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  • Potent neutralizing antibodies from COVID-19 patients define multiple targets of vulnerability.
    Science (IF 41.845) Pub Date : 2020-08-07
    Philip J M Brouwer,Tom G Caniels,Karlijn van der Straten,Jonne L Snitselaar,Yoann Aldon,Sandhya Bangaru,Jonathan L Torres,Nisreen M A Okba,Mathieu Claireaux,Gius Kerster,Arthur E H Bentlage,Marlies M van Haaren,Denise Guerra,Judith A Burger,Edith E Schermer,Kirsten D Verheul,Niels van der Velde,Alex van der Kooi,Jelle van Schooten,Mariëlle J van Breemen,Tom P L Bijl,Kwinten Sliepen,Aafke Aartse,Ronald

    The rapid spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has had a large impact on global health, travel, and economy. Therefore, preventative and therapeutic measures are urgently needed. Here, we isolated monoclonal antibodies from three convalescent coronavirus disease 2019 (COVID-19) patients using a SARS-CoV-2 stabilized prefusion spike protein. These antibodies had low

    更新日期:2020-08-06
  • A neutralizing human antibody binds to the N-terminal domain of the Spike protein of SARS-CoV-2.
    Science (IF 41.845) Pub Date : 2020-08-07
    Xiangyang Chi,Renhong Yan,Jun Zhang,Guanying Zhang,Yuanyuan Zhang,Meng Hao,Zhe Zhang,Pengfei Fan,Yunzhu Dong,Yilong Yang,Zhengshan Chen,Yingying Guo,Jinlong Zhang,Yaning Li,Xiaohong Song,Yi Chen,Lu Xia,Ling Fu,Lihua Hou,Junjie Xu,Changming Yu,Jianmin Li,Qiang Zhou,Wei Chen

    Developing therapeutics against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) could be guided by the distribution of epitopes, not only on the receptor binding domain (RBD) of the Spike (S) protein but also across the full Spike (S) protein. We isolated and characterized monoclonal antibodies (mAbs) from 10 convalescent COVID-19 patients. Three mAbs showed neutralizing activities against

    更新日期:2020-08-06
  • Structural insight into precursor ribosomal RNA processing by ribonuclease MRP.
    Science (IF 41.845) Pub Date : 2020-08-07
    Pengfei Lan,Bin Zhou,Ming Tan,Shaobai Li,Mi Cao,Jian Wu,Ming Lei

    Ribonuclease (RNase) MRP is a conserved eukaryotic ribonucleoprotein complex that plays essential roles in precursor ribosomal RNA (pre-rRNA) processing and cell cycle regulation. In contrast to RNase P, which selectively cleaves transfer RNA–like substrates, it has remained a mystery how RNase MRP recognizes its diverse substrates. To address this question, we determined cryo–electron microscopy structures

    更新日期:2020-08-06
  • Ligand-recognizing motifs in plant LysM receptors are major determinants of specificity
    Science (IF 41.845) Pub Date : 2020-08-07
    Zoltan Bozsoki, Kira Gysel, Simon B. Hansen, Damiano Lironi, Christina Krönauer, Feng Feng, Noor de Jong, Maria Vinther, Manoj Kamble, Mikkel B. Thygesen, Ebbe Engholm, Christian Kofoed, Sébastien Fort, John T. Sullivan, Clive W. Ronson, Knud J. Jensen, Mickaël Blaise, Giles Oldroyd, Jens Stougaard, Kasper R. Andersen, Simona Radutoiu

    Plants evolved lysine motif (LysM) receptors to recognize and parse microbial elicitors and drive intracellular signaling to limit or facilitate microbial colonization. We investigated how chitin and nodulation (Nod) factor receptors of Lotus japonicus initiate differential signaling of immunity or root nodule symbiosis. Two motifs in the LysM1 domains of these receptors determine specific recognition

    更新日期:2020-08-06
  • Chemical vapor deposition of layered two-dimensional MoSi2N4 materials
    Science (IF 41.845) Pub Date : 2020-08-07
    Yi-Lun Hong, Zhibo Liu, Lei Wang, Tianya Zhou, Wei Ma, Chuan Xu, Shun Feng, Long Chen, Mao-Lin Chen, Dong-Ming Sun, Xing-Qiu Chen, Hui-Ming Cheng, Wencai Ren

    Identifying two-dimensional layered materials in the monolayer limit has led to discoveries of numerous new phenomena and unusual properties. We introduced elemental silicon during chemical vapor deposition growth of nonlayered molybdenum nitride to passivate its surface, which enabled the growth of centimeter-scale monolayer films of MoSi2N4. This monolayer was built up by septuple atomic layers of

    更新日期:2020-08-06
  • Sequencing of metals in multivariate metal-organic frameworks
    Science (IF 41.845) Pub Date : 2020-08-07
    Zhe Ji, Tong Li, Omar M. Yaghi

    We mapped the metal sequences within crystals of metal-oxide rods in multivariate metal-organic framework–74 containing mixed combinations of cobalt (Co), cadmium (Cd), lead (Pb), and manganese (Mn). Atom probe tomography of these crystals revealed the presence of heterogeneous spatial sequences of metal ions that we describe, depending on the metal and synthesis temperature used, as random (Co, Cd

    更新日期:2020-08-06
  • Emergent helical texture of electric dipoles
    Science (IF 41.845) Pub Date : 2020-08-07
    Dmitry D. Khalyavin, Roger D. Johnson, Fabio Orlandi, Paolo G. Radaelli, Pascal Manuel, Alexei A. Belik

    Long-range ordering of magnetic dipoles in bulk materials gives rise to a broad range of magnetic structures, from simple collinear ferromagnets and antiferromagnets, to complex magnetic helicoidal textures stabilized by competing exchange interactions. In contrast, dipolar order in dielectric crystals is typically limited to parallel (ferroelectric) and antiparallel (antiferroelectric) collinear alignments

    更新日期:2020-08-06
  • A new wrinkle on liquid sheets: Turning the mechanism of viscous bubble collapse upside down
    Science (IF 41.845) Pub Date : 2020-08-07
    Alexandros T. Oratis, John W. M. Bush, Howard A. Stone, James C. Bird

    Viscous bubbles are prevalent in both natural and industrial settings. Their rupture and collapse may be accompanied by features typically associated with elastic sheets, including the development of radial wrinkles. Previous investigators concluded that the film weight is responsible for both the film collapse and wrinkling instability. Conversely, we show here experimentally that gravity plays a

    更新日期:2020-08-06
  • How hair deforms steel
    Science (IF 41.845) Pub Date : 2020-08-07
    Gianluca Roscioli, Seyedeh Mohadeseh Taheri-Mousavi, Cemal Cem Tasan

    Steels for sharp edges or tools typically have martensitic microstructures, high carbide contents, and various coatings to exhibit high hardness and wear resistance. Yet they become practically unusable upon cutting much softer materials such as human hair, cheese, or potatoes. Despite this being an everyday observation, the underlying physical micromechanisms are poorly understood because of the structural

    更新日期:2020-08-06
  • Global maps of the magnetic field in the solar corona
    Science (IF 41.845) Pub Date : 2020-08-07
    Zihao Yang, Christian Bethge, Hui Tian, Steven Tomczyk, Richard Morton, Giulio Del Zanna, Scott W. McIntosh, Bidya Binay Karak, Sarah Gibson, Tanmoy Samanta, Jiansen He, Yajie Chen, Linghua Wang

    Understanding many physical processes in the solar atmosphere requires determination of the magnetic field in each atmospheric layer. However, direct measurements of the magnetic field in the Sun’s corona are difficult to obtain. Using observations with the Coronal Multi-channel Polarimeter, we have determined the spatial distribution of the plasma density in the corona and the phase speed of the prevailing

    更新日期:2020-08-06
  • Cell-cell adhesion in plant grafting is facilitated by β-1,4-glucanases
    Science (IF 41.845) Pub Date : 2020-08-07
    Michitaka Notaguchi, Ken-ichi Kurotani, Yoshikatsu Sato, Ryo Tabata, Yaichi Kawakatsu, Koji Okayasu, Yu Sawai, Ryo Okada, Masashi Asahina, Yasunori Ichihashi, Ken Shirasu, Takamasa Suzuki, Masaki Niwa, Tetsuya Higashiyama

    Plant grafting is conducted for fruit and vegetable propagation, whereby a piece of living tissue is attached to another through cell-cell adhesion. However, graft compatibility limits combinations to closely related species, and the mechanism is poorly understood. We found that Nicotiana is capable of graft adhesion with a diverse range of angiosperms. Comparative transcriptomic analyses on graft

    更新日期:2020-08-06
  • Unexpected air pollution with marked emission reductions during the COVID-19 outbreak in China.
    Science (IF 41.845) Pub Date : 2020-08-07
    Tianhao Le,Yuan Wang,Lang Liu,Jiani Yang,Yuk L Yung,Guohui Li,John H Seinfeld

    The absence of motor vehicle traffic and suspended manufacturing during the coronavirus disease 2019 (COVID-19) pandemic in China enabled assessment of the efficiency of air pollution mitigation. Up to 90% reduction of certain emissions during the city-lockdown period can be identified from satellite and ground-based observations. Unexpectedly, extreme particulate matter levels simultaneously occurred

    更新日期:2020-08-06
  • Type III interferons disrupt the lung epithelial barrier upon viral recognition.
    Science (IF 41.845) Pub Date : 2020-08-07
    Achille Broggi,Sreya Ghosh,Benedetta Sposito,Roberto Spreafico,Fabio Balzarini,Antonino Lo Cascio,Nicola Clementi,Maria De Santis,Nicasio Mancini,Francesca Granucci,Ivan Zanoni

    Viral infections of the lower respiratory tract are a leading cause of mortality. Mounting evidence indicates that most severe cases are characterized by aberrant immune responses and do not depend on viral burden. In this study, we assessed how type III interferons (IFN-λ) contribute to the pathogenesis induced by RNA viruses. We report that IFN-λ is present in the lower, but not upper, airways of

    更新日期:2020-08-06
  • Type I and III interferons disrupt lung epithelial repair during recovery from viral infection.
    Science (IF 41.845) Pub Date : 2020-08-07
    Jack Major,Stefania Crotta,Miriam Llorian,Teresa M McCabe,Hans Henrik Gad,Simon L Priestnall,Rune Hartmann,Andreas Wack

    Excessive cytokine signaling frequently exacerbates lung tissue damage during respiratory viral infection. Type I (IFN-α and IFN-β) and III (IFN-λ) interferons are host-produced antiviral cytokines. Prolonged IFN-α and IFN-β responses can lead to harmful proinflammatory effects, whereas IFN-λ mainly signals in epithelia, thereby inducing localized antiviral immunity. In this work, we show that IFN

    更新日期:2020-08-06
  • Impaired type I interferon activity and inflammatory responses in severe COVID-19 patients
    Science (IF 41.845) Pub Date : 2020-08-07
    Jérôme Hadjadj, Nader Yatim, Laura Barnabei, Aurélien Corneau, Jeremy Boussier, Nikaïa Smith, Hélène Péré, Bruno Charbit, Vincent Bondet, Camille Chenevier-Gobeaux, Paul Breillat, Nicolas Carlier, Rémy Gauzit, Caroline Morbieu, Frédéric Pène, Nathalie Marin, Nicolas Roche, Tali-Anne Szwebel, Sarah H. Merkling, Jean-Marc Treluyer, David Veyer, Luc Mouthon, Catherine Blanc, Pierre-Louis Tharaux, Flore

    Coronavirus disease 2019 (COVID-19) is characterized by distinct patterns of disease progression that suggest diverse host immune responses. We performed an integrated immune analysis on a cohort of 50 COVID-19 patients with various disease severity. A distinct phenotype was observed in severe and critical patients, consisting of a highly impaired interferon (IFN) type I response (characterized by

    更新日期:2020-08-06
  • A short de novo synthesis of nucleoside analogs
    Science (IF 41.845) Pub Date : 2020-08-07
    Michael Meanwell, Steven M. Silverman, Johannes Lehmann, Bharanishashank Adluri, Yang Wang, Ryan Cohen, Louis-Charles Campeau, Robert Britton

    Nucleoside analogs are commonly used in the treatment of cancer and viral infections. Their syntheses benefit from decades of research but are often protracted, unamenable to diversification, and reliant on a limited pool of chiral carbohydrate starting materials. We present a process for rapidly constructing nucleoside analogs from simple achiral materials. Using only proline catalysis, heteroaryl-substituted

    更新日期:2020-08-06
  • Broad neutralization of SARS-related viruses by human monoclonal antibodies.
    Science (IF 41.845) Pub Date : 2020-08-07
    Anna Z Wec,Daniel Wrapp,Andrew S Herbert,Daniel P Maurer,Denise Haslwanter,Mrunal Sakharkar,Rohit K Jangra,M Eugenia Dieterle,Asparouh Lilov,Deli Huang,Longping V Tse,Nicole V Johnson,Ching-Lin Hsieh,Nianshuang Wang,Juergen H Nett,Elizabeth Champney,Irina Burnina,Michael Brown,Shu Lin,Melanie Sinclair,Carl Johnson,Sarat Pudi,Robert Bortz,Ariel S Wirchnianski,Ethan Laudermilch,Catalina Florez,J Maximilian

    Broadly protective vaccines against known and preemergent human coronaviruses (HCoVs) are urgently needed. To gain a deeper understanding of cross-neutralizing antibody responses, we mined the memory B cell repertoire of a convalescent severe acute respiratory syndrome (SARS) donor and identified 200 SARS coronavirus 2 (SARS-CoV-2) binding antibodies that target multiple conserved sites on the spike

    更新日期:2020-08-06
  • The proteasome controls ESCRT-III–mediated cell division in an archaeon
    Science (IF 41.845) Pub Date : 2020-08-07
    Gabriel Tarrason Risa, Fredrik Hurtig, Sian Bray, Anne E. Hafner, Lena Harker-Kirschneck, Peter Faull, Colin Davis, Dimitra Papatziamou, Delyan R. Mutavchiev, Catherine Fan, Leticia Meneguello, Andre Arashiro Pulschen, Gautam Dey, Siân Culley, Mairi Kilkenny, Diorge P. Souza, Luca Pellegrini, Robertus A. M. de Bruin, Ricardo Henriques, Ambrosius P. Snijders, Anđela Šarić, Ann-Christin Lindås, Nicholas

    Sulfolobus acidocaldarius is the closest experimentally tractable archaeal relative of eukaryotes and, despite lacking obvious cyclin-dependent kinase and cyclin homologs, has an ordered eukaryote-like cell cycle with distinct phases of DNA replication and division. Here, in exploring the mechanism of cell division in S. acidocaldarius, we identify a role for the archaeal proteasome in regulating the

    更新日期:2020-08-06
  • A molecular pore spans the double membrane of the coronavirus replication organelle
    Science (IF 41.845) Pub Date : 2020-08-06
    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 micro-environment for viral RNA synthesis in the infected cell. However, it is unclear how newly synthesized genomes and mRNAs can travel from these sealed replication compartments to the cytosol to ensure their translation and the assembly of progeny virions. Here, we used

    更新日期:2020-08-06
  • Rotational resonances in the H2CO roaming reaction are revealed by detailed correlations
    Science (IF 41.845) Pub Date : 2020-08-06
    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 perform detailed experiments on H2CO photodissociation, determining fully correlated quantum state distributions of the H2 and CO products. These experiments

    更新日期:2020-08-06
  • 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
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