoire breadth and prevent autoimmunity. However, newborn serum contains abundant autoantibodies, suggesting that B cell tolerance during gestation is not yet fully established. To investigate this apparent paradox, we evaluated the reactivities of more than 450 antibodies cloned from single B cells from human

    更新日期:2020-07-17
  • Susceptible supply limits the role of climate in the early SARS-CoV-2 pandemic.
    Science (IF 41.845) Pub Date : 2020-07-17
    Rachel E Baker,Wenchang Yang,Gabriel A Vecchi,C Jessica E Metcalf,Bryan T Grenfell

    Preliminary evidence suggests that climate may modulate the transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Yet it remains unclear whether seasonal and geographic variations in climate can substantially alter the pandemic trajectory, given that high susceptibility is a core driver. Here, we use a climate-dependent epidemic model to simulate the SARS-CoV-2 pandemic by probing

    更新日期:2020-07-17
  • N-Aryl–linked spirocyclic polymers for membrane separations of complex hydrocarbon mixtures
    Science (IF 41.845) Pub Date : 2020-07-17
    Kirstie A. Thompson, Ronita Mathias, Daeok Kim, Jihoon Kim, Neel Rangnekar, J. R. Johnson, Scott J. Hoy, Irene Bechis, Andrew Tarzia, Kim E. Jelfs, Benjamin A. McCool, Andrew G. Livingston, Ryan P. Lively, M. G. Finn

    The fractionation of crude-oil mixtures through distillation is a large-scale, energy-intensive process. Membrane materials can avoid phase changes in such mixtures and thereby reduce the energy intensity of these thermal separations. With this application in mind, we created spirocyclic polymers with N-aryl bonds that demonstrated noninterconnected microporosity in the absence of ladder linkages.

    更新日期:2020-07-17
  • Molecular square dancing in CO-CO collisions
    Science (IF 41.845) Pub Date : 2020-07-17
    Zhong-Fa Sun, Marc C. van Hemert, Jérôme Loreau, Ad van der Avoird, Arthur G. Suits, David H. Parker

    Knowledge of rotational energy transfer (RET) involving carbon monoxide (CO) molecules is crucial for the interpretation of astrophysical data. As of now, our nearly perfect understanding of atom-molecule scattering shows that RET usually occurs by only a simple “bump” between partners. To advance molecular dynamics to the next step in complexity, we studied molecule-molecule scattering in great detail

    更新日期:2020-07-17
  • Boron-enabled geometric isomerization of alkenes via selective energy-transfer catalysis
    Science (IF 41.845) Pub Date : 2020-07-17
    John J. Molloy, Michael Schäfer, Max Wienhold, Tobias Morack, Constantin G. Daniliuc, Ryan Gilmour

    Isomerization-based strategies to enable the stereodivergent construction of complex polyenes from geometrically defined alkene linchpins remain conspicuously underdeveloped. Mitigating the thermodynamic constraints inherent to isomerization is further frustrated by the considerations of atom efficiency in idealized low–molecular weight precursors. In this work, we report a general ambiphilic C3 scaffold

    更新日期:2020-07-17
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