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  •   mRNA vaccines induce durable immune memory to SARS-CoV-2 and variants of concern
    Science (IF 47.728) Pub Date : 2021-10-14
    Rishi R. Goel, Mark M. Painter, Sokratis A. Apostolidis, Divij Mathew, Wenzhao Meng, Aaron M. Rosenfeld, Kendall A. Lundgreen, Arnold Reynaldi, David S. Khoury, Ajinkya Pattekar, Sigrid Gouma, Leticia Kuri-Cervantes, Philip Hicks, Sarah Dysinger, Amanda Hicks, Harsh Sharma, Sarah Herring, Scott Korte, Amy E. Baxter, Derek A. Oldridge, Josephine R. Giles, Madison E. Weirick, Christopher M. McAllister

    The durability of immune memory after SARS-CoV-2 mRNA vaccination remains unclear. Here, we longitudinally profiled vaccine responses in SARS-CoV-2 naïve and recovered individuals for 6 months after vaccination. Antibodies declined from peak levels but remained detectable in most subjects at 6 months. We found mRNA vaccines generated functional memory B cells that increased from 3-6 months post-vaccination

  •   Mapping the proteo-genomic convergence of human diseases
    Science (IF 47.728) Pub Date : 2021-10-14
    Maik Pietzner, Eleanor Wheeler, Julia Carrasco-Zanini, Adrian Cortes, Mine Koprulu, Maria A. Wörheide, Erin Oerton, James Cook, Isobel D. Stewart, Nicola D. Kerrison, Jian’an Luan, Johannes Raffler, Matthias Arnold, Wiebke Arlt, Stephen O’Rahilly, Gabi Kastenmüller, Eric R. Gamazon, Aroon D. Hingorani, Robert A. Scott, Nicholas J. Wareham, Claudia Langenberg

    Characterization of the genetic regulation of proteins is essential for understanding disease etiology and developing therapies. We identified 10,674 genetic associations for 3,892 plasma proteins to create a cis-anchored gene-protein-disease map of 1,859 connections that highlights strong cross-disease biological convergence. This proteo-genomic map provides a framework to 1) connect etiologically

  •   Replication and single-cycle delivery of SARS-CoV-2 replicons
    Science (IF 47.728) Pub Date : 2021-10-14
    Inna Ricardo-Lax, Joseph M. Luna, Tran Thi Nhu Thao, Jérémie Le Pen, Yingpu Yu, H.-Heinrich Hoffmann, William M. Schneider, Brandon S. Razooky, Javier Fernandez-Martinez, Fabian Schmidt, Yiska Weisblum, Bettina Salome Trüeb, Inês Berenguer Veiga, Kimberly Schmied, Nadine Ebert, Eleftherios Michailidis, Avery Peace, Francisco J. Sánchez-Rivera, Scott W. Lowe, Michael P. Rout, Theodora Hatziioannou,

    Molecular virology tools are critical for basic studies of the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) and for developing new therapeutics. There remains a need for experimental systems that do not rely on viruses capable of spread that could potentially be used in lower containment settings. Here, we develop spike-deleted SARS-CoV-2 self-replicating RNAs using a yeast-based reverse

  •   Assessing mass incarceration’s effects on families
    Science (IF 47.728) Pub Date : 2021-10-15
    Hedwig Lee, Christopher Wildeman

    In this Review, we assess how mass incarceration, a monumental American policy experiment, has affected families over the past five decades. We reach four conclusions. First, family member incarceration is now common for American families. Second, individuals who will eventually have a family member incarcerated are worse off than those who never will, even before the incarceration takes place. Third

  •   The predatory dimensions of criminal justice
    Science (IF 47.728) Pub Date : 2021-10-15
    Joshua Page, Joe Soss

    Over the past 35 years, public and private actors have turned US criminal justice institutions into a vast network of revenue-generating operations. Today, practices such as fines, fees, forfeitures, prison charges, and bail premiums transfer billions of dollars from oppressed communities to governments and corporations. Guided by scholarship on racial capitalism, we argue that to understand how and

  •   Exclusion and exploitation: The incarceration of Black Americans from slavery to the present
    Science (IF 47.728) Pub Date : 2021-10-15
    Christopher Muller

    Understanding long-run patterns in the incarceration of Black Americans requires integrating the study of racial inequality with the study of political economy. I offer a parsimonious framework describing how the Black incarceration rate has been affected by the dynamics of exploitation and exclusion over time and across space. This framework helps to explain otherwise puzzling facts, like why the

  •   Toward an understanding of structural racism: Implications for criminal justice
    Science (IF 47.728) Pub Date : 2021-10-15
    Julian M. Rucker, Jennifer A. Richeson

    Racial inequality is a foundational feature of the criminal justice system in the United States. Here we offer a psychological account for how Americans have come to tolerate a system that is so at odds with their professed egalitarian values. We argue that beliefs about the nature of racism—as being solely due to prejudiced individuals rather than structural factors that disadvantage marginalized

  •   Univariate classification of phosphine ligation state and reactivity in cross-coupling catalysis
    Science (IF 47.728) Pub Date : 2021-10-15
    Samuel H. Newman-Stonebraker, Sleight R. Smith, Julia E. Borowski, Ellyn Peters, Tobias Gensch, Heather C. Johnson, Matthew S. Sigman, Abigail G. Doyle

    Chemists often use statistical analysis of reaction data with molecular descriptors to identify structure-reactivity relationships, which can enable prediction and mechanistic understanding. In this study, we developed a broadly applicable and quantitative classification workflow that identifies reactivity cliffs in 11 Ni- and Pd-catalyzed cross-coupling datasets using monodentate phosphine ligands

  •   Electrically tunable Feshbach resonances in twisted bilayer semiconductors
    Science (IF 47.728) Pub Date : 2021-10-15
    Ido Schwartz, Yuya Shimazaki, Clemens Kuhlenkamp, Kenji Watanabe, Takashi Taniguchi, Martin Kroner, Ataç Imamoğlu

    Moiré superlattices in transition metal dichalcogenide bilayers provide a platform for exploring strong correlations with optical spectroscopy. Despite the observation of rich Mott-Wigner physics stemming from an interplay between the periodic potential and Coulomb interactions, the absence of tunnel coupling–induced hybridization of electronic states has ensured a classical layer degree of freedom

  •   The Gulf Stream and Kuroshio Current are synchronized
    Science (IF 47.728) Pub Date : 2021-10-15
    Tsubasa Kohyama, Yoko Yamagami, Hiroaki Miura, Shoichiro Kido, Hiroaki Tatebe, Masahiro Watanabe

    Observations show that sea surface temperatures along the Gulf Stream and the Kuroshio Current tend to synchronize at decadal time scales. This synchronization, which we refer to as the boundary current synchronization (BCS), is reproduced in global climate models with high spatial resolution. Both in observations and model simulations, BCS is associated with meridional migrations of the atmospheric

  •   Astrocyte Ca2+-evoked ATP release regulates myelinated axon excitability and conduction speed
    Science (IF 47.728) Pub Date : 2021-10-15
    Jonathan Lezmy, I. Lorena Arancibia-Cárcamo, Tania Quintela-López, Diane L. Sherman, Peter J. Brophy, David Attwell

    In the brain’s gray matter, astrocytes regulate synapse properties, but their role is unclear for the white matter, where myelinated axons rapidly transmit information between gray matter areas. We found that in rodents, neuronal activity raised the intracellular calcium concentration ([Ca2+]i) in astrocyte processes located near action potential–generating sites in the axon initial segment (AIS) and

  •   Modulation of tactile feedback for the execution of dexterous movement
    Science (IF 47.728) Pub Date : 2021-10-15
    James M. Conner, Andrew Bohannon, Masakazu Igarashi, James Taniguchi, Nicholas Baltar, Eiman Azim

    Although dexterity relies on the constant transmission of sensory information, unchecked feedback can be disruptive. Yet how somatosensory feedback from the hands is regulated and whether this modulation influences movement remain unclear. We found that mouse tactile afferents recruit neurons in the brainstem cuneate nucleus, whose activity is modulated by distinct classes of local inhibitory neurons

  •   A compositional link between rocky exoplanets and their host stars
    Science (IF 47.728) Pub Date : 2021-10-15
    Vardan Adibekyan, Caroline Dorn, Sérgio G. Sousa, Nuno C. Santos, Bertram Bitsch, Garik Israelian, Christoph Mordasini, Susana C. C. Barros, Elisa Delgado Mena, Olivier D. S. Demangeon, João P. Faria, Pedro Figueira, Artur A. Hakobyan, Mahmoudreza Oshagh, Bárbara M. T. B. Soares, Masanobu Kunitomo, Yoichi Takeda, Emiliano Jofré, Romina Petrucci, Eder Martioli

    Stars and planets both form by accreting material from a surrounding disk. Because they grow from the same material, theory predicts that there should be a relationship between their compositions. In this study, we search for a compositional link between rocky exoplanets and their host stars. We estimate the iron-mass fraction of rocky exoplanets from their masses and radii and compare it with the

  •   Physical disturbance by recovering sea otter populations increases eelgrass genetic diversity
    Science (IF 47.728) Pub Date : 2021-10-15
    Erin Foster, Jane Watson, Matthew A. Lemay, M. Tim Tinker, James A. Estes, Rebecca Piercey, Lauren Henson, Carol Ritland, Allyson Miscampbell, Linda Nichol, Margot Hessing-Lewis, Anne K. Salomon, Chris T. Darimont

    Most knowledge regarding the role of predators is ecological in nature. Here, we report how disturbance generated by sea otters (Enhydra lutris) digging for infaunal prey in eelgrass (Zostera marina) meadows increases genetic diversity by promoting conditions for sexual reproduction of plants. Eelgrass allelic richness and genotypic diversity were, respectively, 30 and 6% higher in areas where recovering

  •   Mitochondrial translation is required for sustained killing by cytotoxic T cells
    Science (IF 47.728) Pub Date : 2021-10-15
    Miriam Lisci, Philippa R. Barton, Lyra O. Randzavola, Claire Y. Ma, Julia M. Marchingo, Doreen A. Cantrell, Vincent Paupe, Julien Prudent, Jane C. Stinchcombe, Gillian M. Griffiths

    T cell receptor activation of naïve CD8+ T lymphocytes initiates their maturation into effector cytotoxic T lymphocytes (CTLs), which can kill cancer and virally infected cells. Although CTLs show an increased reliance on glycolysis upon acquisition of effector function, we found an essential requirement for mitochondria in target cell–killing. Acute mitochondrial depletion in USP30 (ubiquitin carboxyl-terminal

  •   Muscle repair after physiological damage relies on nuclear migration for cellular reconstruction
    Science (IF 47.728) Pub Date : 2021-10-15
    William Roman, Helena Pinheiro, Mafalda R. Pimentel, Jessica Segalés, Luis M. Oliveira, Esther García-Domínguez, Mari Carmen Gómez-Cabrera, Antonio L. Serrano, Edgar R. Gomes, Pura Muñoz-Cánoves

    Regeneration of skeletal muscle is a highly synchronized process that requires muscle stem cells (satellite cells). We found that localized injuries, as experienced through exercise, activate a myofiber self-repair mechanism that is independent of satellite cells in mice and humans. Mouse muscle injury triggers a signaling cascade involving calcium, Cdc42, and phosphokinase C that attracts myonuclei

  •   Heuristics in the delivery room
    Science (IF 47.728) Pub Date : 2021-10-15
    Manasvini Singh

    Clinical decisions made in the delivery setting are often made under high pressure and great uncertainty, and have serious consequences for mother and baby. Theories of decision-making suggest that individuals in such settings may resort to using heuristics, or simplified decision rules, to aid complex decision-making. This study investigates whether physicians’ delivery mode decisions (i.e., when

  •   Bioelectric signaling and the control of cardiac cell identity in response to mechanical forces
    Science (IF 47.728) Pub Date : 2021-10-15
    Hajime Fukui, Renee Wei-Yan Chow, Jing Xie, Yoke Yin Foo, Choon Hwai Yap, Nicolas Minc, Naoki Mochizuki, Julien Vermot

    Developing cardiovascular systems use mechanical forces to take shape, but how ubiquitous blood flow forces instruct local cardiac cell identity is still unclear. By manipulating mechanical forces in vivo, we show here that shear stress is necessary and sufficient to promote valvulogenesis. We found that valve formation is associated with the activation of an extracellular adenosine triphosphate (ATP)–dependent

  •   G1 cyclin–Cdk promotes cell cycle entry through localized phosphorylation of RNA polymerase II
    Science (IF 47.728) Pub Date : 2021-10-15
    Mardo Kõivomägi, Matthew P. Swaffer, Jonathan J. Turner, Georgi Marinov, Jan M. Skotheim

    Cell division is thought to be initiated by cyclin-dependent kinases (Cdks) inactivating key transcriptional inhibitors. In budding yeast, the G1 cyclin Cln3-Cdk1 complex is thought to directly phosphorylate the Whi5 protein, thereby releasing the transcription factor SBF and committing cells to division. We report that Whi5 is a poor substrate of Cln3-Cdk1, which instead phosphorylates the RNA polymerase

  •   Genomic characterization and epidemiology of an emerging SARS-CoV-2 variant in Delhi, India
    Science (IF 47.728) Pub Date : 2021-10-14
    Mahesh S. Dhar, Robin Marwal, Radhakrishnan VS, Kalaiarasan Ponnusamy, Bani Jolly, Rahul C. Bhoyar, Viren Sardana, Salwa Naushin, Mercy Rophina, Thomas A. Mellan, Swapnil Mishra, Charles Whittaker, Saman Fatihi, Meena Datta, Priyanka Singh, Uma Sharma, Rajat Ujjainiya, Nitin Bhatheja, Mohit Kumar Divakar, Manoj K. Singh, Mohamed Imran, Vigneshwar Senthivel, Ranjeet Maurya, Neha Jha, Priyanka Mehta

    Delhi, the national capital of India, has experienced multiple SARS-CoV-2 outbreaks in 2020 and reached population seropositivity of over 50% by 2021. During April 2021, the city became overwhelmed by COVID-19 cases and fatalities, as a new variant B.1.617.2 (Delta) replaced B.1.1.7 (Alpha). A Bayesian model explains the growth advantage of Delta through a combination of increased transmissibility

  •   Mechanism of siRNA production by a plant Dicer-RNA complex in dicing-competent conformation
    Science (IF 47.728) Pub Date : 2021-10-14
    Qian Wang, Yan Xue, Laixing Zhang, Zhenhui Zhong, Suhua Feng, Changshi Wang, Lifan Xiao, Zhenlin Yang, C. Jake Harris, Zhe Wu, Jixian Zhai, Maojun Yang, Sisi Li, Steven E. Jacobsen, Jiamu Du

    In eukaryotes, small RNAs (sRNAs) play critical roles in multiple biological processes. Dicer endonucleases are central to sRNA biogenesis. In plants, DICER-LIKE PROTEIN 3 (DCL3) produces 24-nt small interfering RNAs (siRNAs) that determine the specificity of the RNA-directed DNA methylation (RdDM) pathway. Here, we determined structure of a DCL3-pre-siRNA complex in an active dicing-competent state

  •   CD4+ T cells contribute to neurodegeneration in Lewy body dementia
    Science (IF 47.728) Pub Date : 2021-10-14
    David Gate, Emma Tapp, Olivia Leventhal, Marian Shahid, Tim J. Nonninger, Andrew C. Yang, Katharina Strempfl, Michael S. Unger, Tobias Fehlmann, Hamilton Oh, Divya Channappa, Victor W. Henderson, Andreas Keller, Ludwig Aigner, Douglas R. Galasko, Mark M. Davis, Kathleen L. Poston, Tony Wyss-Coray

    Recent studies indicate that the adaptive immune system plays a role in Lewy body dementia (LBD). However, the mechanism regulating T cell brain homing in LBD is unknown. Here, we observed T cells adjacent to Lewy bodies and dopaminergic neurons in post-mortem LBD brains. Single-cell RNA sequencing of cerebrospinal fluid (CSF) identified up-regulated expression of C-X-C Motif Chemokine Receptor 4 (CXCR4)

  •   Evasion of tipping in complex systems through spatial pattern formation
    Science (IF 47.728) Pub Date : 2021-10-08
    Max Rietkerk, Robbin Bastiaansen, Swarnendu Banerjee, Johan van de Koppel, Mara Baudena, Arjen Doelman

    The concept of tipping points and critical transitions helps inform our understanding of the catastrophic effects that global change may have on ecosystems, Earth system components, and the whole Earth system. The search for early warning indicators is ongoing, and spatial self-organization has been interpreted as one such signal. Here, we review how spatial self-organization can aid complex systems

  •   Levitodynamics: Levitation and control of microscopic objects in vacuum
    Science (IF 47.728) Pub Date : 2021-10-08
    C. Gonzalez-Ballestero, M. Aspelmeyer, L. Novotny, R. Quidant, O. Romero-Isart

    The control of levitated nano- and micro-objects in vacuum—which capitalizes on scientific achievements in the fields of atomic physics, control theory, and optomechanics—is of considerable interest. The ability to couple the motion of levitated systems to internal degrees of freedom, as well as to external forces and systems, provides opportunities for science and technology. Attractive research directions

  •   Solvation sheath reorganization enables divalent metal batteries with fast interfacial charge transfer kinetics
    Science (IF 47.728) Pub Date : 2021-10-08
    Singyuk Hou, Xiao Ji, Karen Gaskell, Peng-fei Wang, Luning Wang, Jijian Xu, Ruimin Sun, Oleg Borodin, Chunsheng Wang

    Rechargeable magnesium and calcium metal batteries (RMBs and RCBs) are promising alternatives to lithium-ion batteries because of the high crustal abundance and capacity of magnesium and calcium. Yet, they are plagued by sluggish kinetics and parasitic reactions. We found a family of methoxyethyl-amine chelants that greatly promote interfacial charge transfer kinetics and suppress side reactions on

  •   Microfluidic-like fabrication of metal ion–cured bioadhesives by mussels
    Science (IF 47.728) Pub Date : 2021-10-08
    Tobias Priemel, Gurveer Palia, Frank Förste, Franziska Jehle, Sanja Sviben, Ioanna Mantouvalou, Paul Zaslansky, Luca Bertinetti, Matthew J. Harrington

    To anchor in seashore habitats, mussels fabricate adhesive byssus fibers that are mechanically reinforced by protein-metal coordination mediated by 3,4-dihydroxyphenylalanine (DOPA). The mechanism by which metal ions are integrated during byssus formation remains unknown. In this study, we investigated the byssus formation process in the blue mussel, Mytilus edulis, combining traditional and advanced

  •   Conformer-specific photochemistry imaged in real space and time
    Science (IF 47.728) Pub Date : 2021-10-08
    E. G. Champenois, D. M. Sanchez, J. Yang, J. P. Figueira Nunes, A. Attar, M. Centurion, R. Forbes, M. Gühr, K. Hegazy, F. Ji, S. K. Saha, Y. Liu, M.-F. Lin, D. Luo, B. Moore, X. Shen, M. R. Ware, X. J. Wang, T. J. Martínez, T. J. A. Wolf

    Conformational isomers (conformers) of molecules play a decisive role in biology and organic chemistry. However, experimental methods for investigating chemical reaction dynamics are typically not conformer-sensitive. We report on a gas-phase megaelectronvolt ultrafast electron diffraction investigation of α-phellandrene undergoing an electrocyclic ring-opening reaction. We directly imaged the evolution

  •   Topological phonon-polariton funneling in midinfrared metasurfaces
    Science (IF 47.728) Pub Date : 2021-10-08
    S. Guddala, F. Komissarenko, S. Kiriushechkina, A. Vakulenko, M. Li, V. M. Menon, A. Alù, A. B. Khanikaev

    Topological photonics offers enhanced control over electromagnetic fields by providing a platform for robust trapping and guiding of topological states of light. By combining the strong coupling between topological photons with phonons in hexagonal boron nitride (hBN), we demonstrate a platform to control and guide hybrid states of light and lattice vibrations. The observed topological edge states

  •   Grain boundary velocity and curvature are not correlated in Ni polycrystals
    Science (IF 47.728) Pub Date : 2021-10-08
    Aditi Bhattacharya, Yu-Feng Shen, Christopher M. Hefferan, Shiu Fai Li, Jonathan Lind, Robert M. Suter, Carl E. KrillIII, Gregory S. Rohrer

    Grain boundary velocity has been believed to be correlated to curvature, and this is an important relationship for modeling how polycrystalline materials coarsen during annealing. We determined the velocities and curvatures of approximately 52,000 grain boundaries in a nickel polycrystal using three-dimensional orientation maps measured by high-energy diffraction microscopy before and after annealing

  •   Population-specific neuromodulation prolongs therapeutic benefits of deep brain stimulation
    Science (IF 47.728) Pub Date : 2021-10-08
    Teresa A. Spix, Shruti Nanivadekar, Noelle Toong, Irene M. Kaplow, Brian R. Isett, Yazel Goksen, Andreas R. Pfenning, Aryn H. Gittis

    Symptoms of neurological diseases emerge through the dysfunction of neural circuits whose diffuse and intertwined architectures pose serious challenges for delivering therapies. Deep brain stimulation (DBS) improves Parkinson’s disease symptoms acutely but does not differentiate between neuronal circuits, and its effects decay rapidly if stimulation is discontinued. Recent findings suggest that optogenetic

  •   Ten millennia of hepatitis B virus evolution
    Science (IF 47.728) Pub Date : 2021-10-08
    Arthur Kocher, Luka Papac, Rodrigo Barquera, Felix M. Key, Maria A. Spyrou, Ron Hübler, Adam B. Rohrlach, Franziska Aron, Raphaela Stahl, Antje Wissgott, Florian van Bömmel, Maria Pfefferkorn, Alissa Mittnik, Vanessa Villalba-Mouco, Gunnar U. Neumann, Maïté Rivollat, Marieke S. van de Loosdrecht, Kerttu Majander, Rezeda I. Tukhbatova, Lyazzat Musralina, Ayshin Ghalichi, Sandra Penske, Susanna Sabin

    Hepatitis B virus (HBV) has been infecting humans for millennia and remains a global health problem, but its past diversity and dispersal routes are largely unknown. We generated HBV genomic data from 137 Eurasians and Native Americans dated between ~10,500 and ~400 years ago. We date the most recent common ancestor of all HBV lineages to between ~20,000 and 12,000 years ago, with the virus present

  •   Fracture, fatigue, and friction of polymers in which entanglements greatly outnumber cross-links
    Science (IF 47.728) Pub Date : 2021-10-08
    Junsoo Kim, Guogao Zhang, Meixuanzi Shi, Zhigang Suo

    In gels and elastomers, the role of entanglements on deformation has been studied, but their effects on fracture, fatigue, and friction are less well understood. In this study, we synthesized polymers in which entanglements greatly outnumber cross-links. The dense entanglements enable transmission of tension in a polymer chain along its length and to many other chains. The sparse cross-links prevent

  •   Toughening hydrogels through force-triggered chemical reactions that lengthen polymer strands
    Science (IF 47.728) Pub Date : 2021-10-08
    Zi Wang, Xujun Zheng, Tetsu Ouchi, Tatiana B. Kouznetsova, Haley K. Beech, Sarah Av-Ron, Takahiro Matsuda, Brandon H. Bowser, Shu Wang, Jeremiah A. Johnson, Julia A. Kalow, Bradley D. Olsen, Jian Ping Gong, Michael Rubinstein, Stephen L. Craig

    The utility and lifetime of materials made from polymer networks, including hydrogels, depend on their capacity to stretch and resist tearing. In gels and elastomers, those mechanical properties are often limited by the covalent chemical structure of the polymer strands between cross-links, which is typically fixed during the material synthesis. We report polymer networks in which the constituent strands

  •   Commensal bacteria promote endocrine resistance in prostate cancer through androgen biosynthesis
    Science (IF 47.728) Pub Date : 2021-10-08
    Nicolò Pernigoni, Elena Zagato, Arianna Calcinotto, Martina Troiani, Ricardo Pereira Mestre, Bianca Calì, Giuseppe Attanasio, Jacopo Troisi, Mirko Minini, Simone Mosole, Ajinkya Revandkar, Emiliano Pasquini, Angela Rita Elia, Daniela Bossi, Andrea Rinaldi, Pasquale Rescigno, Penny Flohr, Joanne Hunt, Antje Neeb, Lorenzo Buroni, Christina Guo, Jonathan Welti, Matteo Ferrari, Matteo Grioni, Josée Gauthier

    The microbiota comprises the microorganisms that live in close contact with the host, with mutual benefit for both counterparts. The contribution of the gut microbiota to the emergence of castration-resistant prostate cancer (CRPC) has not yet been addressed. We found that androgen deprivation in mice and humans promotes the expansion of defined commensal microbiota that contributes to the onset of

  •   The G protein signaling regulator RGS3 enhances the GTPase activity of KRAS
    Science (IF 47.728) Pub Date : 2021-10-08
    Chuanchuan Li, Alberto Vides, Dongsung Kim, Jenny Y. Xue, Yulei Zhao, Piro Lito

    Recently reported to be effective in patients with lung cancer, KRASG12C inhibitors bind to the inactive, or guanosine diphosphate (GDP)–bound, state of the oncoprotein and require guanosine triphosphate (GTP) hydrolysis for inhibition. However, KRAS mutations prevent the catalytic arginine of GTPase-activating proteins (GAPs) from enhancing an otherwise slow hydrolysis rate. If KRAS mutants are indeed

  •   Reconstitution of an intact clock reveals mechanisms of circadian timekeeping
    Science (IF 47.728) Pub Date : 2021-10-08
    Archana G. Chavan, Jeffrey A. Swan, Joel Heisler, Cigdem Sancar, Dustin C. Ernst, Mingxu Fang, Joseph G. Palacios, Rebecca K. Spangler, Clive R. Bagshaw, Sarvind Tripathi, Priya Crosby, Susan S. Golden, Carrie L. Partch, Andy LiWang

    Circadian clocks control gene expression to provide an internal representation of local time. We report reconstitution of a complete cyanobacterial circadian clock in vitro, including the central oscillator, signal transduction pathways, downstream transcription factor, and promoter DNA. The entire system oscillates autonomously and remains phase coherent for many days with a fluorescence-based readout

  •   Myelin: A gatekeeper of activity-dependent circuit plasticity?
    Science (IF 47.728) Pub Date : 2021-10-07
    Giulia Bonetto, David Belin, Ragnhildur Thóra Káradóttir

    The brain is responsive to an ever-changing environment, enabling the organism to learn and change behavior accordingly. Efforts to understand the underpinnings of this plasticity have almost exclusively focused on the functional and underlying structural changes that neurons undergo at neurochemical synapses. What has received comparatively little attention is the involvement of activity-dependent

  •   Monetary incentives increase COVID-19 vaccinations
    Science (IF 47.728) Pub Date : 2021-10-07
    Pol Campos-Mercade, Armando N. Meier, Florian H. Schneider, Stephan Meier, Devin Pope, Erik Wengström

    Stalling COVID-19 vaccination rates threaten public health. To increase vaccination rates, governments across the globe are considering using monetary incentives. We present evidence on the effect of guaranteed payments on COVID-19 vaccination uptake. We ran a large pre-registered randomized controlled trial (N = 8,286) in Sweden and linked the data to population-wide administrative vaccination records

  •   Age and composition of young basalts on the Moon, measured from samples returned by Chang’e-5
    Science (IF 47.728) Pub Date : 2021-10-07
    Xiaochao Che, Alexander Nemchin, Dunyi Liu, Tao Long, Chen Wang, Marc D. Norman, Katherine H. Joy, Romain Tartese, James Head, Bradley Jolliff, Joshua F. Snape, Clive R. Neal, Martin J. Whitehouse, Carolyn Crow, Gretchen Benedix, Fred Jourdan, Zhiqing Yang, Chun Yang, Jianhui Liu, Shiwen Xie, Zemin Bao, Runlong Fan, Dapeng Li, Zengsheng Li, Stuart G. Webb

    Orbital data indicate that the youngest volcanic units on the Moon are basalt lavas in Oceanus Procellarum, a region with high levels of the heat-producing elements potassium, thorium, and uranium. The Chang’e-5 mission collected samples of these young lunar basalts and returned them to Earth for laboratory analysis. We measure an age of 1963 ± 57 Ma for these lavas and determine their chemical and

  •   Perseverance rover reveals an ancient delta-lake system and flood deposits at Jezero crater, Mars
    Science (IF 47.728) Pub Date : 2021-10-07
    N. Mangold, S. Gupta, O. Gasnault, G. Dromart, J. D. Tarnas, S. F. Sholes, B. Horgan, C. Quantin-Nataf, A. J. Brown, S. Le Mouélic, R. A. Yingst, J. F. Bell, O. Beyssac, T. Bosak, F. CalefIII, B. L. Ehlmann, K. A. Farley, J. P. Grotzinger, K. Hickman-Lewis, S. Holm-Alwmark, L. C. Kah, J. Martinez-Frias, S. M. McLennan, S. Maurice, J. I. Nuñez, A. M. Ollila, P. Pilleri, J. W. RiceJr., M. Rice, J. I

    Observations from orbital spacecraft have shown that Jezero crater, Mars, contains a prominent fan-shaped body of sedimentary rock deposited at its western margin. The Perseverance rover landed in Jezero crater in February 2021. We analyze images taken by the rover in the three months after landing. The fan has outcrop faces that were invisible from orbit, which record the hydrological evolution of

  •   COVID-19 transmission dynamics underlying epidemic waves in Kenya
    Science (IF 47.728) Pub Date : 2021-10-07
    Samuel P. C. Brand, John Ojal, Rabia Aziza, Vincent Were, Emelda A. Okiro, Ivy K Kombe, Caroline Mburu, Morris Ogero, Ambrose Agweyu, George M. Warimwe, James Nyagwange, Henry Karanja, John N. Gitonga, Daisy Mugo, Sophie Uyoga, Ifedayo M. O. Adetifa, J. Anthony G. Scott, Edward Otieno, Nickson Murunga, Mark Otiende, Lynette I. Ochola-Oyier, Charles N. Agoti, George Githinji, Kadondi Kasera, Patrick

    Policy decisions on COVID-19 interventions should be informed by a local, regional and national understanding of SARS-CoV-2 transmission. Epidemic waves may result when restrictions are lifted or poorly adhered to, variants with new phenotypic properties successfully invade, or when infection spreads to susceptible sub-populations. Three COVID-19 epidemic waves have been observed in Kenya. Using a

  •   The glial framework reveals white-matter fiber architecture in human and primate brains
    Science (IF 47.728) Pub Date : 2021-10-07
    Roey Schurr, Aviv A. Mezer

    Uncovering the architecture of white-matter axons is fundamental to the study of brain networks. We developed a method for quantifying axonal orientations at ~15 micron resolution. This method is based on the common Nissl staining of postmortem histological slices. Nissl staining reveals the spatial organization of glial cells along axons. Using structure tensor analysis, we leveraged this patterned

  •   Mammalian in vitro gametogenesis
    Science (IF 47.728) Pub Date : 2021-10-01
    Mitinori Saitou, Katsuhiko Hayashi

    Germ cells differentiate into sexually dimorphic gametes, oocytes, and spermatozoa, which unite to form new individuals. Accordingly, germ cell development entails intricate regulations of genome functions for genetic and epigenetic inheritance. The past decade has seen considerable advances in in vitro gametogenesis (IVG), which aims to recreate germ cell development from pluripotent stem cells (PSCs)

  •   Decadal climate variability in the tropical Pacific: Characteristics, causes, predictability, and prospects
    Science (IF 47.728) Pub Date : 2021-10-01
    Scott Power, Matthieu Lengaigne, Antonietta Capotondi, Myriam Khodri, Jérôme Vialard, Beyrem Jebri, Eric Guilyardi, Shayne McGregor, Jong-Seong Kug, Matthew Newman, Michael J. McPhaden, Gerald Meehl, Doug Smith, Julia Cole, Julien Emile-Geay, Daniel Vimont, Andrew T. Wittenberg, Mat Collins, Geon-Il Kim, Wenju Cai, Yuko Okumura, Christine Chung, Kim M. Cobb, François Delage, Yann Y. Planton, Aaron

    Climate variability in the tropical Pacific affects global climate on a wide range of time scales. On interannual time scales, the tropical Pacific is home to the El Niño–Southern Oscillation (ENSO). Decadal variations and changes in the tropical Pacific, referred to here collectively as tropical Pacific decadal variability (TPDV), also profoundly affect the climate system. Here, we use TPDV to refer

  •   Achieving net-zero greenhouse gas emission plastics by a circular carbon economy
    Science (IF 47.728) Pub Date : 2021-10-01
    Raoul Meys, Arne Kätelhön, Marvin Bachmann, Benedikt Winter, Christian Zibunas, Sangwon Suh, André Bardow

    Mitigating life-cycle greenhouse gas emissions of plastics is perceived as energy intensive and costly. We developed a bottom-up model that represents the life cycle of 90% of global plastics to examine pathways to net-zero emission plastics. Our results show that net-zero emission plastics can be achieved by combining biomass and carbon dioxide (CO2) utilization with an effective recycling rate of

  •   High-strength scalable MXene films through bridging-induced densification
    Science (IF 47.728) Pub Date : 2021-10-01
    Sijie Wan, Xiang Li, Ying Chen, Nana Liu, Yi Du, Shixue Dou, Lei Jiang, Qunfeng Cheng

    MXenes are a growing family of two-dimensional transition metal carbides and/or nitrides that are densely stacked into macroscopically layered films and have been considered for applications such as flexible electromagnetic interference (EMI) shielding materials. However, the mechanical and electrical reliabilities of titanium carbide MXene films are affected by voids in their structure. We applied

  •   Detection and potential early warning of catastrophic flow events with regional seismic networks
    Science (IF 47.728) Pub Date : 2021-10-01
    Kristen L. Cook, Rajesh Rekapalli, Michael Dietze, Marco Pilz, Simone Cesca, N. Purnachandra Rao, D. Srinagesh, Himangshu Paul, Malte Metz, Prantik Mandal, G. Suresh, Fabrice Cotton, V. M. Tiwari, Niels Hovius

    Early warning is a critical potential tool for mitigating the impacts of large mass wasting and flood events, a major hazard in the Himalaya. We used data from a dense seismic network in Uttarakhand, India, to detect and track a fatal rockslide to mass flow to flood cascade and examine the potential for regional networks to provide early warning for extreme flow events. Detection limits of the 7 February

  •   Iron-catalyzed arene C−H hydroxylation
    Science (IF 47.728) Pub Date : 2021-10-01
    Lu Cheng, Huihui Wang, Hengrui Cai, Jie Zhang, Xu Gong, Wei Han

    The sustainable, undirected, and selective catalytic hydroxylation of arenes remains an ongoing research challenge because of the relative inertness of aryl carbon-hydrogen bonds, the higher reactivity of the phenolic products leading to over-oxidized by-products, and the frequently insufficient regioselectivity. We report that iron coordinated by a bioinspired l-cystine–derived ligand can catalyze

  •   Ultrahigh energy storage in superparaelectric relaxor ferroelectrics
    Science (IF 47.728) Pub Date : 2021-10-01
    Hao Pan, Shun Lan, Shiqi Xu, Qinghua Zhang, Hongbao Yao, Yiqian Liu, Fanqi Meng, Er-Jia Guo, Lin Gu, Di Yi, Xiao Renshaw Wang, Houbing Huang, Judith L. MacManus-Driscoll, Long-Qing Chen, Kui-Juan Jin, Ce-Wen Nan, Yuan-Hua Lin

    Electrostatic energy storage technology based on dielectrics is fundamental to advanced electronics and high-power electrical systems. Recently, relaxor ferroelectrics characterized by nanodomains have shown great promise as dielectrics with high energy density and high efficiency. We demonstrate substantial enhancements of energy storage properties in relaxor ferroelectric films with a superparaelectric

  •   Light-induced mobile factors from shoots regulate rhizobium-triggered soybean root nodulation
    Science (IF 47.728) Pub Date : 2021-10-01
    Tao Wang, Jing Guo, Yaqi Peng, Xiangguang Lyu, Bin Liu, Shiyong Sun, Xuelu Wang

    Symbiotic nitrogen fixation is an energy-expensive process, and the light available to plants has been proposed to be a primary influencer. We demonstrate that the light-induced soybean TGACG-motif binding factor 3/4 (GmSTF3/4) and FLOWERING LOCUS T (GmFTs), which move from shoots to roots, interdependently induce nodule organogenesis. Rhizobium-activated calcium- and calmodulin-dependent protein kinase

  •   The stress-sensing domain of activated IRE1α forms helical filaments in narrow ER membrane tubes
    Science (IF 47.728) Pub Date : 2021-10-01
    Ngoc-Han Tran, Stephen D. Carter, Ann De Mazière, Avi Ashkenazi, Judith Klumperman, Peter Walter, Grant J. Jensen

    The signaling network of the unfolded protein response (UPR) adjusts the protein-folding capacity of the endoplasmic reticulum (ER) according to need. The most conserved UPR sensor, IRE1α, spans the ER membrane and activates through oligomerization. IRE1α oligomers accumulate in dynamic foci. We determined the in situ structure of IRE1α foci by cryogenic correlated light and electron microscopy combined

  •   Imaging the short-lived hydroxyl-hydronium pair in ionized liquid water
    Science (IF 47.728) Pub Date : 2021-10-01
    M.-F. Lin, N. Singh, S. Liang, M. Mo, J. P. F. Nunes, K. Ledbetter, J. Yang, M. Kozina, S. Weathersby, X. Shen, A. A. Cordones, T. J. A. Wolf, C. D. Pemmaraju, M. Ihme, X. J. Wang

    The radiolysis of water is ubiquitous in nature and plays a critical role in numerous biochemical and technological applications. Although the elementary reaction pathways for ionized water have been studied, the short-lived intermediate complex and structural dynamic response after the proton transfer reaction remain poorly understood. Using a liquid-phase ultrafast electron diffraction technique

  •   Interpretation of cancer mutations using a multiscale map of protein systems
    Science (IF 47.728) Pub Date : 2021-10-01
    Fan Zheng, Marcus R. Kelly, Dana J. Ramms, Marissa L. Heintschel, Kai Tao, Beril Tutuncuoglu, John J. Lee, Keiichiro Ono, Helene Foussard, Michael Chen, Kari A. Herrington, Erica Silva, Sophie N. Liu, Jing Chen, Christopher Churas, Nicholas Wilson, Anton Kratz, Rudolf T. Pillich, Devin N. Patel, Jisoo Park, Brent Kuenzi, Michael K. Yu, Katherine Licon, Dexter Pratt, Jason F. Kreisberg, Minkyu Kim,

    A major goal of cancer research is to understand how mutations distributed across diverse genes affect common cellular systems, including multiprotein complexes and assemblies. Two challenges—how to comprehensively map such systems and how to identify which are under mutational selection—have hindered this understanding. Accordingly, we created a comprehensive map of cancer protein systems integrating

  •   A protein interaction landscape of breast cancer
    Science (IF 47.728) Pub Date : 2021-10-01
    Minkyu Kim, Jisoo Park, Mehdi Bouhaddou, Kyumin Kim, Ajda Rojc, Maya Modak, Margaret Soucheray, Michael J. McGregor, Patrick O’Leary, Denise Wolf, Erica Stevenson, Tzeh Keong Foo, Dominique Mitchell, Kari A. Herrington, Denise P. Muñoz, Beril Tutuncuoglu, Kuei-Ho Chen, Fan Zheng, Jason F. Kreisberg, Morgan E. Diolaiti, John D. Gordan, Jean-Philippe Coppé, Danielle L. Swaney, Bing Xia, Laura van ’t

    Cancers have been associated with a diverse array of genomic alterations. To help mechanistically understand such alterations in breast-invasive carcinoma, we applied affinity purification–mass spectrometry to delineate comprehensive biophysical interaction networks for 40 frequently altered breast cancer (BC) proteins, with and without relevant mutations, across three human breast cell lines. These

  •   A protein network map of head and neck cancer reveals PIK3CA mutant drug sensitivity
    Science (IF 47.728) Pub Date : 2021-10-01
    Danielle L. Swaney, Dana J. Ramms, Zhiyong Wang, Jisoo Park, Yusuke Goto, Margaret Soucheray, Neil Bhola, Kyumin Kim, Fan Zheng, Yan Zeng, Michael McGregor, Kari A. Herrington, Rachel O’Keefe, Nan Jin, Nathan K. VanLandingham, Helene Foussard, John Von Dollen, Mehdi Bouhaddou, David Jimenez-Morales, Kirsten Obernier, Jason F. Kreisberg, Minkyu Kim, Daniel E. Johnson, Natalia Jura, Jennifer R. Grandis

    We outline a framework for elucidating tumor genetic complexity through multidimensional protein-protein interaction maps and apply it to enhancing our understanding of head and neck squamous cell carcinoma. This network uncovers 771 interactions from cancer and noncancerous cell states, including WT and mutant protein isoforms. Prioritization of cancer-enriched interactions reveals a previously unidentified

  •   Microscopic evolution of doped Mott insulators from polaronic metal to Fermi liquid
    Science (IF 47.728) Pub Date : 2021-10-01
    Joannis Koepsell, Dominik Bourgund, Pimonpan Sompet, Sarah Hirthe, Annabelle Bohrdt, Yao Wang, Fabian Grusdt, Eugene Demler, Guillaume Salomon, Christian Gross, Immanuel Bloch

    The competition between antiferromagnetism and hole motion in two-dimensional Mott insulators lies at the heart of a doping-dependent transition from an anomalous metal to a conventional Fermi liquid. We observe such a crossover in Fermi-Hubbard systems on a cold-atom quantum simulator and reveal the transformation of multipoint correlations between spins and holes upon increasing doping at temperatures

  •   Endemic persistence of a highly contagious pathogen: Foot-and-mouth disease in its wildlife host
    Science (IF 47.728) Pub Date : 2021-10-01
    Anna Jolles, Erin Gorsich, Simon Gubbins, Brianna Beechler, Peter Buss, Nick Juleff, Lin-Mari de Klerk-Lorist, Francois Maree, Eva Perez-Martin, O.L. van Schalkwyk, Katherine Scott, Fuquan Zhang, Jan Medlock, Bryan Charleston

    Extremely contagious pathogens are a global biosecurity threat because of their high burden of morbidity and mortality, as well as their capacity for fast-moving epidemics that are difficult to quell. Understanding the mechanisms enabling persistence of highly transmissible pathogens in host populations is thus a central problem in disease ecology. Through a combination of experimental and theoretical

  •   Single-cell nuclear architecture across cell types in the mouse brain
    Science (IF 47.728) Pub Date : 2021-09-30
    Yodai Takei, Shiwei Zheng, Jina Yun, Sheel Shah, Nico Pierson, Jonathan White, Simone Schindler, Carsten H. Tischbirek, Guo-Cheng Yuan, Long Cai

    Diverse cell types in tissues have distinct gene expression programs, chromatin states and nuclear architectures. To correlate such multimodal information across thousands of single cells in mouse brain tissue sections, we demonstrate integrated spatial genomics, imaging thousands of genomic loci along with RNAs and epigenetic markers simultaneously in individual cells. We revealed that cell type–specific

  •   A prenylated dsRNA sensor protects against severe COVID-19
    Science (IF 47.728) Pub Date : 2021-09-28
    Arthur Wickenhagen, Elena Sugrue, Spyros Lytras, Srikeerthana Kuchi, Marko Noerenberg, Matthew L. Turnbull, Colin Loney, Vanessa Herder, Jay Allan, Innes Jarmson, Natalia Cameron-Ruiz, Margus Varjak, Rute M. Pinto, Jeffrey Y. Lee, Louisa Iselin, Natasha Palmalux, Douglas G. Stewart, Simon Swingler, Edward J. D. Greenwood, Thomas W. M. Crozier, Quan Gu, Emma L. Davies, Sara Clohisey, Bo Wang, Fabio

    Inherited genetic factors can influence the severity of COVID-19, but the molecular explanation underpinning a genetic association is often unclear. Intracellular antiviral defenses can inhibit the replication of viruses and reduce disease severity. To better understand the antiviral defenses relevant to COVID-19, we used interferon-stimulated gene (ISG) expression screening to reveal that OAS1, through

  •   Discovery and implications of polygenicity of common diseases
    Science (IF 47.728) Pub Date : 2021-09-24
    Peter M. Visscher, Loic Yengo, Nancy J. Cox, Naomi R. Wray

    The sequencing of the human genome has allowed the study of the genetic architecture of common diseases: the number of genomic variants that contribute to risk of disease and their joint frequency and effect size distribution. Common diseases are polygenic, with many loci contributing to phenotype, and the cumulative burden of risk alleles determines individual risk in conjunction with environmental

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