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  •   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

  •   Nuclear pores dilate and constrict in cellulo
    Science (IF 47.728) Pub Date : 2021-11-11
    Christian E. Zimmerli, Matteo Allegretti, Vasileios Rantos, Sara K. Goetz, Agnieszka Obarska-Kosinska, Ievgeniia Zagoriy, Aliaksandr Halavatyi, Gerhard Hummer, Julia Mahamid, Jan Kosinski, Martin Beck

    In eukaryotic cells, nuclear pore complexes (NPCs) fuse the inner and outer nuclear membranes and mediate nucleocytoplasmic exchange. They are made of 30 different nucleoporins and form a cylindrical architecture around an aqueous central channel. This architecture is highly dynamic in space and time. Variations in NPC diameter have been reported, but the physiological circumstances and the molecular

  •   Molecular basis of immune evasion by the Delta and Kappa SARS-CoV-2 variants
    Science (IF 47.728) Pub Date : 2021-11-09
    Matthew McCallum, Alexandra C. Walls, Kaitlin R. Sprouse, John E. Bowen, Laura E. Rosen, Ha V. Dang, Anna De Marco, Nicholas Franko, Sasha W. Tilles, Jennifer Logue, Marcos C. Miranda, Margaret Ahlrichs, Lauren Carter, Gyorgy Snell, Matteo Samuele Pizzuto, Helen Y. Chu, Wesley C. Van Voorhis, Davide Corti, David Veesler

    Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission leads to the emergence of variants, including the B.1.617.2 (Delta) variant of concern which is causing a new wave of infections and has become globally dominant. We show that these variants dampen the in vitro potency of vaccine-elicited serum neutralizing antibodies and provide a structural framework for describing their immune

  •   Subatomic species transport through atomically thin membranes: Present and future applications
    Science (IF 47.728) Pub Date : 2021-11-05
    Piran R. Kidambi, Pavan Chaturvedi, Nicole K. Moehring

    Atomically thin two-dimensional materials present opportunities for selective transport of subatomic species. The pristine lattice of monolayer graphene and hexagonal boron nitride, although impermeable to helium atoms, allows for transmission of electrons and permits transport of thermal protons and its isotopes. We discuss advances in selective subatomic species transport through atomically thin

  •   Radiocarbon: A key tracer for studying Earth’s dynamo, climate system, carbon cycle, and Sun
    Science (IF 47.728) Pub Date : 2021-11-05
    T. J. Heaton, E. Bard, C. Bronk Ramsey, M. Butzin, P. Köhler, R. Muscheler, P. J. Reimer, L. Wacker

    Radiocarbon (14C), as a consequence of its production in the atmosphere and subsequent dispersal through the carbon cycle, is a key tracer for studying the Earth system. Knowledge of past 14C levels improves our understanding of climate processes, the Sun, the geodynamo, and the carbon cycle. Recently updated radiocarbon calibration curves (IntCal20, SHCal20, and Marine20) provide unprecedented accuracy

  •   Resistance to inflammation underlies enhanced fitness in clonal hematopoiesis
    Science (IF 47.728) Pub Date : 2021-11-05
    S. Avagyan, J. E. Henninger, W. P. Mannherz, M. Mistry, J. Yoon, S. Yang, M. C. Weber, J. L. Moore, L. I. Zon

    Clonal hematopoiesis results from enhanced fitness of a mutant hematopoietic stem and progenitor cell (HSPC), but how such clones expand is unclear. We developed a technique that combines mosaic mutagenesis with color labeling of HSPCs to study how acquired mutations affect clonal fitness in a native environment. Mutations in clonal hematopoiesis–associated genes such as asxl1 promoted clonal dominance

  •   Enantioselective catalytic 1,2-boronate rearrangements
    Science (IF 47.728) Pub Date : 2021-11-05
    Hayden A. Sharma, Jake Z. Essman, Eric N. Jacobsen

    A strategy that facilitates the construction of a wide variety of trisubstituted stereocenters through a catalytically accessed common chiral intermediate could prove highly enabling for the field of synthetic chemistry. We report the discovery of enantioselective, catalytic 1,2-boronate rearrangements for the synthesis of α-chloro pinacol boronic esters from readily available boronic esters and dichloromethane

  •   Carbonyl 1,2-transposition through triflate-mediated α-amination
    Science (IF 47.728) Pub Date : 2021-11-05
    Zhao Wu, Xiaolong Xu, Jianchun Wang, Guangbin Dong

    To date, it remains challenging to selectively migrate a carbonyl oxygen within a given molecular scaffold, especially to an adjacent carbon. In this work, we describe a simple one- or two-pot protocol that transposes a ketone to the vicinal carbon. This approach first converts the ketone to the corresponding alkenyl triflate, which can then undergo the palladium- and norbornene-catalyzed regioselective

  •   Scalable Birch reduction with lithium and ethylenediamine in tetrahydrofuran
    Science (IF 47.728) Pub Date : 2021-11-05
    James Burrows, Shogo Kamo, Kazunori Koide

    The Birch reduction dearomatizes arenes into 1,4-cyclohexadienes. Despite substantial efforts devoted to avoiding ammonia and cryogenic conditions, the traditional, cumbersome, and dangerous procedure remains the standard. The Benkeser reduction with lithium in ethylenediamine converts arenes to a mixture of cyclohexenes and cyclohexanes; this is operationally easier than the Birch reduction but does

  •   Convergence of adenosine and GABA signaling for synapse stabilization during development
    Science (IF 47.728) Pub Date : 2021-11-05
    Ferran Gomez-Castro, Stefania Zappettini, Jessica C. Pressey, Carla G. Silva, Marion Russeau, Nicolas Gervasi, Marta Figueiredo, Claire Montmasson, Marianne Renner, Paula M. Canas, Francisco Q. Gonçalves, Sofia Alçada-Morais, Eszter Szabó, Ricardo J. Rodrigues, Paula Agostinho, Angelo R. Tomé, Ghislaine Caillol, Olivier Thoumine, Xavier Nicol, Christophe Leterrier, Rafael Lujan, Shiva K. Tyagarajan

    During development, neural circuit formation requires the stabilization of active γ-aminobutyric acid–mediated (GABAergic) synapses and the elimination of inactive ones. Here, we demonstrate that, although the activation of postsynaptic GABA type A receptors (GABAARs) and adenosine A2A receptors (A2ARs) stabilizes GABAergic synapses, only A2AR activation is sufficient. Both GABAAR- and A2AR-dependent

  •   Profiling cellular diversity in sponges informs animal cell type and nervous system evolution
    Science (IF 47.728) Pub Date : 2021-11-05
    Jacob M. Musser, Klaske J. Schippers, Michael Nickel, Giulia Mizzon, Andrea B. Kohn, Constantin Pape, Paolo Ronchi, Nikolaos Papadopoulos, Alexander J. Tarashansky, Jörg U. Hammel, Florian Wolf, Cong Liang, Ana Hernández-Plaza, Carlos P. Cantalapiedra, Kaia Achim, Nicole L. Schieber, Leslie Pan, Fabian Ruperti, Warren R. Francis, Sergio Vargas, Svenja Kling, Maike Renkert, Maxim Polikarpov, Gleb Bourenkov

    The evolutionary origin of metazoan cell types such as neurons and muscles is not known. Using whole-body single-cell RNA sequencing in a sponge, an animal without nervous system and musculature, we identified 18 distinct cell types. These include nitric oxide–sensitive contractile pinacocytes, amoeboid phagocytes, and secretory neuroid cells that reside in close contact with digestive choanocytes

  •   Modular polyketide synthase contains two reaction chambers that operate asynchronously
    Science (IF 47.728) Pub Date : 2021-11-05
    Saket R. Bagde, Irimpan I. Mathews, J. Christopher Fromme, Chu-Young Kim

    Type I modular polyketide synthases are homodimeric multidomain assembly line enzymes that synthesize a variety of polyketide natural products by performing polyketide chain extension and β-keto group modification reactions. We determined the 2.4-angstrom-resolution x-ray crystal structure and the 3.1-angstrom-resolution cryo–electron microscopy structure of the Lsd14 polyketide synthase, stalled at

  •   Mapping the catalytic conformations of an assembly-line polyketide synthase module
    Science (IF 47.728) Pub Date : 2021-11-05
    Dillon P. Cogan, Kaiming Zhang, Xiuyuan Li, Shanshan Li, Grigore D. Pintilie, Soung-Hun Roh, Charles S. Craik, Wah Chiu, Chaitan Khosla

    Assembly-line polyketide synthases, such as the 6-deoxyerythronolide B synthase (DEBS), are large enzyme factories prized for their ability to produce specific and complex polyketide products. By channeling protein-tethered substrates across multiple active sites in a defined linear sequence, these enzymes facilitate programmed small-molecule syntheses that could theoretically be harnessed to access

  •   Abating ammonia is more cost-effective than nitrogen oxides for mitigating PM2.5 air pollution
    Science (IF 47.728) Pub Date : 2021-11-05
    Baojing Gu, Lin Zhang, Rita Van Dingenen, Massimo Vieno, Hans JM Van Grinsven, Xiuming Zhang, Shaohui Zhang, Youfan Chen, Sitong Wang, Chenchen Ren, Shilpa Rao, Mike Holland, Wilfried Winiwarter, Deli Chen, Jianming Xu, Mark A. Sutton

    Fine particulate matter (PM2.5, particles with a mass median aerodynamic diameter of less than 2.5 micrometers) in the atmosphere is associated with severe negative impacts on human health, and the gases sulfur dioxide, nitrogen oxides, and ammonia are the main PM2.5 precursors. However, their contribution to global health impacts has not yet been analyzed. Here, we show that nitrogen accounted for

  •   Small proline-rich protein 2A is a gut bactericidal protein deployed during helminth infection
    Science (IF 47.728) Pub Date : 2021-11-05
    Zehan Hu, Chenlu Zhang, Luis Sifuentes-Dominguez, Christina M. Zarek, Daniel C. Propheter, Zheng Kuang, Yuhao Wang, Mihir Pendse, Kelly A. Ruhn, Brian Hassell, Cassie L. Behrendt, Bo Zhang, Prithvi Raj, Tamia A. Harris-Tryon, Tiffany A. Reese, Lora V. Hooper

    A diverse group of antimicrobial proteins (AMPs) helps protect the mammalian intestine from varied microbial challenges. We show that small proline-rich protein 2A (SPRR2A) is an intestinal antibacterial protein that is phylogenetically unrelated to previously discovered mammalian AMPs. In this study, SPRR2A was expressed in Paneth cells and goblet cells and selectively killed Gram-positive bacteria

  •   A surface-promoted redox reaction occurs spontaneously on solvating inorganic aerosol surfaces
    Science (IF 47.728) Pub Date : 2021-11-05
    Xiangrui Kong, Dimitri Castarède, Erik S. Thomson, Anthony Boucly, Luca Artiglia, Markus Ammann, Ivan Gladich, Jan B. C. Pettersson

    A surface-promoted sulfate-reducing ammonium oxidation reaction was discovered to spontaneously take place on common inorganic aerosol surfaces undergoing solvation. Several key intermediate species—including elemental sulfur (S0), bisulfide (HS−), nitrous acid (HONO), and aqueous ammonia [NH3(aq)]—were identified as reaction components associated with the solvation process. Depth profiles of relative

  •   Sabatier principle of metal-support interaction for design of ultrastable metal nanocatalysts
    Science (IF 47.728) Pub Date : 2021-11-04
    Sulei Hu, Wei-Xue Li

    The stability of supported nanocatalysts is crucial to meet environmental and energy challenges and necessitates fundamental theory to relieve trial-and-error experimentation and accelerate lab-to-fab translation. Here, we report a Sabatier principle of metal-support interaction for stabilizing metal nanocatalysts against sintering based on the kinetic simulations of 323 metal-support pairs using scaling

  •   Many-body-localized discrete time crystal with a programmable spin-based quantum simulator
    Science (IF 47.728) Pub Date : 2021-11-04
    J. Randall, C. E. Bradley, F. V. van der Gronden, A. Galicia, M. H. Abobeih, M. Markham, D. J. Twitchen, F. Machado, N. Y. Yao, T. H. Taminiau

    The discrete time crystal (DTC) is a non-equilibrium phase of matter that spontaneously breaks time-translation symmetry. Disorder-induced many-body-localization can stabilize the DTC phase by breaking ergodicity and preventing thermalization. Here, we observe the hallmark signatures of the many-body-localized DTC using a novel quantum simulation platform based on individually controllable 13C nuclear

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