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  • Reframing strategic, managed retreat for transformative climate adaptation
    Science (IF 41.845) Pub Date : 2021-06-18
    Katharine J. Mach, A. R. Siders

    Human societies will transform to address climate change and other stressors. How they choose to transform will depend on what societal values they prioritize. Managed retreat can play a powerful role in expanding the range of possible futures that transformation could achieve and in articulating the values that shape those futures. Consideration of retreat raises tensions about what losses are unacceptable

  • Structural basis of ribosomal frameshifting during translation of the SARS-CoV-2 RNA genome
    Science (IF 41.845) Pub Date : 2021-06-18
    Pramod R. Bhatt, Alain Scaiola, Gary Loughran, Marc Leibundgut, Annika Kratzel, Romane Meurs, René Dreos, Kate M. O’Connor, Angus McMillan, Jeffrey W. Bode, Volker Thiel, David Gatfield, John F. Atkins, Nenad Ban

    Programmed ribosomal frameshifting is a key event during translation of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA genome that allows synthesis of the viral RNA-dependent RNA polymerase and downstream proteins. Here, we present the cryo–electron microscopy structure of a translating mammalian ribosome primed for frameshifting on the viral RNA. The viral RNA adopts a pseudoknot

  • Resolving multifrequential oscillations and nanoscale interfacet communication in single-particle catalysis
    Science (IF 41.845) Pub Date : 2021-06-18
    Y. Suchorski, J. Zeininger, S. Buhr, M. Raab, M. Stöger-Pollach, J. Bernardi, H. Grönbeck, G. Rupprechter

    In heterogeneous catalysis research, the reactivity of individual nanofacets of single particles is typically not resolved. We applied in situ field electron microscopy to the apex of a curved rhodium crystal (radius of 650 nanometers), providing high spatial (~2 nanometers) and time resolution (~2 milliseconds) of oscillatory catalytic hydrogen oxidation, to image adsorbed species and reaction fronts

  • Geometric squeezing into the lowest Landau level
    Science (IF 41.845) Pub Date : 2021-06-18
    Richard J. Fletcher, Airlia Shaffer, Cedric C. Wilson, Parth B. Patel, Zhenjie Yan, Valentin Crépel, Biswaroop Mukherjee, Martin W. Zwierlein

    The equivalence between particles under rotation and charged particles in a magnetic field relates phenomena as diverse as spinning atomic nuclei, weather patterns, and the quantum Hall effect. For such systems, quantum mechanics dictates that translations along different directions do not commute, implying a Heisenberg uncertainty relation between spatial coordinates. We implement squeezing of this

  • Imaging orbital ferromagnetism in a moiré Chern insulator
    Science (IF 41.845) Pub Date : 2021-06-18
    C. L. Tschirhart, M. Serlin, H. Polshyn, A. Shragai, Z. Xia, J. Zhu, Y. Zhang, K. Watanabe, T. Taniguchi, M. E. Huber, A. F. Young

    Electrons in moiré flat band systems can spontaneously break time-reversal symmetry, giving rise to a quantized anomalous Hall effect. In this study, we use a superconducting quantum interference device to image stray magnetic fields in twisted bilayer graphene aligned to hexagonal boron nitride. We find a magnetization of several Bohr magnetons per charge carrier, demonstrating that the magnetism

  • Lead halide–templated crystallization of methylamine-free perovskite for efficient photovoltaic modules
    Science (IF 41.845) Pub Date : 2021-06-18
    Tongle Bu, Jing Li, Hengyi Li, Congcong Tian, Jie Su, Guoqing Tong, Luis K. Ono, Chao Wang, Zhipeng Lin, Nianyao Chai, Xiao-Li Zhang, Jingjing Chang, Jianfeng Lu, Jie Zhong, Wenchao Huang, Yabing Qi, Yi-Bing Cheng, Fuzhi Huang

    Upscaling efficient and stable perovskite layers is one of the most challenging issues in the commercialization of perovskite solar cells. Here, a lead halide–templated crystallization strategy is developed for printing formamidinium (FA)–cesium (Cs) lead triiodide perovskite films. High-quality large-area films are achieved through controlled nucleation and growth of a lead halide•N-methyl-2-pyrrolidone

  • Approaching the motional ground state of a 10-kg object
    Science (IF 41.845) Pub Date : 2021-06-18
    Chris Whittle, Evan D. Hall, Sheila Dwyer, Nergis Mavalvala, Vivishek Sudhir, R. Abbott, A. Ananyeva, C. Austin, L. Barsotti, J. Betzwieser, C. D. Blair, A. F. Brooks, D. D. Brown, A. Buikema, C. Cahillane, J. C. Driggers, A. Effler, A. Fernandez-Galiana, P. Fritschel, V. V. Frolov, T. Hardwick, M. Kasprzack, K. Kawabe, N. Kijbunchoo, J. S. Kissel, G. L. Mansell, F. Matichard, L. McCuller, T. McRae

    The motion of a mechanical object, even a human-sized object, should be governed by the rules of quantum mechanics. Coaxing them into a quantum state is, however, difficult because the thermal environment masks any quantum signature of the object’s motion. The thermal environment also masks the effects of proposed modifications of quantum mechanics at large mass scales. We prepared the center-of-mass

  • Clonal analysis of immunodominance and cross-reactivity of the CD4 T cell response to SARS-CoV-2
    Science (IF 41.845) Pub Date : 2021-06-18
    Jun Siong Low, Daniela Vaqueirinho, Federico Mele, Mathilde Foglierini, Josipa Jerak, Michela Perotti, David Jarrossay, Sandra Jovic, Laurent Perez, Rosalia Cacciatore, Tatiana Terrot, Alessandra Franzetti Pellanda, Maira Biggiogero, Christian Garzoni, Paolo Ferrari, Alessandro Ceschi, Antonio Lanzavecchia, Federica Sallusto, Antonino Cassotta

    The identification of CD4+ T cell epitopes is instrumental for the design of subunit vaccines for broad protection against coronaviruses. Here, we demonstrate in COVID-19–recovered individuals a robust CD4+ T cell response to naturally processed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike (S) protein and nucleoprotein (N), including effector, helper, and memory T cells. By characterizing

  • Transition to marine ice cliff instability controlled by ice thickness gradients and velocity
    Science (IF 41.845) Pub Date : 2021-06-18
    J. N. Bassis, B. Berg, A. J. Crawford, D. I. Benn

    Portions of ice sheets grounded deep beneath sea level can disintegrate if tall ice cliffs at the ice-ocean boundary start to collapse under their own weight. This process, called marine ice cliff instability, could lead to catastrophic retreat of sections of West Antarctica on decadal-to-century time scales. Here we use a model that resolves flow and failure of ice to show that dynamic thinning can

  • Who do we invent for? Patents by women focus more on women’s health, but few women get to invent
    Science (IF 41.845) Pub Date : 2021-06-18
    Rembrand Koning, Sampsa Samila, John-Paul Ferguson

    Women engage in less commercial patenting and invention than do men, which may affect what is invented. Using text analysis of all U.S. biomedical patents filed from 1976 through 2010, we found that patents with all-female inventor teams are 35% more likely than all-male teams to focus on women’s health. This effect holds over decades and across research areas. We also found that female researchers

  • NF-κB dynamics determine the stimulus specificity of epigenomic reprogramming in macrophages
    Science (IF 41.845) Pub Date : 2021-06-18
    Quen J. Cheng, Sho Ohta, Katherine M. Sheu, Roberto Spreafico, Adewunmi Adelaja, Brooks Taylor, Alexander Hoffmann

    The epigenome of macrophages can be reprogrammed by extracellular cues, but the extent to which different stimuli achieve this is unclear. Nuclear factor κB (NF-κB) is a transcription factor that is activated by all pathogen-associated stimuli and can reprogram the epigenome by activating latent enhancers. However, we show that NF-κB does so only in response to a subset of stimuli. This stimulus specificity

  • Echolocation in soft-furred tree mice
    Science (IF 41.845) Pub Date : 2021-06-18
    Kai He, Qi Liu, Dong-Ming Xu, Fei-Yan Qi, Jing Bai, Shui-Wang He, Peng Chen, Xin Zhou, Wan-Zhi Cai, Zhong-Zheng Chen, Zhen Liu, Xue-Long Jiang, Peng Shi

    Echolocation is the use of reflected sound to sense features of the environment. Here, we show that soft-furred tree mice (Typhlomys) echolocate based on multiple independent lines of evidence. Behavioral experiments show that these mice can locate and avoid obstacles in darkness using hearing and ultrasonic pulses. The proximal portion of their stylohyal bone fuses with the tympanic bone, a form previously

  • Common genetic variation influencing human white matter microstructure
    Science (IF 41.845) Pub Date : 2021-06-18
    Bingxin Zhao, Tengfei Li, Yue Yang, Xifeng Wang, Tianyou Luo, Yue Shan, Ziliang Zhu, Di Xiong, Mads E. Hauberg, Jaroslav Bendl, John F. Fullard, Panagiotis Roussos, Yun Li, Jason L. Stein, Hongtu Zhu

    Brain regions communicate with each other through tracts of myelinated axons, commonly referred to as white matter. We identified common genetic variants influencing white matter microstructure using diffusion magnetic resonance imaging of 43,802 individuals. Genome-wide association analysis identified 109 associated loci, 30 of which were detected by tract-specific functional principal components

  • Neutrophils self-limit swarming to contain bacterial growth in vivo
    Science (IF 41.845) Pub Date : 2021-06-18
    Korbinian Kienle, Katharina M. Glaser, Sarah Eickhoff, Michael Mihlan, Konrad Knöpper, Eduardo Reátegui, Maximilian W. Epple, Matthias Gunzer, Ralf Baumeister, Teresa K. Tarrant, Ronald N. Germain, Daniel Irimia, Wolfgang Kastenmüller, Tim Lämmermann

    Neutrophils communicate with each other to form swarms in infected organs. Coordination of this population response is critical for the elimination of bacteria and fungi. Using transgenic mice, we found that neutrophils have evolved an intrinsic mechanism to self-limit swarming and avoid uncontrolled aggregation during inflammation. G protein–coupled receptor (GPCR) desensitization acts as a negative

  • Plant “helper” immune receptors are Ca2+-permeable nonselective cation channels
    Science (IF 41.845) Pub Date : 2021-06-17
    Pierre Jacob, Nak Hyun Kim, Feihua Wu, Farid El-Kasmi, Yuan Chi, William G. Walton, Oliver J. Furzer, Adam D. Lietzan, Sruthi Sunil, Korina Kempthorn, Matthew R. Redinbo, Zhen-Ming Pei, Li Wan, Jeffery L. Dangl

    Plant nucleotide-binding leucine-rich repeat receptors (NLRs) regulate immunity and cell death. In Arabidopsis, a subfamily of “helper” NLRs are required by many “sensor” NLRs. Active NRG1.1 oligomerized, was enriched in plasma membrane puncta and conferred cytoplasmic Ca2+ influx in plant and human cells. NRG1.1-dependent Ca2+ influx and cell death were sensitive to Ca2+ channel blockers and were

  • Inhibitors of bacterial H2S biogenesis targeting antibiotic resistance and tolerance
    Science (IF 41.845) Pub Date : 2021-06-11
    Konstantin Shatalin, Ashok Nuthanakanti, Abhishek Kaushik, Dmitry Shishov, Alla Peselis, Ilya Shamovsky, Bibhusita Pani, Mirna Lechpammer, Nikita Vasilyev, Elena Shatalina, Dmitri Rebatchouk, Alexander Mironov, Peter Fedichev, Alexander Serganov, Evgeny Nudler

    Emergent resistance to all clinical antibiotics calls for the next generation of therapeutics. Here we report an effective antimicrobial strategy targeting the bacterial hydrogen sulfide (H2S)–mediated defense system. We identified cystathionine γ-lyase (CSE) as the primary generator of H2S in two major human pathogens, Staphylococcus aureus and Pseudomonas aeruginosa, and discovered small molecules

  • Cell size controlled in plants using DNA content as an internal scale
    Science (IF 41.845) Pub Date : 2021-06-11
    Marco D’Ario, Rafael Tavares, Katharina Schiessl, Bénédicte Desvoyes, Crisanto Gutierrez, Martin Howard, Robert Sablowski

    How eukaryotic cells assess and maintain sizes specific for their species and cell type remains unclear. We show that in the Arabidopsis shoot stem cell niche, cell size variability caused by asymmetric divisions is corrected by adjusting the growth period before DNA synthesis. KIP-related protein 4 (KRP4) inhibits progression to DNA synthesis and associates with mitotic chromosomes. The F BOX-LIKE

  • Spatiotemporal imaging of 2D polariton wave packet dynamics using free electrons
    Science (IF 41.845) Pub Date : 2021-06-11
    Yaniv Kurman, Raphael Dahan, Hanan Herzig Sheinfux, Kangpeng Wang, Michael Yannai, Yuval Adiv, Ori Reinhardt, Luiz H. G. Tizei, Steffi Y. Woo, Jiahan Li, James H. Edgar, Mathieu Kociak, Frank H. L. Koppens, Ido Kaminer

    Coherent optical excitations in two-dimensional (2D) materials, 2D polaritons, can generate a plethora of optical phenomena that arise from the extraordinary dispersion relations that do not exist in regular materials. Probing of the dynamical phenomena of 2D polaritons requires simultaneous spatial and temporal imaging capabilities and could reveal unknown coherent optical phenomena in 2D materials

  • Nitrogen reduction to ammonia at high efficiency and rates based on a phosphonium proton shuttle
    Science (IF 41.845) Pub Date : 2021-06-11
    Bryan H. R. Suryanto, Karolina Matuszek, Jaecheol Choi, Rebecca Y. Hodgetts, Hoang-Long Du, Jacinta M. Bakker, Colin S. M. Kang, Pavel V. Cherepanov, Alexandr N. Simonov, Douglas R. MacFarlane

    Ammonia (NH3) is a globally important commodity for fertilizer production, but its synthesis by the Haber-Bosch process causes substantial emissions of carbon dioxide. Alternative, zero-carbon emission NH3 synthesis methods being explored include the promising electrochemical lithium-mediated nitrogen reduction reaction, which has nonetheless required sacrificial sources of protons. In this study,

  • Observation of a prethermal discrete time crystal
    Science (IF 41.845) Pub Date : 2021-06-11
    A. Kyprianidis, F. Machado, W. Morong, P. Becker, K. S. Collins, D. V. Else, L. Feng, P. W. Hess, C. Nayak, G. Pagano, N. Y. Yao, C. Monroe

    Extending the framework of statistical physics to the nonequilibrium setting has led to the discovery of previously unidentified phases of matter, often catalyzed by periodic driving. However, preventing the runaway heating that is associated with driving a strongly interacting quantum system remains a challenge in the investigation of these newly discovered phases. In this work, we utilize a trapped-ion

  • Very weak bonds to artificial atoms formed by quantum corrals
    Science (IF 41.845) Pub Date : 2021-06-11
    Fabian Stilp, Andreas Bereczuk, Julian Berwanger, Nadine Mundigl, Klaus Richter, Franz J. Giessibl

    We explored the bonding properties of the quantum corral (a circle of 48 iron atoms placed on a copper surface) reported by Crommie et al. in 1993, along with variants, as an artificial atom using an atomic force microscope (AFM). The original corral geometry confines 102 electrons to 28 discrete energy states, and we found that these states can form a bond to the front atom of the AFM with an energy

  • Spiral morphology in an intensely star-forming disk galaxy more than 12 billion years ago
    Science (IF 41.845) Pub Date : 2021-06-11
    Takafumi Tsukui, Satoru Iguchi

    Spiral galaxies have distinct internal structures, including a stellar bulge, a disk, and spiral arms. It is unknown when in cosmic history these structures formed. In this study, we analyzed observations of BRI 1335–0417, an intensely star-forming galaxy in the distant Universe, at a redshift of 4.41. The [C ii] gas kinematics shows a steep velocity rise near the galaxy center and has a two-armed

  • Release of stem cells from quiescence reveals gliogenic domains in the adult mouse brain
    Science (IF 41.845) Pub Date : 2021-06-11
    Ana C. Delgado, Angel R. Maldonado-Soto, Violeta Silva-Vargas, Dogukan Mizrak, Thomas von Känel, Kelly R. Tan, Alex Paul, Aviv Madar, Henar Cuervo, Jan Kitajewski, Chyuan-Sheng Lin, Fiona Doetsch

    Quiescent neural stem cells (NSCs) in the adult mouse ventricular-subventricular zone (V-SVZ) undergo activation to generate neurons and some glia. Here we show that platelet-derived growth factor receptor beta (PDGFRβ) is expressed by adult V-SVZ NSCs that generate olfactory bulb interneurons and glia. Selective deletion of PDGFRβ in adult V-SVZ NSCs leads to their release from quiescence, uncovering

  • Using large-scale experiments and machine learning to discover theories of human decision-making
    Science (IF 41.845) Pub Date : 2021-06-11
    Joshua C. Peterson, David D. Bourgin, Mayank Agrawal, Daniel Reichman, Thomas L. Griffiths

    Predicting and understanding how people make decisions has been a long-standing goal in many fields, with quantitative models of human decision-making informing research in both the social sciences and engineering. We show how progress toward this goal can be accelerated by using large datasets to power machine-learning algorithms that are constrained to produce interpretable psychological theories

  • Substrate and product complexes reveal mechanisms of Hedgehog acylation by HHAT
    Science (IF 41.845) Pub Date : 2021-06-11
    Yiyang Jiang, Thomas L. Benz, Stephen B. Long

    Hedgehog proteins govern crucial developmental steps in animals and drive certain human cancers. Before they can function as signaling molecules, Hedgehog precursor proteins must undergo amino-terminal palmitoylation by Hedgehog acyltransferase (HHAT). We present cryo–electron microscopy structures of human HHAT in complex with its palmitoyl–coenzyme A substrate and of a product complex with a palmitoylated

  • Evolution of a virus-like architecture and packaging mechanism in a repurposed bacterial protein
    Science (IF 41.845) Pub Date : 2021-06-11
    Stephan Tetter, Naohiro Terasaka, Angela Steinauer, Richard J. Bingham, Sam Clark, Andrew J. P. Scott, Nikesh Patel, Marc Leibundgut, Emma Wroblewski, Nenad Ban, Peter G. Stockley, Reidun Twarock, Donald Hilvert

    Viruses are ubiquitous pathogens of global impact. Prompted by the hypothesis that their earliest progenitors recruited host proteins for virion formation, we have used stringent laboratory evolution to convert a bacterial enzyme that lacks affinity for nucleic acids into an artificial nucleocapsid that efficiently packages and protects multiple copies of its own encoding messenger RNA. Revealing remarkable

  • Nicotinamide mononucleotide increases muscle insulin sensitivity in prediabetic women
    Science (IF 41.845) Pub Date : 2021-06-11
    Mihoko Yoshino, Jun Yoshino, Brandon D. Kayser, Gary J. Patti, Michael P. Franczyk, Kathryn F. Mills, Miriam Sindelar, Terri Pietka, Bruce W. Patterson, Shin-Ichiro Imai, Samuel Klein

    In rodents, obesity and aging impair nicotinamide adenine dinucleotide (NAD+) biosynthesis, which contributes to metabolic dysfunction. Nicotinamide mononucleotide (NMN) availability is a rate-limiting factor in mammalian NAD+ biosynthesis. We conducted a 10-week, randomized, placebo-controlled, double-blind trial to evaluate the effect of NMN supplementation on metabolic function in postmenopausal

  • The world of two-dimensional carbides and nitrides (MXenes)
    Science (IF 41.845) Pub Date : 2021-06-11
    Armin VahidMohammadi, Johanna Rosen, Yury Gogotsi

    A decade after the first report, the family of two-dimensional (2D) carbides and nitrides (MXenes) includes structures with three, five, seven, or nine layers of atoms in an ordered or solid solution form. Dozens of MXene compositions have been produced, resulting in MXenes with mixed surface terminations. MXenes have shown useful and tunable electronic, optical, mechanical, and electrochemical properties

  • Analysis of multispectral imaging with the AstroPath platform informs efficacy of PD-1 blockade
    Science (IF 41.845) Pub Date : 2021-06-11
    Sneha Berry, Nicolas A. Giraldo, Benjamin F. Green, Tricia R. Cottrell, Julie E. Stein, Elizabeth L. Engle, Haiying Xu, Aleksandra Ogurtsova, Charles Roberts, Daphne Wang, Peter Nguyen, Qingfeng Zhu, Sigfredo Soto-Diaz, Jose Loyola, Inbal B. Sander, Pok Fai Wong, Shlomit Jessel, Joshua Doyle, Danielle Signer, Richard Wilton, Jeffrey S. Roskes, Margaret Eminizer, Seyoun Park, Joel C. Sunshine, Elizabeth

    Next-generation tissue-based biomarkers for immunotherapy will likely include the simultaneous analysis of multiple cell types and their spatial interactions, as well as distinct expression patterns of immunoregulatory molecules. Here, we introduce a comprehensive platform for multispectral imaging and mapping of multiple parameters in tumor tissue sections with high-fidelity single-cell resolution

  • Exit time as a measure of ecological resilience
    Science (IF 41.845) Pub Date : 2021-06-11
    Babak M. S. Arani, Stephen R. Carpenter, Leo Lahti, Egbert H. van Nes, Marten Scheffer

    Ecological resilience is the magnitude of the largest perturbation from which a system can still recover to its original state. However, a transition into another state may often be invoked by a series of minor synergistic perturbations rather than a single big one. We show how resilience can be estimated in terms of average life expectancy, accounting for this natural regime of variability. We use

  • Time-resolved structured illumination microscopy reveals key principles of Xist RNA spreading
    Science (IF 41.845) Pub Date : 2021-06-11
    Lisa Rodermund, Heather Coker, Roel Oldenkamp, Guifeng Wei, Joseph Bowness, Bramman Rajkumar, Tatyana Nesterova, David Miguel Susano Pinto, Lothar Schermelleh, Neil Brockdorff

    X-inactive specific transcript (Xist) RNA directs the process of X chromosome inactivation in mammals by spreading in cis along the chromosome from which it is transcribed and recruiting chromatin modifiers to silence gene transcription. To elucidate mechanisms of Xist RNA cis-confinement, we established a sequential dual-color labeling, super-resolution imaging approach to trace individual Xist RNA

  • A massive rock and ice avalanche caused the 2021 disaster at Chamoli, Indian Himalaya
    Science (IF 41.845) Pub Date : 2021-06-10
    D. H. Shugar, M. Jacquemart, D. Shean, S. Bhushan, K. Upadhyay, A. Sattar, W. Schwanghart, S. McBride, M. Van Wyk de Vries, M. Mergili, A. Emmer, C. Deschamps-Berger, M. McDonnell, R. Bhambri, S. Allen, E. Berthier, J. L. Carrivick, J. J. Clague, M. Dokukin, S. A. Dunning, H. Frey, S. Gascoin, U. K. Haritashya, C. Huggel, A. Kääb, J. S. Kargel, J. L. Kavanaugh, P. Lacroix, D. Petley, S. Rupper, M.

    On 7 Feb 2021, a catastrophic mass flow descended the Ronti Gad, Rishiganga, and Dhauliganga valleys in Chamoli, Uttarakhand, India, causing widespread devastation and severely damaging two hydropower projects. Over 200 people were killed or are missing. Our analysis of satellite imagery, seismic records, numerical model results, and eyewitness videos reveals that ~27x106 m3 of rock and glacier ice

  • Glaciohydrology of the Himalaya-Karakoram
    Science (IF 41.845) Pub Date : 2021-06-10
    Mohd. Farooq Azam, Jeffrey S. Kargel, Joseph M. Shea, Santosh Nepal, Umesh K. Haritashya, Smriti Srivastava, Fabien Maussion, Nuzhat Qazi, Pierre Chevallier, A. P. Dimri, Anil V. Kulkarni, J. Graham Cogley, Isa M. Bahuguna

    Understanding the response of Himalayan-Karakoram (HK) rivers to climate change is crucial for ~1 billion people who partly depend on these water resources. Policymakers tasked with the sustainable water resources management for agriculture, hydropower, drinking, sanitation, and hazards require an assessment of rivers’ current status and potential future changes. This review demonstrates that glacier

  • Interfacial ferroelectricity by van der Waals sliding
    Science (IF 41.845) Pub Date : 2021-06-10
    M. Vizner Stern, Y. Waschitz, W. Cao, I. Nevo, K. Watanabe, T. Taniguchi, E. Sela, M. Urbakh, O. Hod, M. Ben Shalom

    Despite their partial ionic nature, many layered diatomic crystals avoid internal electric polarization by forming a centrosymmetric lattice at their optimal van-der-Waals stacking. Here, we report a stable ferroelectric order emerging at the interface between two naturally-grown flakes of hexagonal-boron-nitride, which are stacked together in a metastable non-centrosymmetric parallel orientation.

  • Senolytics reduce coronavirus-related mortality in old mice
    Science (IF 41.845) Pub Date : 2021-06-08
    Christina D. Camell, Matthew J. Yousefzadeh, Yi Zhu, Larissa G. P. Langhi Prata, Matthew A. Huggins, Mark Pierson, Lei Zhang, Ryan D. O’Kelly, Tamar Pirtskhalava, Pengcheng Xun, Keisuke Ejima, Ailing Xue, Utkarsh Tripathi, Jair Machado Espindola-Netto, Nino Giorgadze, Elizabeth J. Atkinson, Christina L. Inman, Kurt O. Johnson, Stephanie H. Cholensky, Timothy W. Carlson, Nathan K. LeBrasseur, Sundeep

    The COVID-19 pandemic has revealed the pronounced vulnerability of the elderly and chronically-ill to SARS-CoV-2-induced morbidity and mortality. Cellular senescence contributes to inflammation, multiple chronic diseases, and age-related dysfunction, but effects on responses to viral infection are unclear. Here, we demonstrate that senescent cells (SnC) become hyper-inflammatory in response to pathogen-associated

  • Structures of the human Mediator and Mediator-bound preinitiation complex
    Science (IF 41.845) Pub Date : 2021-06-04
    Xizi Chen, Xiaotong Yin, Jiabei Li, Zihan Wu, Yilun Qi, Xinxin Wang, Weida Liu, Yanhui Xu

    The 1.3-megadalton transcription factor IID (TFIID) is required for preinitiation complex (PIC) assembly and RNA polymerase II (Pol II)–mediated transcription initiation on almost all genes. The 26-subunit Mediator stimulates transcription and cyclin-dependent kinase 7 (CDK7)–mediated phosphorylation of the Pol II C-terminal domain (CTD). We determined the structures of human Mediator in the Tail module–extended

  • Sense codon reassignment enables viral resistance and encoded polymer synthesis
    Science (IF 41.845) Pub Date : 2021-06-04
    Wesley E. Robertson, Louise F. H. Funke, Daniel de la Torre, Julius Fredens, Thomas S. Elliott, Martin Spinck, Yonka Christova, Daniele Cervettini, Franz L. Böge, Kim C. Liu, Salvador Buse, Sarah Maslen, George P. C. Salmond, Jason W. Chin

    It is widely hypothesized that removing cellular transfer RNAs (tRNAs)—making their cognate codons unreadable—might create a genetic firewall to viral infection and enable sense codon reassignment. However, it has been impossible to test these hypotheses. In this work, following synonymous codon compression and laboratory evolution in Escherichia coli, we deleted the tRNAs and release factor 1, which

  • Establishing gold and platinum standards to 1 terapascal using shockless compression
    Science (IF 41.845) Pub Date : 2021-06-04
    D. E. Fratanduono, M. Millot, D. G. Braun, S. J. Ali, A. Fernandez-Pañella, C. T. Seagle, J.-P. Davis, J. L. Brown, Y. Akahama, R. G. Kraus, M. C. Marshall, R. F. Smith, E. F. O’Bannon, J. M. McNaney, J. H. Eggert

    New techniques are advancing the frontier of high-pressure physics beyond 1 terapascal, leading to new discoveries and offering stringent tests for condensed-matter theory and advanced numerical methods. However, the ability to absolutely determine the pressure state remains challenging, and well-calibrated pressure-density reference materials are required. We conducted shockless dynamic compression

  • Reciprocal repulsions instruct the precise assembly of parallel hippocampal networks
    Science (IF 41.845) Pub Date : 2021-06-04
    Daniel T. Pederick, Jan H. Lui, Ellen C. Gingrich, Chuanyun Xu, Mark J. Wagner, Yuanyuan Liu, Zhigang He, Stephen R. Quake, Liqun Luo

    Mammalian medial and lateral hippocampal networks preferentially process spatial- and object-related information, respectively. However, the mechanisms underlying the assembly of such parallel networks during development remain largely unknown. Our study shows that, in mice, complementary expression of cell surface molecules teneurin-3 (Ten3) and latrophilin-2 (Lphn2) in the medial and lateral hippocampal

  • CO2 electrolysis to multicarbon products in strong acid
    Science (IF 41.845) Pub Date : 2021-06-04
    Jianan Erick Huang, Fengwang Li, Adnan Ozden, Armin Sedighian Rasouli, F. Pelayo García de Arquer, Shijie Liu, Shuzhen Zhang, Mingchuan Luo, Xue Wang, Yanwei Lum, Yi Xu, Koen Bertens, Rui Kai Miao, Cao-Thang Dinh, David Sinton, Edward H. Sargent

    Carbon dioxide electroreduction (CO2R) is being actively studied as a promising route to convert carbon emissions to valuable chemicals and fuels. However, the fraction of input CO2 that is productively reduced has typically been very low, <2% for multicarbon products; the balance reacts with hydroxide to form carbonate in both alkaline and neutral reactors. Acidic electrolytes would overcome this

  • Tough hydrogels with rapid self-reinforcement
    Science (IF 41.845) Pub Date : 2021-06-04
    Chang Liu, Naoya Morimoto, Lan Jiang, Sohei Kawahara, Takako Noritomi, Hideaki Yokoyama, Koichi Mayumi, Kohzo Ito

    Most tough hydrogels are reinforced by introducing sacrificial structures that can dissipate input energy. However, because the sacrificial damage cannot rapidly recover, the toughness of these gels drops substantially during consecutive cyclic loadings. We propose a damageless reinforcement strategy for hydrogels using strain-induced crystallization. For slide-ring gels in which polyethylene glycol

  • Revealing x-ray and gamma ray temporal and spectral similarities in the GRB 190829A afterglow
    Science (IF 41.845) Pub Date : 2021-06-04
    H.E.S.S. Collaboration, H. Abdalla, F. Aharonian, F. Ait Benkhali, E. O. Angüner, C. Arcaro, C. Armand, T. Armstrong, H. Ashkar, M. Backes, V. Baghmanyan, V. Barbosa Martins, A. Barnacka, M. Barnard, Y. Becherini, D. Berge, K. Bernlöhr, B. Bi, E. Bissaldi, M. Böttcher, C. Boisson, J. Bolmont, M. de Bony de Lavergne, M. Breuhaus, F. Brun, P. Brun, M. Bryan, M. Büchele, T. Bulik, T. Bylund, S. Caroff

    Gamma-ray bursts (GRBs), which are bright flashes of gamma rays from extragalactic sources followed by fading afterglow emission, are associated with stellar core collapse events. We report the detection of very-high-energy (VHE) gamma rays from the afterglow of GRB 190829A, between 4 and 56 hours after the trigger, using the High Energy Stereoscopic System (H.E.S.S.). The low luminosity and redshift

  • Extensive pleiotropism and allelic heterogeneity mediate metabolic effects of IRX3 and IRX5
    Science (IF 41.845) Pub Date : 2021-06-04
    Débora R. Sobreira, Amelia C. Joslin, Qi Zhang, Iain Williamson, Grace T. Hansen, Kathryn M. Farris, Noboru J. Sakabe, Nasa Sinnott-Armstrong, Grazyna Bozek, Sharon O. Jensen-Cody, Kyle H. Flippo, Carole Ober, Wendy A. Bickmore, Matthew Potthoff, Mengjie Chen, Melina Claussnitzer, Ivy Aneas, Marcelo A. Nóbrega

    Whereas coding variants often have pleiotropic effects across multiple tissues, noncoding variants are thought to mediate their phenotypic effects by specific tissue and temporal regulation of gene expression. Here, we investigated the genetic and functional architecture of a genomic region within the FTO gene that is strongly associated with obesity risk. We show that multiple variants on a common

  • Household COVID-19 risk and in-person schooling
    Science (IF 41.845) Pub Date : 2021-06-04
    Justin Lessler, M. Kate Grabowski, Kyra H. Grantz, Elena Badillo-Goicoechea, C. Jessica E. Metcalf, Carly Lupton-Smith, Andrew S. Azman, Elizabeth A. Stuart

    In-person schooling has proved contentious and difficult to study throughout the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. Data from a massive online survey in the United States indicate an increased risk of COVID-19–related outcomes among respondents living with a child attending school in person. School-based mitigation measures are associated with significant reductions

  • Antarctic surface temperature and elevation during the Last Glacial Maximum
    Science (IF 41.845) Pub Date : 2021-06-04
    Christo Buizert, T. J. Fudge, William H. G. Roberts, Eric J. Steig, Sam Sherriff-Tadano, Catherine Ritz, Eric Lefebvre, Jon Edwards, Kenji Kawamura, Ikumi Oyabu, Hideaki Motoyama, Emma C. Kahle, Tyler R. Jones, Ayako Abe-Ouchi, Takashi Obase, Carlos Martin, Hugh Corr, Jeffrey P. Severinghaus, Ross Beaudette, Jenna A. Epifanio, Edward J. Brook, Kaden Martin, Jérôme Chappellaz, Shuji Aoki, Takakiyo Nakazawa

    Water-stable isotopes in polar ice cores are a widely used temperature proxy in paleoclimate reconstruction, yet calibration remains challenging in East Antarctica. Here, we reconstruct the magnitude and spatial pattern of Last Glacial Maximum surface cooling in Antarctica using borehole thermometry and firn properties in seven ice cores. West Antarctic sites cooled ~10°C relative to the preindustrial

  • Antibody fucosylation predicts disease severity in secondary dengue infection
    Science (IF 41.845) Pub Date : 2021-06-04
    Stylianos Bournazos, Hoa Thi My Vo, Veasna Duong, Heidi Auerswald, Sowath Ly, Anavaj Sakuntabhai, Philippe Dussart, Tineke Cantaert, Jeffrey V. Ravetch

    Although antiviral antibodies generally confer protective functions, antibodies against dengue virus (DENV) are associated with enhanced disease susceptibility. Antibodies can mediate DENV infection of leukocytes via Fcγ receptors, likely contributing to dengue disease pathogenesis. To determine if this mechanism accounts for variable disease severity, we examined Fab and Fc structures of anti-DENV

  • An early Miocene extinction in pelagic sharks
    Science (IF 41.845) Pub Date : 2021-06-04
    Elizabeth C. Sibert, Leah D. Rubin

    Shark populations have been decimated in recent decades because of overfishing and other anthropogenic stressors; however, the long-term impacts of such changes in marine predator abundance and diversity are poorly constrained. We present evidence for a previously unknown major extinction event in sharks that occurred in the early Miocene, ~19 million years ago. During this interval, sharks virtually

  • Prevalent, protective, and convergent IgG recognition of SARS-CoV-2 non-RBD spike epitopes
    Science (IF 41.845) Pub Date : 2021-06-04
    William N. Voss, Yixuan J. Hou, Nicole V. Johnson, George Delidakis, Jin Eyun Kim, Kamyab Javanmardi, Andrew P. Horton, Foteini Bartzoka, Chelsea J. Paresi, Yuri Tanno, Chia-Wei Chou, Shawn A. Abbasi, Whitney Pickens, Katia George, Daniel R. Boutz, Dalton M. Towers, Jonathan R. McDaniel, Daniel Billick, Jule Goike, Lori Rowe, Dhwani Batra, Jan Pohl, Justin Lee, Shivaprakash Gangappa, Suryaprakash Sambhara

    The molecular composition and binding epitopes of the immunoglobulin G (IgG) antibodies that circulate in blood plasma after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection are unknown. Proteomic deconvolution of the IgG repertoire to the spike glycoprotein in convalescent subjects revealed that the response is directed predominantly (>80%) against epitopes residing outside the

  • The first 5 years of gravitational-wave astrophysics
    Science (IF 41.845) Pub Date : 2021-06-04
    Salvatore Vitale

    Gravitational waves are ripples in spacetime generated by the acceleration of astrophysical objects; a direct consequence of general relativity, they were first directly observed in 2015. Here, I review the first 5 years of gravitational-wave detections. More than 50 gravitational-wave events have been found, emitted by pairs of merging compact objects such as neutron stars and black holes. These signals

  • Canonical T cell receptor docking on peptide–MHC is essential for T cell signaling
    Science (IF 41.845) Pub Date : 2021-06-04
    Pirooz Zareie, Christopher Szeto, Carine Farenc, Sachith D. Gunasinghe, Elizabeth M. Kolawole, Angela Nguyen, Chantelle Blyth, Xavier Y. X. Sng, Jasmine Li, Claerwen M. Jones, Alex J. Fulcher, Jesica R. Jacobs, Qianru Wei, Lukasz Wojciech, Jan Petersen, Nicholas R.J. Gascoigne, Brian D. Evavold, Katharina Gaus, Stephanie Gras, Jamie Rossjohn, Nicole L. La Gruta

    T cell receptor (TCR) recognition of peptide–major histocompatibility complexes (pMHCs) is characterized by a highly conserved docking polarity. Whether this polarity is driven by recognition or signaling constraints remains unclear. Using “reversed-docking” TCRβ-variable (TRBV) 17+ TCRs from the naïve mouse CD8+ T cell repertoire that recognizes the H-2Db–NP366 epitope, we demonstrate that their inability

  • Fe-S cofactors in the SARS-CoV-2 RNA-dependent RNA polymerase are potential antiviral targets
    Science (IF 41.845) Pub Date : 2021-06-03
    Nunziata Maio, Bernard A. P. Lafont, Debangsu Sil, Yan Li, J. Martin Bollinger, Carsten Krebs, Theodore C. Pierson, W. Marston Linehan, Tracey A. Rouault

    Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causal agent of coronavirus disease 2019 (COVID-19), uses an RNA-dependent RNA polymerase (RdRp) for the replication of its genome and the transcription of its genes. We found that the catalytic subunit of the RdRp, nsp12, ligates two iron-sulfur metal cofactors in sites that were modeled as zinc centers in the available cryo-electron

  • Estimating epidemiologic dynamics from cross-sectional viral load distributions
    Science (IF 41.845) Pub Date : 2021-06-03
    James A. Hay, Lee Kennedy-Shaffer, Sanjat Kanjilal, Niall J. Lennon, Stacey B. Gabriel, Marc Lipsitch, Michael J. Mina

    Estimating an epidemic’s trajectory is crucial for developing public health responses to infectious diseases, but case data used for such estimation are confounded by variable testing practices. We show that the population distribution of viral loads observed under random or symptom-based surveillance, in the form of cycle threshold (Ct) values obtained from reverse-transcription quantitative polymerase

  • MBD5 and MBD6 couple DNA methylation to gene silencing through the J-domain protein SILENZIO
    Science (IF 41.845) Pub Date : 2021-06-03
    Lucia Ichino, Brandon A. Boone, Luke Strauskulage, C. Jake Harris, Gundeep Kaur, Matthew A. Gladstone, Maverick Tan, Suhua Feng, Yasaman Jami-Alahmadi, Sascha H. Duttke, James A. Wohlschlegel, Xiaodong Cheng, Sy Redding, Steven E. Jacobsen

    DNA methylation is associated with transcriptional repression of eukaryotic genes and transposons, but the downstream mechanism of gene silencing is largely unknown. Here we describe two Arabidopsis methyl-CpG binding domain proteins, MBD5 and MBD6, that are recruited to chromatin by recognition of CG methylation, and redundantly repress a subset of genes and transposons without affecting DNA methylation

  • Heterogeneity of meningeal B cells reveals a lymphopoietic niche at the CNS borders
    Science (IF 41.845) Pub Date : 2021-06-03
    Simone Brioschi, Wei-Le Wang, Vincent Peng, Meng Wang, Irina Shchukina, Zev J. Greenberg, Jennifer K. Bando, Natalia Jaeger, Rafael S. Czepielewski, Amanda Swain, Denis A. Mogilenko, Wandy L. Beatty, Peter Bayguinov, James A. J. Fitzpatrick, Laura G. Schuettpelz, Catrina C. Fronick, Igor Smirnov, Jonathan Kipnis, Virginia S. Shapiro, Gregory F. Wu, Susan Gilfillan, Marina Cella, Maxim N. Artyomov,

    The meninges contain adaptive immune cells that provide immunosurveillance of the CNS. These cells are thought to derive from the systemic circulation. Through single-cell analyses, confocal imaging, bone marrow chimeras, and parabiosis experiments, we show that meningeal B cells derive locally from the calvaria, which harbors a bone marrow niche for hematopoiesis. B cells reach the meninges from the

  • Skull and vertebral bone marrow are myeloid cell reservoirs for the meninges and CNS parenchyma
    Science (IF 41.845) Pub Date : 2021-06-03
    Andrea Cugurra, Tornike Mamuladze, Justin Rustenhoven, Taitea Dykstra, Giorgi Beroshvili, Zev J. Greenberg, Wendy Baker, Zach Papadopoulos, Antoine Drieu, Susan Blackburn, Mitsuhiro Kanamori, Simone Brioschi, Jasmin Herz, Laura G. Schuettpelz, Marco Colonna, Igor Smirnov, Jonathan Kipnis

    The meninges are a membranous structure enveloping the central nervous system (CNS) that host a rich repertoire of immune cells mediating CNS immune surveillance. Here, we report that the meninges contain a pool of monocytes and neutrophils supplied not from the blood, but by adjacent skull and vertebral bone marrow. Under pathological conditions, including spinal cord injury and neuroinflammation

  • Stacking-engineered ferroelectricity in bilayer boron nitride
    Science (IF 41.845) Pub Date : 2021-06-03
    Kenji Yasuda, Xirui Wang, Kenji Watanabe, Takashi Taniguchi, Pablo Jarillo-Herrero

    2D ferroelectrics with robust polarization down to atomic thicknesses provide building blocks for functional heterostructures. Experimental realization remains challenging because of the requirement of a layered polar crystal. Here, we demonstrate a rational design approach to engineering 2D ferroelectrics from a non-ferroelectric parent compound via employing van der Waals assembly. Parallel-stacked

  • Dynamic remodeling of host membranes by self-organizing bacterial effectors
    Science (IF 41.845) Pub Date : 2021-05-28
    Ting-Sung Hsieh, Victor A. Lopez, Miles H. Black, Adam Osinski, Krzysztof Pawłowski, Diana R. Tomchick, Jen Liou, Vincent S. Tagliabracci

    During infection, intracellular bacterial pathogens translocate a variety of effectors into host cells that modify host membrane trafficking for their benefit. We found a self-organizing system consisting of a bacterial phosphoinositide kinase and its opposing phosphatase that formed spatiotemporal patterns, including traveling waves, to remodel host cellular membranes. The Legionella effector MavQ

  • Noncanonical crRNAs derived from host transcripts enable multiplexable RNA detection by Cas9
    Science (IF 41.845) Pub Date : 2021-05-28
    Chunlei Jiao, Sahil Sharma, Gaurav Dugar, Natalia L. Peeck, Thorsten Bischler, Franziska Wimmer, Yanying Yu, Lars Barquist, Christoph Schoen, Oliver Kurzai, Cynthia M. Sharma, Chase L. Beisel

    CRISPR-Cas systems recognize foreign genetic material using CRISPR RNAs (crRNAs). In type II systems, a trans-activating crRNA (tracrRNA) hybridizes to crRNAs to drive their processing and utilization by Cas9. While analyzing Cas9-RNA complexes from Campylobacter jejuni, we discovered tracrRNA hybridizing to cellular RNAs, leading to formation of “noncanonical” crRNAs capable of guiding DNA targeting

  • Quantum walks on a programmable two-dimensional 62-qubit superconducting processor
    Science (IF 41.845) Pub Date : 2021-05-28
    Ming Gong, Shiyu Wang, Chen Zha, Ming-Cheng Chen, He-Liang Huang, Yulin Wu, Qingling Zhu, Youwei Zhao, Shaowei Li, Shaojun Guo, Haoran Qian, Yangsen Ye, Fusheng Chen, Chong Ying, Jiale Yu, Daojin Fan, Dachao Wu, Hong Su, Hui Deng, Hao Rong, Kaili Zhang, Sirui Cao, Jin Lin, Yu Xu, Lihua Sun, Cheng Guo, Na Li, Futian Liang, V. M. Bastidas, Kae Nemoto, W. J. Munro, Yong-Heng Huo, Chao-Yang Lu, Cheng-Zhi

    Quantum walks are the quantum mechanical analog of classical random walks and an extremely powerful tool in quantum simulations, quantum search algorithms, and even for universal quantum computing. In our work, we have designed and fabricated an 8-by-8 two-dimensional square superconducting qubit array composed of 62 functional qubits. We used this device to demonstrate high-fidelity single- and two-particle

  • Role of the ionic environment in enhancing the activity of reacting molecules in zeolite pores
    Science (IF 41.845) Pub Date : 2021-05-28
    Niklas Pfriem, Peter H. Hintermeier, Sebastian Eckstein, Sungmin Kim, Qiang Liu, Hui Shi, Lara Milakovic, Yuanshuai Liu, Gary L. Haller, Eszter Baráth, Yue Liu, Johannes A. Lercher

    Tailoring the molecular environment around catalytically active sites allows for the enhancement of catalytic reactivity through a hitherto unexplored pathway. In zeolites, the presence of water creates an ionic environment via the formation of hydrated hydronium ions and the negatively charged framework aluminum tetrahedra. The high density of cation-anion pairs determined by the aluminum concentration

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