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  • 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
  • Neutrophilic inflammation in the respiratory mucosa predisposes to RSV infection
    Science (IF 41.845) Pub Date : 2020-10-09
    Maximillian S. Habibi, Ryan S. Thwaites, Meiping Chang, Agnieszka Jozwik, Allan Paras, Freja Kirsebom, Augusto Varese, Amber Owen, Leah Cuthbertson, Phillip James, Tanushree Tunstall, David Nickle, Trevor T. Hansel, Miriam F. Moffatt, Cecilia Johansson, Christopher Chiu, Peter J. M. Openshaw

    The variable outcome of viral exposure is only partially explained by known factors. We administered respiratory syncytial virus (RSV) to 58 volunteers, of whom 57% became infected. Mucosal neutrophil activation before exposure was highly predictive of symptomatic RSV disease. This was associated with a rapid, presymptomatic decline in mucosal interleukin-17A (IL-17A) and other mediators. Conversely

    更新日期:2020-10-11
  • Generation of helical topological exciton-polaritons
    Science (IF 41.845) Pub Date : 2020-10-08
    Wenjing Liu, Zhurun Ji, Yuhui Wang, Gaurav Modi, Minsoo Hwang, Biyuan Zheng, Volker J. Sorger, Anlian Pan, Ritesh Agarwal

    Topological photonics in strongly coupled light-matter systems offer the possibility for fabricating tunable optical devices that are robust against disorder and defects. Topological polaritons, i.e., hybrid exciton-photon quasiparticles, have been proposed to demonstrate scatter-free chiral propagation, but their experimental realization to date have been at deep cryogenic temperatures and under strong

    更新日期:2020-10-11
  • Variations in color and reflectance on the surface of asteroid (101955) Bennu
    Science (IF 41.845) Pub Date : 2020-10-08
    D. N. DellaGiustina, K. N. Burke, K. J. Walsh, P. H. Smith, D. R. Golish, E. B. Bierhaus, R.-L. Ballouz, T. L. Becker, H. Campins, E. Tatsumi, K. Yumoto, S. Sugita, J. D. Prasanna Deshapriya, E. A. Cloutis, B. E. Clark, A. R. Hendrix, A. Sen, M. M. Al Asad, M. G. Daly, D. M. Applin, C. Avdellidou, M. A. Barucci, K. J. Becker, C. A. Bennett, W. F. Bottke, J. I. Brodbeck, H. C. Connolly, M. Delbo, J

    Visible-wavelength color and reflectance provide information about the geologic history of planetary surfaces. We present multispectral images (0.44 to 0.89 microns) of near-Earth asteroid (101955) Bennu. The surface has variable colors overlain on a moderately blue global terrain. Two primary boulder types are distinguishable by their reflectance and texture. Space weathering of Bennu surface materials

    更新日期:2020-10-11
  • Bright carbonate veins on asteroid (101955) Bennu: Implications for aqueous alteration history
    Science (IF 41.845) Pub Date : 2020-10-08
    H. H. Kaplan, D. S. Lauretta, A. A. Simon, V. E. Hamilton, D. N. DellaGiustina, D. R. Golish, D. C. Reuter, C. A. Bennett, K. N. Burke, H. Campins, H. C. Connolly, J. P. Dworkin, J. P. Emery, D. P. Glavin, T. D. Glotch, R. Hanna, K. Ishimaru, E. R. Jawin, T. J. McCoy, N. Porter, S. A. Sandford, S. Ferrone, B. E. Clark, J.-Y. Li, X.-D. Zou, M. G. Daly, O. S. Barnouin, J. A. Seabrook, H. L. Enos

    The composition of asteroids and their connection to meteorites provide insight into geologic processes that occurred in the early Solar System. We present spectra of the Nightingale crater region on near-Earth asteroid Bennu with a distinct infrared absorption around 3.4 μm. Corresponding images of boulders show centimeters-thick, roughly meter-long bright veins. We interpret the veins as being composed

    更新日期:2020-10-11
  • Widespread carbon-bearing materials on near-Earth asteroid (101955) Bennu
    Science (IF 41.845) Pub Date : 2020-10-08
    Amy A. Simon, Hannah H. Kaplan, Victoria E. Hamilton, Dante S. Lauretta, Humberto Campins, Joshua P. Emery, M. Antonietta Barucci, Daniella N. DellaGiustina, Dennis C. Reuter, Scott A. Sandford, Dathon R. Golish, Lucy F. Lim, Andrew Ryan, Benjamin Rozitis, Carina A. Bennett

    (101955) Bennu is a dark asteroid on an Earth-crossing orbit, thought to have assembled from the fragments of an ancient collision. We use spatially-resolved visible and near-infrared spectra of Bennu to investigate its surface properties and composition. In addition to a hydrated phyllosilicate band, we detect a ubiquitous 3.4-micron absorption feature, which we attribute to a mix of organic and carbonate

    更新日期:2020-10-11
  • Behavioral nudges reduce failure to appear for court
    Science (IF 41.845) Pub Date : 2020-10-08
    Alissa Fishbane, Aurelie Ouss, Anuj K. Shah

    Each year, millions of Americans fail to appear in court for low-level offenses, and warrants are then issued for their arrest. In two field studies in New York City, we make critical information salient by redesigning the summons form and providing text message reminders. These interventions reduce failures to appear by 13-21% and lead to 30,000 fewer arrest warrants over a 3-year period. In lab experiments

    更新日期:2020-10-11
  • Glymphatic failure as a final common pathway to dementia
    Science (IF 41.845) Pub Date : 2020-10-02
    Maiken Nedergaard, Steven A. Goldman

    Sleep is evolutionarily conserved across all species, and impaired sleep is a common trait of the diseased brain. Sleep quality decreases as we age, and disruption of the regular sleep architecture is a frequent antecedent to the onset of dementia in neurodegenerative diseases. The glymphatic system, which clears the brain of protein waste products, is mostly active during sleep. Yet the glymphatic

    更新日期:2020-10-02
  • Beyond aggregation: Pathological phase transitions in neurodegenerative disease
    Science (IF 41.845) Pub Date : 2020-10-02
    Cécile Mathieu, Rohit V. Pappu, J. Paul Taylor

    Over the past decade, phase transitions have emerged as a fundamental mechanism of cellular organization. In parallel, a wealth of evidence has accrued indicating that aberrations in phase transitions are early events in the pathogenesis of several neurodegenerative diseases. We review the key evidence of defects at multiple levels, from phase transition of individual proteins to the dynamic behavior

    更新日期:2020-10-02
  • Translating genetic risk of Alzheimer’s disease into mechanistic insight and drug targets
    Science (IF 41.845) Pub Date : 2020-10-02
    Annerieke Sierksma, Valentina Escott-Price, Bart De Strooper

    To provide better prevention and treatment, we need to understand the environmental and genetic risks of Alzheimer’s disease (AD). However, the definition of AD has been confounded with dementia in many studies. Thus, overinterpretation of genetic findings with regard to mechanisms and drug targets may explain, in part, controversies in the field. Here, we analyze the different forms of genetic risk

    更新日期:2020-10-02
  • Microglia modulate neurodegeneration in Alzheimer’s and Parkinson’s diseases
    Science (IF 41.845) Pub Date : 2020-10-02
    Tim Bartels, Sebastiaan De Schepper, Soyon Hong

    Dementia is a rapidly rising global health crisis that silently disables families and ends lives and livelihoods around the world. To date, however, no early biomarkers or effective therapies exist. It is now clear that brain microglia are more than mere bystanders or amyloid phagocytes; they can act as governors of neuronal function and homeostasis in the adult brain. Here, we highlight the fundamental

    更新日期:2020-10-02
  • Extensive heterogeneity in somatic mutation and selection in the human bladder
    Science (IF 41.845) Pub Date : 2020-10-02
    Andrew R. J. Lawson, Federico Abascal, Tim H. H. Coorens, Yvette Hooks, Laura O’Neill, Calli Latimer, Keiran Raine, Mathijs A. Sanders, Anne Y. Warren, Krishnaa T. A. Mahbubani, Bethany Bareham, Timothy M. Butler, Luke M. R. Harvey, Alex Cagan, Andrew Menzies, Luiza Moore, Alexandra J. Colquhoun, William Turner, Benjamin Thomas, Vincent Gnanapragasam, Nicholas Williams, Doris M. Rassl, Harald Vöhringer

    The extent of somatic mutation and clonal selection in the human bladder remains unknown. We sequenced 2097 bladder microbiopsies from 20 individuals using targeted (n = 1914 microbiopsies), whole-exome (n = 655), and whole-genome (n = 88) sequencing. We found widespread positive selection in 17 genes. Chromatin remodeling genes were frequently mutated, whereas mutations were absent in several major

    更新日期:2020-10-02
  • Macroscopic somatic clonal expansion in morphologically normal human urothelium
    Science (IF 41.845) Pub Date : 2020-10-02
    Ruoyan Li, Yiqing Du, Zhanghua Chen, Deshu Xu, Tianxin Lin, Shanzhao Jin, Gongwei Wang, Ziyang Liu, Min Lu, Xu Chen, Tao Xu, Fan Bai

    Knowledge of somatic mutation accumulation in normal cells, which is essential for understanding cancer development and evolution, remains largely lacking. In this study, we investigated somatic clonal events in morphologically normal human urothelium (MNU; epithelium lining the bladder and ureter) and identified macroscopic clonal expansions. Aristolochic acid (AA), a natural herb-derived compound

    更新日期:2020-10-02
  • Selective and cross-reactive SARS-CoV-2 T cell epitopes in unexposed humans.
    Science (IF 41.845) Pub Date : 2020-10-02
    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,Alessandro Sette,Daniela

    Many unknowns exist about human immune responses to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus. SARS-CoV-2–reactive CD4+ T cells have been reported in unexposed individuals, suggesting preexisting cross-reactive T cell memory in 20 to 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

    更新日期:2020-10-02
  • Multiplicity of dislocation pathways in a refractory multiprincipal element alloy
    Science (IF 41.845) Pub Date : 2020-10-02
    Fulin Wang, Glenn H. Balbus, Shuozhi Xu, Yanqing Su, Jungho Shin, Paul F. Rottmann, Keith E. Knipling, Jean-Charles Stinville, Leah H. Mills, Oleg N. Senkov, Irene J. Beyerlein, Tresa M. Pollock, Daniel S. Gianola

    Refractory multiprincipal element alloys (MPEAs) are promising materials to meet the demands of aggressive structural applications, yet require fundamentally different avenues for accommodating plastic deformation in the body-centered cubic (bcc) variants of these alloys. We show a desirable combination of homogeneous plastic deformability and strength in the bcc MPEA MoNbTi, enabled by the rugged

    更新日期:2020-10-02
  • A universal system for digitization and automatic execution of the chemical synthesis literature
    Science (IF 41.845) Pub Date : 2020-10-02
    S. Hessam M. Mehr, Matthew Craven, Artem I. Leonov, Graham Keenan, Leroy Cronin

    Robotic systems for chemical synthesis are growing in popularity but can be difficult to run and maintain because of the lack of a standard operating system or capacity for direct access to the literature through natural language processing. Here we show an extendable chemical execution architecture that can be populated by automatically reading the literature, leading to a universal autonomous workflow

    更新日期:2020-10-02
  • Impact of strain relaxation on performance of α-formamidinium lead iodide perovskite solar cells
    Science (IF 41.845) Pub Date : 2020-10-02
    Gwisu Kim, Hanul Min, Kyoung Su Lee, Do Yoon Lee, So Me Yoon, Sang Il Seok

    High-efficiency lead halide perovskite solar cells (PSCs) have been fabricated with α-phase formamidinium lead iodide (FAPbI3) stabilized with multiple cations. The alloyed cations greatly affect the bandgap, carrier dynamics, and stability, as well as lattice strain that creates unwanted carrier trap sites. We substituted cesium (Cs) and methylenediammonium (MDA) cations in FA sites of FAPbI3 and

    更新日期:2020-10-02
  • An adhesion code ensures robust pattern formation during tissue morphogenesis
    Science (IF 41.845) Pub Date : 2020-10-02
    Tony Y.-C. Tsai, Mateusz Sikora, Peng Xia, Tugba Colak-Champollion, Holger Knaut, Carl-Philipp Heisenberg, Sean G. Megason

    Animal development entails the organization of specific cell types in space and time, and spatial patterns must form in a robust manner. In the zebrafish spinal cord, neural progenitors form stereotypic patterns despite noisy morphogen signaling and large-scale cellular rearrangements during morphogenesis and growth. By directly measuring adhesion forces and preferences for three types of endogenous

    更新日期:2020-10-02
  • Integrated terrestrial-freshwater planning doubles conservation of tropical aquatic species
    Science (IF 41.845) Pub Date : 2020-10-02
    Cecília G. Leal, Gareth D. Lennox, Silvio F. B. Ferraz, Joice Ferreira, Toby A. Gardner, James R. Thomson, Erika Berenguer, Alexander C. Lees, Robert M. Hughes, Ralph MacNally, Luiz E. O. C. Aragão, Janaina G. de Brito, Leandro Castello, Rachael D. Garrett, Neusa Hamada, Leandro Juen, Rafael P. Leitão, Julio Louzada, Thiago F. Morello, Nárgila G. Moura, Jorge L. Nessimian, José Max B. Oliveira-Junior

    Conservation initiatives overwhelmingly focus on terrestrial biodiversity, and little is known about the freshwater cobenefits of terrestrial conservation actions. We sampled more than 1500 terrestrial and freshwater species in the Amazon and simulated conservation for species from both realms. Prioritizations based on terrestrial species yielded on average just 22% of the freshwater benefits achieved

    更新日期:2020-10-02
  • The mouse Sry locus harbors a cryptic exon that is essential for male sex determination
    Science (IF 41.845) Pub Date : 2020-10-02
    Shingo Miyawaki, Shunsuke Kuroki, Ryo Maeda, Naoki Okashita, Peter Koopman, Makoto Tachibana

    The mammalian sex-determining gene Sry induces male development. Since its discovery 30 years ago, Sry has been believed to be a single-exon gene. Here, we identified a cryptic second exon of mouse Sry and a corresponding two-exon type Sry (Sry-T) transcript. XY mice lacking Sry-T were sex-reversed, and ectopic expression of Sry-T in XX mice induced male development. Sry-T messenger RNA is expressed

    更新日期:2020-10-02
  • Giant temperature span in electrocaloric regenerator
    Science (IF 41.845) Pub Date : 2020-10-02
    A. Torelló, P. Lheritier, T. Usui, Y. Nouchokgwe, M. Gérard, O. Bouton, S. Hirose, E. Defay

    Cooling devices based on caloric materials have emerged as promising candidates to become the next generation of coolers. Several electrocaloric (EC) heat exchangers have been proposed that use different mechanisms and working principles. However, a prototype that demonstrates a competitive temperature span has been missing. We developed a parallel-plate active EC regenerator based on lead scandium

    更新日期:2020-10-02
  • A high-performance solid-state electrocaloric cooling system
    Science (IF 41.845) Pub Date : 2020-10-02
    Yunda Wang, Ziyang Zhang, Tomoyasu Usui, Michael Benedict, Sakyo Hirose, Joseph Lee, Jamie Kalb, David Schwartz

    Electrocaloric (EC) cooling is an emerging technology that has broad potential to disrupt conventional air conditioning and refrigeration as well as electronics cooling applications. EC coolers can be highly efficient, solid state, and compact; have few moving parts; and contain no environmentally harmful or combustible refrigerants. We report a scalable, high-performance system architecture, demonstrated

    更新日期:2020-10-02
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