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  • SARS-CoV-2 uses a multipronged strategy to impede host protein synthesis
    Nature (IF 42.778) Pub Date : 2021-05-12
    Yaara Finkel, Avi Gluck, Aharon Nachshon, Roni Winkler, Tal Fisher, Batsheva Rozman, Orel Mizrahi, Yoav Lubelsky, Binyamin Zuckerman, Boris Slobodin, Yfat Yahalom-Ronen, Hadas Tamir, Igor Ulitsky, Tomer Israely, Nir Paran, Michal Schwartz, Noam Stern-Ginossar

    Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of the ongoing coronavirus disease 19 pandemic1. Coronaviruses developed varied mechanisms to repress host mRNA translation to allow the translation of viral mRNAs and concomitantly block the cellular innate immune response2,3. Although different SARS-CoV-2 proteins are implicated in host expression shutoff4–7, a comprehensive

  • The epidemiological impact of the NHS COVID-19 App
    Nature (IF 42.778) Pub Date : 2021-05-12
    Chris Wymant, Luca Ferretti, Daphne Tsallis, Marcos Charalambides, Lucie Abeler-Dörner, David Bonsall, Robert Hinch, Michelle Kendall, Luke Milsom, Matthew Ayres, Chris Holmes, Mark Briers, Christophe Fraser

    The COVID-19 pandemic has seen digital contact tracing emerge around the world to help prevent spread of the disease. A mobile phone app records proximity events between app users, and when a user tests positive for COVID-19, their recent contacts can be notified instantly. Theoretical evidence has supported this new public health intervention1–6, but its epidemiological impact has remained uncertain7

  • Skeletal editing through direct nitrogen deletion of secondary amines
    Nature (IF 42.778) Pub Date : 2021-05-12
    Sean H. Kennedy, Balu D. Dherange, Kathleen J. Berger, Mark D. Levin

    Synthetic chemistry aims to build up molecular complexity from simple feedstocks1. However, the ability to exert precise changes that manipulate the connectivity of the molecular skeleton itself remains limited, despite possessing substantial potential to expand the accessible chemical space2,3. Here we report a reaction that ‘deletes’ nitrogen from organic molecules. We show that N-pivaloyloxy-N-alkoxyamides

  • Thymic development of gut-microbiota-specific T cells
    Nature (IF 42.778) Pub Date : 2021-05-12
    Daniel F. Zegarra-Ruiz, Dasom V. Kim, Kendra Norwood, Myunghoo Kim, Wan-Jung H. Wu, Fatima B. Saldana-Morales, Andrea A. Hill, Shubhabrata Majumdar, Stephanie Orozco, Rickesha Bell, June L. Round, Randy S. Longman, Takeshi Egawa, Matthew L. Bettini, Gretchen E. Diehl

    Humans and their microbiota have coevolved a mutually beneficial relationship in which the human host provides a hospitable environment for the microorganisms and the microbiota provides many advantages for the host, including nutritional benefits and protection from pathogen infection1. Maintaining this relationship requires a careful immune balance to contain commensal microorganisms within the lumen

  • Structure and dynamics of a mycobacterial type VII secretion system
    Nature (IF 42.778) Pub Date : 2021-05-12
    Catalin M. Bunduc, Dirk Fahrenkamp, Jiri Wald, Roy Ummels, Wilbert Bitter, Edith N. G. Houben, Thomas C. Marlovits

    Mycobacterium tuberculosis is the cause of one of the most important infectious diseases in humans, which leads to 1.4 million deaths every year1. Specialized protein transport systems—known as type VII secretion systems (T7SSs)—are central to the virulence of this pathogen, and are also crucial for nutrient and metabolite transport across the mycobacterial cell envelope2,3. Here we present the structure

  • Ultralow contact resistance between semimetal and monolayer semiconductors
    Nature (IF 42.778) Pub Date : 2021-05-12
    Pin-Chun Shen, Cong Su, Yuxuan Lin, Ang-Sheng Chou, Chao-Ching Cheng, Ji-Hoon Park, Ming-Hui Chiu, Ang-Yu Lu, Hao-Ling Tang, Mohammad Mahdi Tavakoli, Gregory Pitner, Xiang Ji, Zhengyang Cai, Nannan Mao, Jiangtao Wang, Vincent Tung, Ju Li, Jeffrey Bokor, Alex Zettl, Chih-I Wu, Tomás Palacios, Lain-Jong Li, Jing Kong

    Advanced beyond-silicon electronic technology requires both channel materials and also ultralow-resistance contacts to be discovered1,2. Atomically thin two-dimensional semiconductors have great potential for realizing high-performance electronic devices1,3. However, owing to metal-induced gap states (MIGS)4,5,6,7, energy barriers at the metal–semiconductor interface—which fundamentally lead to high

  • Structures of telomerase at several steps of telomere repeat synthesis
    Nature (IF 42.778) Pub Date : 2021-05-12
    Yao He, Yaqiang Wang, Baocheng Liu, Christina Helmling, Lukas Sušac, Ryan Cheng, Z. Hong Zhou, Juli Feigon

    Telomerase is unique among the reverse transcriptases in containing a noncoding RNA (known as telomerase RNA (TER)) that includes a short template that is used for the processive synthesis of G-rich telomeric DNA repeats at the 3′ ends of most eukaryotic chromosomes1. Telomerase maintains genomic integrity, and its activity or dysregulation are critical determinants of human longevity, stem cell renewal

  • Lineage tracing of human development through somatic mutations
    Nature (IF 42.778) Pub Date : 2021-05-12
    Michael Spencer Chapman, Anna Maria Ranzoni, Brynelle Myers, Nicholas Williams, Tim H. H. Coorens, Emily Mitchell, Timothy Butler, Kevin J. Dawson, Yvette Hooks, Luiza Moore, Jyoti Nangalia, Philip S. Robinson, Kenichi Yoshida, Elizabeth Hook, Peter J. Campbell, Ana Cvejic

    The ontogeny of the human haematopoietic system during fetal development has previously been characterized mainly through careful microscopic observations1. Here we reconstruct a phylogenetic tree of blood development using whole-genome sequencing of 511 single-cell-derived haematopoietic colonies from healthy human fetuses at 8 and 18 weeks after conception, coupled with deep targeted sequencing of

  • High-performance brain-to-text communication via handwriting
    Nature (IF 42.778) Pub Date : 2021-05-12
    Francis R. Willett, Donald T. Avansino, Leigh R. Hochberg, Jaimie M. Henderson, Krishna V. Shenoy

    Brain–computer interfaces (BCIs) can restore communication to people who have lost the ability to move or speak. So far, a major focus of BCI research has been on restoring gross motor skills, such as reaching and grasping1,2,3,4,5 or point-and-click typing with a computer cursor6,7. However, rapid sequences of highly dexterous behaviours, such as handwriting or touch typing, might enable faster rates

  • DHODH-mediated ferroptosis defence is a targetable vulnerability in cancer
    Nature (IF 42.778) Pub Date : 2021-05-12
    Chao Mao, Xiaoguang Liu, Yilei Zhang, Guang Lei, Yuelong Yan, Hyemin Lee, Pranavi Koppula, Shiqi Wu, Li Zhuang, Bingliang Fang, Masha V. Poyurovsky, Kellen Olszewski, Boyi Gan

    Ferroptosis, a form of regulated cell death that is induced by excessive lipid peroxidation, is a key tumour suppression mechanism1,2,3,4. Glutathione peroxidase 4 (GPX4)5,6 and ferroptosis suppressor protein 1 (FSP1)7,8 constitute two major ferroptosis defence systems. Here we show that treatment of cancer cells with GPX4 inhibitors results in acute depletion of N-carbamoyl-l-aspartate, a pyrimidine

  • Reconstruction of ancient microbial genomes from the human gut
    Nature (IF 42.778) Pub Date : 2021-05-12
    Marsha C. Wibowo, Zhen Yang, Maxime Borry, Alexander Hübner, Kun D. Huang, Braden T. Tierney, Samuel Zimmerman, Francisco Barajas-Olmos, Cecilia Contreras-Cubas, Humberto García-Ortiz, Angélica Martínez-Hernández, Jacob M. Luber, Philipp Kirstahler, Tre Blohm, Francis E. Smiley, Richard Arnold, Sonia A. Ballal, Sünje Johanna Pamp, Julia Russ, Frank Maixner, Omar Rota-Stabelli, Nicola Segata, Karl Reinhard

    Loss of gut microbial diversity1,2,3,4,5,6 in industrial populations is associated with chronic diseases7, underscoring the importance of studying our ancestral gut microbiome. However, relatively little is known about the composition of pre-industrial gut microbiomes. Here we performed a large-scale de novo assembly of microbial genomes from palaeofaeces. From eight authenticated human palaeofaeces

  • Cross-tissue organization of the fibroblast lineage
    Nature (IF 42.778) Pub Date : 2021-05-12
    Matthew B. Buechler, Rachana N. Pradhan, Akshay T. Krishnamurty, Christian Cox, Aslihan Karabacak Calviello, Amber W. Wang, Yeqing Angela Yang, Lucinda Tam, Roger Caothien, Merone Roose-Girma, Zora Modrusan, Joseph R. Arron, Richard Bourgon, Sören Müller, Shannon. J. Turley

    Fibroblasts are non-haematopoietic structural cells that define the architecture of organs, support the homeostasis of tissue-resident cells and have key roles in fibrosis, cancer, autoimmunity and wound healing1. Recent studies have described fibroblast heterogeneity within individual tissues1. However, the field lacks a characterization of fibroblasts at single-cell resolution across tissues in healthy

  • CMOS-based cryogenic control of silicon quantum circuits
    Nature (IF 42.778) Pub Date : 2021-05-12
    Xiao Xue, Bishnu Patra, Jeroen P. G. van Dijk, Nodar Samkharadze, Sushil Subramanian, Andrea Corna, Brian Paquelet Wuetz, Charles Jeon, Farhana Sheikh, Esdras Juarez-Hernandez, Brando Perez Esparza, Huzaifa Rampurawala, Brent Carlton, Surej Ravikumar, Carlos Nieva, Sungwon Kim, Hyung-Jin Lee, Amir Sammak, Giordano Scappucci, Menno Veldhorst, Fabio Sebastiano, Masoud Babaie, Stefano Pellerano, Edoardo

    The most promising quantum algorithms require quantum processors that host millions of quantum bits when targeting practical applications1. A key challenge towards large-scale quantum computation is the interconnect complexity. In current solid-state qubit implementations, an important interconnect bottleneck appears between the quantum chip in a dilution refrigerator and the room-temperature electronics

  • An aged immune system drives senescence and ageing of solid organs
    Nature (IF 42.778) Pub Date : 2021-05-12
    Matthew J. Yousefzadeh, Rafael R. Flores, Yi Zhu, Zoe C. Schmiechen, Robert W. Brooks, Christy E. Trussoni, Yuxiang Cui, Luise Angelini, Kyoo-A Lee, Sara J. McGowan, Adam L. Burrack, Dong Wang, Qing Dong, Aiping Lu, Tokio Sano, Ryan D. O’Kelly, Collin A. McGuckian, Jonathan I. Kato, Michael P. Bank, Erin A. Wade, Smitha P. S. Pillai, Jenna Klug, Warren C. Ladiges, Christin E. Burd, Sara E. Lewis, Nicholas

    Ageing of the immune system, or immunosenescence, contributes to the morbidity and mortality of the elderly1,2. To define the contribution of immune system ageing to organism ageing, here we selectively deleted Ercc1, which encodes a crucial DNA repair protein3,4, in mouse haematopoietic cells to increase the burden of endogenous DNA damage and thereby senescence5,6,7 in the immune system only. We

  • Ubiquitous atmospheric production of organic acids mediated by cloud droplets
    Nature (IF 42.778) Pub Date : 2021-05-12
    B. Franco, T. Blumenstock, C. Cho, L. Clarisse, C. Clerbaux, P.-F. Coheur, M. De Mazière, I. De Smedt, H.-P. Dorn, T. Emmerichs, H. Fuchs, G. Gkatzelis, D. W. T. Griffith, S. Gromov, J. W. Hannigan, F. Hase, T. Hohaus, N. Jones, A. Kerkweg, A. Kiendler-Scharr, E. Lutsch, E. Mahieu, A. Novelli, I. Ortega, C. Paton-Walsh, M. Pommier, A. Pozzer, D. Reimer, S. Rosanka, R. Sander, M. Schneider, K. Strong

    Atmospheric acidity is increasingly determined by carbon dioxide and organic acids1,2,3. Among the latter, formic acid facilitates the nucleation of cloud droplets4 and contributes to the acidity of clouds and rainwater1,5. At present, chemistry–climate models greatly underestimate the atmospheric burden of formic acid, because key processes related to its sources and sinks remain poorly understood2

  • Widespread six degrees Celsius cooling on land during the Last Glacial Maximum
    Nature (IF 42.778) Pub Date : 2021-05-12
    Alan M. Seltzer, Jessica Ng, Werner Aeschbach, Rolf Kipfer, Justin T. Kulongoski, Jeffrey P. Severinghaus, Martin Stute

    The magnitude of global cooling during the Last Glacial Maximum (LGM, the coldest multimillennial interval of the last glacial period) is an important constraint for evaluating estimates of Earth’s climate sensitivity1,2. Reliable LGM temperatures come from high-latitude ice cores3,4, but substantial disagreement exists between proxy records in the low latitudes1,5,6,7,8, where quantitative low-elevation

  • A dynamic stability design strategy for lithium metal solid state batteries
    Nature (IF 42.778) Pub Date : 2021-05-12
    Luhan Ye, Xin Li

    A solid-state electrolyte is expected to suppress lithium (Li) dendrite penetration with high mechanical strength1,2,3,4. However, in practice it still remains challenging to realise a lithium metal anode for batteries, because micrometre- or submicrometre-sized cracks in ceramic pellets can frequently be generated during battery assembly or long-time cycling3,5. Once cracks form, lithium dendrite

  • Hippocampal AMPA receptor assemblies and mechanism of allosteric inhibition
    Nature (IF 42.778) Pub Date : 2021-05-12
    Jie Yu, Prashant Rao, Sarah Clark, Jaba Mitra, Taekjip Ha, Eric Gouaux

    AMPA-selective glutamate receptors mediate the transduction of signals between the neuronal circuits of the hippocampus1. The trafficking, localization, kinetics and pharmacology of AMPA receptors are tuned by an ensemble of auxiliary protein subunits, which are integral membrane proteins that associate with the receptor to yield bona fide receptor signalling complexes2. Thus far, extensive studies

  • Neutralizing antibody vaccine for pandemic and pre-emergent coronaviruses
    Nature (IF 42.778) Pub Date : 2021-05-10
    Kevin O. Saunders, Esther Lee, Robert Parks, David R. Martinez, Dapeng Li, Haiyan Chen, Robert J. Edwards, Sophie Gobeil, Maggie Barr, Katayoun Mansouri, S. Munir Alam, Laura L. Sutherland, Fangping Cai, Aja M. Sanzone, Madison Berry, Kartik Manne, Kevin W. Bock, Mahnaz Minai, Bianca M. Nagata, Anyway B. Kapingidza, Mihai Azoitei, Longping V. Tse, Trevor D. Scobey, Rachel L. Spreng, R. Wes Rountree

    Betacoronaviruses (betaCoVs) caused the severe acute respiratory syndrome (SARS) and Middle East Respiratory Syndrome (MERS) outbreaks, and the SARS-CoV-2 pandemic1–4. Vaccines that elicit protective immunity against SARS-CoV-2 and betaCoVs circulating in animals have the potential to prevent future betaCoV pandemics. Here, we show that macaque immunization with a multimeric SARS-CoV-2 receptor binding

  • 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

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