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  • Correlative operando microscopy of oxygen evolution electrocatalysts
    Nature (IF 42.778) Pub Date : 2021-05-05
    J. Tyler Mefford, Andrew R. Akbashev, Minkyung Kang, Cameron L. Bentley, William E. Gent, Haitao D. Deng, Daan Hein Alsem, Young-Sang Yu, Norman J. Salmon, David A. Shapiro, Patrick R. Unwin, William C. Chueh

    Transition metal (oxy)hydroxides are promising electrocatalysts for the oxygen evolution reaction1,2,3. The properties of these materials evolve dynamically and heterogeneously4 with applied voltage through ion insertion redox reactions, converting materials that are inactive under open circuit conditions into active electrocatalysts during operation5. The catalytic state is thus inherently far from

  • ARAF mutations confer resistance to the RAF inhibitor belvarafenib in melanoma
    Nature (IF 42.778) Pub Date : 2021-05-05
    Ivana Yen, Frances Shanahan, Jeeyun Lee, Yong Sang Hong, Sang Joon Shin, Amanda R. Moore, Jawahar Sudhamsu, Matthew T. Chang, Inhwan Bae, Darlene Dela Cruz, Thomas Hunsaker, Christiaan Klijn, Nicholas P. D. Liau, Eva Lin, Scott E. Martin, Zora Modrusan, Robert Piskol, Ehud Segal, Avinashnarayan Venkatanarayan, Xin Ye, Jianping Yin, Liangxuan Zhang, Jin-Soo Kim, Hyeong-Seok Lim, Kyu-Pyo Kim, Yu Jung

    Although RAF monomer inhibitors (type I.5, BRAF(V600)) are clinically approved for the treatment of BRAFV600-mutant melanoma, they are ineffective in non-BRAFV600 mutant cells1,2,3. Belvarafenib is a potent and selective RAF dimer (type II) inhibitor that exhibits clinical activity in patients with BRAFV600E- and NRAS-mutant melanomas. Here we report the first-in-human phase I study investigating the

  • Rashba valleys and quantum Hall states in few-layer black arsenic
    Nature (IF 42.778) Pub Date : 2021-05-05
    Feng Sheng, Chenqiang Hua, Man Cheng, Jie Hu, Xikang Sun, Qian Tao, Hengzhe Lu, Yunhao Lu, Mianzeng Zhong, Kenji Watanabe, Takashi Taniguchi, Qinglin Xia, Zhu-An Xu, Yi Zheng

    Exciting phenomena may emerge in non-centrosymmetric two-dimensional electronic systems when spin–orbit coupling (SOC)1 interplays dynamically with Coulomb interactions2,3, band topology4,5 and external modulating forces6,7,8. Here we report synergetic effects between SOC and the Stark effect in centrosymmetric few-layer black arsenic, which manifest as particle–hole asymmetric Rashba valley formation

  • Response of the microbiome–gut–brain axis in Drosophila to amino acid deficit
    Nature (IF 42.778) Pub Date : 2021-05-05
    Boram Kim, Makoto I. Kanai, Yangkyun Oh, Minsoo Kyung, Eun-Kyoung Kim, In-Hwan Jang, Ji-Hoon Lee, Sang-Gyu Kim, Greg S. B. Suh, Won-Jae Lee

    A balanced intake of macronutrients—protein, carbohydrate and fat—is essential for the well-being of organisms. An adequate calorific intake but with insufficient protein consumption can lead to several ailments, including kwashiorkor1. Taste receptors (T1R1–T1R3)2 can detect amino acids in the environment, and cellular sensors (Gcn2 and Tor)3 monitor the levels of amino acids in the cell. When deprived

  • Distinct fission signatures predict mitochondrial degradation or biogenesis
    Nature (IF 42.778) Pub Date : 2021-05-05
    Tatjana Kleele, Timo Rey, Julius Winter, Sofia Zaganelli, Dora Mahecic, Hélène Perreten Lambert, Francesco Paolo Ruberto, Mohamed Nemir, Timothy Wai, Thierry Pedrazzini, Suliana Manley

    Mitochondrial fission is a highly regulated process that, when disrupted, can alter metabolism, proliferation and apoptosis1,2,3. Dysregulation has been linked to neurodegeneration3,4, cardiovascular disease3 and cancer5. Key components of the fission machinery include the endoplasmic reticulum6 and actin7, which initiate constriction before dynamin-related protein 1 (DRP1)8 binds to the outer mitochondrial

  • A lysine–cysteine redox switch with an NOS bridge regulates enzyme function
    Nature (IF 42.778) Pub Date : 2021-05-05
    Marie Wensien, Fabian Rabe von Pappenheim, Lisa-Marie Funk, Patrick Kloskowski, Ute Curth, Ulf Diederichsen, Jon Uranga, Jin Ye, Pan Fang, Kuan-Ting Pan, Henning Urlaub, Ricardo A. Mata, Viktor Sautner, Kai Tittmann

    Disulfide bonds between cysteine residues are important post-translational modifications in proteins that have critical roles for protein structure and stability, as redox-active catalytic groups in enzymes or allosteric redox switches that govern protein function1,2,3,4. In addition to forming disulfide bridges, cysteine residues are susceptible to oxidation by reactive oxygen species, and are thus

  • Epigenetic silencing by SETDB1 suppresses tumour intrinsic immunogenicity
    Nature (IF 42.778) Pub Date : 2021-05-05
    Gabriel K. Griffin, Jingyi Wu, Arvin Iracheta-Vellve, James C. Patti, Jeffrey Hsu, Thomas Davis, Deborah Dele-Oni, Peter P. Du, Aya G. Halawi, Jeffrey J. Ishizuka, Sarah Y. Kim, Susan Klaeger, Nelson H. Knudsen, Brian C. Miller, Tung H. Nguyen, Kira E. Olander, Malvina Papanastasiou, Suzanna Rachimi, Emily J. Robitschek, Emily M. Schneider, Mitchell D. Yeary, Margaret D. Zimmer, Jacob D. Jaffe, Steven

    Epigenetic dysregulation is a defining feature of tumorigenesis that is implicated in immune escape1,2. Here, to identify factors that modulate the immune sensitivity of cancer cells, we performed in vivo CRISPR–Cas9 screens targeting 936 chromatin regulators in mouse tumour models treated with immune checkpoint blockade. We identified the H3K9 methyltransferase SETDB1 and other members of the HUSH

  • Earliest known human burial in Africa
    Nature (IF 42.778) Pub Date : 2021-05-05
    María Martinón-Torres, Francesco d’Errico, Elena Santos, Ana Álvaro Gallo, Noel Amano, William Archer, Simon J. Armitage, Juan Luis Arsuaga, José María Bermúdez de Castro, James Blinkhorn, Alison Crowther, Katerina Douka, Stéphan Dubernet, Patrick Faulkner, Pilar Fernández-Colón, Nikos Kourampas, Jorge González García, David Larreina, François-Xavier Le Bourdonnec, George MacLeod, Laura Martín-Francés

    The origin and evolution of hominin mortuary practices are topics of intense interest and debate1,2,3. Human burials dated to the Middle Stone Age (MSA) are exceedingly rare in Africa and unknown in East Africa1,2,3,4,5,6. Here we describe the partial skeleton of a roughly 2.5- to 3.0-year-old child dating to 78.3 ± 4.1 thousand years ago, which was recovered in the MSA layers of Panga ya Saidi (PYS)

  • The Paris Climate Agreement and future sea-level rise from Antarctica
    Nature (IF 42.778) Pub Date : 2021-05-05
    Robert M. DeConto, David Pollard, Richard B. Alley, Isabella Velicogna, Edward Gasson, Natalya Gomez, Shaina Sadai, Alan Condron, Daniel M. Gilford, Erica L. Ashe, Robert E. Kopp, Dawei Li, Andrea Dutton

    The Paris Agreement aims to limit global mean warming in the twenty-first century to less than 2 degrees Celsius above preindustrial levels, and to promote further efforts to limit warming to 1.5 degrees Celsius1. The amount of greenhouse gas emissions in coming decades will be consequential for global mean sea level (GMSL) on century and longer timescales through a combination of ocean thermal expansion

  • Fast odour dynamics are encoded in the olfactory system and guide behaviour
    Nature (IF 42.778) Pub Date : 2021-05-05
    Tobias Ackels, Andrew Erskine, Debanjan Dasgupta, Alina Cristina Marin, Tom P. A. Warner, Sina Tootoonian, Izumi Fukunaga, Julia J. Harris, Andreas T. Schaefer

    Odours are transported in turbulent plumes, which result in rapid concentration fluctuations1,2 that contain rich information about the olfactory scenery, such as the composition and location of an odour source2,3,4. However, it is unclear whether the mammalian olfactory system can use the underlying temporal structure to extract information about the environment. Here we show that ten-millisecond

  • Polypeptide organic radical batteries
    Nature (IF 42.778) Pub Date : 2021-05-05
    Tan P. Nguyen, Alexandra D. Easley, Nari Kang, Sarosh Khan, Soon-Mi Lim, Yohannes H. Rezenom, Shaoyang Wang, David K. Tran, Jingwei Fan, Rachel A. Letteri, Xun He, Lu Su, Cheng-Han Yu, Jodie L. Lutkenhaus, Karen L. Wooley

    In only a few decades, lithium-ion batteries have revolutionized technologies, enabling the proliferation of portable devices and electric vehicles1, with substantial benefits for society. However, the rapid growth in technology has highlighted the ethical and environmental challenges of mining lithium, cobalt and other mineral ore resources, and the issues associated with the safe usage and non-hazardous

  • Jets from MRC 0600-399 bent by magnetic fields in the cluster Abell 3376
    Nature (IF 42.778) Pub Date : 2021-05-05
    James O. Chibueze, Haruka Sakemi, Takumi Ohmura, Mami Machida, Hiroki Akamatsu, Takuya Akahori, Hiroyuki Nakanishi, Viral Parekh, Ruby van Rooyen, Tsutomu T. Takeuchi

    Galaxy clusters are known to harbour magnetic fields, the nature of which remains unresolved. Intra-cluster magnetic fields can be observed at the density contact discontinuity formed by cool and dense plasma running into hot ambient plasma1,2, and the discontinuity exists3 near the second-brightest galaxy4, MRC 0600-399, in the merging galaxy cluster Abell 3376 (redshift 0.0461). Elongated X-ray emission

  • A high-quality bonobo genome refines the analysis of hominid evolution
    Nature (IF 42.778) Pub Date : 2021-05-05
    Yafei Mao, Claudia R. Catacchio, LaDeana W. Hillier, David Porubsky, Ruiyang Li, Arvis Sulovari, Jason D. Fernandes, Francesco Montinaro, David S. Gordon, Jessica M. Storer, Marina Haukness, Ian T. Fiddes, Shwetha Canchi Murali, Philip C. Dishuck, PingHsun Hsieh, William T. Harvey, Peter A. Audano, Ludovica Mercuri, Ilaria Piccolo, Francesca Antonacci, Katherine M. Munson, Alexandra P. Lewis, Carl

    The divergence of chimpanzee and bonobo provides one of the few examples of recent hominid speciation1,2. Here we describe a fully annotated, high-quality bonobo genome assembly, which was constructed without guidance from reference genomes by applying a multiplatform genomics approach. We generate a bonobo genome assembly in which more than 98% of genes are completely annotated and 99% of the gaps

  • Replication stress promotes cell elimination by extrusion
    Nature (IF 42.778) Pub Date : 2021-05-05
    Vivek K. Dwivedi, Carlos Pardo-Pastor, Rita Droste, Ji Na Kong, Nolan Tucker, Daniel P. Denning, Jody Rosenblatt, H. Robert Horvitz

    Cell extrusion is a mechanism of cell elimination that is used by organisms as diverse as sponges, nematodes, insects and mammals1,2,3. During extrusion, a cell detaches from a layer of surrounding cells while maintaining the continuity of that layer4. Vertebrate epithelial tissues primarily eliminate cells by extrusion, and the dysregulation of cell extrusion has been linked to epithelial diseases

  • Projected land ice contributions to twenty-first-century sea level rise
    Nature (IF 42.778) Pub Date : 2021-05-05
    Tamsin L. Edwards, Sophie Nowicki, Ben Marzeion, Regine Hock, Heiko Goelzer, Hélène Seroussi, Nicolas C. Jourdain, Donald A. Slater, Fiona E. Turner, Christopher J. Smith, Christine M. McKenna, Erika Simon, Ayako Abe-Ouchi, Jonathan M. Gregory, Eric Larour, William H. Lipscomb, Antony J. Payne, Andrew Shepherd, Cécile Agosta, Patrick Alexander, Torsten Albrecht, Brian Anderson, Xylar Asay-Davis, Andy

    The land ice contribution to global mean sea level rise has not yet been predicted1 using ice sheet and glacier models for the latest set of socio-economic scenarios, nor using coordinated exploration of uncertainties arising from the various computer models involved. Two recent international projects generated a large suite of projections using multiple models2,3,4,5,6,7,8, but primarily used previous-generation

  • Global miRNA dosage control of embryonic germ layer specification
    Nature (IF 42.778) Pub Date : 2021-05-05
    Yingzi Cui, Xuehui Lyu, Li Ding, Lan Ke, Dechang Yang, Mehdi Pirouz, Ye Qi, Jennie Ong, Ge Gao, Peng Du, Richard I. Gregory

    MicroRNAs (miRNAs) have essential functions during embryonic development, and their dysregulation causes cancer1,2. Altered global miRNA abundance is found in different tissues and tumours, which implies that precise control of miRNA dosage is important1,3,4, but the underlying mechanism(s) of this control remain unknown. The protein complex Microprocessor, which comprises one DROSHA and two DGCR8

  • A molecular single-cell lung atlas of lethal COVID-19
    Nature (IF 42.778) Pub Date : 2021-04-29
    Johannes C. Melms, Jana Biermann, Huachao Huang, Yiping Wang, Ajay Nair, Somnath Tagore, Igor Katsyv, André F. Rendeiro, Amit Dipak Amin, Denis Schapiro, Chris J. Frangieh, Adrienne M. Luoma, Aveline Filliol, Yinshan Fang, Hiranmayi Ravichandran, Mariano G. Clausi, George A. Alba, Meri Rogava, Sean W. Chen, Patricia Ho, Daniel T. Montoro, Adam E. Kornberg, Arnold S. Han, Mathieu F. Bakhoum, Niroshana

    Respiratory failure is the leading cause of death in patients with severe SARS-CoV-2 infection1,2, yet the host response at the lung tissue-level is poorly understood. Here, we performed single-nucleus RNA-sequencing of ~116,000 nuclei of lungs from 19 COVID-19 decedents who underwent rapid autopsy and 7 control lungs. Integrated analyses revealed significant alterations in cellular composition, transcriptional

  • COVID-19 tissue atlases reveal SARS-CoV-2 pathology and cellular targets
    Nature (IF 42.778) Pub Date : 2021-04-29
    Toni M. Delorey, Carly G. K. Ziegler, Graham Heimberg, Rachelly Normand, Yiming Yang, Åsa Segerstolpe, Domenic Abbondanza, Stephen J. Fleming, Ayshwarya Subramanian, Daniel T. Montoro, Karthik A. Jagadeesh, Kushal K. Dey, Pritha Sen, Michal Slyper, Yered H. Pita-Juárez, Devan Phillips, Jana Biermann, Zohar Bloom-Ackermann, Nick Barkas, Andrea Ganna, James Gomez, Johannes C. Melms, Igor Katsyv, Erica

    COVID-19, caused by SARS-CoV-2, can result in acute respiratory distress syndrome and multiple-organ failure1–4, but little is known about its pathophysiology. Here, we generated single-cell atlases of 23 lung, 16 kidney, 16 liver and 19 heart COVID-19 autopsy donor tissue samples, and spatial atlases of 14 lung donors. Integrated computational analysis uncovered substantial remodeling in the lung

  • Phosphorus-mediated sp 2 - sp 3 couplings for C–H fluoroalkylation of azines
    Nature (IF 42.778) Pub Date : 2021-04-28
    Xuan Zhang, Kyle G. Nottingham, Chirag Patel, Juan V. Alegre-Requena, Jeffrey N. Levy, Robert S. Paton, Andrew McNally

    Fluoroalkyl groups profoundly affect the physical properties of pharmaceuticals and influence virtually all metrics associated with their pharmacokinetic and pharmacodynamic profiles.1–4 Drug candidates increasingly contain CF3 and CF2H groups, and the same trend in agrochemical development shows that the effect of fluoroalkylation translates across human, insect, and plant life.5,6 New fluoroalkylation

  • PIK3CA and CCM mutations fuel cavernomas through a cancer-like mechanism
    Nature (IF 42.778) Pub Date : 2021-04-28
    Aileen A. Ren, Daniel A. Snellings, Yourong S. Su, Courtney C. Hong, Marco Castro, Alan T. Tang, Matthew R. Detter, Nicholas Hobson, Romuald Girard, Sharbel Romanos, Rhonda Lightle, Thomas Moore, Robert Shenkar, Christian Benavides, M. Makenzie Beaman, Helge Mueller-Fielitz, Mei Chen, Patricia Mericko, Jisheng Yang, Derek C. Sung, Michael T. Lawton, Michael Ruppert, Markus Schwaninger, Jakob Körbelin

    Vascular malformations are considered monogenic disorders that result in dysregulated vessel growth. Cerebral cavernous malformations (CCMs) arise owing to inactivation of the endothelial CCM protein complex required to dampen MEKK3 activity1–4. Environmental factors explain differences in CCM natural history between individuals5, but why single CCMs often exhibit sudden, rapid growth culminating in

  • Evolutionary and biomedical insights from a marmoset diploid genome assembly
    Nature (IF 42.778) Pub Date : 2021-04-28
    Chentao Yang, Yang Zhou, Stephanie Marcus, Giulio Formenti, Lucie A. Bergeron, Zhenzhen Song, Xupeng Bi, Juraj Bergman, Marjolaine Marie C. Rousselle, Chengran Zhou, Long Zhou, Yuan Deng, Miaoquan Fang, Duo Xie, Yuanzhen Zhu, Shangjin Tan, Jacquelyn Mountcastle, Bettina Haase, Jennifer Balacco, Jonathan Wood, William Chow, Arang Rhie, Martin Pippel, Margaret M. Fabiszak, Sergey Koren, Olivier Fedrigo

    The accurate and complete assembly of both haplotype sequences of a diploid organism is essential to understanding the role of variation in genome functions, phenotypes, and diseases1. Here, using a trio-binning approach, we present a high-quality, diploid reference genome, with both haplotypes assembled independently at the chromosome level, for the common marmoset (Callithrix jacchus), an important

  • Direct assessment of the acidity of individual surface hydroxyls
    Nature (IF 42.778) Pub Date : 2021-04-28
    Margareta Wagner, Bernd Meyer, Martin Setvin, Michael Schmid, Ulrike Diebold

    The state of deprotonation/protonation of surfaces has far-ranging implications in chemistry, from acid–base catalysis1 and the electrocatalytic and photocatalytic splitting of water2, to the behaviour of minerals3 and biochemistry4. An entity’s acidity is described by its proton affinity and its acid dissociation constant pKa (the negative logarithm of the equilibrium constant of the proton transfer

  • Towards complete and error-free genome assemblies of all vertebrate species
    Nature (IF 42.778) Pub Date : 2021-04-28
    Arang Rhie, Shane A. McCarthy, Olivier Fedrigo, Joana Damas, Giulio Formenti, Sergey Koren, Marcela Uliano-Silva, William Chow, Arkarachai Fungtammasan, Juwan Kim, Chul Lee, Byung June Ko, Mark Chaisson, Gregory L. Gedman, Lindsey J. Cantin, Francoise Thibaud-Nissen, Leanne Haggerty, Iliana Bista, Michelle Smith, Bettina Haase, Jacquelyn Mountcastle, Sylke Winkler, Sadye Paez, Jason Howard, Sonja C

    High-quality and complete reference genome assemblies are fundamental for the application of genomics to biology, disease, and biodiversity conservation. However, such assemblies are available for only a few non-microbial species1,2,3,4. To address this issue, the international Genome 10K (G10K) consortium5,6 has worked over a five-year period to evaluate and develop cost-effective methods for assembling

  • Universal nomenclature for oxytocin–vasotocin ligand and receptor families
    Nature (IF 42.778) Pub Date : 2021-04-28
    Constantina Theofanopoulou, Gregory Gedman, James A. Cahill, Cedric Boeckx, Erich D. Jarvis

    Oxytocin (OXT; hereafter OT) and arginine vasopressin or vasotocin (AVP or VT; hereafter VT) are neurotransmitter ligands that function through specific receptors to control diverse functions1,2. Here we performed genomic analyses on 35 species that span all major vertebrate lineages, including newly generated high-contiguity assemblies from the Vertebrate Genomes Project3,4. Our findings support the

  • Direct observation of chemical short-range order in a medium-entropy alloy
    Nature (IF 42.778) Pub Date : 2021-04-28
    Xuefei Chen, Qi Wang, Zhiying Cheng, Mingliu Zhu, Hao Zhou, Ping Jiang, Lingling Zhou, Qiqi Xue, Fuping Yuan, Jing Zhu, Xiaolei Wu, En Ma

    Complex concentrated solutions of multiple principal elements are being widely investigated as high- or medium-entropy alloys (HEAs or MEAs)1,2,3,4,5,6,7,8,9,10,11, often assuming that these materials have the high configurational entropy of an ideal solution. However, enthalpic interactions among constituent elements are also expected at normal temperatures, resulting in various degrees of local chemical

  • Expanded diversity of Asgard archaea and their relationships with eukaryotes
    Nature (IF 42.778) Pub Date : 2021-04-28
    Yang Liu, Kira S. Makarova, Wen-Cong Huang, Yuri I. Wolf, Anastasia N. Nikolskaya, Xinxu Zhang, Mingwei Cai, Cui-Jing Zhang, Wei Xu, Zhuhua Luo, Lei Cheng, Eugene V. Koonin, Meng Li

    Asgard is a recently discovered superphylum of archaea that appears to include the closest archaeal relatives of eukaryotes1,2,3,4,5. Debate continues as to whether the archaeal ancestor of eukaryotes belongs within the Asgard superphylum or whether this ancestor is a sister group to all other archaea (that is, a two-domain versus a three-domain tree of life)6,7,8. Here we present a comparative analysis

  • Plume-driven recratonization of deep continental lithospheric mantle
    Nature (IF 42.778) Pub Date : 2021-04-28
    Jingao Liu, D. Graham Pearson, Lawrence Hongliang Wang, Kathy A. Mather, Bruce A. Kjarsgaard, Andrew J. Schaeffer, Gordon J. Irvine, Maya G. Kopylova, John P. Armstrong

    Cratons are Earth’s ancient continental land masses that remain stable for billions of years. The mantle roots of cratons are renowned as being long-lived, stable features of Earth’s continents, but there is also evidence of their disruption in the recent1,2,3,4,5,6 and more distant7,8,9 past. Despite periods of lithospheric thinning during the Proterozoic and Phanerozoic eons, the lithosphere beneath

  • Coupling of activity, metabolism and behaviour across the Drosophila brain
    Nature (IF 42.778) Pub Date : 2021-04-28
    Kevin Mann, Stephane Deny, Surya Ganguli, Thomas R. Clandinin

    Coordinated activity across networks of neurons is a hallmark of both resting and active behavioural states in many species1,2,3,4,5. These global patterns alter energy metabolism over seconds to hours, which underpins the widespread use of oxygen consumption and glucose uptake as proxies of neural activity6,7. However, whether changes in neural activity are causally related to metabolic flux in intact

  • Transition from an atomic to a molecular Bose–Einstein condensate
    Nature (IF 42.778) Pub Date : 2021-04-28
    Zhendong Zhang, Liangchao Chen, Kai-Xuan Yao, Cheng Chin

    Molecular quantum gases (that is, ultracold and dense molecular gases) have many potential applications, including quantum control of chemical reactions, precision measurements, quantum simulation and quantum information processing1,2,3. For molecules, to reach the quantum regime usually requires efficient cooling at high densities, which is frequently hindered by fast inelastic collisions that heat

  • Structural basis of GABA B receptor–G i protein coupling
    Nature (IF 42.778) Pub Date : 2021-04-28
    Cangsong Shen, Chunyou Mao, Chanjuan Xu, Nan Jin, Huibing Zhang, Dan-Dan Shen, Qingya Shen, Xiaomei Wang, Tingjun Hou, Zhong Chen, Philippe Rondard, Jean-Philippe Pin, Yan Zhang, Jianfeng Liu

    G-protein-coupled receptors (GPCRs) have central roles in intercellular communication1,2. Structural studies have revealed how GPCRs can activate G proteins. However, whether this mechanism is conserved among all classes of GPCR remains unknown. Here we report the structure of the class-C heterodimeric GABAB receptor, which is activated by the inhibitory transmitter GABA, in its active form complexed

  • Accelerated global glacier mass loss in the early twenty-first century
    Nature (IF 42.778) Pub Date : 2021-04-28
    Romain Hugonnet, Robert McNabb, Etienne Berthier, Brian Menounos, Christopher Nuth, Luc Girod, Daniel Farinotti, Matthias Huss, Ines Dussaillant, Fanny Brun, Andreas Kääb

    Glaciers distinct from the Greenland and Antarctic ice sheets are shrinking rapidly, altering regional hydrology1, raising global sea level2 and elevating natural hazards3. Yet, owing to the scarcity of constrained mass loss observations, glacier evolution during the satellite era is known only partially, as a geographic and temporal patchwork4,5. Here we reveal the accelerated, albeit contrasting

  • C. difficile exploits a host metabolite produced during toxin-mediated disease
    Nature (IF 42.778) Pub Date : 2021-04-28
    Kali M. Pruss, Justin L. Sonnenburg

    Several enteric pathogens can gain specific metabolic advantages over other members of the microbiota by inducing host pathology and inflammation. The pathogen Clostridium difficile is responsible for a toxin-mediated colitis that causes 450,000 infections and 15,000 deaths in the United States each year1; however, the molecular mechanisms by which C. difficile benefits from this pathology remain unclear

  • X-ray quasi-periodic eruptions from two previously quiescent galaxies
    Nature (IF 42.778) Pub Date : 2021-04-28
    R. Arcodia, A. Merloni, K. Nandra, J. Buchner, M. Salvato, D. Pasham, R. Remillard, J. Comparat, G. Lamer, G. Ponti, A. Malyali, J. Wolf, Z. Arzoumanian, D. Bogensberger, D. A. H. Buckley, K. Gendreau, M. Gromadzki, E. Kara, M. Krumpe, C. Markwardt, M. E. Ramos-Ceja, A. Rau, M. Schramm, A. Schwope

    Quasi-periodic eruptions (QPEs) are very-high-amplitude bursts of X-ray radiation recurring every few hours and originating near the central supermassive black holes of galactic nuclei1,2. It is currently unknown what triggers these events, how long they last and how they are connected to the physical properties of the inner accretion flows. Previously, only two such sources were known, found either

  • Structure of human Mediator–RNA polymerase II pre-initiation complex
    Nature (IF 42.778) Pub Date : 2021-04-26
    Srinivasan Rengachari, Sandra Schilbach, Shintaro Aibara, Christian Dienemann, Patrick Cramer

    Mediator is a conserved coactivator that enables regulated transcription initiation at eukaryotic genes1–3. Mediator is recruited by transcriptional activators and binds the pre-initiation complex (PIC) to stimulate RNA polymerase II (Pol II) phosphorylation and promoter escape1–6. Here we prepare a recombinant human Mediator, reconstitute a 50-subunit Mediator-PIC complex, and determine the structure

  • Structures of mammalian RNA polymerase II pre-initiation complexes
    Nature (IF 42.778) Pub Date : 2021-04-26
    Shintaro Aibara, Sandra Schilbach, Patrick Cramer

    The initiation of transcription is a focal point for the regulation of gene activity during mammalian cell differentiation and development. For transcription initiation, RNA polymerase II (Pol II) assembles with general transcription factors into a pre-initiation complex (PIC) that opens promoter DNA. Previous work provided the molecular architecture of the yeast1–9 and human10,11 PIC and a topological

  • Small molecule inhibition of METTL3 as a strategy against myeloid leukaemia
    Nature (IF 42.778) Pub Date : 2021-04-26
    Eliza Yankova, Wesley Blackaby, Mark Albertella, Justyna Rak, Etienne De Braekeleer, Georgia Tsagkogeorga, Ewa S. Pilka, Demetrios Aspris, Dan Leggate, Alan G. Hendrick, Natalie A. Webster, Byron Andrews, Richard Fosbeary, Patrick Guest, Nerea Irigoyen, Maria Eleftheriou, Malgorzata Gozdecka, Joao M. L. Dias, Andrew J. Bannister, Binje Vick, Irmela Jeremias, George S. Vassiliou, Oliver Rausch, Konstantinos

    The N6-methyladenosine (m6A) is an abundant internal RNA modification1,2 catalysed predominantly by the METTL3–METTL14 methyltransferase complex3,4. The m6A writer METTL3 has been linked to the initiation and maintenance of acute myeloid leukaemia (AML), but its true therapeutic importance is still unknown5–7. Here we present the identification and characterization of a highly potent and selective

  • High-dimensional characterization of post-acute sequalae of COVID-19
    Nature (IF 42.778) Pub Date : 2021-04-22
    Ziyad Al-Aly, Yan Xie, Benjamin Bowe

    The acute clinical manifestations of COVID-19 are well characterized1,2; however, its post-acute sequalae have not been comprehensively described. Here, we use the national healthcare databases of the US Department of Veterans Affairs to systematically and comprehensively identify 6-month incident sequalae including diagnoses, medication use, and laboratory abnormalities in 30-day survivors of COVID-19

  • Overriding water table control on managed peatland greenhouse gas emissions
    Nature (IF 42.778) Pub Date : 2021-04-21
    C. D. Evans, M. Peacock, A. J. Baird, R. R. E. Artz, A. Burden, N. Callaghan, P. J. Chapman, H. M. Cooper, M. Coyle, E. Craig, A. Cumming, S. Dixon, V. Gauci, R. P. Grayson, C. Helfter, C. M. Heppell, J. Holden, D. L. Jones, J. Kaduk, P. Levy, R. Matthews, N. P. McNamara, T. Misselbrook, S. Oakley, S. Page, M. Rayment, L. M. Ridley, K. M. Stanley, J. L. Williamson, F. Worrall, R. Morrison

    Global peatlands store more carbon than is naturally present in the atmosphere1,2. However, many peatlands are under pressure from drainage-based agriculture, plantation development and fire, with the equivalent of around 3% of all anthropogenic greenhouse gases emitted from drained peatland3–5. Efforts to curb such emissions are intensifying through the conservation of undrained peatlands and rewetting

  • All-sky dynamical response of the Galactic halo to the Large Magellanic Cloud
    Nature (IF 42.778) Pub Date : 2021-04-21
    Charlie Conroy, Rohan P. Naidu, Nicolás Garavito-Camargo, Gurtina Besla, Dennis Zaritsky, Ana Bonaca, Benjamin D. Johnson

    Gravitational interactions between the Large Magellanic Cloud (LMC) and the stellar and dark matter halo of the Milky Way are expected to give rise to disequilibrium phenomena in the outer Milky Way1,2,3,4,5,6,7. A local wake is predicted to trail the orbit of the LMC, and a large-scale overdensity is predicted to exist across a large area of the northern Galactic hemisphere. Here we report the detection

  • The changing landscape of atherosclerosis
    Nature (IF 42.778) Pub Date : 2021-04-21
    Peter Libby

    Emerging evidence has spurred a considerable evolution of concepts relating to atherosclerosis, and has called into question many previous notions. Here I review this evidence, and discuss its implications for understanding of atherosclerosis. The risk of developing atherosclerosis is no longer concentrated in Western countries, and it is instead involved in the majority of deaths worldwide. Atherosclerosis

  • High CO 2 levels drive the TCA cycle backwards towards autotrophy
    Nature (IF 42.778) Pub Date : 2021-04-21
    Lydia Steffens, Eugenio Pettinato, Thomas M. Steiner, Achim Mall, Simone König, Wolfgang Eisenreich, Ivan A. Berg

    It has recently been shown that in anaerobic microorganisms the tricarboxylic acid (TCA) cycle, including the seemingly irreversible citrate synthase reaction, can be reversed and used for autotrophic fixation of carbon1,2. This reversed oxidative TCA cycle requires ferredoxin-dependent 2-oxoglutarate synthase instead of the NAD-dependent dehydrogenase as well as extremely high levels of citrate synthase

  • Overshooting tipping point thresholds in a changing climate
    Nature (IF 42.778) Pub Date : 2021-04-21
    Paul D. L. Ritchie, Joseph J. Clarke, Peter M. Cox, Chris Huntingford

    Palaeorecords suggest that the climate system has tipping points, where small changes in forcing cause substantial and irreversible alteration to Earth system components called tipping elements. As atmospheric greenhouse gas concentrations continue to rise as a result of fossil fuel burning, human activity could also trigger tipping, and the impacts would be difficult to adapt to. Previous studies

  • Multistable inflatable origami structures at the metre scale
    Nature (IF 42.778) Pub Date : 2021-04-21
    David Melancon, Benjamin Gorissen, Carlos J. García-Mora, Chuck Hoberman, Katia Bertoldi

    From stadium covers to solar sails, we rely on deployability for the design of large-scale structures that can quickly compress to a fraction of their size1,2,3,4. Historically, two main strategies have been used to design deployable systems. The first and most frequently used approach involves mechanisms comprising interconnected bar elements, which can synchronously expand and retract5,6,7, occasionally

  • Gasdermin D pore structure reveals preferential release of mature interleukin-1
    Nature (IF 42.778) Pub Date : 2021-04-21
    Shiyu Xia, Zhibin Zhang, Venkat Giri Magupalli, Juan Lorenzo Pablo, Ying Dong, Setu M. Vora, Longfei Wang, Tian-Min Fu, Matthew P. Jacobson, Anna Greka, Judy Lieberman, Jianbin Ruan, Hao Wu

    As organelles of the innate immune system, inflammasomes activate caspase-1 and other inflammatory caspases that cleave gasdermin D (GSDMD). Caspase-1 also cleaves inactive precursors of the interleukin (IL)-1 family to generate mature cytokines such as IL-1β and IL-18. Cleaved GSDMD forms transmembrane pores to enable the release of IL-1 and to drive cell lysis through pyroptosis1,2,3,4,5,6,7,8,9

  • Equity is more important for the social cost of methane than climate uncertainty
    Nature (IF 42.778) Pub Date : 2021-04-21
    Frank C. Errickson, Klaus Keller, William D. Collins, Vivek Srikrishnan, David Anthoff

    The social cost of methane (SC-CH4) measures the economic loss of welfare caused by emitting one tonne of methane into the atmosphere. This valuation may in turn be used in cost–benefit analyses or to inform climate policies1,2,3. However, current SC-CH4 estimates have not included key scientific findings and observational constraints. Here we estimate the SC-CH4 by incorporating the recent upward

  • Mouse prefrontal cortex represents learned rules for categorization
    Nature (IF 42.778) Pub Date : 2021-04-21
    Sandra Reinert, Mark Hübener, Tobias Bonhoeffer, Pieter M. Goltstein

    The ability to categorize sensory stimuli is crucial for an animal’s survival in a complex environment. Memorizing categories instead of individual exemplars enables greater behavioural flexibility and is computationally advantageous. Neurons that show category selectivity have been found in several areas of the mammalian neocortex1,2,3,4, but the prefrontal cortex seems to have a prominent role4,5

  • A single-molecule van der Waals compass
    Nature (IF 42.778) Pub Date : 2021-04-21
    Boyuan Shen, Xiao Chen, Huiqiu Wang, Hao Xiong, Eric G. T. Bosch, Ivan Lazić, Dali Cai, Weizhong Qian, Shifeng Jin, Xin Liu, Yu Han, Fei Wei

    Single-molecule imaging is challenging but highly beneficial for investigating intermolecular interactions at the molecular level1,2,3,4,5,6. Van der Waals interactions at the sub-nanometre scale strongly influence various molecular behaviours under confinement conditions7,8,9,10,11. Inspired by the traditional compass12, here we use a para-xylene molecule as a rotating pointer to detect the host–guest

  • Unveiling African rainforest composition and vulnerability to global change
    Nature (IF 42.778) Pub Date : 2021-04-21
    Maxime Réjou-Méchain, Frédéric Mortier, Jean-François Bastin, Guillaume Cornu, Nicolas Barbier, Nicolas Bayol, Fabrice Bénédet, Xavier Bry, Gilles Dauby, Vincent Deblauwe, Jean-Louis Doucet, Charles Doumenge, Adeline Fayolle, Claude Garcia, Jean-Paul Kibambe Lubamba, Jean-Joël Loumeto, Alfred Ngomanda, Pierre Ploton, Bonaventure Sonké, Catherine Trottier, Ruppert Vimal, Olga Yongo, Raphaël Pélissier

    Africa is forecasted to experience large and rapid climate change1 and population growth2 during the twenty-first century, which threatens the world’s second largest rainforest. Protecting and sustainably managing these African forests requires an increased understanding of their compositional heterogeneity, the environmental drivers of forest composition and their vulnerability to ongoing changes

  • Near-complete depolymerization of polyesters with nano-dispersed enzymes
    Nature (IF 42.778) Pub Date : 2021-04-21
    Christopher DelRe, Yufeng Jiang, Philjun Kang, Junpyo Kwon, Aaron Hall, Ivan Jayapurna, Zhiyuan Ruan, Le Ma, Kyle Zolkin, Tim Li, Corinne D. Scown, Robert O. Ritchie, Thomas P. Russell, Ting Xu

    Successfully interfacing enzymes and biomachinery with polymers affords on-demand modification and/or programmable degradation during the manufacture, utilization and disposal of plastics, but requires controlled biocatalysis in solid matrices with macromolecular substrates1,2,3,4,5,6,7. Embedding enzyme microparticles speeds up polyester degradation, but compromises host properties and unintentionally

  • High-entropy ejecta plumes in Cassiopeia A from neutrino-driven convection
    Nature (IF 42.778) Pub Date : 2021-04-21
    Toshiki Sato, Keiichi Maeda, Shigehiro Nagataki, Takashi Yoshida, Brian Grefenstette, Brian J. Williams, Hideyuki Umeda, Masaomi Ono, John P. Hughes

    Recent multi-dimensional simulations suggest that high-entropy buoyant plumes help massive stars to explode1,2. Outwardly protruding iron (Fe)-rich fingers of gas in the galactic supernova remnant3,4 Cassiopeia A seem to match this picture. Detecting the signatures of specific elements synthesized in the high-entropy nuclear burning regime (that is, α-rich freeze out) would constitute strong substantiating

  • Structure of human telomerase holoenzyme with bound telomeric DNA
    Nature (IF 42.778) Pub Date : 2021-04-21
    George E. Ghanim, Adam J. Fountain, Anne-Marie M. van Roon, Ramya Rangan, Rhiju Das, Kathleen Collins, Thi Hoang Duong Nguyen

    Telomerase adds telomeric repeats at chromosome ends to compensate for the telomere loss that is caused by incomplete genome end replication1. In humans, telomerase is upregulated during embryogenesis and in cancers, and mutations that compromise the function of telomerase result in disease2. A previous structure of human telomerase at a resolution of 8 Å revealed a vertebrate-specific composition

  • Adjuvanting a subunit COVID-19 vaccine to induce protective immunity
    Nature (IF 42.778) Pub Date : 2021-04-19
    Prabhu S. Arunachalam, Alexandra C. Walls, Nadia Golden, Caroline Atyeo, Stephanie Fischinger, Chunfeng Li, Pyone Aye, Mary Jane Navarro, Lilin Lai, Venkata Viswanadh Edara, Katharina Röltgen, Kenneth Rogers, Lisa Shirreff, Douglas E. Ferrell, Samuel Wrenn, Deleah Pettie, John C. Kraft, Marcos C. Miranda, Elizabeth Kepl, Claire Sydeman, Natalie Brunette, Michael Murphy, Brooke Fiala, Lauren Carter

    The development of a portfolio of COVID-19 vaccines to vaccinate the global population remains an urgent public health imperative1. Here we demonstrate the capacity of a subunit vaccine, comprising the SARS-CoV-2 spike receptor binding domain displayed on a protein nanoparticle (RBD-NP), to stimulate robust and durable neutralizing antibody (nAb) responses and protection against SARS-CoV-2 in non-human

  • HP1 drives de novo 3D genome reorganization in early Drosophila embryos
    Nature (IF 42.778) Pub Date : 2021-04-14
    Fides Zenk, Yinxiu Zhan, Pavel Kos, Eva Löser, Nazerke Atinbayeva, Melanie Schächtle, Guido Tiana, Luca Giorgetti, Nicola Iovino

    Fundamental features of 3D genome organization are established de novo in the early embryo, including clustering of pericentromeric regions, the folding of chromosome arms and the segregation of chromosomes into active (A-) and inactive (B-) compartments. However, the molecular mechanisms that drive de novo organization remain unknown1,2. Here, by combining chromosome conformation capture (Hi-C), chromatin

  • Liquid-induced topological transformations of cellular microstructures
    Nature (IF 42.778) Pub Date : 2021-04-14
    Shucong Li, Bolei Deng, Alison Grinthal, Alyssha Schneider-Yamamura, Jinliang Kang, Reese S. Martens, Cathy T. Zhang, Jian Li, Siqin Yu, Katia Bertoldi, Joanna Aizenberg

    The fundamental topology of cellular structures—the location, number and connectivity of nodes and compartments—can profoundly affect their acoustic1,2,3,4, electrical5, chemical6,7, mechanical8,9,10 and optical11 properties, as well as heat1,12, fluid13,14 and particle transport15. Approaches that harness swelling16,17,18, electromagnetic actuation19,20 and mechanical instabilities21,22,23 in cellular

  • A quantum magnetic analogue to the critical point of water
    Nature (IF 42.778) Pub Date : 2021-04-14
    J. Larrea Jiménez, S. P. G. Crone, E. Fogh, M. E. Zayed, R. Lortz, E. Pomjakushina, K. Conder, A. M. Läuchli, L. Weber, S. Wessel, A. Honecker, B. Normand, Ch. Rüegg, P. Corboz, H. M. Rønnow, F. Mila

    At the liquid–gas phase transition in water, the density has a discontinuity at atmospheric pressure; however, the line of these first-order transitions defined by increasing the applied pressure terminates at the critical point1, a concept ubiquitous in statistical thermodynamics2. In correlated quantum materials, it was predicted3 and then confirmed experimentally4,5 that a critical point terminates

  • Dynamics of large effusive eruptions driven by caldera collapse
    Nature (IF 42.778) Pub Date : 2021-04-14
    Alberto Roman, Paul Lundgren

    The largest effusive basaltic eruptions are associated with caldera collapse and are manifest through quasi-periodic ground displacements and moderate-size earthquakes1,2,3, but the mechanism that governs their dynamics remains unclear. Here we provide a physical model that explains these processes, which accounts for both the quasi-periodic stick–slip collapse of the caldera roof and the long-term

  • CRL4 AMBRA1 is a master regulator of D-type cyclins
    Nature (IF 42.778) Pub Date : 2021-04-14
    Daniele Simoneschi, Gergely Rona, Nan Zhou, Yeon-Tae Jeong, Shaowen Jiang, Giacomo Milletti, Arnaldo A. Arbini, Alfie O’Sullivan, Andrew A. Wang, Sorasicha Nithikasem, Sarah Keegan, Yik Siu, Valentina Cianfanelli, Emiliano Maiani, Francesca Nazio, Francesco Cecconi, Francesco Boccalatte, David Fenyö, Drew R. Jones, Luca Busino, Michele Pagano

    D-type cyclins are central regulators of the cell division cycle and are among the most frequently deregulated therapeutic targets in human cancer1, but the mechanisms that regulate their turnover are still being debated2,3. Here, by combining biochemical and genetics studies in somatic cells, we identify CRL4AMBRA1 (also known as CRL4DCAF3) as the ubiquitin ligase that targets all three D-type cyclins

  • The antibiotic darobactin mimics a β-strand to inhibit outer membrane insertase
    Nature (IF 42.778) Pub Date : 2021-04-14
    Hundeep Kaur, Roman P. Jakob, Jan K. Marzinek, Robert Green, Yu Imai, Jani Reddy Bolla, Elia Agustoni, Carol V. Robinson, Peter J. Bond, Kim Lewis, Timm Maier, Sebastian Hiller

    Antibiotics that target Gram-negative bacteria in new ways are needed to resolve the antimicrobial resistance crisis1,2,3. Gram-negative bacteria are protected by an additional outer membrane, rendering proteins on the cell surface attractive drug targets4,5. The natural compound darobactin targets the bacterial insertase BamA6—the central unit of the essential BAM complex, which facilitates the folding

  • Genomic insights into population history and biological adaptation in Oceania
    Nature (IF 42.778) Pub Date : 2021-04-14
    Jeremy Choin, Javier Mendoza-Revilla, Lara R. Arauna, Sebastian Cuadros-Espinoza, Olivier Cassar, Maximilian Larena, Albert Min-Shan Ko, Christine Harmant, Romain Laurent, Paul Verdu, Guillaume Laval, Anne Boland, Robert Olaso, Jean-François Deleuze, Frédérique Valentin, Ying-Chin Ko, Mattias Jakobsson, Antoine Gessain, Laurent Excoffier, Mark Stoneking, Etienne Patin, Lluis Quintana-Murci

    The Pacific region is of major importance for addressing questions regarding human dispersals, interactions with archaic hominins and natural selection processes1. However, the demographic and adaptive history of Oceanian populations remains largely uncharacterized. Here we report high-coverage genomes of 317 individuals from 20 populations from the Pacific region. We find that the ancestors of Papuan-related

  • Organelle degradation in the lens by PLAAT phospholipases
    Nature (IF 42.778) Pub Date : 2021-04-14
    Hideaki Morishita, Tomoya Eguchi, Satoshi Tsukamoto, Yuriko Sakamaki, Satoru Takahashi, Chieko Saito, Ikuko Koyama-Honda, Noboru Mizushima

    The eye lens of vertebrates is composed of fibre cells in which all membrane-bound organelles undergo degradation during terminal differentiation to form an organelle-free zone1. The mechanism that underlies this large-scale organelle degradation remains largely unknown, although it has previously been shown to be independent of macroautophagy2,3. Here we report that phospholipases in the PLAAT (phospholipase

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