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  •   The primitive streak and cellular principles of building an amniote body through gastrulation
    Science (IF 47.728) Pub Date : 2021-12-03
    Guojun Sheng, Alfonso Martinez Arias, Ann Sutherland

    The primitive streak, a transient embryonic structure, marks bilateral symmetry in mammalian and avian embryos and helps confer anterior-posterior and dorsal-ventral spatial information to early differentiating cells during gastrulation. Its recapitulation in vitro may facilitate derivation of tissues and organs with in vivo–like complexity. Proper understanding of the primitive streak and what it

  •   Realizing topologically ordered states on a quantum processor
    Science (IF 47.728) Pub Date : 2021-12-03
    K. J. Satzinger, Y.-J Liu, A. Smith, C. Knapp, M. Newman, C. Jones, Z. Chen, C. Quintana, X. Mi, A. Dunsworth, C. Gidney, I. Aleiner, F. Arute, K. Arya, J. Atalaya, R. Babbush, J. C. Bardin, R. Barends, J. Basso, A. Bengtsson, A. Bilmes, M. Broughton, B. B. Buckley, D. A. Buell, B. Burkett, N. Bushnell, B. Chiaro, R. Collins, W. Courtney, S. Demura, A. R. Derk, D. Eppens, C. Erickson, L. Faoro, E.

    The discovery of topological order has revised the understanding of quantum matter and provided the theoretical foundation for many quantum error–correcting codes. Realizing topologically ordered states has proven to be challenging in both condensed matter and synthetic quantum systems. We prepared the ground state of the toric code Hamiltonian using an efficient quantum circuit on a superconducting

  •   Strong Southern Ocean carbon uptake evident in airborne observations
    Science (IF 47.728) Pub Date : 2021-12-03
    Matthew C. Long, Britton B. Stephens, Kathryn McKain, Colm Sweeney, Ralph F. Keeling, Eric A. Kort, Eric J. Morgan, Jonathan D. Bent, Naveen Chandra, Frederic Chevallier, Róisín Commane, Bruce C. Daube, Paul B. Krummel, Zoë Loh, Ingrid T. Luijkx, David Munro, Prabir Patra, Wouter Peters, Michel Ramonet, Christian Rödenbeck, Ann Stavert, Pieter Tans, Steven C. Wofsy

    The Southern Ocean plays an important role in determining atmospheric carbon dioxide (CO2), yet estimates of air-sea CO2 flux for the region diverge widely. In this study, we constrained Southern Ocean air-sea CO2 exchange by relating fluxes to horizontal and vertical CO2 gradients in atmospheric transport models and applying atmospheric observations of these gradients to estimate fluxes. Aircraft-based

  •   Continuous-wave frequency upconversion with a molecular optomechanical nanocavity
    Science (IF 47.728) Pub Date : 2021-12-03
    Wen Chen, Philippe Roelli, Huatian Hu, Sachin Verlekar, Sakthi Priya Amirtharaj, Angela I. Barreda, Tobias J. Kippenberg, Miroslavna Kovylina, Ewold Verhagen, Alejandro Martínez, Christophe Galland

    Coherent upconversion of terahertz and mid-infrared signals into visible light opens new horizons for spectroscopy, imaging, and sensing but represents a challenge for conventional nonlinear optics. Here, we used a plasmonic nanocavity hosting a few hundred molecules to demonstrate optomechanical transduction of submicrowatt continuous-wave signals from the mid-infrared (32 terahertz) onto the visible

  •   Detecting mid-infrared light by molecular frequency upconversion in dual-wavelength nanoantennas
    Science (IF 47.728) Pub Date : 2021-12-03
    Angelos Xomalis, Xuezhi Zheng, Rohit Chikkaraddy, Zsuzsanna Koczor-Benda, Ermanno Miele, Edina Rosta, Guy A. E. Vandenbosch, Alejandro Martínez, Jeremy J. Baumberg

    Coherent interconversion of signals between optical and mechanical domains is enabled by optomechanical interactions. Extreme light-matter coupling produced by confining light to nanoscale mode volumes can then access single mid-infrared (MIR) photon sensitivity. Here, we used the infrared absorption and Raman activity of molecular vibrations in plasmonic nanocavities to demonstrate frequency upconversion

  •   Ground tissue circuitry regulates organ complexity in maize and Setaria
    Science (IF 47.728) Pub Date : 2021-12-03
    Carlos Ortiz-Ramírez, Bruno Guillotin, Xiaosa Xu, Ramin Rahni, Sanqiang Zhang, Zhe Yan, Poliana Coqueiro Dias Araujo, Edgar Demesa-Arevalo, Laura Lee, Joyce Van Eck, Thomas R. Gingeras, David Jackson, Kimberly L. Gallagher, Kenneth D. Birnbaum

    Most plant roots have multiple cortex layers that make up the bulk of the organ and play key roles in physiology, such as flood tolerance and symbiosis. However, little is known about the formation of cortical layers outside of the highly reduced anatomy of Arabidopsis. Here, we used single-cell RNA sequencing to rapidly generate a cell-resolution map of the maize root, revealing an alternative configuration

  •   Error-prone, stress-induced 3′ flap–based Okazaki fragment maturation supports cell survival
    Science (IF 47.728) Pub Date : 2021-12-03
    Haitao Sun, Zhaoning Lu, Amanpreet Singh, Yajing Zhou, Eric Zheng, Mian Zhou, Jinhui Wang, Xiwei Wu, Zunsong Hu, Zhaohui Gu, Judith L. Campbell, Li Zheng, Binghui Shen

    How cells with DNA replication defects acquire mutations that allow them to escape apoptosis under environmental stress is a long-standing question. Here, we report that an error-prone Okazaki fragment maturation (OFM) pathway is activated at restrictive temperatures in rad27Δ yeast cells. Restrictive temperature stress activated Dun1, facilitating transformation of unprocessed 5′ flaps into 3′ flaps

  •   Probing topological spin liquids on a programmable quantum simulator
    Science (IF 47.728) Pub Date : 2021-12-03
    G. Semeghini, H. Levine, A. Keesling, S. Ebadi, T. T. Wang, D. Bluvstein, R. Verresen, H. Pichler, M. Kalinowski, R. Samajdar, A. Omran, S. Sachdev, A. Vishwanath, M. Greiner, V. Vuletić, M. D. Lukin

    Quantum spin liquids, exotic phases of matter with topological order, have been a major focus in physics for the past several decades. Such phases feature long-range quantum entanglement that can potentially be exploited to realize robust quantum computation. We used a 219-atom programmable quantum simulator to probe quantum spin liquid states. In our approach, arrays of atoms were placed on the links

  •   Fumarate is a terminal electron acceptor in the mammalian electron transport chain
    Science (IF 47.728) Pub Date : 2021-12-03
    Jessica B. Spinelli, Paul C. Rosen, Hans-Georg Sprenger, Anna M. Puszynska, Jessica L. Mann, Julian M. Roessler, Andrew L. Cangelosi, Antonia Henne, Kendall J. Condon, Tong Zhang, Tenzin Kunchok, Caroline A. Lewis, Navdeep S. Chandel, David M. Sabatini

    For electrons to continuously enter and flow through the mitochondrial electron transport chain (ETC), they must ultimately land on a terminal electron acceptor (TEA), which is known to be oxygen in mammals. Paradoxically, we find that complex I and dihydroorotate dehydrogenase (DHODH) can still deposit electrons into the ETC when oxygen reduction is impeded. Cells lacking oxygen reduction accumulate

  •   Genetic and functional evidence links a missense variant in B4GALT1 to lower LDL and fibrinogen
    Science (IF 47.728) Pub Date : 2021-12-03
    May E. Montasser, Cristopher V. Van Hout, Lawrence Miloscio, Alicia D. Howard, Avraham Rosenberg, Myrasol Callaway, Biao Shen, Ning Li, Adam E. Locke, Niek Verweij, Tanima De, Manuel A. Ferreira, Luca A. Lotta, Aris Baras, Thomas J. Daly, Suzanne A. Hartford, Wei Lin, Yuan Mao, Bin Ye, Derek White, Guochun Gong, James A. Perry, Kathleen A. Ryan, Qing Fang, Gannie Tzoneva, Evangelos Pefanis, Charleen

    Increased blood levels of low-density lipoprotein cholesterol (LDL-C) and fibrinogen are independent risk factors for cardiovascular disease. We identified associations between an Amish-enriched missense variant (p.Asn352Ser) in a functional domain of beta-1,4-galactosyltransferase 1 (B4GALT1) and 13.9 milligrams per deciliter lower LDL-C (P = 4.1 × 10–19) and 29 milligrams per deciliter lower plasma

  •   GJ 367b: A dense, ultrashort-period sub-Earth planet transiting a nearby red dwarf star
    Science (IF 47.728) Pub Date : 2021-12-03
    Kristine W. F. Lam, Szilárd Csizmadia, Nicola Astudillo-Defru, Xavier Bonfils, Davide Gandolfi, Sebastiano Padovan, Massimiliano Esposito, Coel Hellier, Teruyuki Hirano, John Livingston, Felipe Murgas, Alexis M. S. Smith, Karen A. Collins, Savita Mathur, Rafael A. Garcia, Steve B. Howell, Nuno C. Santos, Fei Dai, George R. Ricker, Roland Vanderspek, David W. Latham, Sara Seager, Joshua N. Winn, Jon

    Ultrashort-period (USP) exoplanets have orbital periods shorter than 1 day. Precise masses and radii of USP exoplanets could provide constraints on their unknown formation and evolution processes. We report the detection and characterization of the USP planet GJ 367b using high-precision photometry and radial velocity observations. GJ 367b orbits a bright (V-band magnitude of 10.2), nearby, and red

  •   Impact of community masking on COVID-19: A cluster-randomized trial in Bangladesh
    Science (IF 47.728) Pub Date : 2021-12-02
    Jason Abaluck, Laura H. Kwong, Ashley Styczynski, Ashraful Haque, Md. Alamgir Kabir, Ellen Bates-Jefferys, Emily Crawford, Jade Benjamin-Chung, Shabib Raihan, Shadman Rahman, Salim Benhachmi, Neeti Zaman Bintee, Peter J. Winch, Maqsud Hossain, Hasan Mahmud Reza, Abdullah All Jaber, Shawkee Gulshan Momen, Aura Rahman, Faika Laz Banti, Tahrima Saiha Huq, Stephen P. Luby, Ahmed Mushfiq Mobarak

    We conducted a cluster-randomized trial to measure the effect of community-level mask distribution and promotion on symptomatic SARS-CoV-2 infections in rural Bangladesh from November 2020 to April 2021 (N = 600 villages, N = 342,183 adults). We cross-randomized mask type (cloth vs. surgical) and promotion strategies at the village and household level. Proper mask-wearing increased from 13.3% in the

  •   4′-Fluorouridine is an oral antiviral that blocks respiratory syncytial virus and SARS-CoV-2 replication
    Science (IF 47.728) Pub Date : 2021-12-02
    Julien Sourimant, Carolin M. Lieber, Megha Aggarwal, Robert M. Cox, Josef D. Wolf, Jeong-Joong Yoon, Mart Toots, Chengin Ye, Zachary Sticher, Alexander A. Kolykhalov, Luis Martinez-Sobrido, Gregory R. Bluemling, Michael G. Natchus, George R. Painter, Richard K. Plemper

    The COVID-19 pandemic has underscored the critical need for broad-spectrum therapeutics against respiratory viruses. Respiratory syncytial virus (RSV) is a major threat to pediatric patients and the elderly. We describe 4′-fluorouridine (4′-FlU, EIDD-2749), a ribonucleoside analog that inhibits RSV, related RNA viruses, and SARS-CoV-2 with high selectivity index in cells and human airway epithelia

  •   Visualizing broken symmetry and topological defects in a quantum Hall ferromagnet
    Science (IF 47.728) Pub Date : 2021-12-02
    Xiaomeng Liu, Gelareh Farahi, Cheng-Li Chiu, Zlatko Papic, Kenji Watanabe, Takashi Taniguchi, Michael P. Zaletel, Ali Yazdani

    The interaction between electrons in graphene under high magnetic fields drives the formation of a rich set of quantum Hall ferromagnetic phases (QHFM), with broken spin or valley symmetry. Visualizing atomic scale electronic wavefunctions with scanning tunneling spectroscopy (STS), we resolve microscopic signatures of valley ordering in QHFM and spectral features of fractional quantum Hall phases

  •   Structural basis for continued antibody evasion by the SARS-CoV-2 receptor binding domain
    Science (IF 47.728) Pub Date : 2021-12-02
    Katherine G. Nabel, Sarah A. Clark, Sundaresh Shankar, Junhua Pan, Lars E. Clark, Pan Yang, Adrian Coscia, Lindsay G. A. McKay, Haley H. Varnum, Vesna Brusic, Nicole V. Tolan, Guohai Zhou, Michaël Desjardins, Sarah E. Turbett, Sanjat Kanjilal, Amy C. Sherman, Anand Dighe, Regina C. LaRocque, Edward T. Ryan, Casey Tylek, Joel F. Cohen-Solal, Anhdao T. Darcy, Davide Tavella, Anca Clabbers, Yao Fan, Anthony

    Many studies have examined the impact of SARS-CoV-2 variants on neutralizing antibody activity after they have become dominant strains. Here, we evaluate the consequences of further viral evolution. We demonstrate mechanisms through which the SARS-CoV-2 receptor binding domain (RBD) can tolerate large numbers of simultaneous antibody escape mutations and show that pseudotypes containing up to seven

  •   Heterologous infection and vaccination shapes immunity against SARS-CoV-2 variants
    Science (IF 47.728) Pub Date : 2021-12-02
    Catherine J. Reynolds, Joseph M. Gibbons, Corinna Pade, Kai-Min Lin, Diana Munoz Sandoval, Franziska Pieper, David K. Butler, Siyi Liu, Ashley D. Otter, George Joy, Katia Menacho, Marianna Fontana, Angelique Smit, Beatrix Kele, Teresa Cutino-Moguel, Mala K. Maini, Mahdad Noursadeghi, COVIDsortium Immune Correlates Network‡, Tim Brooks, Amanda Semper, Charlotte Manisty, Thomas A. Treibel, James C. Moon

    The impact of initial severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infecting strain on downstream immunity to heterologous variants of concern (VOC) is unknown. Studying a longitudinal healthcare worker cohort, we found that after three antigen exposures (infection+two vaccine doses), S1 antibody, memory B cells and heterologous neutralization of B.1.351, P.1 and B.1.617.2 plateaued

  •   Evidence for a delocalization quantum phase transition without symmetry breaking in CeCoIn5
    Science (IF 47.728) Pub Date : 2021-12-02
    Nikola Maksimovic, Daniel H. Eilbott, Tessa Cookmeyer, Fanghui Wan, Jan Rusz, Vikram Nagarajan, Shannon C. Haley, Eran Maniv, Amanda Gong, Stefano Faubel, Ian M. Hayes, Ali Bangura, John Singleton, Johanna C. Palmstrom, Laurel Winter, Ross McDonald, Sooyoung Jang, Ping Ai, Yi Lin, Samuel Ciocys, Jacob Gobbo, Yochai Werman, Peter M. Oppeneer, Ehud Altman, Alessandra Lanzara, James G. Analytis

    The study of quantum phase transitions that are not clearly associated with a broken symmetry is a major effort in condensed matter physics, particularly in the problem of high-temperature superconductivity where such transitions are thought to underlie the mechanism of superconductivity itself. In this study, we argue that the putative quantum critical point in the prototypical unconventional superconductor

  •   The spectrum of inflammatory responses
    Science (IF 47.728) Pub Date : 2021-11-26
    Ruslan Medzhitov

    Inflammation is an integral part of animal biology. It provides critical protection from adverse environmental factors by enforcing the defense of homeostasis and the functional and structural integrity of tissues and organs. Recent advances have uncovered a broad range of biological processes that involve inflammatory control, calling for a renewed framework of inflammation beyond its classical roles

  •   Mechanisms of viral inflammation and disease in humans
    Science (IF 47.728) Pub Date : 2021-11-26
    Jean-Laurent Casanova, Laurent Abel

    Disease and accompanying inflammation are uncommon outcomes of viral infection in humans. Clinical inflammation occurs if steady-state cell-intrinsic and leukocytic immunity to viruses fails. Inflammation attests to the attempts of newly recruited and activated leukocytes to resolve infection in the blood or tissues. In the confusing battle between a myriad of viruses and cells, studies of human genetics

  •   Signaling inflammation across the gut-brain axis
    Science (IF 47.728) Pub Date : 2021-11-26
    Gulistan Agirman, Kristie B. Yu, Elaine Y. Hsiao

    The brain and gastrointestinal tract are critical sensory organs responsible for detecting, relaying, integrating, and responding to signals derived from the internal and external environment. At the interface of this sensory function, immune cells in the intestines and brain consistently survey environmental factors, eliciting responses that inform on the physiological state of the body. Recent research

  •   Dying cells fan the flames of inflammation
    Science (IF 47.728) Pub Date : 2021-11-26
    Kim Newton, Vishva M. Dixit, Nobuhiko Kayagaki

    Inflammatory processes that recruit leukocytes to injured or infected tissues are crucial for tissue repair and the elimination of pathogens. However, excessive or chronic inflammation promotes tissue damage and disease, as in arthritis, atherosclerosis, inflammatory bowel disease, and COVID-19. Intracellular constituents released from dying cells are among the stimuli that trigger proinflammatory

  •   Adaptive evolution of flight in Morpho butterflies
    Science (IF 47.728) Pub Date : 2021-11-26
    Camille Le Roy, Dario Amadori, Samuel Charberet, Jaap Windt, Florian T. Muijres, Violaine Llaurens, Vincent Debat

    The diversity of flying animals suggests that countless combinations of flight morphologies and behaviors have evolved with specific lifestyles, thereby exploiting diverse aerodynamic mechanisms. How morphology, flight behavior, and aerodynamic properties together diversify with contrasting ecology remains to be elucidated. We studied the adaptive codivergence in wing shape, flight behavior, and aerodynamic

  •   Orbiting resonances in formaldehyde reveal coupling of roaming, radical, and molecular channels
    Science (IF 47.728) Pub Date : 2021-11-26
    Casey D. Foley, Changjian Xie, Hua Guo, Arthur G. Suits

    The roaming chemical reaction mechanism involves near-dissociation of an energized molecule to radicals that leads instead to intramolecular reaction after reorientation at long range. Surprisingly, no clear quantum signatures of roaming have been observed to date, despite the quantum nature of the roaming event. We found evidence of quantum dynamics in the photodissociation of formaldehyde near the

  •   Direct visualization of magnetic domains and moiré magnetism in twisted 2D magnets
    Science (IF 47.728) Pub Date : 2021-11-26
    Tiancheng Song, Qi-Chao Sun, Eric Anderson, Chong Wang, Jimin Qian, Takashi Taniguchi, Kenji Watanabe, Michael A. McGuire, Rainer Stöhr, Di Xiao, Ting Cao, Jörg Wrachtrup, Xiaodong Xu

    Moiré superlattices of twisted nonmagnetic two-dimensional (2D) materials are highly controllable platforms for the engineering of exotic correlated and topological states. Here, we report emerging magnetic textures in small-angle twisted 2D magnet chromium triiodide (CrI3). Using single-spin quantum magnetometry, we directly visualized nanoscale magnetic domains and periodic patterns, a signature

  •   Global response of fire activity to late Quaternary grazer extinctions
    Science (IF 47.728) Pub Date : 2021-11-26
    Allison T. Karp, J. Tyler Faith, Jennifer R. Marlon, A. Carla Staver

    Fire activity varies substantially at global scales because of the influence of climate, but at broad spatiotemporal scales, the possible effects of herbivory on fire activity are unknown. Here, we used late Quaternary large-bodied herbivore extinctions as a global exclusion experiment to examine the responses of grassy ecosystem paleofire activity (through charcoal proxies) to continental differences

  •   Accelerated dinuclear palladium catalyst identification through unsupervised machine learning
    Science (IF 47.728) Pub Date : 2021-11-26
    Julian A. Hueffel, Theresa Sperger, Ignacio Funes-Ardoiz, Jas S. Ward, Kari Rissanen, Franziska Schoenebeck

    Although machine learning bears enormous potential to accelerate developments in homogeneous catalysis, the frequent need for extensive experimental data can be a bottleneck for implementation. Here, we report an unsupervised machine learning workflow that uses only five experimental data points. It makes use of generalized parameter databases that are complemented with problem-specific in silico data

  •   Stem cells expand potency and alter tissue fitness by accumulating diverse epigenetic memories
    Science (IF 47.728) Pub Date : 2021-11-26
    Kevin Andrew Uy Gonzales, Lisa Polak, Irina Matos, Matthew T. Tierney, Anita Gola, Ellen Wong, Nicole R. Infarinato, Maria Nikolova, Shijing Luo, Siqi Liu, Jesse S. S. Novak, Kenneth Lay, Hilda Amalia Pasolli, Elaine Fuchs

    Immune and tissue stem cells retain an epigenetic memory of inflammation that intensifies sensitivity to future encounters. We investigated whether and to what consequence stem cells possess and accumulate memories of diverse experiences. Monitoring a choreographed response to wounds, we found that as hair follicle stem cells leave their niche, migrate to repair damaged epidermis, and take up long-term

  •   Genetic ancestry effects on the response to viral infection are pervasive but cell type specific
    Science (IF 47.728) Pub Date : 2021-11-26
    Haley E. Randolph, Jessica K. Fiege, Beth K. Thielen, Clayton K. Mickelson, Mari Shiratori, João Barroso-Batista, Ryan A. Langlois, Luis B. Barreiro

    Humans differ in their susceptibility to infectious disease, partly owing to variation in the immune response after infection. We used single-cell RNA sequencing to quantify variation in the response to influenza infection in peripheral blood mononuclear cells from European- and African-ancestry males. Genetic ancestry effects are common but highly cell type specific. Higher levels of European ancestry

  •   A ubiquitous disordered protein interaction module orchestrates transcription elongation
    Science (IF 47.728) Pub Date : 2021-11-26
    Katerina Cermakova, Jonas Demeulemeester, Vanda Lux, Monika Nedomova, Seth R. Goldman, Eric A. Smith, Pavel Srb, Rozalie Hexnerova, Milan Fabry, Marcela Madlikova, Magdalena Horejsi, Jan De Rijck, Zeger Debyser, Karen Adelman, H. Courtney Hodges, Vaclav Veverka

    During eukaryotic transcription elongation, RNA polymerase II (RNAP2) is regulated by a chorus of factors. Here, we identified a common binary interaction module consisting of TFIIS N-terminal domains (TNDs) and natively unstructured TND-interacting motifs (TIMs). This module was conserved among the elongation machinery and linked complexes including transcription factor TFIIS, Mediator, super elongation

  •   Floquet Hamiltonian engineering of an isolated many-body spin system
    Science (IF 47.728) Pub Date : 2021-11-26
    Sebastian Geier, Nithiwadee Thaicharoen, Clément Hainaut, Titus Franz, Andre Salzinger, Annika Tebben, David Grimshandl, Gerhard Zürn, Matthias Weidemüller

    Controlling interactions is the key element for the quantum engineering of many-body systems. Using time-periodic driving, a naturally given many-body Hamiltonian of a closed quantum system can be transformed into an effective target Hamiltonian that exhibits vastly different dynamics. We demonstrate such Floquet engineering with a system of spins represented by Rydberg states in an ultracold atomic

  •   Community policing does not build citizen trust in police or reduce crime in the Global South
    Science (IF 47.728) Pub Date : 2021-11-26
    Graeme Blair, Jeremy M. Weinstein, Fotini Christia, Eric Arias, Emile Badran, Robert A. Blair, Ali Cheema, Ahsan Farooqui, Thiemo Fetzer, Guy Grossman, Dotan Haim, Zulfiqar Hameed, Rebecca Hanson, Ali Hasanain, Dorothy Kronick, Benjamin S. Morse, Robert Muggah, Fatiq Nadeem, Lily L. Tsai, Matthew Nanes, Tara Slough, Nico Ravanilla, Jacob N. Shapiro, Barbara Silva, Pedro C. L. Souza, Anna M. Wilke

    Is it possible to reduce crime without exacerbating adversarial relationships between police and citizens? Community policing is a celebrated reform with that aim, which is now adopted on six continents. However, the evidence base is limited, studying reform components in isolation in a limited set of countries, and remaining largely silent on citizen-police trust. We designed six field experiments

  •   Structural basis of branch site recognition by the human spliceosome
    Science (IF 47.728) Pub Date : 2021-11-25
    Jonas Tholen, Michal Razew, Felix Weis, Wojciech P. Galej

    Recognition of the intron branch site (BS) by the U2 snRNP is a critical event during spliceosome assembly. In mammals, BS sequences are poorly conserved and unambiguous intron recognition cannot be achieved solely via a base-pairing mechanism. We isolated human 17S U2 snRNP and reconstituted in vitro its ATP-dependent remodeling and binding to the pre-mRNA substrate. We determined a series of high-resolution

  •   Metastable Dion-Jacobson 2D structure enables efficient and stable perovskite solar cells
    Science (IF 47.728) Pub Date : 2021-11-25
    Fei Zhang, So Yeon Park, Canglang Yao, Haipeng Lu, Sean P. Dunfield, Chuanxiao Xiao, Soňa Uličná, Xiaoming Zhao, Linze Du Hill, Xihan Chen, Xiaoming Wang, Laura E. Mundt, Kevin H. Stone, Laura T. Schelhas, Glenn Teeter, Sean Parkin, Erin L. Ratcliff, Yueh-Lin Loo, Joseph J. Berry, Matthew C. Beard, Yanfa Yan, Bryon W. Larson, Kai Zhu

    The performance of three-dimensional (3D) organic-inorganic halide perovskite solar cells (PSCs) can be enhanced by surface treatment with 2D layered perovskites that have efficient charge transport. We maximized hole transport across the layers of a metastable Dion-Jacobson (DJ) 2D perovskite that tuned the orientational arrangements of asymmetric bulky organic molecules. The reduced energy barrier

  •   Immune correlates analysis of the mRNA-1273 COVID-19 vaccine efficacy clinical trial
    Science (IF 47.728) Pub Date : 2021-11-23
    Peter B. Gilbert, David C. Montefiori, Adrian B. McDermott, Youyi Fong, David Benkeser, Weiping Deng, Honghong Zhou, Christopher R. Houchens, Karen Martins, Lakshmi Jayashankar, Flora Castellino, Britta Flach, Bob C. Lin, Sarah O’Connell, Charlene McDanal, Amanda Eaton, Marcella Sarzotti-Kelsoe, Yiwen Lu, Chenchen Yu, Bhavesh Borate, Lars W. P. van der Laan, Nima S. Hejazi, Chuong Huynh, Jacqueline

    In the coronavirus efficacy (COVE) phase 3 clinical trial, vaccine recipients were assessed for neutralizing and binding antibodies as correlates of risk for COVID-19 disease and as correlates of protection. These immune markers were measured at second vaccination and 4 weeks later, with values reported in standardized WHO International Units. All markers were inversely associated with COVID-19 risk

  •   Antiaging diets: Separating fact from fiction
    Science (IF 47.728) Pub Date : 2021-11-19
    Mitchell B. Lee, Cristal M. Hill, Alessandro Bitto, Matt Kaeberlein

    Caloric restriction has been known for nearly a century to extend life span and delay age-associated pathology in laboratory animals. More recently, alternative “antiaging” diet modalities have been described that provide new mechanistic insights and potential clinical applications. These include intermittent fasting, fasting-mimicking diets, ketogenic diets, time-restricted feeding, protein restriction

  •   Quantum mechanical double slit for molecular scattering
    Science (IF 47.728) Pub Date : 2021-11-19
    Haowen Zhou, William E. Perreault, Nandini Mukherjee, Richard N. Zare

    Interference observed in a double-slit experiment most conclusively demonstrates the wave properties of particles. We construct a quantum mechanical double-slit interferometer by rovibrationally exciting molecular deuterium (D2) in a biaxial (v = 2, j = 2) state using Stark-induced adiabatic Raman passage, where v and j represent the vibrational and rotational quantum numbers, respectively. In D2 (v

  •   Antigenic evolution of dengue viruses over 20 years
    Science (IF 47.728) Pub Date : 2021-11-19
    Leah C. Katzelnick, Ana Coello Escoto, Angkana T. Huang, Bernardo Garcia-Carreras, Nayeem Chowdhury, Irina Maljkovic Berry, Chris Chavez, Philippe Buchy, Veasna Duong, Philippe Dussart, Gregory Gromowski, Louis Macareo, Butsaya Thaisomboonsuk, Stefan Fernandez, Derek J. Smith, Richard Jarman, Stephen S. Whitehead, Henrik Salje, Derek A. T. Cummings

    Infection with one of dengue viruses 1 to 4 (DENV1-4) induces protective antibodies against homotypic infection. However, a notable feature of dengue viruses is the ability to use preexisting heterotypic antibodies to infect Fcγ receptor–bearing immune cells, leading to higher viral load and immunopathological events that augment disease. We tracked the antigenic dynamics of each DENV serotype by using

  •   Fear balance is maintained by bodily feedback to the insular cortex in mice
    Science (IF 47.728) Pub Date : 2021-11-19
    Alexandra S. Klein, Nate Dolensek, Caroline Weiand, Nadine Gogolla

    How does the brain maintain fear within an adaptive range? We found that the insular cortex acts as a state-dependent regulator of fear that is necessary to establish an equilibrium between the extinction and maintenance of fear memories in mice. Whereas insular cortex responsiveness to fear-evoking cues increased with their certainty to predict harm, this activity was attenuated through negative bodily

  •   Biosynthesis of fluopsin C, a copper-containing antibiotic from Pseudomonas aeruginosa
    Science (IF 47.728) Pub Date : 2021-11-19
    Jon B. Patteson, Andrew T. Putz, Lizhi Tao, William C. Simke, L. Henry BryantIII, R. David Britt, Bo Li

    Metal-binding natural products contribute to metal acquisition and bacterial virulence, but their roles in metal stress response are underexplored. We show that a five-enzyme pathway in Pseudomonas aeruginosa synthesizes a small-molecule copper complex, fluopsin C, in response to elevated copper concentrations. Fluopsin C is a broad-spectrum antibiotic that contains a copper ion chelated by two minimal

  •   Pauli blocking of light scattering in degenerate fermions
    Science (IF 47.728) Pub Date : 2021-11-19
    Yair Margalit, Yu-Kun Lu, Furkan Çağrı Top, Wolfgang Ketterle

    Pauli blocking of spontaneous emission is responsible for the stability of atoms. Electrons cannot decay to lower-lying internal states that are already occupied. Pauli blocking also occurs when free atoms scatter light elastically (Rayleigh scattering) and the final external momentum states are already populated. This was predicted more than 30 years ago but is challenging to realize experimentally

  •   Pauli blocking of atom-light scattering
    Science (IF 47.728) Pub Date : 2021-11-19
    Christian Sanner, Lindsay Sonderhouse, Ross B. Hutson, Lingfeng Yan, William R. Milner, Jun Ye

    Transition rates between coupled states in a quantum system depend on the density of available final states. The radiative decay of an excited atomic state has been suppressed by reducing the density of electromagnetic vacuum modes near the atomic transition. Likewise, reducing the density of available momentum modes of the atomic motion when it is embedded inside a Fermi sea will suppress spontaneous

  •   Observation of Pauli blocking in light scattering from quantum degenerate fermions
    Science (IF 47.728) Pub Date : 2021-11-19
    Amita B. Deb, Niels Kjærgaard

    The Pauli exclusion principle forbids indistinguishable fermions from occupying the same quantum mechanical state. The implications of this are profound; for example, it accounts for the electronic shell structure of atoms. Here, we performed measurements on the scattering of light from ultracold ensembles of atoms. For a Fermi gas in the quantum degenerate regime, we observed a marked suppression

  •   A viral RNA hijacks host machinery using dynamic conformational changes of a tRNA-like structure
    Science (IF 47.728) Pub Date : 2021-11-19
    Steve L. Bonilla, Madeline E. Sherlock, Andrea MacFadden, Jeffrey S. Kieft

    Viruses require multifunctional structured RNAs to hijack their host’s biochemistry, but their mechanisms can be obscured by the difficulty of solving conformationally dynamic RNA structures. Using cryo–electron microscopy (cryo-EM), we visualized the structure of the mysterious viral transfer RNA (tRNA)–like structure (TLS) from the brome mosaic virus, which affects replication, translation, and genome

  •   The X chromosome dosage compensation program during the development of cynomolgus monkeys
    Science (IF 47.728) Pub Date : 2021-11-19
    Ikuhiro Okamoto, Tomonori Nakamura, Kotaro Sasaki, Yukihiro Yabuta, Chizuru Iwatani, Hideaki Tsuchiya, Shin-ichiro Nakamura, Masatsugu Ema, Takuya Yamamoto, Mitinori Saitou

    X chromosome dosage compensation ensures balanced gene dosage between the X chromosome and autosomes and between the sexes, involving divergent mechanisms among mammals. We elucidated a distinct mechanism for X chromosome inactivation (XCI) in cynomolgus monkeys, a model for human development. The trophectoderm and cytotrophoblast acquire XCI around implantation through an active intermediate bearing

  •   Structural basis of synergistic neutralization of Crimean-Congo hemorrhagic fever virus by human antibodies
    Science (IF 47.728) Pub Date : 2021-11-18
    Akaash K. Mishra, Jan Hellert, Natalia Freitas, Pablo Guardado-Calvo, Ahmed Haouz, J. Maximilian Fels, Daniel P. Maurer, Dafna M. Abelson, Zachary A. Bornholdt, Laura M. Walker, Kartik Chandran, François-Loïc Cosset, Jason S. McLellan, Felix A. Rey

    Crimean-Congo hemorrhagic fever virus (CCHFV) is the most widespread tick-borne zoonotic virus, with a 30% case fatality rate in humans. Structural information on the CCHFV membrane fusion glycoprotein Gc—the main target of the host neutralizing antibody response—as well as on antibody-mediated neutralization mechanisms is lacking. We describe the structure of prefusion Gc bound to the antigen-binding

  •   Cryo-EM structure of human GPR158 receptor coupled to the RGS7-Gβ5 signaling complex
    Science (IF 47.728) Pub Date : 2021-11-18
    Dipak N. Patil, Shikha Singh, Thibaut Laboute, Timothy S. Strutzenberg, Xingyu Qiu, Di Wu, Scott J. Novick, Carol V. Robinson, Patrick R. Griffin, John F. Hunt, Tina Izard, Appu K. Singh, Kirill A. Martemyanov

    GPR158 is an orphan G-protein-coupled receptor (GPCR) highly expressed in the brain where it controls synapse formation and function. GPR158 has also been implicated in depression, carcinogenesis and cognition. However, the structural organization and signaling mechanisms of GPR158 are largely unknown. Here, we report structures of the human GPR158 alone and bound to an RGS signaling complex, determined

  •   Discovery of davemaoite, CaSiO3-perovskite, as a mineral from the lower mantle
    Science (IF 47.728) Pub Date : 2021-11-12
    Oliver Tschauner, Shichun Huang, Shuying Yang, Munir Humayun, Wenjun Liu, Stephanie N . Gilbert Corder, Hans A. Bechtel, Jon Tischler, George R. Rossman

    Calcium silicate perovskite, CaSiO3, is arguably the most geochemically important phase in the lower mantle, because it concentrates elements that are incompatible in the upper mantle, including the heat-generating elements thorium and uranium, which have half-lives longer than the geologic history of Earth. We report CaSiO3-perovskite as an approved mineral (IMA2020-012a) with the name davemaoite

  •   Real-space imaging of anisotropic charge of σ-hole by means of Kelvin probe force microscopy
    Science (IF 47.728) Pub Date : 2021-11-12
    B. Mallada, A. Gallardo, M. Lamanec, B. de la Torre, V. Špirko, P. Hobza, P. Jelinek

    An anisotropic charge distribution on individual atoms, such as σ-holes, may strongly affect the material and structural properties of systems. However, the spatial resolution of such anisotropic charge distributions on an atom represents a long-standing experimental challenge. In particular, the existence of the σ-hole on halogen atoms has been demonstrated only indirectly through the determination

  •   Structural basis of Integrator-mediated transcription regulation
    Science (IF 47.728) Pub Date : 2021-11-12
    Isaac Fianu, Ying Chen, Christian Dienemann, Olexandr Dybkov, Andreas Linden, Henning Urlaub, Patrick Cramer

    Integrator and protein phosphatase 2A (PP2A) form a complex that dephosphorylates paused RNA polymerase II (Pol II), cleaves the nascent RNA, and terminates transcription. We report the structure of the pretermination complex containing the human Integrator-PP2A complex bound to paused Pol II. Integrator binds Pol II and the pausing factors DSIF and NELF to exclude binding of the elongation factors

  •   Stepwise synaptic plasticity events drive the early phase of memory consolidation
    Science (IF 47.728) Pub Date : 2021-11-12
    Akihiro Goto, Ayaka Bota, Ken Miya, Jingbo Wang, Suzune Tsukamoto, Xinzhi Jiang, Daichi Hirai, Masanori Murayama, Tomoki Matsuda, Thomas J. McHugh, Takeharu Nagai, Yasunori Hayashi

    Memories are initially encoded in the hippocampus but subsequently consolidated to the cortex. Although synaptic plasticity is key to these processes, its precise spatiotemporal profile remains poorly understood. Using optogenetics to selectively erase long-term potentiation (LTP) within a defined temporal window, we found that distinct phases of synaptic plasticity play differential roles. The first

  •   Symmetry breaking in the female germline cyst
    Science (IF 47.728) Pub Date : 2021-11-12
    D. Nashchekin, L. Busby, M. Jakobs, I. Squires, D. St. Johnston

    In mammals and flies, only one cell in a multicellular female germline cyst becomes an oocyte, but how symmetry is broken to select the oocyte is unknown. Here, we show that the microtubule (MT) minus end-stabilizing protein Patronin/CAMSAP marks the future Drosophila oocyte and is required for oocyte specification. The spectraplakin Shot recruits Patronin to the fusome, a branched structure extending

  •   The genetic and epigenetic landscape of the Arabidopsis centromeres
    Science (IF 47.728) Pub Date : 2021-11-12
    Matthew Naish, Michael Alonge, Piotr Wlodzimierz, Andrew J. Tock, Bradley W. Abramson, Anna Schmücker, Terezie Mandáková, Bhagyshree Jamge, Christophe Lambing, Pallas Kuo, Natasha Yelina, Nolan Hartwick, Kelly Colt, Lisa M. Smith, Jurriaan Ton, Tetsuji Kakutani, Robert A. Martienssen, Korbinian Schneeberger, Martin A. Lysak, Frédéric Berger, Alexandros Bousios, Todd P. Michael, Michael C. Schatz, Ian

    Centromeres attach chromosomes to spindle microtubules during cell division and, despite this conserved role, show paradoxically rapid evolution and are typified by complex repeats. We used long-read sequencing to generate the Col-CEN Arabidopsis thaliana genome assembly that resolves all five centromeres. The centromeres consist of megabase-scale tandemly repeated satellite arrays, which support CENTROMERE

  •   Bioactive scaffolds with enhanced supramolecular motion promote recovery from spinal cord injury
    Science (IF 47.728) Pub Date : 2021-11-12
    Z. Álvarez, A. N. Kolberg-Edelbrock, I. R. Sasselli, J. A. Ortega, R. Qiu, Z. Syrgiannis, P. A. Mirau, F. Chen, S. M. Chin, S. Weigand, E. Kiskinis, S. I. Stupp

    The signaling of cells by scaffolds of synthetic molecules that mimic proteins is known to be effective in the regeneration of tissues. Here, we describe peptide amphiphile supramolecular polymers containing two distinct signals and test them in a mouse model of severe spinal cord injury. One signal activates the transmembrane receptor β1-integrin and a second one activates the basic fibroblast growth

  •   Origins and evolution of extreme life span in Pacific Ocean rockfishes
    Science (IF 47.728) Pub Date : 2021-11-12
    Sree Rohit Raj Kolora, Gregory L. Owens, Juan Manuel Vazquez, Alexander Stubbs, Kamalakar Chatla, Conner Jainese, Katelin Seeto, Merit McCrea, Michael W. Sandel, Juliana A. Vianna, Katherine Maslenikov, Doris Bachtrog, James W. Orr, Milton Love, Peter H. Sudmant

    Pacific Ocean rockfishes (genus Sebastes) exhibit extreme variation in life span, with some species being among the most long-lived extant vertebrates. We de novo assembled the genomes of 88 rockfish species and from these identified repeated signatures of positive selection in DNA repair pathways in long-lived taxa and 137 longevity-associated genes with direct effects on life span through insulin

  •   Methoxyl stable isotopic constraints on the origins and limits of coal-bed methane
    Science (IF 47.728) Pub Date : 2021-11-12
    M. K. Lloyd, E. Trembath-Reichert, K. S. Dawson, S. J. Feakins, M. Mastalerz, V. J. Orphan, A. L. Sessions, J. M. Eiler

    Microbial coal-bed methane is an important economic resource and source of a potent greenhouse gas, but controls on its formation are poorly understood. To test whether the microbial degradability of coal limits microbial methane, we monitored methoxyl group demethylation—a reaction that feeds methanogenesis—in a global sample suite ranging in maturity from wood to bituminous coal. Carbon isotopic

  •   Tool use and language share syntactic processes and neural patterns in the basal ganglia
    Science (IF 47.728) Pub Date : 2021-11-12
    Simon Thibault, Raphaël Py, Angelo Mattia Gervasi, Romeo Salemme, Eric Koun, Martin Lövden, Véronique Boulenger, Alice C. Roy, Claudio Brozzoli

    Does tool use share syntactic processes with language? Acting with a tool is thought to add a hierarchical level into the motor plan. In the linguistic domain, syntax is the cognitive function handling interdependent elements. Using functional magnetic resonance imaging, we detected common neurofunctional substrates in the basal ganglia subserving both tool use and syntax in language. The two abilities

  •   Computed structures of core eukaryotic protein complexes
    Science (IF 47.728) Pub Date : 2021-11-11
    Ian R. Humphreys, Jimin Pei, Minkyung Baek, Aditya Krishnakumar, Ivan Anishchenko, Sergey Ovchinnikov, Jing Zhang, Travis J. Ness, Sudeep Banjade, Saket R. Bagde, Viktoriya G. Stancheva, Xiao-Han Li, Kaixian Liu, Zhi Zheng, Daniel J. Barrero, Upasana Roy, Jochen Kuper, Israel S. Fernández, Barnabas Szakal, Dana Branzei, Josep Rizo, Caroline Kisker, Eric C. Greene, Sue Biggins, Scott Keeney, Elizabeth

    Protein-protein interactions play critical roles in biology, but the structures of many eukaryotic protein complexes are unknown, and there are likely many interactions not yet identified. We take advantage of advances in proteome-wide amino acid coevolution analysis and deep-learning-based structure modeling to systematically identify and build accurate models of core eukaryotic protein complexes

  •   Voltage compartmentalization in dendritic spines in vivo
    Science (IF 47.728) Pub Date : 2021-11-11
    Victor Hugo Cornejo, Netanel Ofer, Rafael Yuste

    Dendritic spines mediate most excitatory neurotransmission in the nervous system, so their function must be critical for the brain. Spines are biochemical compartments, but could also electrically modify synaptic potentials. Using two-photon microscopy and a genetically-encoded voltage indicator, we measured membrane potentials in spines and dendrites from pyramidal neurons in somatosensory cortex

  •   A biomimetic SH2 cross-coupling mechanism for quaternary sp3-carbon formation
    Science (IF 47.728) Pub Date : 2021-11-11
    Wei Liu, Marissa N. Lavagnino, Colin A. Gould, Jesús Alcázar, David W. C. MacMillan

    Bimolecular homolytic substitution (SH2) is an open-shell mechanism that is implicated across a host of biochemical alkylation pathways. Surprisingly, however, this radical substitution manifold has not been generally deployed as a design element in synthetic C–C bond formation. Here, we demonstrate that the SH2 mechanism can be leveraged to enable a biomimetic sp3-sp3 cross-coupling platform that

  •   Ligand-controlled divergent dehydrogenative reactions of carboxylic acids via C–H activation
    Science (IF 47.728) Pub Date : 2021-11-11
    Zhen Wang, Liang Hu, Nikita Chekshin, Zhe Zhuang, Shaoqun Qian, Jennifer X. Qiao, Jin-Quan Yu

    Dehydrogenative transformations of alkyl chains to alkenes through methylene C–H activation remain a substantial challenge. We report two classes of pyridine-pyridone ligands that enable divergent dehydrogenation reactions through Pd-catalyzed β-methylene C–H activation of carboxylic acids, leading to the direct syntheses of α,β-unsaturated carboxylic acids or γ-alkylidene butenolides. The directed

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