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  • Aziridines by coupling amines and alkenes via an electro-generated dication
    Nature (IF 42.778) Pub Date : 2021-06-22
    Dylan E. Holst, Diana J. Wang, Min Ji Kim, Ilia A. Guzei, Zachary K. Wickens

    Aziridines, three-membered nitrogen-containing cyclic molecules, are important synthetic targets. Their significant ring strain and resultant proclivity towards ring opening reactions makes them versatile precursors to diverse amine products1–3 and, in some cases, the aziridine functional group itself imbues important biological (e.g. anti-tumor) activity4–6. Transformation of ubiquitous alkenes into

  • In vivo monoclonal antibody efficacy against SARS-CoV-2 variant strains
    Nature (IF 42.778) Pub Date : 2021-06-21
    Rita E. Chen, Emma S. Winkler, James Brett Case, Ishmael D. Aziati, Traci L. Bricker, Astha Joshi, Tamarand L. Darling, Baoling Ying, John M. Errico, Swathi Shrihari, Laura A. VanBlargan, Xuping Xie, Pavlo Gilchuk, Seth J. Zost, Lindsay Droit, Zhuoming Liu, Spencer Stumpf, David Wang, Scott A. Handley, W. Blaine Stine, Pei-Yong Shi, Meredith E. Davis-Gardner, Mehul S. Suthar, Miguel Garcia Knight,

    Rapidly-emerging variants jeopardize antibody-based countermeasures against SARS-CoV-2. While cell culture experiments have demonstrated loss of potency of several anti-spike neutralizing antibodies against SARS-CoV-2 variant strains1–3, the in vivo significance of these results remains uncertain. Using a panel of monoclonal antibodies (mAbs) corresponding to many in advanced clinical development by

  • Dysregulation of brain and choroid plexus cell types in severe COVID-19
    Nature (IF 42.778) Pub Date : 2021-06-21
    Andrew C. Yang, Fabian Kern, Patricia M. Losada, Maayan R. Agam, Christina A. Maat, Georges P. Schmartz, Tobias Fehlmann, Julian A. Stein, Nicholas Schaum, Davis P. Lee, Kruti Calcuttawala, Ryan T. Vest, Daniela Berdnik, Nannan Lu, Oliver Hahn, David Gate, M. Windy McNerney, Divya Channappa, Inma Cobos, Nicole Ludwig, Walter J. Schulz-Schaeffer, Andreas Keller, Tony Wyss-Coray

    Though SARS-CoV-2 primarily targets the respiratory system, patients and survivors can suffer neurological symptoms1–3. Yet, an unbiased understanding of the cellular and molecular processes affected in the brains of COVID-19 patients is still missing. Here, we profile 65,309 single-nucleus transcriptomes from 30 frontal cortex and choroid plexus samples across 14 control (including 1 terminal influenza)

  • Correlated charge noise and relaxation errors in superconducting qubits
    Nature (IF 42.778) Pub Date : 2021-06-16
    C. D. Wilen, S. Abdullah, N. A. Kurinsky, C. Stanford, L. Cardani, G. D’Imperio, C. Tomei, L. Faoro, L. B. Ioffe, C. H. Liu, A. Opremcak, B. G. Christensen, J. L. DuBois, R. McDermott

    The central challenge in building a quantum computer is error correction. Unlike classical bits, which are susceptible to only one type of error, quantum bits (qubits) are susceptible to two types of error, corresponding to flips of the qubit state about the X and Z directions. Although the Heisenberg uncertainty principle precludes simultaneous monitoring of X- and Z-flips on a single qubit, it is

  • Double-helical assembly of heterodimeric nanoclusters into supercrystals
    Nature (IF 42.778) Pub Date : 2021-06-16
    Yingwei Li, Meng Zhou, Yongbo Song, Tatsuya Higaki, He Wang, Rongchao Jin

    DNA has long been used as a template for the construction of helical assemblies of inorganic nanoparticles1,2,3,4,5. For example, gold nanoparticles decorated with DNA (or with peptides) can create helical assemblies6,7,8,9. But without such biological ligands, helices are difficult to achieve and their mechanism of formation is challenging to understand10,11. Atomically precise nanoclusters that are

  • Tissue-resident macrophages provide a pro-tumorigenic niche to early NSCLC cells
    Nature (IF 42.778) Pub Date : 2021-06-16
    María Casanova-Acebes, Erica Dalla, Andrew M. Leader, Jessica LeBerichel, Jovan Nikolic, Blanca M. Morales, Markus Brown, Christie Chang, Leanna Troncoso, Steven T. Chen, Ana Sastre-Perona, Matthew D. Park, Alexandra Tabachnikova, Maxime Dhainaut, Pauline Hamon, Barbara Maier, Catherine M. Sawai, Esperanza Agulló-Pascual, Markus Schober, Brian D. Brown, Boris Reizis, Thomas Marron, Ephraim Kenigsberg

    Macrophages have a key role in shaping the tumour microenvironment (TME), tumour immunity and response to immunotherapy, which makes them an important target for cancer treatment1,2. However, modulating macrophages has proved extremely difficult, as we still lack a complete understanding of the molecular and functional diversity of the tumour macrophage compartment. Macrophages arise from two distinct

  • Symmetry-enforced topological nodal planes at the Fermi surface of a chiral magnet
    Nature (IF 42.778) Pub Date : 2021-06-16
    Marc A. Wilde, Matthias Dodenhöft, Arthur Niedermayr, Andreas Bauer, Moritz M. Hirschmann, Kirill Alpin, Andreas P. Schnyder, Christian Pfleiderer

    Despite recent efforts to advance spintronics devices and quantum information technology using materials with non-trivial topological properties, three key challenges are still unresolved1,2,3,4,5,6,7,8,9. First, the identification of topological band degeneracies that are generically rather than accidentally located at the Fermi level. Second, the ability to easily control such topological degeneracies

  • ctDNA guiding adjuvant immunotherapy in urothelial carcinoma
    Nature (IF 42.778) Pub Date : 2021-06-16
    Thomas Powles, Zoe June Assaf, Nicole Davarpanah, Romain Banchereau, Bernadett E. Szabados, Kobe C. Yuen, Petros Grivas, Maha Hussain, Stephane Oudard, Jürgen E. Gschwend, Peter Albers, Daniel Castellano, Hiroyuki Nishiyama, Siamak Daneshmand, Shruti Sharma, Bernhard G. Zimmermann, Himanshu Sethi, Alexey Aleshin, Maurizio Perdicchio, Jingbin Zhang, David S. Shames, Viraj Degaonkar, Xiaodong Shen, Corey

    Minimally invasive approaches to detect residual disease after surgery are needed to identify patients with cancer who are at risk for metastatic relapse. Circulating tumour DNA (ctDNA) holds promise as a biomarker for molecular residual disease and relapse1. We evaluated outcomes in 581 patients who had undergone surgery and were evaluable for ctDNA from a randomized phase III trial of adjuvant atezolizumab

  • GluD1 is a signal transduction device disguised as an ionotropic receptor
    Nature (IF 42.778) Pub Date : 2021-06-16
    Jinye Dai, Christopher Patzke, Kif Liakath-Ali, Erica Seigneur, Thomas C. Südhof

    Ionotropic glutamate delta receptors 1 (GluD1) and 2 (GluD2) exhibit the molecular architecture of postsynaptic ionotropic glutamate receptors, but assemble into trans-synaptic adhesion complexes by binding to secreted cerebellins that in turn interact with presynaptic neurexins1,2,3,4. It is unclear whether neurexin–cerebellin–GluD1/2 assemblies serve an adhesive synapse-formation function or mediate

  • Peopling of the Americas as inferred from ancient genomics
    Nature (IF 42.778) Pub Date : 2021-06-16
    Eske Willerslev, David J. Meltzer

    In less than a decade, analyses of ancient genomes have transformed our understanding of the Indigenous peopling and population history of the Americas. These studies have shown that this history, which began in the late Pleistocene epoch and continued episodically into the Holocene epoch, was far more complex than previously thought. It is now evident that the initial dispersal involved the movement

  • A dusty veil shading Betelgeuse during its Great Dimming
    Nature (IF 42.778) Pub Date : 2021-06-16
    M. Montargès, E. Cannon, E. Lagadec, A. de Koter, P. Kervella, J. Sanchez-Bermudez, C. Paladini, F. Cantalloube, L. Decin, P. Scicluna, K. Kravchenko, A. K. Dupree, S. Ridgway, M. Wittkowski, N. Anugu, R. Norris, G. Rau, G. Perrin, A. Chiavassa, S. Kraus, J. D. Monnier, F. Millour, J.-B. Le Bouquin, X. Haubois, B. Lopez, P. Stee, W. Danchi

    Red supergiants are the most common final evolutionary stage of stars that have initial masses between 8 and 35 times that of the Sun1. During this stage, which lasts roughly 100,000 years1, red supergiants experience substantial mass loss. However, the mechanism for this mass loss is unknown2. Mass loss may affect the evolutionary path, collapse and future supernova light curve3 of a red supergiant

  • Global prevalence of non-perennial rivers and streams
    Nature (IF 42.778) Pub Date : 2021-06-16
    Mathis Loïc Messager, Bernhard Lehner, Charlotte Cockburn, Nicolas Lamouroux, Hervé Pella, Ton Snelder, Klement Tockner, Tim Trautmann, Caitlin Watt, Thibault Datry

    Flowing waters have a unique role in supporting global biodiversity, biogeochemical cycles and human societies1,2,3,4,5. Although the importance of permanent watercourses is well recognized, the prevalence, value and fate of non-perennial rivers and streams that periodically cease to flow tend to be overlooked, if not ignored6,7,8. This oversight contributes to the degradation of the main source of

  • Geometry of abstract learned knowledge in the hippocampus
    Nature (IF 42.778) Pub Date : 2021-06-16
    Edward H. Nieh, Manuel Schottdorf, Nicolas W. Freeman, Ryan J. Low, Sam Lewallen, Sue Ann Koay, Lucas Pinto, Jeffrey L. Gauthier, Carlos D. Brody, David W. Tank

    Hippocampal neurons encode physical variables1,2,3,4,5,6,7 such as space1 or auditory frequency6 in cognitive maps8. In addition, functional magnetic resonance imaging studies in humans have shown that the hippocampus can also encode more abstract, learned variables9,10,11. However, their integration into existing neural representations of physical variables12,13 is unknown. Here, using two-photon

  • Localization atomic force microscopy
    Nature (IF 42.778) Pub Date : 2021-06-16
    George R. Heath, Ekaterina Kots, Janice L. Robertson, Shifra Lansky, George Khelashvili, Harel Weinstein, Simon Scheuring

    Understanding structural dynamics of biomolecules at the single-molecule level is vital to advancing our knowledge of molecular mechanisms. Currently, there are few techniques that can capture dynamics at the sub-nanometre scale and in physiologically relevant conditions. Atomic force microscopy (AFM)1 has the advantage of analysing unlabelled single molecules in physiological buffer and at ambient

  • Naturally enhanced neutralizing breadth against SARS-CoV-2 one year after infection
    Nature (IF 42.778) Pub Date : 2021-06-14
    Zijun Wang, Frauke Muecksch, Dennis Schaefer-Babajew, Shlomo Finkin, Charlotte Viant, Christian Gaebler, Hans- Heinrich Hoffmann, Christopher O. Barnes, Melissa Cipolla, Victor Ramos, Thiago Y. Oliveira, Alice Cho, Fabian Schmidt, Justin da Silva, Eva Bednarski, Lauren Aguado, Jim Yee, Mridushi Daga, Martina Turroja, Katrina G. Millard, Mila Jankovic, Anna Gazumyan, Zhen Zhao, Charles M. Rice, Paul

    Over one year after its inception, the coronavirus disease-2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) remains difficult to control despite the availability of several excellent vaccines. Progress in controlling the pandemic is slowed by the emergence of variants that appear to be more transmissible and more resistant to antibodies1,2. Here we report

  • 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

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