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  • BNT162b2-elicited neutralization of B.1.617 and other SARS-CoV-2 variants
    Nature (IF 42.778) Pub Date : 2021-06-10
    Jianying Liu, Yang Liu, Hongjie Xia, Jing Zou, Scott C. Weaver, Kena A. Swanson, Hui Cai, Mark Cutler, David Cooper, Alexander Muik, Kathrin U. Jansen, Ugur Sahin, Xuping Xie, Philip R. Dormitzer, Pei-Yong Shi

    Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to evolve around the world, generating new variants that are of concern based on their potential for altered transmissibility, pathogenicity, and coverage by vaccines and therapeutics1–5. Here we report that 20 human sera, drawn 2 or 4 weeks after two doses of BNT162b2, neutralize engineered SARS-CoV-2 with a USA-WA1/2020 genetic

  • Immunogenicity of Ad26.COV2.S vaccine against SARS-CoV-2 variants in humans
    Nature (IF 42.778) Pub Date : 2021-06-09
    Galit Alter, Jingyou Yu, Jinyan Liu, Abishek Chandrashekar, Erica N. Borducchi, Lisa H. Tostanoski, Katherine McMahan, Catherine Jacob-Dolan, David R. Martinez, Aiquan Chang, Tochi Anioke, Michelle Lifton, Joseph Nkolola, Kathryn E. Stephenson, Caroline Atyeo, Sally Shin, Paul Fields, Ian Kaplan, Harlan Robins, Fatima Amanat, Florian Krammer, Ralph S. Baric, Mathieu Le Gars, Jerald Sadoff, Anne Marit

    The Ad26.COV2.S vaccine1–3 has demonstrated clinical efficacy against symptomatic COVID-19, including against the B.1.351 variant that is partially resistant to neutralizing antibodies1. However, the immunogenicity of this vaccine in humans against SARS-CoV-2 variants of concern remains unclear. Here we report humoral and cellular immune responses from 20 Ad26.COV2.S vaccinated individuals from the

  • Observation of first and second sound in a BKT superfluid
    Nature (IF 42.778) Pub Date : 2021-06-09
    Panagiotis Christodoulou, Maciej Gałka, Nishant Dogra, Raphael Lopes, Julian Schmitt, Zoran Hadzibabic

    Superfluidity in its various forms has been of interest since the observation of frictionless flow in liquid helium II1,2. In three spatial dimensions it is conceptually associated with the emergence of long-range order at a critical temperature. One of the hallmarks of superfluidity, as predicted by the two-fluid model3,4 and observed in both liquid helium5 and in ultracold atomic gases6,7, is the

  • Quantum-enhanced nonlinear microscopy
    Nature (IF 42.778) Pub Date : 2021-06-09
    Catxere A. Casacio, Lars S. Madsen, Alex Terrasson, Muhammad Waleed, Kai Barnscheidt, Boris Hage, Michael A. Taylor, Warwick P. Bowen

    The performance of light microscopes is limited by the stochastic nature of light, which exists in discrete packets of energy known as photons. Randomness in the times that photons are detected introduces shot noise, which fundamentally constrains sensitivity, resolution and speed1. Although the long-established solution to this problem is to increase the intensity of the illumination light, this is

  • Experimental observation of non-Abelian topological charges and edge states
    Nature (IF 42.778) Pub Date : 2021-06-09
    Qinghua Guo, Tianshu Jiang, Ruo-Yang Zhang, Lei Zhang, Zhao-Qing Zhang, Biao Yang, Shuang Zhang, C. T. Chan

    In the last few decades, topological phase1,2,3,4,5,6,7,8,9,10,11 has emerged as a new classification of matter states beyond the Ginzburg–Landau symmetry-breaking paradigm. The underlying global invariant is usually well characterized by integers, such as Chern numbers or winding numbers—the Abelian charges12,13,14,15. Very recently, researchers proposed the notion of non-Abelian topological charges16

  • Anisotropic satellite galaxy quenching modulated by black hole activity
    Nature (IF 42.778) Pub Date : 2021-06-09
    Ignacio Martín-Navarro, Annalisa Pillepich, Dylan Nelson, Vicente Rodriguez-Gomez, Martina Donnari, Lars Hernquist, Volker Springel

    The evolution of satellite galaxies is shaped by their constant interaction with the circumgalactic medium surrounding central galaxies, which in turn may be affected by gas and energy ejected from the central supermassive black hole1,2,3,4,5,6. The nature of such a coupling between black holes and galaxies is, however, much debated7,8,9 and observational evidence remains scarce10,11. Here we report

  • Representational drift in primary olfactory cortex
    Nature (IF 42.778) Pub Date : 2021-06-09
    Carl E. Schoonover, Sarah N. Ohashi, Richard Axel, Andrew J. P. Fink

    Perceptual constancy requires the brain to maintain a stable representation of sensory input. In the olfactory system, activity in primary olfactory cortex (piriform cortex) is thought to determine odour identity1,2,3,4,5. Here we present the results of electrophysiological recordings of single units maintained over weeks to examine the stability of odour-evoked responses in mouse piriform cortex.

  • NORAD-induced Pumilio phase separation is required for genome stability
    Nature (IF 42.778) Pub Date : 2021-06-09
    Mahmoud M. Elguindy, Joshua T. Mendell

    Liquid–liquid phase separation is a major mechanism of subcellular compartmentalization1,2. Although the segregation of RNA into phase-separated condensates broadly affects RNA metabolism3,4, whether and how specific RNAs use phase separation to regulate interacting factors such as RNA-binding proteins (RBPs), and the phenotypic consequences of such regulatory interactions, are poorly understood. Here

  • Tracing the origin of hair follicle stem cells
    Nature (IF 42.778) Pub Date : 2021-06-09
    Ritsuko Morita, Noriko Sanzen, Hiroko Sasaki, Tetsutaro Hayashi, Mana Umeda, Mika Yoshimura, Takaki Yamamoto, Tatsuo Shibata, Takaya Abe, Hiroshi Kiyonari, Yasuhide Furuta, Itoshi Nikaido, Hironobu Fujiwara

    Tissue stem cells are generated from a population of embryonic progenitors through organ-specific morphogenetic events1,2. Although tissue stem cells are central to organ homeostasis and regeneration, it remains unclear how they are induced during development, mainly because of the lack of markers that exclusively label prospective stem cells. Here we combine marker-independent long-term 3D live imaging

  • TIM-3 restrains anti-tumour immunity by regulating inflammasome activation
    Nature (IF 42.778) Pub Date : 2021-06-09
    Karen O. Dixon, Marcin Tabaka, Markus A. Schramm, Sheng Xiao, Ruihan Tang, Danielle Dionne, Ana. C. Anderson, Orit Rozenblatt-Rosen, Aviv Regev, Vijay K. Kuchroo

    T cell immunoglobulin and mucin-containing molecule 3 (TIM-3), first identified as a molecule expressed on interferon-γ producing T cells1, is emerging as an important immune-checkpoint molecule, with therapeutic blockade of TIM-3 being investigated in multiple human malignancies. Expression of TIM-3 on CD8+ T cells in the tumour microenvironment is considered a cardinal sign of T cell dysfunction;

  • A graph placement methodology for fast chip design
    Nature (IF 42.778) Pub Date : 2021-06-09
    Azalia Mirhoseini, Anna Goldie, Mustafa Yazgan, Joe Wenjie Jiang, Ebrahim Songhori, Shen Wang, Young-Joon Lee, Eric Johnson, Omkar Pathak, Azade Nazi, Jiwoo Pak, Andy Tong, Kavya Srinivasa, William Hang, Emre Tuncer, Quoc V. Le, James Laudon, Richard Ho, Roger Carpenter, Jeff Dean

    Chip floorplanning is the engineering task of designing the physical layout of a computer chip. Despite five decades of research1, chip floorplanning has defied automation, requiring months of intense effort by physical design engineers to produce manufacturable layouts. Here we present a deep reinforcement learning approach to chip floorplanning. In under six hours, our method automatically generates

  • Concerted cutting by Spo11 illuminates meiotic DNA break mechanics
    Nature (IF 42.778) Pub Date : 2021-06-09
    Dominic Johnson, Margaret Crawford, Tim Cooper, Corentin Claeys Bouuaert, Scott Keeney, Bertrand Llorente, Valerie Garcia, Matthew J. Neale

    Genetic recombination arises during meiosis through the repair of DNA double-strand breaks (DSBs) that are created by Spo11, a topoisomerase-like protein1,2. Spo11 DSBs form preferentially in nucleosome-depleted regions termed hotspots3,4, yet how Spo11 engages with its DNA substrate to catalyse DNA cleavage is poorly understood. Although most recombination events are initiated by a single Spo11 cut

  • Nanobodies from camelid mice and llamas neutralize SARS-CoV-2 variants
    Nature (IF 42.778) Pub Date : 2021-06-07
    Jianliang Xu, Kai Xu, Seolkyoung Jung, Andrea Conte, Jenna Lieberman, Frauke Muecksch, Julio Cesar Cetrulo Lorenzi, Solji Park, Fabian Schmidt, Zijun Wang, Yaoxing Huang, Yang Luo, Manoj Nair, Pengfei Wang, Jonathan E. Schulz, Lino Tessarollo, Tatsiana Bylund, Gwo-Yu Chuang, Adam S. Olia, Tyler Stephens, I-Ting Teng, Yaroslav Tsybovsky, Tongqing Zhou, Vincent Munster, David D. Ho, Theodora Hatziioannou

    Since the start of the COVID-19 pandemic, SARS-CoV-2 has caused millions of deaths worldwide. While many vaccines have been deployed to date, the continual evolution of the viral receptor-binding domain (RBD) has challenged their efficacy. In particular, emerging variants B.1.1.7 (U.K.), B.1.351 (South Africa) and P.1 (Brazil) have compromised convalescent sera and immunotherapies that received emergency

  • Spread of a SARS-CoV-2 variant through Europe in the summer of 2020
    Nature (IF 42.778) Pub Date : 2021-06-07
    Emma B. Hodcroft, Moira Zuber, Sarah Nadeau, Timothy G. Vaughan, Katharine H. D. Crawford, Christian L. Althaus, Martina L. Reichmuth, John E. Bowen, Alexandra C. Walls, Davide Corti, Jesse D. Bloom, David Veesler, David Mateo, Alberto Hernando, Iñaki Comas, Fernando González Candelas, Tanja Stadler, Richard A. Neher

    Following its emergence in late 2019, the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)1,2 has been tracked via phylogenetic analysis of viral genome sequences in unprecedented detail3–5. While the virus spread globally in early 2020 before borders closed, intercontinental travel has since been greatly reduced. However, within Europe travel resumed in the summer of 2020. Here

  • Nasal delivery of an IgM offers broad protection from SARS-CoV-2 variants
    Nature (IF 42.778) Pub Date : 2021-06-03
    Zhiqiang Ku, Xuping Xie, Paul R. Hinton, Xinli Liu, Xiaohua Ye, Antonio E. Muruato, Dean C. Ng, Sujit Biswas, Jing Zou, Yang Liu, Deepal Pandya, Vineet D. Menachery, Sachi Rahman, Yu-An Cao, Hui Deng, Wei Xiong, Kevin B. Carlin, Junquan Liu, Hang Su, Elizabeth J. Haanes, Bruce A. Keyt, Ningyan Zhang, Stephen F. Carroll, Pei-Yong Shi, Zhiqiang An

    Resistance represents a major challenge for antibody-based therapy for coronavirus disease 2019 (COVID-19)1–4. Here we engineered an immunoglobulin M (IgM) neutralizing antibody (IgM-14) to overcome the resistance encountered by IgG-based therapeutics. IgM-14 is >230-fold more potent than its parental IgG-14 in neutralizing the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). IgM-14 potently

  • Intrinsic toughening and stable crack propagation in hexagonal boron nitride
    Nature (IF 42.778) Pub Date : 2021-06-02
    Yingchao Yang, Zhigong Song, Guangyuan Lu, Qinghua Zhang, Boyu Zhang, Bo Ni, Chao Wang, Xiaoyan Li, Lin Gu, Xiaoming Xie, Huajian Gao, Jun Lou

    If a bulk material can withstand a high load without any irreversible damage (such as plastic deformation), it is usually brittle and can fail catastrophically1,2. This trade-off between strength and fracture toughness also extends into two-dimensional materials space3,4,5. For example, graphene has ultrahigh intrinsic strength (about 130 gigapascals) and elastic modulus (approximately 1.0 terapascal)

  • Widespread deoxygenation of temperate lakes
    Nature (IF 42.778) Pub Date : 2021-06-02
    Stephen F. Jane, Gretchen J. A. Hansen, Benjamin M. Kraemer, Peter R. Leavitt, Joshua L. Mincer, Rebecca L. North, Rachel M. Pilla, Jonathan T. Stetler, Craig E. Williamson, R. Iestyn Woolway, Lauri Arvola, Sudeep Chandra, Curtis L. DeGasperi, Laura Diemer, Julita Dunalska, Oxana Erina, Giovanna Flaim, Hans-Peter Grossart, K. David Hambright, Catherine Hein, Josef Hejzlar, Lorraine L. Janus, Jean-Philippe

    The concentration of dissolved oxygen in aquatic systems helps to regulate biodiversity1,2, nutrient biogeochemistry3, greenhouse gas emissions4, and the quality of drinking water5. The long-term declines in dissolved oxygen concentrations in coastal and ocean waters have been linked to climate warming and human activity6,7, but little is known about the changes in dissolved oxygen concentrations in

  • Hepatic stellate cells suppress NK cell-sustained breast cancer dormancy
    Nature (IF 42.778) Pub Date : 2021-06-02
    Ana Luísa Correia, Joao C. Guimaraes, Priska Auf der Maur, Duvini De Silva, Marcel P. Trefny, Ryoko Okamoto, Sandro Bruno, Alexander Schmidt, Kirsten Mertz, Katrin Volkmann, Luigi Terracciano, Alfred Zippelius, Marcus Vetter, Christian Kurzeder, Walter Paul Weber, Mohamed Bentires-Alj

    The persistence of undetectable disseminated tumour cells (DTCs) after primary tumour resection poses a major challenge to effective cancer treatment1,2,3. These enduring dormant DTCs are seeds of future metastases, and the mechanisms that switch them from dormancy to outgrowth require definition. Because cancer dormancy provides a unique therapeutic window for preventing metastatic disease, a comprehensive

  • Tracing oncogene-driven remodelling of the intestinal stem cell niche
    Nature (IF 42.778) Pub Date : 2021-06-02
    Min Kyu Yum, Seungmin Han, Juergen Fink, Szu-Hsien Sam Wu, Catherine Dabrowska, Teodora Trendafilova, Roxana Mustata, Lemonia Chatzeli, Roberta Azzarelli, Irina Pshenichnaya, Eunmin Lee, Frances England, Jong Kyoung Kim, Daniel E. Stange, Anna Philpott, Joo-Hyeon Lee, Bon-Kyoung Koo, Benjamin D. Simons

    Interactions between tumour cells and the surrounding microenvironment contribute to tumour progression, metastasis and recurrence1,2,3. Although mosaic analyses in Drosophila have advanced our understanding of such interactions4,5, it has been difficult to engineer parallel approaches in vertebrates. Here we present an oncogene-associated, multicolour reporter mouse model—the Red2Onco system—that

  • Apc-mutant cells act as supercompetitors in intestinal tumour initiation
    Nature (IF 42.778) Pub Date : 2021-06-02
    Sanne M. van Neerven, Nina E. de Groot, Lisanne E. Nijman, Brendon P. Scicluna, Milou S. van Driel, Maria C. Lecca, Daniël O. Warmerdam, Vaishali Kakkar, Leandro F. Moreno, Felipe A. Vieira Braga, Delano R. Sanches, Prashanthi Ramesh, Sanne ten Hoorn, Arthur S. Aelvoet, Marouska F. van Boxel, Lianne Koens, Przemek M. Krawczyk, Jan Koster, Evelien Dekker, Jan Paul Medema, Douglas J. Winton, Maarten

    A delicate equilibrium of WNT agonists and antagonists in the intestinal stem cell (ISC) niche is critical to maintaining the ISC compartment, as it accommodates the rapid renewal of the gut lining. Disruption of this balance by mutations in the tumour suppressor gene APC, which are found in approximately 80% of all human colon cancers, leads to unrestrained activation of the WNT pathway1,2. It has

  • Signatures of moiré trions in WSe2/MoSe2 heterobilayers
    Nature (IF 42.778) Pub Date : 2021-06-02
    Erfu Liu, Elyse Barré, Jeremiah van Baren, Matthew Wilson, Takashi Taniguchi, Kenji Watanabe, Yong-Tao Cui, Nathaniel M. Gabor, Tony F. Heinz, Yia-Chung Chang, Chun Hung Lui

    Moiré superlattices formed by van der Waals materials can support a wide range of electronic phases, including Mott insulators1,2,3,4, superconductors5,6,7,8,9,10 and generalized Wigner crystals2. When excitons are confined by a moiré superlattice, a new class of exciton emerges, which holds promise for realizing artificial excitonic crystals and quantum optical effects11,12,13,14,15,16. When such

  • CO2 doping of organic interlayers for perovskite solar cells
    Nature (IF 42.778) Pub Date : 2021-06-02
    Jaemin Kong, Yongwoo Shin, Jason A. Röhr, Hang Wang, Juan Meng, Yueshen Wu, Adlai Katzenberg, Geunjin Kim, Dong Young Kim, Tai-De Li, Edward Chau, Francisco Antonio, Tana Siboonruang, Sooncheol Kwon, Kwanghee Lee, Jin Ryoun Kim, Miguel A. Modestino, Hailiang Wang, André D. Taylor

    In perovskite solar cells, doped organic semiconductors are often used as charge-extraction interlayers situated between the photoactive layer and the electrodes. The π-conjugated small molecule 2,2′,7,7′-tetrakis[N,N-di(4-methoxyphenyl)amino]-9,9-spirobifluorene (spiro-OMeTAD) is the most frequently used semiconductor in the hole-conducting layer1,2,3,4,5,6, and its electrical properties considerably

  • NOTUM from Apc-mutant cells biases clonal competition to initiate cancer
    Nature (IF 42.778) Pub Date : 2021-06-02
    Dustin J. Flanagan, Nalle Pentinmikko, Kalle Luopajärvi, Nicky J. Willis, Kathryn Gilroy, Alexander P. Raven, Lynn Mcgarry, Johanna I. Englund, Anna T. Webb, Sandra Scharaw, Nadia Nasreddin, Michael C. Hodder, Rachel A. Ridgway, Emma Minnee, Nathalie Sphyris, Ella Gilchrist, Arafath K. Najumudeen, Beatrice Romagnolo, Christine Perret, Ann C. Williams, Hans Clevers, Pirjo Nummela, Marianne Lähde, Kari

    The tumour suppressor APC is the most commonly mutated gene in colorectal cancer. Loss of Apc in intestinal stem cells drives the formation of adenomas in mice via increased WNT signalling1, but reduced secretion of WNT ligands increases the ability of Apc-mutant intestinal stem cells to colonize a crypt (known as fixation)2. Here we investigated how Apc-mutant cells gain a clonal advantage over wild-type

  • Asymmetric response of interfacial water to applied electric fields
    Nature (IF 42.778) Pub Date : 2021-06-02
    Angelo Montenegro, Chayan Dutta, Muhammet Mammetkuliev, Haotian Shi, Bingya Hou, Dhritiman Bhattacharyya, Bofan Zhao, Stephen B. Cronin, Alexander V. Benderskii

    Our understanding of the dielectric response of interfacial water, which underlies the solvation properties and reaction rates at aqueous interfaces, relies on the linear response approximation: an external electric field induces a linearly proportional polarization. This implies antisymmetry with respect to the sign of the field. Atomistic simulations have suggested, however, that the polarization

  • Gating and modulation of a hetero-octameric AMPA glutamate receptor
    Nature (IF 42.778) Pub Date : 2021-06-02
    Danyang Zhang, Jake F. Watson, Peter M. Matthews, Ondrej Cais, Ingo H. Greger

    AMPA receptors (AMPARs) mediate the majority of excitatory transmission in the brain and enable the synaptic plasticity that underlies learning1. A diverse array of AMPAR signalling complexes are established by receptor auxiliary subunits, which associate with the AMPAR in various combinations to modulate trafficking, gating and synaptic strength2. However, their mechanisms of action are poorly understood

  • A proximity-dependent biotinylation map of a human cell
    Nature (IF 42.778) Pub Date : 2021-06-02
    Christopher D. Go, James D. R. Knight, Archita Rajasekharan, Bhavisha Rathod, Geoffrey G. Hesketh, Kento T. Abe, Ji-Young Youn, Payman Samavarchi-Tehrani, Hui Zhang, Lucie Y. Zhu, Evelyn Popiel, Jean-Philippe Lambert, Étienne Coyaud, Sally W. T. Cheung, Dushyandi Rajendran, Cassandra J. Wong, Hana Antonicka, Laurence Pelletier, Alexander F. Palazzo, Eric A. Shoubridge, Brian Raught, Anne-Claude Gingras

    Compartmentalization is a defining characteristic of eukaryotic cells, and partitions distinct biochemical processes into discrete subcellular locations. Microscopy1 and biochemical fractionation coupled with mass spectrometry2,3,4 have defined the proteomes of a variety of different organelles, but many intracellular compartments have remained refractory to such approaches. Proximity-dependent biotinylation

  • Telecom-heralded entanglement between multimode solid-state quantum memories
    Nature (IF 42.778) Pub Date : 2021-06-02
    Dario Lago-Rivera, Samuele Grandi, Jelena V. Rakonjac, Alessandro Seri, Hugues de Riedmatten

    Future quantum networks will enable the distribution of entanglement between distant locations and allow applications in quantum communication, quantum sensing and distributed quantum computation1. At the core of this network lies the ability to generate and store entanglement at remote, interconnected quantum nodes2. Although various remote physical systems have been successfully entangled3,4,5,6

  • Heralded entanglement distribution between two absorptive quantum memories
    Nature (IF 42.778) Pub Date : 2021-06-02
    Xiao Liu, Jun Hu, Zong-Feng Li, Xue Li, Pei-Yun Li, Peng-Jun Liang, Zong-Quan Zhou, Chuan-Feng Li, Guang-Can Guo

    Owing to the inevitable loss in communication channels, the distance of entanglement distribution is limited to approximately 100 kilometres on the ground1. Quantum repeaters can circumvent this problem by using quantum memory and entanglement swapping2. As the elementary link of a quantum repeater, the heralded distribution of two-party entanglement between two remote nodes has only been realized

  • Base editing of haematopoietic stem cells rescues sickle cell disease in mice
    Nature (IF 42.778) Pub Date : 2021-06-02
    Gregory A. Newby, Jonathan S. Yen, Kaitly J. Woodard, Thiyagaraj Mayuranathan, Cicera R. Lazzarotto, Yichao Li, Heather Sheppard-Tillman, Shaina N. Porter, Yu Yao, Kalin Mayberry, Kelcee A. Everette, Yoonjeong Jang, Christopher J. Podracky, Elizabeth Thaman, Christophe Lechauve, Akshay Sharma, Jordana M. Henderson, Michelle F. Richter, Kevin T. Zhao, Shannon M. Miller, Tina Wang, Luke W. Koblan, Anton

    Sickle cell disease (SCD) is caused by a mutation in the β-globin gene HBB1. We used a custom adenine base editor (ABE8e-NRCH)2,3 to convert the SCD allele (HBBS) into Makassar β-globin (HBBG), a non-pathogenic variant4,5. Ex vivo delivery of mRNA encoding the base editor with a targeting guide RNA into haematopoietic stem and progenitor cells (HSPCs) from patients with SCD resulted in 80% conversion

  • BNT162b2 vaccine induces neutralizing antibodies and poly-specific T cells in humans
    Nature (IF 42.778) Pub Date : 2021-05-27
    Ugur Sahin, Alexander Muik, Isabel Vogler, Evelyna Derhovanessian, Lena M. Kranz, Mathias Vormehr, Jasmin Quandt, Nicole Bidmon, Alexander Ulges, Alina Baum, Kristen E. Pascal, Daniel Maurus, Sebastian Brachtendorf, Verena Lörks, Julian Sikorski, Peter Koch, Rolf Hilker, Dirk Becker, Ann-Kathrin Eller, Jan Grützner, Manuel Tonigold, Carsten Boesler, Corinna Rosenbaum, Ludwig Heesen, Marie-Cristine

    BNT162b2, a lipid nanoparticle (LNP) formulated nucleoside-modified messenger RNA (mRNA) that encodes the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) spike glycoprotein (S) stabilized in the prefusion conformation, has demonstrated 95% efficacy in preventing coronavirus disease-19 (COVID-19)1. Here we extend our previous phase 1/2 trial report2 and present BNT162b2 prime/boost induced

  • Swarm Learning for decentralized and confidential clinical machine learning
    Nature (IF 42.778) Pub Date : 2021-05-26
    Stefanie Warnat-Herresthal, Hartmut Schultze, Krishnaprasad Lingadahalli Shastry, Sathyanarayanan Manamohan, Saikat Mukherjee, Vishesh Garg, Ravi Sarveswara, Kristian Händler, Peter Pickkers, N. Ahmad Aziz, Sofia Ktena, Florian Tran, Michael Bitzer, Stephan Ossowski, Nicolas Casadei, Christian Herr, Daniel Petersheim, Uta Behrends, Fabian Kern, Tobias Fehlmann, Philipp Schommers, Clara Lehmann, Max

    Fast and reliable detection of patients with severe and heterogeneous illnesses is a major goal of precision medicine1,2. Patients with leukaemia can be identified using machine learning on the basis of their blood transcriptomes3. However, there is an increasing divide between what is technically possible and what is allowed, because of privacy legislation4,5. Here, to facilitate the integration of

  • A 10 per cent increase in global land evapotranspiration from 2003 to 2019
    Nature (IF 42.778) Pub Date : 2021-05-26
    Madeleine Pascolini-Campbell, John T. Reager, Hrishikesh A. Chandanpurkar, Matthew Rodell

    Accurate quantification of global land evapotranspiration is necessary for understanding variability in the global water cycle, which is expected to intensify under climate change1,2,3. Current global evapotranspiration products are derived from a variety of sources, including models4,5, remote sensing6,7 and in situ observations8,9,10. However, existing approaches contain extensive uncertainties;

  • Intercalated amygdala clusters orchestrate a switch in fear state
    Nature (IF 42.778) Pub Date : 2021-05-26
    Kenta M. Hagihara, Olena Bukalo, Martin Zeller, Ayla Aksoy-Aksel, Nikolaos Karalis, Aaron Limoges, Tanner Rigg, Tiffany Campbell, Adriana Mendez, Chase Weinholtz, Mathias Mahn, Larry S. Zweifel, Richard D. Palmiter, Ingrid Ehrlich, Andreas Lüthi, Andrew Holmes

    Adaptive behaviour necessitates the formation of memories for fearful events, but also that these memories can be extinguished. Effective extinction prevents excessive and persistent reactions to perceived threat, as can occur in anxiety and ‘trauma- and stressor-related’ disorders1. However, although there is evidence that fear learning and extinction are mediated by distinct neural circuits, the

  • Structural basis of antifolate recognition and transport by PCFT
    Nature (IF 42.778) Pub Date : 2021-05-26
    Joanne L. Parker, Justin C. Deme, Gabriel Kuteyi, Zhiyi Wu, Jiandong Huo, I. David Goldman, Raymond J. Owens, Philip C. Biggin, Susan M. Lea, Simon Newstead

    Folates (also known as vitamin B9) have a critical role in cellular metabolism as the starting point in the synthesis of nucleic acids, amino acids and the universal methylating agent S-adenylsmethionine1,2. Folate deficiency is associated with a number of developmental, immune and neurological disorders3,4,5. Mammals cannot synthesize folates de novo; several systems have therefore evolved to take

  • Mesozoic cupules and the origin of the angiosperm second integument
    Nature (IF 42.778) Pub Date : 2021-05-26
    Gongle Shi, Fabiany Herrera, Patrick S. Herendeen, Elizabeth G. Clark, Peter R. Crane

    The second integument of the angiosperm ovule is unique among seed plants, with developmental genetics that are distinct from those of the inner integument1. Understanding how the second integument should be compared to structures in other seed plants is therefore crucial to resolving the long-standing question of the origin of angiosperms2,3,4,5,6. Attention has focused on several extinct plants with

  • Enhancer release and retargeting activates disease-susceptibility genes
    Nature (IF 42.778) Pub Date : 2021-05-26
    Soohwan Oh, Jiaofang Shao, Joydeep Mitra, Feng Xiong, Matteo D’Antonio, Ruoyu Wang, Ivan Garcia-Bassets, Qi Ma, Xiaoyu Zhu, Joo-Hyung Lee, Sreejith J. Nair, Feng Yang, Kenneth Ohgi, Kelly A. Frazer, Zhengdong D. Zhang, Wenbo Li, Michael G. Rosenfeld

    The functional engagement between an enhancer and its target promoter ensures precise gene transcription1. Understanding the basis of promoter choice by enhancers has important implications for health and disease. Here we report that functional loss of a preferred promoter can release its partner enhancer to loop to and activate an alternative promoter (or alternative promoters) in the neighbourhood

  • Long-range nontopological edge currents in charge-neutral graphene
    Nature (IF 42.778) Pub Date : 2021-05-26
    A. Aharon-Steinberg, A. Marguerite, D. J. Perello, K. Bagani, T. Holder, Y. Myasoedov, L. S. Levitov, A. K. Geim, E. Zeldov

    Van der Waals heterostructures display numerous unique electronic properties. Nonlocal measurements, wherein a voltage is measured at contacts placed far away from the expected classical flow of charge carriers, have been widely used in the search for novel transport mechanisms, including dissipationless spin and valley transport1,2,3,4,5,6,7,8,9, topological charge-neutral currents10,11,12, hydrodynamic

  • A phase-separated nuclear GBPL circuit controls immunity in plants
    Nature (IF 42.778) Pub Date : 2021-05-26
    Shuai Huang, Shiwei Zhu, Pradeep Kumar, John D. MacMicking

    Liquid–liquid phase separation (LLPS) has emerged as a central paradigm for understanding how membraneless organelles compartmentalize diverse cellular activities in eukaryotes1,2,3. Here we identify a superfamily of plant guanylate-binding protein (GBP)-like GTPases (GBPLs) that assemble LLPS-driven condensates within the nucleus to protect against infection and autoimmunity. In Arabidopsis thaliana

  • Perovskite-type superlattices from lead halide perovskite nanocubes
    Nature (IF 42.778) Pub Date : 2021-05-26
    Ihor Cherniukh, Gabriele Rainò, Thilo Stöferle, Max Burian, Alex Travesset, Denys Naumenko, Heinz Amenitsch, Rolf Erni, Rainer F. Mahrt, Maryna I. Bodnarchuk, Maksym V. Kovalenko

    Atomically defined assemblies of dye molecules (such as H and J aggregates) have been of interest for more than 80 years because of the emergence of collective phenomena in their optical spectra1,2,3, their coherent long-range energy transport, their conceptual similarity to natural light-harvesting complexes4,5, and their potential use as light sources and in photovoltaics. Another way of creating

  • Evidence of hydrogen−helium immiscibility at Jupiter-interior conditions
    Nature (IF 42.778) Pub Date : 2021-05-26
    S. Brygoo, P. Loubeyre, M. Millot, J. R. Rygg, P. M. Celliers, J. H. Eggert, R. Jeanloz, G. W. Collins

    The phase behaviour of warm dense hydrogen−helium (H−He) mixtures affects our understanding of the evolution of Jupiter and Saturn and their interior structures1,2. For example, precipitation of He from a H−He atmosphere at about 1−10 megabar and a few thousand kelvin has been invoked to explain both the excess luminosity of Saturn1,3, and the depletion of He and neon (Ne) in Jupiter’s atmosphere as

  • The universal visitation law of human mobility
    Nature (IF 42.778) Pub Date : 2021-05-26
    Markus Schläpfer, Lei Dong, Kevin O’Keeffe, Paolo Santi, Michael Szell, Hadrien Salat, Samuel Anklesaria, Mohammad Vazifeh, Carlo Ratti, Geoffrey B. West

    Human mobility impacts many aspects of a city, from its spatial structure1,2,3 to its response to an epidemic4,5,6,7. It is also ultimately key to social interactions8, innovation9,10 and productivity11. However, our quantitative understanding of the aggregate movements of individuals remains incomplete. Existing models—such as the gravity law12,13 or the radiation model14—concentrate on the purely

  • MARK4 controls ischaemic heart failure through microtubule detyrosination
    Nature (IF 42.778) Pub Date : 2021-05-26
    Xian Yu, Xiao Chen, Mamta Amrute-Nayak, Edward Allgeyer, Aite Zhao, Hannah Chenoweth, Marc Clement, James Harrison, Christian Doreth, George Sirinakis, Thomas Krieg, Huiyu Zhou, Hongda Huang, Kiyotaka Tokuraku, Daniel St Johnston, Ziad Mallat, Xuan Li

    Myocardial infarction is a major cause of premature death in adults. Compromised cardiac function after myocardial infarction leads to chronic heart failure with systemic health complications and a high mortality rate1. Effective therapeutic strategies are needed to improve the recovery of cardiac function after myocardial infarction. More specifically, there is a major unmet need for a new class of

  • An invariant Trypanosoma vivax vaccine antigen induces protective immunity
    Nature (IF 42.778) Pub Date : 2021-05-26
    Delphine Autheman, Cécile Crosnier, Simon Clare, David A. Goulding, Cordelia Brandt, Katherine Harcourt, Charlotte Tolley, Francis Galaway, Malhar Khushu, Han Ong, Alessandra Romero-Ramirez, Craig W. Duffy, Andrew P. Jackson, Gavin J. Wright

    Trypanosomes are protozoan parasites that cause infectious diseases, including African trypanosomiasis (sleeping sickness) in humans and nagana in economically important livestock1,2. An effective vaccine against trypanosomes would be an important control tool, but the parasite has evolved sophisticated immunoprotective mechanisms—including antigenic variation3—that present an apparently insurmountable

  • NF1 mutation drives neuronal activity-dependent initiation of optic glioma
    Nature (IF 42.778) Pub Date : 2021-05-26
    Yuan Pan, Jared D. Hysinger, Tara Barron, Nicki F. Schindler, Olivia Cobb, Xiaofan Guo, Belgin Yalçın, Corina Anastasaki, Sara B. Mulinyawe, Anitha Ponnuswami, Suzanne Scheaffer, Yu Ma, Kun-Che Chang, Xin Xia, Joseph A. Toonen, James J. Lennon, Erin M. Gibson, John R. Huguenard, Linda M. Liau, Jeffrey L. Goldberg, Michelle Monje, David H. Gutmann

    Neurons have recently emerged as essential cellular constituents of the tumour microenvironment, and their activity has been shown to increase the growth of a diverse number of solid tumours1. Although the role of neurons in tumour progression has previously been demonstrated2, the importance of neuronal activity to tumour initiation is less clear—particularly in the setting of cancer predisposition

  • SARS-CoV-2 infection induces long-lived bone marrow plasma cells in humans
    Nature (IF 42.778) Pub Date : 2021-05-24
    Jackson S. Turner, Wooseob Kim, Elizaveta Kalaidina, Charles W. Goss, Adriana M. Rauseo, Aaron J. Schmitz, Lena Hansen, Alem Haile, Michael K. Klebert, Iskra Pusic, Jane A. O’Halloran, Rachel M. Presti, Ali H. Ellebedy

    Long-lived bone marrow plasma cells (BMPCs) are a persistent and essential source of protective antibodies1–7. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) convalescent individuals have a significantly lower risk of reinfection8–10. Nonetheless, it has been reported that anti-SARS-CoV-2 serum antibodies experience rapid decay in the first few months after infection, raising concerns

  • A radical approach for the selective C–H borylation of azines
    Nature (IF 42.778) Pub Date : 2021-05-20
    Ji Hye Kim, T. Constantin, M. Simonetti, J. Llaveria, N. S. Sheikh, D. Leonori

    Boron functional groups are often introduced in place of aromatic carbon–hydrogen bonds to expedite small-molecule diversification through coupling of molecular fragments1–3. Current approaches based on transition metal-catalysed C–H activation are effective for the borylation of many (hetero)aromatic derivatives4,5 but show narrow applicability to azines, N-containing aromatic heterocycles and key

  • Diverse Functional Autoantibodies in Patients with COVID-19
    Nature (IF 42.778) Pub Date : 2021-05-19
    Eric Y. Wang, Tianyang Mao, Jon Klein, Yile Dai, John D. Huck, Jillian R. Jaycox, Feimei Liu, Ting Zhou, Benjamin Israelow, Patrick Wong, Andreas Coppi, Carolina Lucas, Julio Silva, Ji Eun Oh, Eric Song, Emily S. Perotti, Neil S. Zheng, Suzanne Fischer, Melissa Campbell, John B. Fournier, Anne L. Wyllie, Chantal B. F. Vogels, Isabel M. Ott, Chaney C. Kalinich, Mary E. Petrone, Anne E. Watkins, Charles

    COVID-19 manifests with a wide spectrum of clinical phenotypes that are characterized by exaggerated and misdirected host immune responses1–6. While pathological innate immune activation is well documented in severe disease1, the impact of autoantibodies on disease progression is less defined. Here, we used a high-throughput autoantibody (AAb) discovery technique called Rapid Extracellular Antigen

  • Iron and nickel atoms in cometary atmospheres even far from the Sun
    Nature (IF 42.778) Pub Date : 2021-05-19
    J. Manfroid, D. Hutsemékers, E. Jehin

    In comets, iron and nickel are found in refractory dust particles or in metallic and sulfide grains1. So far, no iron- or nickel-bearing molecules have been observed in the gaseous coma of comets2. Iron and a few other heavy atoms, such as copper and cobalt, have been observed only in two exceptional objects: the Great Comet of 18823 and, almost a century later, C/1965 S1 (Ikeya–Seki)4,5,6,7,8,9. These

  • Overwintering fires in boreal forests
    Nature (IF 42.778) Pub Date : 2021-05-19
    Rebecca C. Scholten, Randi Jandt, Eric A. Miller, Brendan M. Rogers, Sander Veraverbeke

    Forest fires are usually viewed within the context of a single fire season, in which weather conditions and fuel supply can combine to create conditions favourable for fire ignition—usually by lightning or human activity—and spread1,2,3. But some fires exhibit ‘overwintering’ behaviour, in which they smoulder through the non-fire season and flare up in the subsequent spring4,5. In boreal (northern)

  • Discovery, characterization and engineering of ligases for amide synthesis
    Nature (IF 42.778) Pub Date : 2021-05-19
    Michael Winn, Michael Rowlinson, Fanghua Wang, Luis Bering, Daniel Francis, Colin Levy, Jason Micklefield

    Coronatine and related bacterial phytotoxins are mimics of the hormone jasmonyl-l-isoleucine (JA-Ile), which mediates physiologically important plant signalling pathways1,2,3,4. Coronatine-like phytotoxins disrupt these essential pathways and have potential in the development of safer, more selective herbicides. Although the biosynthesis of coronatine has been investigated previously, the nature of

  • In vivo CRISPR base editing of PCSK9 durably lowers cholesterol in primates
    Nature (IF 42.778) Pub Date : 2021-05-19
    Kiran Musunuru, Alexandra C. Chadwick, Taiji Mizoguchi, Sara P. Garcia, Jamie E. DeNizio, Caroline W. Reiss, Kui Wang, Sowmya Iyer, Chaitali Dutta, Victoria Clendaniel, Michael Amaonye, Aaron Beach, Kathleen Berth, Souvik Biswas, Maurine C. Braun, Huei-Mei Chen, Thomas V. Colace, John D. Ganey, Soumyashree A. Gangopadhyay, Ryan Garrity, Lisa N. Kasiewicz, Jennifer Lavoie, James A. Madsen, Yuri Matsumoto

    Gene-editing technologies, which include the CRISPR–Cas nucleases1,2,3 and CRISPR base editors4,5, have the potential to permanently modify disease-causing genes in patients6. The demonstration of durable editing in target organs of nonhuman primates is a key step before in vivo administration of gene editors to patients in clinical trials. Here we demonstrate that CRISPR base editors that are delivered

  • Precision test of statistical dynamics with state-to-state ultracold chemistry
    Nature (IF 42.778) Pub Date : 2021-05-19
    Yu Liu, Ming-Guang Hu, Matthew A. Nichols, Dongzheng Yang, Daiqian Xie, Hua Guo, Kang-Kuen Ni

    Chemical reactions represent a class of quantum problems that challenge both the current theoretical understanding and computational capabilities1. Reactions that occur at ultralow temperatures provide an ideal testing ground for quantum chemistry and scattering theories, because they can be experimentally studied with unprecedented control2, yet display dynamics that are highly complex3. Here we report

  • Tunable non-integer high-harmonic generation in a topological insulator
    Nature (IF 42.778) Pub Date : 2021-05-19
    C. P. Schmid, L. Weigl, P. Grössing, V. Junk, C. Gorini, S. Schlauderer, S. Ito, M. Meierhofer, N. Hofmann, D. Afanasiev, J. Crewse, K. A. Kokh, O. E. Tereshchenko, J. Güdde, F. Evers, J. Wilhelm, K. Richter, U. Höfer, R. Huber

    When intense lightwaves accelerate electrons through a solid, the emerging high-order harmonic (HH) radiation offers key insights into the material1,2,3,4,5,6,7,8,9,10,11. Sub-optical-cycle dynamics—such as dynamical Bloch oscillations2,3,4,5, quasiparticle collisions6,12, valley pseudospin switching13 and heating of Dirac gases10—leave fingerprints in the HH spectra of conventional solids. Topologically

  • Gaseous atomic nickel in the coma of interstellar comet 2I/Borisov
    Nature (IF 42.778) Pub Date : 2021-05-19
    Piotr Guzik, Michał Drahus

    On 31 August 2019, an interstellar comet was discovered as it passed through the Solar System (2I/Borisov). On the basis of initial imaging observations, 2I/Borisov seemed to be similar to ordinary Solar System comets1,2—an unexpected characteristic given the multiple peculiarities of the only known previous interstellar visitor, 1I/‘Oumuamua3,4,5,6. Spectroscopic investigations of 2I/Borisov identified

  • MIR-NATs repress MAPT translation and aid proteostasis in neurodegeneration
    Nature (IF 42.778) Pub Date : 2021-05-19
    Roberto Simone, Faiza Javad, Warren Emmett, Oscar G. Wilkins, Filipa Lourenço Almeida, Natalia Barahona-Torres, Justyna Zareba-Paslawska, Mazdak Ehteramyan, Paola Zuccotti, Angelika Modelska, Kavitha Siva, Gurvir S. Virdi, Jamie S. Mitchell, Jasmine Harley, Victoria A. Kay, Geshanthi Hondhamuni, Daniah Trabzuni, Mina Ryten, Selina Wray, Elisavet Preza, Demis A. Kia, Alan Pittman, Raffaele Ferrari,

    The human genome expresses thousands of natural antisense transcripts (NAT) that can regulate epigenetic state, transcription, RNA stability or translation of their overlapping genes1,2. Here we describe MAPT-AS1, a brain-enriched NAT that is conserved in primates and contains an embedded mammalian-wide interspersed repeat (MIR), which represses tau translation by competing for ribosomal RNA pairing

  • Unconventional viral gene expression mechanisms as therapeutic targets
    Nature (IF 42.778) Pub Date : 2021-05-19
    Jessica Sook Yuin Ho, Zeyu Zhu, Ivan Marazzi

    Unlike the human genome that comprises mostly noncoding and regulatory sequences, viruses have evolved under the constraints of maintaining a small genome size while expanding the efficiency of their coding and regulatory sequences. As a result, viruses use strategies of transcription and translation in which one or more of the steps in the conventional gene–protein production line are altered. These

  • Sensory neuron-derived TAFA4 promotes macrophage tissue repair functions
    Nature (IF 42.778) Pub Date : 2021-05-19
    Guillaume Hoeffel, Guilhaume Debroas, Anais Roger, Rafaelle Rossignol, Jordi Gouilly, Caroline Laprie, Lionel Chasson, Pierre-Vincent Barbon, Anaïs Balsamo, Ana Reynders, Aziz Moqrich, Sophie Ugolini

    Inflammation is a defence response to tissue damage that requires tight regulation in order to prevent impaired healing. Tissue-resident macrophages have a key role in tissue repair1, but the precise molecular mechanisms that regulate the balance between inflammatory and pro-repair macrophage responses during healing remain poorly understood. Here we demonstrate a major role for sensory neurons in

  • The nutritional quality of cereals varies geospatially in Ethiopia and Malawi
    Nature (IF 42.778) Pub Date : 2021-05-19
    D. Gashu, P. C. Nalivata, T. Amede, E. L. Ander, E. H. Bailey, L. Botoman, C. Chagumaira, S. Gameda, S. M. Haefele, K. Hailu, E. J. M. Joy, A. A. Kalimbira, D. B. Kumssa, R. M. Lark, I. S. Ligowe, S. P. McGrath, A. E. Milne, A. W. Mossa, M. Munthali, E. K. Towett, M. G. Walsh, L. Wilson, S. D. Young, M. R. Broadley

    Micronutrient deficiencies (MNDs) remain widespread among people in sub-Saharan Africa1,2,3,4,5, where access to sufficient food from plant and animal sources that is rich in micronutrients (vitamins and minerals) is limited due to socioeconomic and geographical reasons4,5,6. Here we report the micronutrient composition (calcium, iron, selenium and zinc) of staple cereal grains for most of the cereal

  • Ubiquitylation of lipopolysaccharide by RNF213 during bacterial infection
    Nature (IF 42.778) Pub Date : 2021-05-19
    Elsje G. Otten, Emma Werner, Ana Crespillo-Casado, Keith B. Boyle, Vimisha Dharamdasani, Claudio Pathe, Balaji Santhanam, Felix Randow

    Ubiquitylation is a widespread post-translational protein modification in eukaryotes and marks bacteria that invade the cytosol as cargo for antibacterial autophagy1,2,3. The identity of the ubiquitylated substrate on bacteria is unknown. Here we show that the ubiquitin coat on Salmonella that invade the cytosol is formed through the ubiquitylation of a non-proteinaceous substrate, the lipid A moiety

  • The data-driven future of high-energy-density physics
    Nature (IF 42.778) Pub Date : 2021-05-19
    Peter W. Hatfield, Jim A. Gaffney, Gemma J. Anderson, Suzanne Ali, Luca Antonelli, Suzan Başeğmez du Pree, Jonathan Citrin, Marta Fajardo, Patrick Knapp, Brendan Kettle, Bogdan Kustowski, Michael J. MacDonald, Derek Mariscal, Madison E. Martin, Taisuke Nagayama, Charlotte A. J. Palmer, J. Luc Peterson, Steven Rose, J J Ruby, Carl Shneider, Matt J. V. Streeter, Will Trickey, Ben Williams

    High-energy-density physics is the field of physics concerned with studying matter at extremely high temperatures and densities. Such conditions produce highly nonlinear plasmas, in which several phenomena that can normally be treated independently of one another become strongly coupled. The study of these plasmas is important for our understanding of astrophysics, nuclear fusion and fundamental physics—however

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