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  • De novo design of picomolar SARS-CoV-2 miniprotein inhibitors.
    Science (IF 41.845) Pub Date : 2020-10-23
    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 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein and the human angiotensin-converting enzyme 2 (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

    更新日期:2020-10-28
  • Orderly compartmental mapping of premotor inhibition in the developing zebrafish spinal cord
    Science (IF 41.845) Pub Date : 2020-10-23
    Sandeep Kishore, Eli B. Cadoff, Moneeza A. Agha, David L. McLean

    In vertebrates, faster movements involve the orderly recruitment of different types of spinal motor neurons. However, it is not known how premotor inhibitory circuits are organized to ensure alternating motor output at different movement speeds. We found that different types of commissural inhibitory interneurons in zebrafish form compartmental microcircuits during development that align inhibitory

    更新日期:2020-10-28
  • Polyethylene upcycling to long-chain alkylaromatics by tandem hydrogenolysis/aromatization
    Science (IF 41.845) Pub Date : 2020-10-23
    Fan Zhang, Manhao Zeng, Ryan D. Yappert, Jiakai Sun, Yu-Hsuan Lee, Anne M. LaPointe, Baron Peters, Mahdi M. Abu-Omar, Susannah L. Scott

    The current scale of plastics production and the accompanying waste disposal problems represent a largely untapped opportunity for chemical upcycling. Tandem catalytic conversion by platinum supported on γ-alumina converts various polyethylene grades in high yields (up to 80 weight percent) to low-molecular-weight liquid/wax products, in the absence of added solvent or molecular hydrogen, with little

    更新日期:2020-10-28
  • Supertwisted spirals of layered materials enabled by growth on non-Euclidean surfaces
    Science (IF 41.845) Pub Date : 2020-10-23
    Yuzhou Zhao, Chenyu Zhang, Daniel D. Kohler, Jason M. Scheeler, John C. Wright, Paul M. Voyles, Song Jin

    Euclidean geometry is the fundamental mathematical framework of classical crystallography. Traditionally, layered materials are grown on flat substrates; growing Euclidean crystals on non-Euclidean surfaces has rarely been studied. We present a general model describing the growth of layered materials with screw-dislocation spirals on non-Euclidean surfaces and show that it leads to continuously twisted

    更新日期:2020-10-28
  • Triple iron isotope constraints on the role of ocean iron sinks in early atmospheric oxygenation
    Science (IF 41.845) Pub Date : 2020-10-23
    Andy W. Heard, Nicolas Dauphas, Romain Guilbaud, Olivier J. Rouxel, Ian B. Butler, Nicole X. Nie, Andrey Bekker

    The role that iron played in the oxygenation of Earth’s surface is equivocal. Iron could have consumed molecular oxygen when Fe3+-oxyhydroxides formed in the oceans, or it could have promoted atmospheric oxidation by means of pyrite burial. Through high-precision iron isotopic measurements of Archean-Paleoproterozoic sediments and laboratory grown pyrites, we show that the triple iron isotopic composition

    更新日期:2020-10-28
  • Structural basis of nucleosome-dependent cGAS inhibition.
    Science (IF 41.845) Pub Date : 2020-10-23
    Joshua A Boyer,Cathy J Spangler,Joshua D Strauss,Andrew P Cesmat,Pengda Liu,Robert K McGinty,Qi Zhang

    Cyclic guanosine monophosphate (GMP)–adenosine monophosphate (AMP) synthase (cGAS) recognizes cytosolic foreign or damaged DNA to activate the innate immune response to infection, inflammatory diseases, and cancer. By 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

    更新日期:2020-10-28
  • Structural basis for the inhibition of cGAS by nucleosomes.
    Science (IF 41.845) Pub Date : 2020-10-23
    Tomoya Kujirai,Christian Zierhut,Yoshimasa Takizawa,Ryan Kim,Lumi Negishi,Nobuki Uruma,Seiya Hirai,Hironori Funabiki,Hitoshi Kurumizaka

    The cyclic guanosine monophosphate–adenosine monophosphate 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–electron microscopy structure of

    更新日期:2020-10-28
  • Metasurface-driven OLED displays beyond 10,000 pixels per inch
    Science (IF 41.845) Pub Date : 2020-10-23
    Won-Jae Joo, Jisoo Kyoung, Majid Esfandyarpour, Sung-Hoon Lee, Hyun Koo, Sunjin Song, Young-Nam Kwon, Seok Ho Song, Jun Cheol Bae, Ara Jo, Myong-Jong Kwon, Sung Hyun Han, Sung-Han Kim, Sungwoo Hwang, Mark L. Brongersma

    Optical metasurfaces are starting to find their way into integrated devices, where they can enhance and control the emission, modulation, dynamic shaping, and detection of light waves. In this study, we show that the architecture of organic light-emitting diode (OLED) displays can be completely reenvisioned through the introduction of nanopatterned metasurface mirrors. In the resulting meta-OLED displays

    更新日期:2020-10-28
  • Lineage analysis reveals an endodermal contribution to the vertebrate pituitary
    Science (IF 41.845) Pub Date : 2020-10-23
    Peter Fabian, Kuo-Chang Tseng, Joanna Smeeton, Joseph J. Lancman, P. Duc Si Dong, Robert Cerny, J. Gage Crump

    Vertebrate sensory organs arise from epithelial thickenings called placodes. Along with neural crest cells, cranial placodes are considered ectodermal novelties that drove evolution of the vertebrate head. The anterior-most placode generates the endocrine lobe [adenohypophysis (ADH)] of the pituitary, a master gland controlling growth, metabolism, and reproduction. In addition to known ectodermal contributions

    更新日期:2020-10-28
  • Proximal colon–derived O-glycosylated mucus encapsulates and modulates the microbiota
    Science (IF 41.845) Pub Date : 2020-10-23
    Kirk Bergstrom, Xindi Shan, David Casero, Albert Batushansky, Venu Lagishetty, Jonathan P. Jacobs, Christopher Hoover, Yuji Kondo, Bojing Shao, Liang Gao, Wesley Zandberg, Benjamin Noyovitz, J. Michael McDaniel, Deanna L. Gibson, Sepideh Pakpour, Negin Kazemian, Samuel McGee, Courtney W. Houchen, Chinthalapally V. Rao, Timothy M. Griffin, Justin L. Sonnenburg, Rodger P. McEver, Jonathan Braun, Lijun

    Colon mucus segregates the intestinal microbiota from host tissues, but how it organizes to function throughout the colon is unclear. In mice, we found that colon mucus consists of two distinct O-glycosylated entities of Muc2: a major form produced by the proximal colon, which encapsulates the fecal material including the microbiota, and a minor form derived from the distal colon, which adheres to

    更新日期:2020-10-28
  • Social selectivity in aging wild chimpanzees
    Science (IF 41.845) Pub Date : 2020-10-23
    Alexandra G. Rosati, Lindsey Hagberg, Drew K. Enigk, Emily Otali, Melissa Emery Thompson, Martin N. Muller, Richard W. Wrangham, Zarin P. Machanda

    Humans prioritize close, positive relationships during aging, and socioemotional selectivity theory proposes that this shift causally depends on capacities for thinking about personal future time horizons. To examine this theory, we tested for key elements of human social aging in longitudinal data on wild chimpanzees. Aging male chimpanzees have more mutual friendships characterized by high, equitable

    更新日期:2020-10-28
  • Experimental evolution makes microbes more cooperative with their local host genotype
    Science (IF 41.845) Pub Date : 2020-10-23
    Rebecca T. Batstone, Anna M. O’Brien, Tia L. Harrison, Megan E. Frederickson

    Advances in microbiome science require a better understanding of how beneficial microbes adapt to hosts. We tested whether hosts select for more-cooperative microbial strains with a year-long evolution experiment and a cross-inoculation experiment designed to explore how nitrogen-fixing bacteria (rhizobia) adapt to legumes. We paired the bacterium Ensifer meliloti with one of five Medicago truncatula

    更新日期:2020-10-28
  • Oxygen-sensing mechanisms across eukaryotic kingdoms and their roles in complex multicellularity
    Science (IF 41.845) Pub Date : 2020-10-23
    Emma U. Hammarlund, Emily Flashman, Sofie Mohlin, Francesco Licausi

    Oxygen-sensing mechanisms of eukaryotic multicellular organisms coordinate hypoxic cellular responses in a spatiotemporal manner. Although this capacity partly allows animals and plants to acutely adapt to oxygen deprivation, its functional and historical roots in hypoxia emphasize a broader evolutionary role. For multicellular life-forms that persist in settings with variable oxygen concentrations

    更新日期:2020-10-28
  • Inborn errors of type I IFN immunity in patients with life-threatening COVID-19
    Science (IF 41.845) Pub Date : 2020-10-23
    Qian Zhang, Paul Bastard, Zhiyong Liu, Jérémie Le Pen, Marcela Moncada-Velez, Jie Chen, Masato Ogishi, Ira K. D. Sabli, Stephanie Hodeib, Cecilia Korol, Jérémie Rosain, Kaya Bilguvar, Junqiang Ye, Alexandre Bolze, Benedetta Bigio, Rui Yang, Andrés Augusto Arias, Qinhua Zhou, Yu Zhang, Fanny Onodi, Sarantis Korniotis, Léa Karpf, Quentin Philippot, Marwa Chbihi, Lucie Bonnet-Madin, Karim Dorgham, Nikaïa

    Clinical outcome upon infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ranges from silent infection to lethal coronavirus disease 2019 (COVID-19). We have found an enrichment in rare variants predicted to be loss-of-function (LOF) at the 13 human loci known to govern Toll-like receptor 3 (TLR3)– and interferon regulatory factor 7 (IRF7)–dependent type I interferon (IFN) immunity

    更新日期:2020-10-28
  • Autoantibodies against type I IFNs in patients with life-threatening COVID-19
    Science (IF 41.845) Pub Date : 2020-10-23
    Paul Bastard, Lindsey B. Rosen, Qian Zhang, Eleftherios Michailidis, Hans-Heinrich Hoffmann, Yu Zhang, Karim Dorgham, Quentin Philippot, Jérémie Rosain, Vivien Béziat, Jérémy Manry, Elana Shaw, Liis Haljasmägi, Pärt Peterson, Lazaro Lorenzo, Lucy Bizien, Sophie Trouillet-Assant, Kerry Dobbs, Adriana Almeida de Jesus, Alexandre Belot, Anne Kallaste, Emilie Catherinot, Yacine Tandjaoui-Lambiotte, Jeremie

    Interindividual clinical variability in the course of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is vast. We report that at least 101 of 987 patients with life-threatening coronavirus disease 2019 (COVID-19) pneumonia had neutralizing immunoglobulin G (IgG) autoantibodies (auto-Abs) against interferon-ω (IFN-ω) (13 patients), against the 13 types of IFN-α (36), or against

    更新日期:2020-10-28
  • Design of higher valency in covalent organic frameworks
    Science (IF 41.845) Pub Date : 2020-10-23
    Cornelius Gropp, Tianqiong Ma, Nikita Hanikel, Omar M. Yaghi

    The valency (connectivity) of building units in covalent organic frameworks (COFs) has been primarily 3 and 4, corresponding to triangles and squares or tetrahedrons, respectively. We report a strategy for making COFs with valency 8 (cubes) and “infinity” (rods). The linker 1,4-boronophenylphosphonic acid—designed to have boron and phosphorus as an isoelectronic combination of carbon-group elements—was

    更新日期:2020-10-28
  • Deep abiotic weathering of pyrite
    Science (IF 41.845) Pub Date : 2020-10-23
    Xin Gu, Peter J. Heaney, Fabio D. A. Aarão Reis, Susan L. Brantley

    Pyrite is a ubiquitous iron sulfide mineral that is oxidized by trace oxygen. The mineral has been largely absent from global sediments since the rise in oxygen concentration in Earth’s early atmosphere. We analyzed weathering in shale, the most common rock exposed at Earth’s surface, with chemical and microscopic analysis. By looking across scales from 10−9 to 102 meters, we determined the factors

    更新日期:2020-10-28
  • Enteroviral 3C protease activates the human NLRP1 inflammasome in airway epithelia
    Science (IF 41.845) Pub Date : 2020-10-22
    Kim S. Robinson, Daniel Eng Thiam Teo, Kai Sen Tan, Gee Ann Toh, Hsiao Hui Ong, Chrissie Kaishi Lim, Kenneth Lay, Bijin Veonice Au, Tian Sheng Lew, Justin Jang Hann Chu, Vincent Tak Kwong Chow, De Yun Wang, Franklin L. Zhong, Bruno Reversade

    Immune sensor proteins are critical to the function of the human innate immune system. The full repertoire of cognate triggers for human immune sensors is not fully understood. Here, we report that human NLRP1 is activated by 3C proteases (3Cpros) of enteroviruses, such as human rhinovirus (HRV). 3Cpros directly cleave human NLRP1 at a single site between Glu130 and Gly131. This cleavage triggers N-glycine–mediated

    更新日期:2020-10-28
  • Structural analysis of full-length SARS-CoV-2 spike protein from an advanced vaccine candidate
    Science (IF 41.845) Pub Date : 2020-10-20
    Sandhya Bangaru, Gabriel Ozorowski, Hannah L. Turner, Aleksandar Antanasijevic, Deli Huang, Xiaoning Wang, Jonathan L. Torres, Jolene K. Diedrich, Jing-Hui Tian, Alyse D. Portnoff, Nita Patel, Michael J. Massare, John R. Yates, David Nemazee, James C. Paulson, Greg Glenn, Gale Smith, Andrew B. Ward

    Vaccine efforts against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) responsible for the current COVID-19 pandemic are focused on SARS-CoV-2 spike glycoprotein, the primary target for neutralizing antibodies. We performed cryo-EM and site-specific glycan analysis of one of the leading subunit vaccine candidates from Novavax based on a full-length spike protein formulated in polysorbate

    更新日期:2020-10-28
  • Neuropilin-1 is a host factor for SARS-CoV-2 infection
    Science (IF 41.845) Pub Date : 2020-10-20
    James L. Daly, Boris Simonetti, Katja Klein, Kai-En Chen, Maia Kavanagh Williamson, Carlos Antón-Plágaro, Deborah K. Shoemark, Lorena Simón-Gracia, Michael Bauer, Reka Hollandi, Urs F. Greber, Peter Horvath, Richard B. Sessions, Ari Helenius, Julian A. Hiscox, Tambet Teesalu, David A. Matthews, Andrew D. Davidson, Brett M. Collins, Peter J. Cullen, Yohei Yamauchi

    SARS-CoV-2, the causative agent of COVID-19, uses the viral Spike (S) protein for host cell attachment and entry. The host protease furin cleaves the full-length precursor S glycoprotein into two associated polypeptides: S1 and S2. Cleavage of S generates a polybasic Arg-Arg-Ala-Arg C-terminal sequence on S1, which conforms to a C-end rule (CendR) motif that binds to cell surface Neuropilin-1 (NRP1)

    更新日期:2020-10-28
  • Neuropilin-1 facilitates SARS-CoV-2 cell entry and infectivity
    Science (IF 41.845) Pub Date : 2020-10-20
    Ludovico Cantuti-Castelvetri, Ravi Ojha, Liliana D. Pedro, Minou Djannatian, Jonas Franz, Suvi Kuivanen, Franziska van der Meer, Katri Kallio, Tuğberk Kaya, Maria Anastasina, Teemu Smura, Lev Levanov, Leonora Szirovicza, Allan Tobi, Hannimari Kallio-Kokko, Pamela Österlund, Merja Joensuu, Frédéric A. Meunier, Sarah J. Butcher, Martin Sebastian Winkler, Brit Mollenhauer, Ari Helenius, Ozgun Gokce, Tambet

    The causative agent of coronavirus induced disease 2019 (COVID-19) is the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). For many viruses, tissue tropism is determined by the availability of virus receptors and entry cofactors on the surface of host cells. Here, we found that neuropilin-1 (NRP1), known to bind furin-cleaved substrates, significantly potentiates SARS-CoV-2 infectivity

    更新日期:2020-10-28
  • Microbiota-modulated CART+ enteric neurons autonomously regulate blood glucose.
    Science (IF 41.845) Pub Date : 2020-10-16
    Paul A Muller,Fanny Matheis,Marc Schneeberger,Zachary Kerner,Veronica Jové,Daniel Mucida

    The gut microbiota affects tissue physiology, metabolism, and function of both the immune and nervous systems. We found that intrinsic enteric-associated neurons (iEANs) in mice are functionally adapted to the intestinal segment they occupy; ileal and colonic neurons are more responsive to microbial colonization than duodenal neurons. Specifically, a microbially responsive subset of viscerofugal CART+

    更新日期:2020-10-15
  • Patterning and growth control in vivo by an engineered GFP gradient
    Science (IF 41.845) Pub Date : 2020-10-16
    Kristina S. Stapornwongkul, Marc de Gennes, Luca Cocconi, Guillaume Salbreux, Jean-Paul Vincent

    Morphogen gradients provide positional information during development. To uncover the minimal requirements for morphogen gradient formation, we have engineered a synthetic morphogen in Drosophila wing primordia. We show that an inert protein, green fluorescent protein (GFP), can form a detectable diffusion-based gradient in the presence of surface-associated anti-GFP nanobodies, which modulate the

    更新日期:2020-10-15
  • Engineering synthetic morphogen systems that can program multicellular patterning
    Science (IF 41.845) Pub Date : 2020-10-16
    Satoshi Toda, Wesley L. McKeithan, Teemu J. Hakkinen, Pilar Lopez, Ophir D. Klein, Wendell A. Lim

    In metazoan tissues, cells decide their fates by sensing positional information provided by specialized morphogen proteins. To explore what features are sufficient for positional encoding, we asked whether arbitrary molecules (e.g., green fluorescent protein or mCherry) could be converted into synthetic morphogens. Synthetic morphogens expressed from a localized source formed a gradient when trapped

    更新日期:2020-10-15
  • Coherently forming a single molecule in an optical trap
    Science (IF 41.845) Pub Date : 2020-10-16
    Xiaodong He, Kunpeng Wang, Jun Zhuang, Peng Xu, Xiang Gao, Ruijun Guo, Cheng Sheng, Min Liu, Jin Wang, Jiaming Li, G. V. Shlyapnikov, Mingsheng Zhan

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

    更新日期:2020-10-15
  • Cartilage-inspired, lipid-based boundary-lubricated hydrogels
    Science (IF 41.845) Pub Date : 2020-10-16
    Weifeng Lin, Monika Kluzek, Noa Iuster, Eyal Shimoni, Nir Kampf, Ronit Goldberg, Jacob Klein

    The lubrication of hydrogels arises from fluid or solvated surface phases. By contrast, the lubricity of articular cartilage, a complex biohydrogel, has been at least partially attributed to nonfluid, lipid-exposing boundary layers. We emulated this behavior in synthetic hydrogels by incorporating trace lipid concentrations to create a molecularly thin, lipid-based boundary layer that renews continuously

    更新日期:2020-10-15
  • Zeptosecond birth time delay in molecular photoionization
    Science (IF 41.845) Pub Date : 2020-10-16
    Sven Grundmann, Daniel Trabert, Kilian Fehre, Nico Strenger, Andreas Pier, Leon Kaiser, Max Kircher, Miriam Weller, Sebastian Eckart, Lothar Ph. H. Schmidt, Florian Trinter, Till Jahnke, Markus S. Schöffler, Reinhard Dörner

    Photoionization is one of the fundamental light-matter interaction processes in which the absorption of a photon launches the escape of an electron. The time scale of this process poses many open questions. Experiments have found time delays in the attosecond (10−18 seconds) domain between electron ejection from different orbitals, from different electronic bands, or in different directions. Here,

    更新日期:2020-10-15
  • Thermosensitive crystallization-boosted liquid thermocells for low-grade heat harvesting.
    Science (IF 41.845) Pub Date : 2020-10-16
    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 kelvin) is abundant and ubiquitous but is mostly wasted because present recovery technologies are not cost-effective. 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

    更新日期:2020-10-15
  • Species richness and redundancy promote persistence of exploited mutualisms in yeast
    Science (IF 41.845) Pub Date : 2020-10-16
    Mayra C. Vidal, Sheng Pei Wang, David M. Rivers, David M. Althoff, Kari A. Segraves

    Mutualisms, or reciprocally beneficial interspecific interactions, constitute the foundation of many ecological communities and agricultural systems. Mutualisms come in different forms, from pairwise interactions to extremely diverse communities, and they are continually challenged with exploitation by nonmutualistic community members (exploiters). Thus, understanding how mutualisms persist remains

    更新日期:2020-10-15
  • The GATOR–Rag GTPase pathway inhibits mTORC1 activation by lysosome-derived amino acids
    Science (IF 41.845) Pub Date : 2020-10-16
    Geoffrey G. Hesketh, Fotini Papazotos, Judy Pawling, Dushyandi Rajendran, James D. R. Knight, Sebastien Martinez, Mikko Taipale, Daniel Schramek, James W. Dennis, Anne-Claude Gingras

    The mechanistic target of rapamycin complex 1 (mTORC1) couples nutrient sufficiency to cell growth. mTORC1 is activated by exogenously acquired amino acids sensed through the GATOR–Rag guanosine triphosphatase (GTPase) pathway, or by amino acids derived through lysosomal degradation of protein by a poorly defined mechanism. Here, we revealed that amino acids derived from the degradation of protein

    更新日期:2020-10-15
  • Structural and spectroscopic characterization of an Fe(VI) bis(imido) complex
    Science (IF 41.845) Pub Date : 2020-10-16
    Jorge L. Martinez, Sean A. Lutz, Hao Yang, Jiaze Xie, Joshua Telser, Brian M. Hoffman, Veronica Carta, Maren Pink, Yaroslav Losovyj, Jeremy M. Smith

    High-valent iron species are key intermediates in oxidative biological processes, but hexavalent complexes apart from the ferrate ion are exceedingly rare. Here, we report the synthesis and structural and spectroscopic characterization of a stable Fe(VI) complex (3) prepared by facile one-electron oxidation of an Fe(V) bis(imido) (2). Single-crystal x-ray diffraction of 2 and 3 revealed four-coordinate

    更新日期:2020-10-15
  • Structural and mechanistic bases for a potent HIV-1 capsid inhibitor
    Science (IF 41.845) Pub Date : 2020-10-16
    Stephanie M. Bester, Guochao Wei, Haiyan Zhao, Daniel Adu-Ampratwum, Naseer Iqbal, Valentine V. Courouble, Ashwanth C. Francis, Arun S. Annamalai, Parmit K. Singh, Nikoloz Shkriabai, Peter Van Blerkom, James Morrison, Eric M. Poeschla, Alan N. Engelman, Gregory B. Melikyan, Patrick R. Griffin, James R. Fuchs, Francisco J. Asturias, Mamuka Kvaratskhelia

    The potent HIV-1 capsid inhibitor GS-6207 is an investigational principal component of long-acting antiretroviral therapy. We found that GS-6207 inhibits HIV-1 by stabilizing and thereby preventing functional disassembly of the capsid shell in infected cells. X-ray crystallography, cryo–electron microscopy, and hydrogen-deuterium exchange experiments revealed that GS-6207 tightly binds two adjoining

    更新日期:2020-10-15
  • Comprehensive quantification of fuel use by the failing and nonfailing human heart
    Science (IF 41.845) Pub Date : 2020-10-16
    Danielle Murashige, Cholsoon Jang, Michael Neinast, Jonathan J. Edwards, Alexis Cowan, Matthew C. Hyman, Joshua D. Rabinowitz, David S. Frankel, Zolt Arany

    The heart consumes circulating nutrients to fuel lifelong contraction, but a comprehensive mapping of human cardiac fuel use is lacking. We used metabolomics on blood from artery, coronary sinus, and femoral vein in 110 patients with or without heart failure to quantify the uptake and release of 277 metabolites, including all major nutrients, by the human heart and leg. The heart primarily consumed

    更新日期:2020-10-15
  • Transient cortical circuits match spontaneous and sensory-driven activity during development
    Science (IF 41.845) Pub Date : 2020-10-16
    Zoltán Molnár, Heiko J. Luhmann, Patrick O. Kanold

    At the earliest developmental stages, spontaneous activity synchronizes local and large-scale cortical networks. These networks form the functional template for the establishment of global thalamocortical networks and cortical architecture. The earliest connections are established autonomously. However, activity from the sensory periphery reshapes these circuits as soon as afferents reach the cortex

    更新日期:2020-10-15
  • Apical stress fibers enable a scaling between cell mechanical response and area in epithelial tissue
    Science (IF 41.845) Pub Date : 2020-10-16
    Jesús M. López-Gay, Hayden Nunley, Meryl Spencer, Florencia di Pietro, Boris Guirao, Floris Bosveld, Olga Markova, Isabelle Gaugue, Stéphane Pelletier, David K. Lubensky, Yohanns Bellaïche

    Biological systems tailor their properties and behavior to their size throughout development and in numerous aspects of physiology. However, such size scaling remains poorly understood as it applies to cell mechanics and mechanosensing. By examining how the Drosophila pupal dorsal thorax epithelium responds to morphogenetic forces, we found that the number of apical stress fibers (aSFs) anchored to

    更新日期:2020-10-15
  • Behavioral state coding by molecularly defined paraventricular hypothalamic cell type ensembles
    Science (IF 41.845) Pub Date : 2020-10-16
    Shengjin Xu, Hui Yang, Vilas Menon, Andrew L. Lemire, Lihua Wang, Fredrick E. Henry, Srinivas C. Turaga, Scott M. Sternson

    Brains encode behaviors using neurons amenable to systematic classification by gene expression. The contribution of molecular identity to neural coding is not understood because of the challenges involved with measuring neural dynamics and molecular information from the same cells. We developed CaRMA (calcium and RNA multiplexed activity) imaging based on recording in vivo single-neuron calcium dynamics

    更新日期:2020-10-15
  • The nucleus measures shape changes for cellular proprioception to control dynamic cell behavior
    Science (IF 41.845) Pub Date : 2020-10-16
    Valeria Venturini, Fabio Pezzano, Frederic Català Castro, Hanna-Maria Häkkinen, Senda Jiménez-Delgado, Mariona Colomer-Rosell, Monica Marro, Queralt Tolosa-Ramon, Sonia Paz-López, Miguel A. Valverde, Julian Weghuber, Pablo Loza-Alvarez, Michael Krieg, Stefan Wieser, Verena Ruprecht

    The physical microenvironment regulates cell behavior during tissue development and homeostasis. How single cells decode information about their geometrical shape under mechanical stress and physical space constraints within tissues remains largely unknown. Here, using a zebrafish model, we show that the nucleus, the biggest cellular organelle, functions as an elastic deformation gauge that enables

    更新日期:2020-10-15
  • The nucleus acts as a ruler tailoring cell responses to spatial constraints
    Science (IF 41.845) Pub Date : 2020-10-16
    A. J. Lomakin, C. J. Cattin, D. Cuvelier, Z. Alraies, M. Molina, G. P. F. Nader, N. Srivastava, P. J. Saez, J. M. Garcia-Arcos, I. Y. Zhitnyak, A. Bhargava, M. K. Driscoll, E. S. Welf, R. Fiolka, R. J. Petrie, N. S. De Silva, J. M. González-Granado, N. Manel, A. M. Lennon-Duménil, D. J. Müller, M. Piel

    The microscopic environment inside a metazoan organism is highly crowded. Whether individual cells can tailor their behavior to the limited space remains unclear. In this study, we found that cells measure the degree of spatial confinement by using their largest and stiffest organelle, the nucleus. Cell confinement below a resting nucleus size deforms the nucleus, which expands and stretches its envelope

    更新日期:2020-10-15
  • Mammalian lipid droplets are innate immune hubs integrating cell metabolism and host defense
    Science (IF 41.845) Pub Date : 2020-10-16
    Marta Bosch, Miguel Sánchez-Álvarez, Alba Fajardo, Ronan Kapetanovic, Bernhard Steiner, Filipe Dutra, Luciana Moreira, Juan Antonio López, Rocío Campo, Montserrat Marí, Frederic Morales-Paytuví, Olivia Tort, Albert Gubern, Rachel M. Templin, James E. B. Curson, Nick Martel, Cristina Català, Francisco Lozano, Francesc Tebar, Carlos Enrich, Jesús Vázquez, Miguel A. Del Pozo, Matthew J. Sweet, Patricia

    Lipid droplets (LDs) are the major lipid storage organelles of eukaryotic cells and a source of nutrients for intracellular pathogens. We demonstrate that mammalian LDs are endowed with a protein-mediated antimicrobial capacity, which is up-regulated by danger signals. In response to lipopolysaccharide (LPS), multiple host defense proteins, including interferon-inducible guanosine triphosphatases and

    更新日期:2020-10-15
  • Comparative host-coronavirus protein interaction networks reveal pan-viral disease mechanisms
    Science (IF 41.845) Pub Date : 2020-10-15
    David E. Gordon, Joseph Hiatt, Mehdi Bouhaddou, Veronica V. Rezelj, Svenja Ulferts, Hannes Braberg, Alexander S. Jureka, Kirsten Obernier, Jeffrey Z. Guo, Jyoti Batra, Robyn M. Kaake, Andrew R. Weckstein, Tristan W. Owens, Meghna Gupta, Sergei Pourmal, Erron W. Titus, Merve Cakir, Margaret Soucheray, Michael McGregor, Zeynep Cakir, Gwendolyn Jang, Matthew J. O’Meara, Tia A. Tummino, Ziyang Zhang, Helene

    The COVID-19 (Coronavirus disease-2019) pandemic, caused by the SARS-CoV-2 coronavirus, is a significant threat to public health and the global economy. SARS-CoV-2 is closely related to the more lethal but less transmissible coronaviruses SARS-CoV-1 and MERS-CoV. Here, we have carried out comparative viral-human protein-protein interaction and viral protein localization analysis for all three viruses

    更新日期:2020-10-15
  • REGN-COV2 antibodies prevent and treat SARS-CoV-2 infection in rhesus macaques and hamsters
    Science (IF 41.845) Pub Date : 2020-10-15
    Alina Baum, Dharani Ajithdoss, Richard Copin, Anbo Zhou, Kathryn Lanza, Nicole Negron, Min Ni, Yi Wei, Kusha Mohammadi, Bret Musser, Gurinder S. Atwal, Adelekan Oyejide, Yenny Goez-Gazi, John Dutton, Elizabeth Clemmons, Hilary M. Staples, Carmen Bartley, Benjamin Klaffke, Kendra Alfson, Michal Gazi, Olga Gonzalez, Edward Dick, Ricardo Carrion, Laurent Pessaint, Maciel Porto, Anthony Cook, Renita Brown

    An urgent global quest for effective therapies to prevent and treat COVID-19 disease is ongoing. We previously described REGN-COV2, a cocktail of two potent neutralizing antibodies (REGN10987+REGN10933) targeting non-overlapping epitopes on the SARS-CoV-2 spike protein. In this report, we evaluate the in vivo efficacy of this antibody cocktail in both rhesus macaques, which may model mild disease,

    更新日期:2020-10-15
  • An extremely metal-deficient globular cluster in the Andromeda Galaxy
    Science (IF 41.845) Pub Date : 2020-10-15
    Søren S. Larsen, Aaron J. Romanowsky, Jean P. Brodie, Asher Wasserman

    Globular clusters (GCs) are dense, gravitationally bound systems of thousands to millions of stars. They are preferentially associated with the oldest components of galaxies, so measurements of their composition can constrain the build-up of chemical elements in galaxies during the early Universe. We report a massive GC in the Andromeda Galaxy (M31), RBC EXT8, that is extremely depleted in heavy elements

    更新日期:2020-10-15
  • Black phosphorus composites with engineered interfaces for high-rate high-capacity lithium storage
    Science (IF 41.845) Pub Date : 2020-10-09
    Hongchang Jin, Sen Xin, Chenghao Chuang, Wangda Li, Haiyun Wang, Jian Zhu, Huanyu Xie, Taiming Zhang, Yangyang Wan, Zhikai Qi, Wensheng Yan, Ying-Rui Lu, Ting-Shan Chan, Xiaojun Wu, John B. Goodenough, Hengxing Ji, Xiangfeng Duan

    High-rate lithium (Li) ion batteries that can be charged in minutes and store enough energy for a 350-mile driving range are highly desired for all-electric vehicles. A high charging rate usually leads to sacrifices in capacity and cycling stability. We report use of black phosphorus (BP) as the active anode for high-rate, high-capacity Li storage. The formation of covalent bonds with graphitic carbon

    更新日期:2020-10-11
  • Spacetime from bits
    Science (IF 41.845) Pub Date : 2020-10-09
    Mark Van Raamsdonk

    In the anti–de Sitter/conformal field theory approach to quantum gravity, the spacetime geometry and gravitational physics of states in some quantum theory of gravity are encoded in the quantum states of an ordinary nongravitational system. Here, I demonstrate that this nongravitational system can be replaced with an arbitrarily large collection of noninteracting systems (“bits”) placed in a highly

    更新日期:2020-10-11
  • In situ structural analysis of SARS-CoV-2 spike reveals flexibility mediated by three hinges.
    Science (IF 41.845) Pub Date : 2020-10-09
    Beata Turoňová,Mateusz Sikora,Christoph Schürmann,Wim J H Hagen,Sonja Welsch,Florian E C Blanc,Sören von Bülow,Michael Gecht,Katrin Bagola,Cindy Hörner,Ger van Zandbergen,Jonathan Landry,Nayara Trevisan Doimo de Azevedo,Shyamal Mosalaganti,Andre Schwarz,Roberto Covino,Michael D Mühlebach,Gerhard Hummer,Jacomine Krijnse Locker,Martin Beck

    The spike protein (S) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is required for cell entry and is the primary focus for vaccine development. In this study, we combined cryo–electron tomography, subtomogram averaging, and molecular dynamics simulations to structurally analyze S in situ. Compared with the recombinant S, the viral S was more heavily glycosylated and occurred mostly

    更新日期:2020-10-11
  • The mole genome reveals regulatory rearrangements associated with adaptive intersexuality
    Science (IF 41.845) Pub Date : 2020-10-09
    Francisca M. Real, Stefan A. Haas, Paolo Franchini, Peiwen Xiong, Oleg Simakov, Heiner Kuhl, Robert Schöpflin, David Heller, M-Hossein Moeinzadeh, Verena Heinrich, Thomas Krannich, Annkatrin Bressin, Michaela F. Hartmann, Stefan A. Wudy, Dina K. N. Dechmann, Alicia Hurtado, Francisco J. Barrionuevo, Magdalena Schindler, Izabela Harabula, Marco Osterwalder, Michael Hiller, Lars Wittler, Axel Visel,

    Linking genomic variation to phenotypical traits remains a major challenge in evolutionary genetics. In this study, we use phylogenomic strategies to investigate a distinctive trait among mammals: the development of masculinizing ovotestes in female moles. By combining a chromosome-scale genome assembly of the Iberian mole, Talpa occidentalis, with transcriptomic, epigenetic, and chromatin interaction

    更新日期:2020-10-11
  • Electro-inductive effect: Electrodes as functional groups with tunable electronic properties
    Science (IF 41.845) Pub Date : 2020-10-09
    Joon Heo, Hojin Ahn, Joonghee Won, Jin Gyeong Son, Hyun Kyong Shon, Tae Geol Lee, Sang Woo Han, Mu-Hyun Baik

    In place of functional groups that impose different inductive effects, we immobilize molecules carrying thiol groups on a gold electrode. By applying different voltages, the properties of the immobilized molecules can be tuned. The base-catalyzed saponification of benzoic esters is fully inhibited by applying a mildly negative voltage of –0.25 volt versus open circuit potential. Furthermore, the rate

    更新日期:2020-10-11
  • Increased extinction in the emergence of novel ecological communities
    Science (IF 41.845) Pub Date : 2020-10-09
    John M. Pandolfi, Timothy L. Staples, Wolfgang Kiessling

    Environmental change is transforming ecological assemblages into new configurations, resulting in novel communities. We developed a robust methodology to detect novel communities, examine patterns of emergence, and quantify probabilities of local demographic turnover in transitions to and from novel communities. Using a global dataset of Cenozoic marine plankton communities, we found that the probability

    更新日期:2020-10-11
  • Cryo-EM with sub–1 Å specimen movement
    Science (IF 41.845) Pub Date : 2020-10-09
    Katerina Naydenova, Peipei Jia, Christopher J. Russo

    Most information loss in cryogenic electron microscopy (cryo-EM) stems from particle movement during imaging, which remains poorly understood. We show that this movement is caused by buckling and subsequent deformation of the suspended ice, with a threshold that depends directly on the shape of the frozen water layer set by the support foil. We describe a specimen support design that eliminates buckling

    更新日期:2020-10-11
  • WUSCHEL triggers innate antiviral immunity in plant stem cells
    Science (IF 41.845) Pub Date : 2020-10-09
    Haijun Wu, Xiaoya Qu, Zhicheng Dong, Linjie Luo, Chen Shao, Joachim Forner, Jan U. Lohmann, Meng Su, Mengchu Xu, Xiaobin Liu, Lei Zhu, Jian Zeng, Sumei Liu, Zhaoxia Tian, Zhong Zhao

    Stem cells in plants constantly supply daughter cells to form new organs and are expected to safeguard the integrity of the cells from biological invasion. Here, we show how stem cells of the Arabidopsis shoot apical meristem and their nascent daughter cells suppress infection by cucumber mosaic virus (CMV). The stem cell regulator WUSCHEL responds to CMV infection and represses virus accumulation

    更新日期:2020-10-11
  • Clean 2D superconductivity in a bulk van der Waals superlattice
    Science (IF 41.845) Pub Date : 2020-10-09
    A. Devarakonda, H. Inoue, S. Fang, C. Ozsoy-Keskinbora, T. Suzuki, M. Kriener, L. Fu, E. Kaxiras, D. C. Bell, J. G. Checkelsky

    Advances in low-dimensional superconductivity are often realized through improvements in material quality. Apart from a small group of organic materials, there is a near absence of clean-limit two-dimensional (2D) superconductors, which presents an impediment to the pursuit of numerous long-standing predictions for exotic superconductivity with fragile pairing symmetries. We developed a bulk superlattice

    更新日期:2020-10-11
  • Influenza vaccine-induced human bone marrow plasma cells decline within a year after vaccination.
    Science (IF 41.845) Pub Date : 2020-10-09
    Carl W Davis,Katherine J L Jackson,Megan M McCausland,Jaime Darce,Cathy Chang,Susanne L Linderman,Chakravarthy Chennareddy,Rebecca Gerkin,Shantoria J Brown,Jens Wrammert,Aneesh K Mehta,Wan Cheung Cheung,Scott D Boyd,Edmund K Waller,Rafi Ahmed

    A universal vaccine against influenza would ideally generate protective immune responses that are not only broadly reactive against multiple influenza strains but also long-lasting. Because long-term serum antibody levels are maintained by bone marrow plasma cells (BMPCs), we investigated the production and maintenance of these cells after influenza vaccination. We found increased numbers of influenza-specific

    更新日期:2020-10-11
  • MHC class II transactivator CIITA induces cell resistance to Ebola virus and SARS-like coronaviruses.
    Science (IF 41.845) Pub Date : 2020-10-09
    Anna Bruchez,Ky Sha,Joshua Johnson,Li Chen,Caroline Stefani,Hannah McConnell,Lea Gaucherand,Rachel Prins,Kenneth A Matreyek,Adam J Hume,Elke Mühlberger,Emmett V Schmidt,Gene G Olinger,Lynda M Stuart,Adam Lacy-Hulbert

    Recent outbreaks of Ebola virus (EBOV) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have exposed our limited therapeutic options for such diseases and our poor understanding of the cellular mechanisms that block viral infections. Using a transposon-mediated gene-activation screen in human cells, we identify that the major histocompatibility complex (MHC) class II transactivator

    更新日期:2020-10-11
  • Alternating sequences of future and past behavior encoded within hippocampal theta oscillations
    Science (IF 41.845) Pub Date : 2020-10-09
    Mengni Wang, David J. Foster, Brad E. Pfeiffer

    Neural networks display the ability to transform forward-ordered activity patterns into reverse-ordered, retrospective sequences. The mechanisms underlying this transformation remain unknown. We discovered that, during active navigation, rat hippocampal CA1 place cell ensembles are inherently organized to produce independent forward- and reverse-ordered sequences within individual theta oscillations

    更新日期:2020-10-11
  • The heterogeneity of persistent slip band nucleation and evolution in metals at the micrometer scale
    Science (IF 41.845) Pub Date : 2020-10-09
    Steven Lavenstein, Yejun Gu, Dylan Madisetti, Jaafar A. El-Awady

    Fatigue damage in metals manifests itself as irreversible dislocation motion followed by crack initiation and propagation. Characterizing the transition from a crack-free to a cracked metal remains one of the most challenging problems in fatigue. Persistent slip bands (PSBs) form in metals during cyclic loading and are one of the most important aspects of this transition. We used in situ microfatigue

    更新日期:2020-10-11
  • Conformational states dynamically populated by a kinase determine its function
    Science (IF 41.845) Pub Date : 2020-10-09
    Tao Xie, Tamjeed Saleh, Paolo Rossi, Charalampos G. Kalodimos

    Protein kinases intrinsically sample a number of conformational states with distinct catalytic and binding activities. We used nuclear magnetic resonance spectroscopy to describe in atomic-level detail how Abl kinase interconverts between an active and two discrete inactive structures. Extensive differences in key structural elements between the conformational states give rise to multiple intrinsic

    更新日期:2020-10-11
  • Coupling of NMDA receptors and TRPM4 guides discovery of unconventional neuroprotectants
    Science (IF 41.845) Pub Date : 2020-10-09
    Jing Yan, C. Peter Bengtson, Bettina Buchthal, Anna M. Hagenston, Hilmar Bading

    Excitotoxicity induced by NMDA receptors (NMDARs) is thought to be intimately linked to high intracellular calcium load. Unexpectedly, NMDAR-mediated toxicity can be eliminated without affecting NMDAR-induced calcium signals. Instead, excitotoxicity requires physical coupling of NMDARs to TRPM4. This interaction is mediated by intracellular domains located in the near-membrane portions of the receptors

    更新日期:2020-10-11
  • Recent advances in solid oxide cell technology for electrolysis
    Science (IF 41.845) Pub Date : 2020-10-09
    A. Hauch, R. Küngas, P. Blennow, A. B. Hansen, J. B. Hansen, B. V. Mathiesen, M. B. Mogensen

    In a world powered by intermittent renewable energy, electrolyzers will play a central role in converting electrical energy into chemical energy, thereby decoupling the production of transport fuels and chemicals from today’s fossil resources and decreasing the reliance on bioenergy. Solid oxide electrolysis cells (SOECs) offer two major advantages over alternative electrolysis technologies. First

    更新日期:2020-10-11
  • Reconstitution and visualization of HIV-1 capsid-dependent replication and integration in vitro
    Science (IF 41.845) Pub Date : 2020-10-09
    Devin E. Christensen, Barbie K. Ganser-Pornillos, Jarrod S. Johnson, Owen Pornillos, Wesley I. Sundquist

    During the first half of the viral life cycle, HIV-1 reverse transcribes its RNA genome and integrates the double-stranded DNA copy into a host cell chromosome. Despite progress in characterizing and inhibiting these processes, in situ mechanistic and structural studies remain challenging. This is because these operations are executed by individual viral preintegration complexes deep within cells.

    更新日期:2020-10-11
  • Bioengineered human blood vessels
    Science (IF 41.845) Pub Date : 2020-10-09
    Laura E. Niklason, Jeffrey H. Lawson

    Since the advent of the vascular anastomosis by Alexis Carrel in the early 20th century, the repair and replacement of blood vessels have been key to treating acute injuries, as well as chronic atherosclerotic disease. Arteries serve diverse mechanical and biological functions, such as conducting blood to tissues, interacting with the coagulation system, and modulating resistance to blood flow. Early

    更新日期:2020-10-11
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