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  •   Exome sequencing and analysis of 454,787 UK Biobank participants
    Nature (IF 49.962) Pub Date : 2021-10-18
    Joshua D. Backman, Alexander H. Li, Anthony Marcketta, Dylan Sun, Joelle Mbatchou, Michael D. Kessler, Christian Benner, Daren Liu, Adam E. Locke, Suganthi Balasubramanian, Ashish Yadav, Nilanjana Banerjee, Christopher Gillies, Amy Damask, Simon Liu, Xiaodong Bai, Alicia Hawes, Evan Maxwell, Lauren Gurski, Kyoko Watanabe, Jack A. Kosmicki, Veera Rajagopal, Jason Mighty, Marcus Jones, Lyndon Mitnaul

    A major goal in human genetics is to use natural variation to understand the phenotypic consequences of altering each protein-coding gene in the genome. Here we used exome sequencing1 to explore protein altering variants and their consequences in 454,787 UK Biobank study participants2. We identified 12 million coding variants, including ~1 million loss-of-function and ~1.8 million deleterious missense

  •   Genomic reconstruction of the SARS-CoV-2 epidemic in England
    Nature (IF 49.962) Pub Date : 2021-10-14
    Harald S. Vöhringer, Theo Sanderson, Matthew Sinnott, Nicola De Maio, Thuy Nguyen, Richard Goater, Frank Schwach, Ian Harrison, Joel Hellewell, Cristina V. Ariani, Sonia Gonçalves, David K. Jackson, Ian Johnston, Alexander W. Jung, Callum Saint, John Sillitoe, Maria Suciu, Nick Goldman, Jasmina Panovska-Griffiths, Ewan Birney, Erik Volz, Sebastian Funk, Dominic Kwiatkowski, Meera Chand, Inigo Martincorena

    The evolution of the SARS-CoV-2 pandemic continuously produces new variants, which warrant timely epidemiological characterisation. Here we use the dense genomic surveillance generated by the COVID-19 Genomics UK Consortium to reconstruct the dynamics of 71 different lineages in each of 315 English local authorities between September 2020 and June 2021. This analysis reveals a series of sub-epidemics

  •   Observation of fractional edge excitations in nanographene spin chains
    Nature (IF 49.962) Pub Date : 2021-10-13
    Shantanu Mishra, Gonçalo Catarina, Fupeng Wu, Ricardo Ortiz, David Jacob, Kristjan Eimre, Ji Ma, Carlo A. Pignedoli, Xinliang Feng, Pascal Ruffieux, Joaquín Fernández-Rossier, Roman Fasel

    Fractionalization is a phenomenon in which strong interactions in a quantum system drive the emergence of excitations with quantum numbers that are absent in the building blocks. Outstanding examples are excitations with charge e/3 in the fractional quantum Hall effect1,2, solitons in one-dimensional conducting polymers3,4 and Majorana states in topological superconductors5. Fractionalization is also

  •   Convergent somatic mutations in metabolism genes in chronic liver disease
    Nature (IF 49.962) Pub Date : 2021-10-13
    Stanley W. K. Ng, Foad J. Rouhani, Simon F. Brunner, Natalia Brzozowska, Sarah J. Aitken, Ming Yang, Federico Abascal, Luiza Moore, Efterpi Nikitopoulou, Lia Chappell, Daniel Leongamornlert, Aleksandra Ivovic, Philip Robinson, Timothy Butler, Mathijs A. Sanders, Nicholas Williams, Tim H. H. Coorens, Jon Teague, Keiran Raine, Adam P. Butler, Yvette Hooks, Beverley Wilson, Natalie Birtchnell, Huw Naylor

    The progression of chronic liver disease to hepatocellular carcinoma is caused by the acquisition of somatic mutations that affect 20–30 cancer genes1,2,3,4,5,6,7,8. Burdens of somatic mutations are higher and clonal expansions larger in chronic liver disease9,10,11,12,13 than in normal liver13,14,15,16, which enables positive selection to shape the genomic landscape9,10,11,12,13. Here we analysed

  •   Oestrogen engages brain MC4R signalling to drive physical activity in female mice
    Nature (IF 49.962) Pub Date : 2021-10-13
    William C. Krause, Ruben Rodriguez, Bruno Gegenhuber, Navneet Matharu, Andreas N. Rodriguez, Adriana M. Padilla-Roger, Kenichi Toma, Candice B. Herber, Stephanie M. Correa, Xin Duan, Nadav Ahituv, Jessica Tollkuhn, Holly A. Ingraham

    Oestrogen depletion in rodents and humans leads to inactivity, fat accumulation and diabetes1,2, underscoring the conserved metabolic benefits of oestrogen that inevitably decrease with age. In rodents, the preovulatory surge in 17β-oestradiol (E2) temporarily increases energy expenditure to coordinate increased physical activity with peak sexual receptivity. Here we report that a subset of oestrogen-sensitive

  •   Day–night cloud asymmetry prevents early oceans on Venus but not on Earth
    Nature (IF 49.962) Pub Date : 2021-10-13
    Martin Turbet, Emeline Bolmont, Guillaume Chaverot, David Ehrenreich, Jérémy Leconte, Emmanuel Marcq

    Earth has had oceans for nearly four billion years1 and Mars had lakes and rivers 3.5–3.8 billion years ago2. However, it is still unknown whether water has ever condensed on the surface of Venus3,4 because the planet—now completely dry5—has undergone global resurfacing events that obscure most of its history6,7. The conditions required for water to have initially condensed on the surface of Solar

  •   A bimodal burst energy distribution of a repeating fast radio burst source
    Nature (IF 49.962) Pub Date : 2021-10-13
    D. Li, P. Wang, W. W. Zhu, B. Zhang, X. X. Zhang, R. Duan, Y. K. Zhang, Y. Feng, N. Y. Tang, S. Chatterjee, J. M. Cordes, M. Cruces, S. Dai, V. Gajjar, G. Hobbs, C. Jin, M. Kramer, D. R. Lorimer, C. C. Miao, C. H. Niu, J. R. Niu, Z. C. Pan, L. Qian, L. Spitler, D. Werthimer, G. Q. Zhang, F. Y. Wang, X. Y. Xie, Y. L. Yue, L. Zhang, Q. J. Zhi, Y. Zhu

    The event rate, energy distribution and time-domain behaviour of repeating fast radio bursts (FRBs) contain essential information regarding their physical nature and central engine, which are as yet unknown1,2. As the first precisely localized source, FRB 121102 (refs. 3,4,5) has been extensively observed and shows non-Poisson clustering of bursts over time and a power-law energy distribution6,7,8

  •   Mutant clones in normal epithelium outcompete and eliminate emerging tumours
    Nature (IF 49.962) Pub Date : 2021-10-13
    B. Colom, A. Herms, M. W. J. Hall, S. C. Dentro, C. King, R. K. Sood, M. P. Alcolea, G. Piedrafita, D. Fernandez-Antoran, S. H. Ong, J. C. Fowler, K. T. Mahbubani, K. Saeb-Parsy, M. Gerstung, B. A. Hall, P. H. Jones

    Human epithelial tissues accumulate cancer-driver mutations with age1,2,3,4,5,6,7,8,9, yet tumour formation remains rare. The positive selection of these mutations suggests that they alter the behaviour and fitness of proliferating cells10,11,12. Thus, normal adult tissues become a patchwork of mutant clones competing for space and survival, with the fittest clones expanding by eliminating their less

  •   An elastic metal–organic crystal with a densely catenated backbone
    Nature (IF 49.962) Pub Date : 2021-10-13
    Wenjing Meng, Shun Kondo, Takuji Ito, Kazuki Komatsu, Jenny Pirillo, Yuh Hijikata, Yuichi Ikuhara, Takuzo Aida, Hiroshi Sato

    What particular mechanical properties can be expected for materials composed of interlocked backbones has been a long-standing issue in materials science since the first reports on polycatenane and polyrotaxane in the 1970s1,2,3. Here we report a three-dimensional porous metal–organic crystal, which is exceptional in that its warps and wefts are connected only by catenation. This porous crystal is

  •   Structure of Venezuelan equine encephalitis virus with its receptor LDLRAD3
    Nature (IF 49.962) Pub Date : 2021-10-13
    Bingting Ma, Cuiqing Huang, Jun Ma, Ye Xiang, Xinzheng Zhang

    Venezuelan equine encephalitis virus (VEEV) is an enveloped RNA virus that causes encephalitis and potentially mortality in infected humans and equines1. At present, no vaccines or drugs are available that prevent or cure diseases caused by VEEV. Low-density lipoprotein receptor class A domain-containing 3 (LDLRAD3) was recently identified as a receptor for the entry of VEEV into host cells2. Here

  •   An endogenous opioid circuit determines state-dependent reward consumption
    Nature (IF 49.962) Pub Date : 2021-10-13
    Daniel C. Castro, Corinna S. Oswell, Eric T. Zhang, Christian E. Pedersen, Sean C. Piantadosi, Mark A. Rossi, Avery C. Hunker, Anthony Guglin, Jose A. Morón, Larry S. Zweifel, Garret D. Stuber, Michael R. Bruchas

    µ-Opioid peptide receptor (MOPR) stimulation alters respiration, analgesia and reward behaviour, and can induce substance abuse and overdose1,2,3. Despite its evident importance, the endogenous mechanisms for MOPR regulation of consummatory behaviour have remained unknown4. Here we report that endogenous MOPR regulation of reward consumption in mice acts through a specific dorsal raphe to nucleus accumbens

  •   A neuroanatomical basis for electroacupuncture to drive the vagal–adrenal axis
    Nature (IF 49.962) Pub Date : 2021-10-13
    Shenbin Liu, Zhifu Wang, Yangshuai Su, Lu Qi, Wei Yang, Mingzhou Fu, Xianghong Jing, Yanqing Wang, Qiufu Ma

    Somatosensory autonomic reflexes allow electroacupuncture stimulation (ES) to modulate body physiology at distant sites1,2,3,4,5,6 (for example, suppressing severe systemic inflammation6,7,8,9). Since the 1970s, an emerging organizational rule about these reflexes has been the presence of body-region specificity1,2,3,4,5,6. For example, ES at the hindlimb ST36 acupoint but not the abdominal ST25 acupoint

  •   Leprosy in wild chimpanzees
    Nature (IF 49.962) Pub Date : 2021-10-13
    Kimberley J. Hockings, Benjamin Mubemba, Charlotte Avanzi, Kamilla Pleh, Ariane Düx, Elena Bersacola, Joana Bessa, Marina Ramon, Sonja Metzger, Livia V. Patrono, Jenny E. Jaffe, Andrej Benjak, Camille Bonneaud, Philippe Busso, Emmanuel Couacy-Hymann, Moussa Gado, Sebastien Gagneux, Roch C. Johnson, Mamoudou Kodio, Joshua Lynton-Jenkins, Irina Morozova, Kerstin Mätz-Rensing, Aissa Regalla, Abílio R

    Humans are considered as the main host for Mycobacterium leprae1, the aetiological agent of leprosy, but spillover has occurred to other mammals that are now maintenance hosts, such as nine-banded armadillos and red squirrels2,3. Although naturally acquired leprosy has also been described in captive nonhuman primates4,5,6,7, the exact origins of infection remain unclear. Here we describe leprosy-like

  •   A Jovian analogue orbiting a white dwarf star
    Nature (IF 49.962) Pub Date : 2021-10-13
    J. W. Blackman, J. P. Beaulieu, D. P. Bennett, C. Danielski, C. Alard, A. A. Cole, A. Vandorou, C. Ranc, S. K. Terry, A. Bhattacharya, I. Bond, E. Bachelet, D. Veras, N. Koshimoto, V. Batista, J. B. Marquette

    Studies1,2 have shown that the remnants of destroyed planets and debris-disk planetesimals can survive the volatile evolution of their host stars into white dwarfs3,4, but few intact planetary bodies around white dwarfs have been detected5,6,7,8. Simulations predict9,10,11 that planets in Jupiter-like orbits around stars of ≲8 M☉ (solar mass) avoid being destroyed by the strong tidal forces of their

  •   Structure of Venezuelan equine encephalitis virus in complex with the LDLRAD3 receptor
    Nature (IF 49.962) Pub Date : 2021-10-13
    Katherine Basore, Hongming Ma, Natasha M. Kafai, Samantha Mackin, Arthur S. Kim, Christopher A. Nelson, Michael S. Diamond, Daved H. Fremont

    LDLRAD3 is a recently defined attachment and entry receptor for Venezuelan equine encephalitis virus (VEEV)1, a New World alphavirus that causes severe neurological disease in humans. Here we present near-atomic-resolution cryo-electron microscopy reconstructions of VEEV virus-like particles alone and in a complex with the ectodomains of LDLRAD3. Domain 1 of LDLRAD3 is a low-density lipoprotein receptor

  •   Systems-level effects of allosteric perturbations to a model molecular switch
    Nature (IF 49.962) Pub Date : 2021-10-13
    Tina Perica, Christopher J. P. Mathy, Jiewei Xu, Gwendolyn Μ. Jang, Yang Zhang, Robyn Kaake, Noah Ollikainen, Hannes Braberg, Danielle L. Swaney, David G. Lambright, Mark J. S. Kelly, Nevan J. Krogan, Tanja Kortemme

    Molecular switch proteins whose cycling between states is controlled by opposing regulators1,2 are central to biological signal transduction. As switch proteins function within highly connected interaction networks3, the fundamental question arises of how functional specificity is achieved when different processes share common regulators. Here we show that functional specificity of the small GTPase

  •   Estimating a social cost of carbon for global energy consumption
    Nature (IF 49.962) Pub Date : 2021-10-13
    Ashwin Rode, Tamma Carleton, Michael Delgado, Michael Greenstone, Trevor Houser, Solomon Hsiang, Andrew Hultgren, Amir Jina, Robert E. Kopp, Kelly E. McCusker, Ishan Nath, James Rising, Jiacan Yuan

    Estimates of global economic damage caused by carbon dioxide (CO2) emissions can inform climate policy1,2,3. The social cost of carbon (SCC) quantifies these damages by characterizing how additional CO2 emissions today impact future economic outcomes through altering the climate4,5,6. Previous estimates have suggested that large, warming-driven increases in energy expenditures could dominate the SCC7

  •   Structural basis of cytokine-mediated activation of ALK family receptors
    Nature (IF 49.962) Pub Date : 2021-10-13
    Steven De Munck, Mathias Provost, Michiko Kurikawa, Ikuko Omori, Junko Mukohyama, Jan Felix, Yehudi Bloch, Omar Abdel-Wahab, J. Fernando Bazan, Akihide Yoshimi, Savvas N. Savvides

    Anaplastic lymphoma kinase (ALK)1 and the related leukocyte tyrosine kinase (LTK)2 are recently deorphanized receptor tyrosine kinases3. Together with their activating cytokines, ALKAL1 and ALKAL24,5,6 (also called FAM150A and FAM150B or AUGβ and AUGα, respectively), they are involved in neural development7, cancer7,8,9 and autoimmune diseases10. Furthermore, mammalian ALK recently emerged as a key

  •   The cellular environment shapes the nuclear pore complex architecture
    Nature (IF 49.962) Pub Date : 2021-10-13
    Anthony P. Schuller, Matthias Wojtynek, David Mankus, Meltem Tatli, Rafael Kronenberg-Tenga, Saroj G. Regmi, Phat V. Dip, Abigail K. R. Lytton-Jean, Edward J. Brignole, Mary Dasso, Karsten Weis, Ohad Medalia, Thomas U. Schwartz

    Nuclear pore complexes (NPCs) create large conduits for cargo transport between the nucleus and cytoplasm across the nuclear envelope (NE)1,2,3. These multi-megadalton structures are composed of about thirty different nucleoporins that are distributed in three main substructures (the inner, cytoplasmic and nucleoplasmic rings) around the central transport channel4,5,6. Here we use cryo-electron tomography

  •   Parallelism of intestinal secretory IgA shapes functional microbial fitness
    Nature (IF 49.962) Pub Date : 2021-10-13
    Tim Rollenske, Sophie Burkhalter, Lukas Muerner, Stephan von Gunten, Jolanta Lukasiewicz, Hedda Wardemann, Andrew J. Macpherson

    Dimeric IgA secreted across mucous membranes in response to nonpathogenic taxa of the microbiota accounts for most antibody production in mammals. Diverse binding specificities can be detected within the polyclonal mucosal IgA antibody response1,2,3,4,5,6,7,8,9,10, but limited monoclonal hybridomas have been studied to relate antigen specificity or polyreactive binding to functional effects on microbial

  •   Neural control of affiliative touch in prosocial interaction
    Nature (IF 49.962) Pub Date : 2021-10-13
    Ye Emily Wu, James Dang, Lyle Kingsbury, Mingmin Zhang, Fangmiao Sun, Rongfeng K. Hu, Weizhe Hong

    The ability to help and care for others fosters social cohesiveness and is vital to the physical and emotional well-being of social species, including humans1,2,3. Affiliative social touch, such as allogrooming (grooming behaviour directed towards another individual), is a major type of prosocial behaviour that provides comfort to others1,2,3,4,5,6. Affiliative touch serves to establish and strengthen

  •   Impact of circulating SARS-CoV-2 variants on mRNA vaccine-induced immunity
    Nature (IF 49.962) Pub Date : 2021-10-11
    Carolina Lucas, Chantal B. F. Vogels, Inci Yildirim, Jessica E. Rothman, Peiwen Lu, Valter Monteiro, Jeff R. Gelhausen, Melissa Campbell, Julio Silva, Alexandra Tabachikova, Mario A. Peña-Hernandez, M. Catherine Muenker, Mallery I. Breban, Joseph R. Fauver, Subhasis Mohanty, Jiefang Huang, Albert C. Shaw, Albert I. Ko, Saad B. Omer, Nathan D. Grubaugh, Akiko Iwasaki

    The emergence of SARS-CoV-2 variants with mutations in major neutralizing antibody-binding sites can affect humoral immunity induced by infection or vaccination1–6. We analysed the development of anti-SARS-CoV-2 antibody and T cell responses in previously infected (recovered) or uninfected (naive) individuals that received mRNA vaccines to SARS-CoV-2. While previously infected individuals sustained

  •   Transposon-associated TnpB is a programmable RNA-guided DNA endonuclease
    Nature (IF 49.962) Pub Date : 2021-10-07
    Tautvydas Karvelis, Gytis Druteika, Greta Bigelyte, Karolina Budre, Rimante Zedaveinyte, Arunas Silanskas, Darius Kazlauskas, Česlovas Venclovas, Virginijus Siksnys

    Transposition plays a key role in reshaping genomes of all living organisms1. Insertion sequences (ISs) of IS200/IS605 and IS607 families2 are among the simplest mobile genetic elements and contain only the genes required for their transposition and its regulation. These elements encode tnpA transposase that is essential for mobilization and often carry an accessory tnpB gene which is dispensable for

  •   Anti-SARS-CoV-2 receptor binding domain antibody evolution after mRNA vaccination
    Nature (IF 49.962) Pub Date : 2021-10-07
    Alice Cho, Frauke Muecksch, Dennis Schaefer-Babajew, Zijun Wang, Shlomo Finkin, Christian Gaebler, Victor Ramos, Melissa Cipolla, Pilar Mendoza, Marianna Agudelo, Eva Bednarski, Justin DaSilva, Irina Shimeliovich, Juan Dizon, Mridushi Daga, Katrina Millard, Martina Turroja, Fabian Schmidt, Fengwen Zhang, Tarek Ben Tanfous, Mila Jankovic, Thiago Y. Oliveria, Anna Gazumyan, Marina Caskey, Paul D. Bieniasz

    Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection produces B cell responses that continue to evolve for at least one year. During that time, memory B cells express increasingly broad and potent antibodies that are resistant to mutations found in variants of concern1. As a result, vaccination of coronavirus disease 2019 (COVID-19) convalescent individuals with currently available

  •   Thalamic circuits for independent control of prefrontal signal and noise
    Nature (IF 49.962) Pub Date : 2021-10-06
    Arghya Mukherjee, Norman H. Lam, Ralf D. Wimmer, Michael M. Halassa

    Interactions between the mediodorsal thalamus and prefrontal cortex are critical for cognition. Studies in humans indicate that these interactions may resolve uncertainty in decision making1, but the precise mechanisms are unknown. Here, we identified two distinct mediodorsal projections to prefrontal cortex that play complementary mechanistic roles in decision making under uncertainty. Specifically

  •   Spatiotemporal origin of soil water taken up by vegetation
    Nature (IF 49.962) Pub Date : 2021-10-06
    Gonzalo Miguez-Macho, Ying Fan

    Vegetation modulates Earth’s water, energy and carbon cycles. How its functions might change in the future largely depends on how it copes with droughts1,2,3,4. There is evidence that, in places and times of drought, vegetation shifts water uptake to deeper soil5,6,7 and rock8,9 moisture as well as groundwater10,11,12. Here we differentiate and assess plant use of four types of water sources: precipitation

  •   Topological complex-energy braiding of non-Hermitian bands
    Nature (IF 49.962) Pub Date : 2021-10-06
    Kai Wang, Avik Dutt, Charles C. Wojcik, Shanhui Fan

    Effects connected with the mathematical theory of knots1 emerge in many areas of science, from physics2,3 to biology4. Recent theoretical work discovered that the braid group characterizes the topology of non-Hermitian periodic systems5, where the complex band energies can braid in momentum space. However, such braids of complex-energy bands have not been realized or controlled experimentally. Here

  •   Morphological diversity of single neurons in molecularly defined cell types
    Nature (IF 49.962) Pub Date : 2021-10-06
    Hanchuan Peng, Peng Xie, Lijuan Liu, Xiuli Kuang, Yimin Wang, Lei Qu, Hui Gong, Shengdian Jiang, Anan Li, Zongcai Ruan, Liya Ding, Zizhen Yao, Chao Chen, Mengya Chen, Tanya L. Daigle, Rachel Dalley, Zhangcan Ding, Yanjun Duan, Aaron Feiner, Ping He, Chris Hill, Karla E. Hirokawa, Guodong Hong, Lei Huang, Sara Kebede, Hsien-Chi Kuo, Rachael Larsen, Phil Lesnar, Longfei Li, Qi Li, Xiangning Li, Yaoyao

    Dendritic and axonal morphology reflects the input and output of neurons and is a defining feature of neuronal types1,2, yet our knowledge of its diversity remains limited. Here, to systematically examine complete single-neuron morphologies on a brain-wide scale, we established a pipeline encompassing sparse labelling, whole-brain imaging, reconstruction, registration and analysis. We fully reconstructed

  •   Genetic dissection of the glutamatergic neuron system in cerebral cortex
    Nature (IF 49.962) Pub Date : 2021-10-06
    Katherine S. Matho, Dhananjay Huilgol, William Galbavy, Miao He, Gukhan Kim, Xu An, Jiangteng Lu, Priscilla Wu, Daniela J. Di Bella, Ashwin S. Shetty, Ramesh Palaniswamy, Joshua Hatfield, Ricardo Raudales, Arun Narasimhan, Eric Gamache, Jesse M. Levine, Jason Tucciarone, Eric Szelenyi, Julie A. Harris, Partha P. Mitra, Pavel Osten, Paola Arlotta, Z. Josh Huang

    Diverse types of glutamatergic pyramidal neurons mediate the myriad processing streams and output channels of the cerebral cortex1,2, yet all derive from neural progenitors of the embryonic dorsal telencephalon3,4. Here we establish genetic strategies and tools for dissecting and fate-mapping subpopulations of pyramidal neurons on the basis of their developmental and molecular programs. We leverage

  •   Mastering the surface strain of platinum catalysts for efficient electrocatalysis
    Nature (IF 49.962) Pub Date : 2021-10-06
    Tianou He, Weicong Wang, Fenglei Shi, Xiaolong Yang, Xiang Li, Jianbo Wu, Yadong Yin, Mingshang Jin

    Platinum (Pt) has found wide use as an electrocatalyst for sustainable energy conversion systems1,2,3. The activity of Pt is controlled by its electronic structure (typically, the d-band centre), which depends sensitively on lattice strain4,5. This dependence can be exploited for catalyst design4,6,7,8, and the use of core–shell structures and elastic substrates has resulted in strain-engineered Pt

  •   Comparative cellular analysis of motor cortex in human, marmoset and mouse
    Nature (IF 49.962) Pub Date : 2021-10-06
    Trygve E. Bakken, Nikolas L. Jorstad, Qiwen Hu, Blue B. Lake, Wei Tian, Brian E. Kalmbach, Megan Crow, Rebecca D. Hodge, Fenna M. Krienen, Staci A. Sorensen, Jeroen Eggermont, Zizhen Yao, Brian D. Aevermann, Andrew I. Aldridge, Anna Bartlett, Darren Bertagnolli, Tamara Casper, Rosa G. Castanon, Kirsten Crichton, Tanya L. Daigle, Rachel Dalley, Nick Dee, Nikolai Dembrow, Dinh Diep, Song-Lin Ding, Weixiu

    The primary motor cortex (M1) is essential for voluntary fine-motor control and is functionally conserved across mammals1. Here, using high-throughput transcriptomic and epigenomic profiling of more than 450,000 single nuclei in humans, marmoset monkeys and mice, we demonstrate a broadly conserved cellular makeup of this region, with similarities that mirror evolutionary distance and are consistent

  •   Structure and assembly of the mammalian mitochondrial supercomplex CIII2CIV
    Nature (IF 49.962) Pub Date : 2021-10-06
    Irene Vercellino, Leonid A. Sazanov

    The enzymes of the mitochondrial electron transport chain are key players of cell metabolism. Despite being active when isolated, in vivo they associate into supercomplexes1, whose precise role is debated. Supercomplexes CIII2CIV1-2 (refs. 2,3), CICIII2 (ref. 4) and CICIII2CIV (respirasome)5,6,7,8,9,10 exist in mammals, but in contrast to CICIII2 and the respirasome, to date the only known eukaryotic

  •   The mouse cortico–basal ganglia–thalamic network
    Nature (IF 49.962) Pub Date : 2021-10-06
    Nicholas N. Foster, Joshua Barry, Laura Korobkova, Luis Garcia, Lei Gao, Marlene Becerra, Yasmine Sherafat, Bo Peng, Xiangning Li, Jun-Hyeok Choi, Lin Gou, Brian Zingg, Sana Azam, Darrick Lo, Neda Khanjani, Bin Zhang, Jim Stanis, Ian Bowman, Kaelan Cotter, Chunru Cao, Seita Yamashita, Amanda Tugangui, Anan Li, Tao Jiang, Xueyan Jia, Zhao Feng, Sarvia Aquino, Hyun-Seung Mun, Muye Zhu, Anthony Santarelli

    The cortico–basal ganglia–thalamo–cortical loop is one of the fundamental network motifs in the brain. Revealing its structural and functional organization is critical to understanding cognition, sensorimotor behaviour, and the natural history of many neurological and neuropsychiatric disorders. Classically, this network is conceptualized to contain three information channels: motor, limbic and associative1

  •   An atlas of cortical arealization identifies dynamic molecular signatures
    Nature (IF 49.962) Pub Date : 2021-10-06
    Aparna Bhaduri, Carmen Sandoval-Espinosa, Marcos Otero-Garcia, Irene Oh, Raymund Yin, Ugomma C. Eze, Tomasz J. Nowakowski, Arnold R. Kriegstein

    The human brain is subdivided into distinct anatomical structures, including the neocortex, which in turn encompasses dozens of distinct specialized cortical areas. Early morphogenetic gradients are known to establish early brain regions and cortical areas, but how early patterns result in finer and more discrete spatial differences remains poorly understood1. Here we use single-cell RNA sequencing

  •   A transcriptomic and epigenomic cell atlas of the mouse primary motor cortex
    Nature (IF 49.962) Pub Date : 2021-10-06
    Zizhen Yao, Hanqing Liu, Fangming Xie, Stephan Fischer, Ricky S. Adkins, Andrew I. Aldridge, Seth A. Ament, Anna Bartlett, M. Margarita Behrens, Koen Van den Berge, Darren Bertagnolli, Hector Roux de Bézieux, Tommaso Biancalani, A. Sina Booeshaghi, Héctor Corrada Bravo, Tamara Casper, Carlo Colantuoni, Jonathan Crabtree, Heather Creasy, Kirsten Crichton, Megan Crow, Nick Dee, Elizabeth L. Dougherty

    Single-cell transcriptomics can provide quantitative molecular signatures for large, unbiased samples of the diverse cell types in the brain1,2,3. With the proliferation of multi-omics datasets, a major challenge is to validate and integrate results into a biological understanding of cell-type organization. Here we generated transcriptomes and epigenomes from more than 500,000 individual cells in the

  •   Metabolic modulation of tumours with engineered bacteria for immunotherapy
    Nature (IF 49.962) Pub Date : 2021-10-06
    Fernando P. Canale, Camilla Basso, Gaia Antonini, Michela Perotti, Ning Li, Anna Sokolovska, Julia Neumann, Michael J. James, Stefania Geiger, Wenjie Jin, Jean-Philippe Theurillat, Kip A. West, Daniel S. Leventhal, Jose M. Lora, Federica Sallusto, Roger Geiger

    The availability of l-arginine in tumours is a key determinant of an efficient anti-tumour T cell response1,2,3,4. Consequently, increases of typically low l-arginine concentrations within the tumour may greatly potentiate the anti-tumour responses of immune checkpoint inhibitors, such as programmed death-ligand 1 (PD-L1)-blocking antibodies5. However, currently no means are available to locally increase

  •   Mechanical computing
    Nature (IF 49.962) Pub Date : 2021-10-06
    Hiromi Yasuda, Philip R. Buskohl, Andrew Gillman, Todd D. Murphey, Susan Stepney, Richard A. Vaia, Jordan R. Raney

    Mechanical mechanisms have been used to process information for millennia, with famous examples ranging from the Antikythera mechanism of the Ancient Greeks to the analytical machines of Charles Babbage. More recently, electronic forms of computation and information processing have overtaken these mechanical forms, owing to better potential for miniaturization and integration. However, several unconventional

  •   Whole-cell organelle segmentation in volume electron microscopy
    Nature (IF 49.962) Pub Date : 2021-10-06
    Larissa Heinrich, Davis Bennett, David Ackerman, Woohyun Park, John Bogovic, Nils Eckstein, Alyson Petruncio, Jody Clements, Song Pang, C. Shan Xu, Jan Funke, Wyatt Korff, Harald F. Hess, Jennifer Lippincott-Schwartz, Stephan Saalfeld, Aubrey V. Weigel

    Cells contain hundreds of organelles and macromolecular assemblies. Obtaining a complete understanding of their intricate organization requires the nanometre-level, three-dimensional reconstruction of whole cells, which is only feasible with robust and scalable automatic methods. Here, to support the development of such methods, we annotated up to 35 different cellular organelle classes—ranging from

  •   A transcriptomic atlas of mouse cerebellar cortex comprehensively defines cell types
    Nature (IF 49.962) Pub Date : 2021-10-06
    Velina Kozareva, Caroline Martin, Tomas Osorno, Stephanie Rudolph, Chong Guo, Charles Vanderburg, Naeem Nadaf, Aviv Regev, Wade G. Regehr, Evan Macosko

    The cerebellar cortex is a well-studied brain structure with diverse roles in motor learning, coordination, cognition and autonomic regulation. However, a complete inventory of cerebellar cell types is currently lacking. Here, using recent advances in high-throughput transcriptional profiling1,2,3, we molecularly define cell types across individual lobules of the adult mouse cerebellum. Purkinje neurons

  •   Neurotoxic reactive astrocytes induce cell death via saturated lipids
    Nature (IF 49.962) Pub Date : 2021-10-06
    Kevin A. Guttenplan, Maya K. Weigel, Priya Prakash, Prageeth R. Wijewardhane, Philip Hasel, Uriel Rufen-Blanchette, Alexandra E. Münch, Jacob A. Blum, Jonathan Fine, Mikaela C. Neal, Kimberley D. Bruce, Aaron D. Gitler, Gaurav Chopra, Shane A. Liddelow, Ben A. Barres

    Astrocytes regulate the response of the central nervous system to disease and injury and have been hypothesized to actively kill neurons in neurodegenerative disease1,2,3,4,5,6. Here we report an approach to isolate one component of the long-sought astrocyte-derived toxic factor5,6. Notably, instead of a protein, saturated lipids contained in APOE and APOJ lipoparticles mediate astrocyte-induced toxicity

  •   DNA methylation atlas of the mouse brain at single-cell resolution
    Nature (IF 49.962) Pub Date : 2021-10-06
    Hanqing Liu, Jingtian Zhou, Wei Tian, Chongyuan Luo, Anna Bartlett, Andrew Aldridge, Jacinta Lucero, Julia K. Osteen, Joseph R. Nery, Huaming Chen, Angeline Rivkin, Rosa G. Castanon, Ben Clock, Yang Eric Li, Xiaomeng Hou, Olivier B. Poirion, Sebastian Preissl, Antonio Pinto-Duarte, Carolyn O’Connor, Lara Boggeman, Conor Fitzpatrick, Michael Nunn, Eran A. Mukamel, Zhuzhu Zhang, Edward M. Callaway, Bing

    Mammalian brain cells show remarkable diversity in gene expression, anatomy and function, yet the regulatory DNA landscape underlying this extensive heterogeneity is poorly understood. Here we carry out a comprehensive assessment of the epigenomes of mouse brain cell types by applying single-nucleus DNA methylation sequencing1,2 to profile 103,982 nuclei (including 95,815 neurons and 8,167 non-neuronal

  •   Epigenomic diversity of cortical projection neurons in the mouse brain
    Nature (IF 49.962) Pub Date : 2021-10-06
    Zhuzhu Zhang, Jingtian Zhou, Pengcheng Tan, Yan Pang, Angeline C. Rivkin, Megan A. Kirchgessner, Elora Williams, Cheng-Ta Lee, Hanqing Liu, Alexis D. Franklin, Paula Assakura Miyazaki, Anna Bartlett, Andrew I. Aldridge, Minh Vu, Lara Boggeman, Conor Fitzpatrick, Joseph R. Nery, Rosa G. Castanon, Mohammad Rashid, Matthew W. Jacobs, Tony Ito-Cole, Carolyn O’Connor, António Pinto-Duartec, Bertha Dominguez

    Neuronal cell types are classically defined by their molecular properties, anatomy and functions. Although recent advances in single-cell genomics have led to high-resolution molecular characterization of cell type diversity in the brain1, neuronal cell types are often studied out of the context of their anatomical properties. To improve our understanding of the relationship between molecular and anatomical

  •   Regulation of prefrontal patterning and connectivity by retinoic acid
    Nature (IF 49.962) Pub Date : 2021-10-01
    Mikihito Shibata, Kartik Pattabiraman, Belen Lorente-Galdos, David Andrijevic, Suel-Kee Kim, Navjot Kaur, Sydney K. Muchnik, Xiaojun Xing, Gabriel Santpere, Andre M. M. Sousa, Nenad Sestan

    The prefrontal cortex (PFC) and its connections with the mediodorsal thalamus are crucial for cognitive flexibility and working memory1 and are thought to be altered in disorders such as autism2,3 and schizophrenia4,5. Although developmental mechanisms that govern the regional patterning of the cerebral cortex have been characterized in rodents6,7,8,9, the mechanisms that underlie the development of

  •   Hominini-specific regulation of CBLN2 increases prefrontal spinogenesis
    Nature (IF 49.962) Pub Date : 2021-10-01
    Mikihito Shibata, Kartik Pattabiraman, Sydney K. Muchnik, Navjot Kaur, Yury M. Morozov, Xiaoyang Cheng, Stephen G. Waxman, Nenad Sestan

    The similarities and differences between nervous systems of various species result from developmental constraints and specific adaptations1,2,3,4. Comparative analyses of the prefrontal cortex (PFC), a cerebral cortex region involved in higher-order cognition and complex social behaviours, have identified true and potential human-specific structural and molecular specializations4,5,6,7,8, such as an

  •   Cascade of correlated electron states in a kagome superconductor CsV3Sb5
    Nature (IF 49.962) Pub Date : 2021-09-29
    He Zhao, Hong Li, Brenden R. Ortiz, Samuel M. L. Teicher, Taka Park, Mengxing Ye, Ziqiang Wang, Leon Balents, Stephen D. Wilson, Ilija Zeljkovic

    The kagome lattice of transition metal atoms provides an exciting platform to study electronic correlations in the presence of geometric frustration and nontrivial band topology1–18, which continues to bear surprises. In this work, using spectroscopic imaging scanning tunneling microscopy, we discover a cascade of different symmetry-broken electronic states as a function of temperature in a new kagome

  •   Roton pair density wave in a strong-coupling kagome superconductor
    Nature (IF 49.962) Pub Date : 2021-09-29
    Hui Chen, Haitao Yang, Bin Hu, Zhen Zhao, Jie Yuan, Yuqing Xing, Guojian Qian, Zihao Huang, Geng Li, Yuhan Ye, Sheng Ma, Shunli Ni, Hua Zhang, Qiangwei Yin, Chunsheng Gong, Zhijun Tu, Hechang Lei, Hengxin Tan, Sen Zhou, Chengmin Shen, Xiaoli Dong, Binghai Yan, Ziqiang Wang, Hong-Jun Gao

    The transition-metal kagome lattice materials host frustrated, correlated, and topological quantum states of matter1–9. Recently, a new family of vanadium-based kagome metals AV3Sb5 (A=K, Rb, and Cs) with topological band structures has been discovered10,11. These layered compounds are nonmagnetic and undergo charge density wave transitions before developing superconductivity at low temperatures11–19

  •   Skilful precipitation nowcasting using deep generative models of radar
    Nature (IF 49.962) Pub Date : 2021-09-29
    Suman Ravuri, Karel Lenc, Matthew Willson, Dmitry Kangin, Remi Lam, Piotr Mirowski, Megan Fitzsimons, Maria Athanassiadou, Sheleem Kashem, Sam Madge, Rachel Prudden, Amol Mandhane, Aidan Clark, Andrew Brock, Karen Simonyan, Raia Hadsell, Niall Robinson, Ellen Clancy, Alberto Arribas, Shakir Mohamed

    Precipitation nowcasting, the high-resolution forecasting of precipitation up to two hours ahead, supports the real-world socioeconomic needs of many sectors reliant on weather-dependent decision-making1,2. State-of-the-art operational nowcasting methods typically advect precipitation fields with radar-based wind estimates, and struggle to capture important non-linear events such as convective initiations3

  •   Mercury stable isotopes constrain atmospheric sources to the ocean
    Nature (IF 49.962) Pub Date : 2021-09-29
    Martin Jiskra, Lars-Eric Heimbürger-Boavida, Marie-Maëlle Desgranges, Mariia V. Petrova, Aurélie Dufour, Beatriz Ferreira-Araujo, Jérémy Masbou, Jérôme Chmeleff, Melilotus Thyssen, David Point, Jeroen E. Sonke

    Human exposure to toxic mercury (Hg) is dominated by the consumption of seafood1,2. Earth system models suggest that Hg in marine ecosystems is supplied by atmospheric wet and dry Hg(ii) deposition, with a three times smaller contribution from gaseous Hg(0) uptake3,4. Observations of marine Hg(ii) deposition and Hg(0) gas exchange are sparse, however5, leaving the suggested importance of Hg(ii) deposition6

  •   Non-Hermitian topological whispering gallery
    Nature (IF 49.962) Pub Date : 2021-09-29
    Bolun Hu, Zhiwang Zhang, Haixiao Zhang, Liyang Zheng, Wei Xiong, Zichong Yue, Xiaoyu Wang, Jianyi Xu, Ying Cheng, Xiaojun Liu, Johan Christensen

    In 1878, Lord Rayleigh observed the highly celebrated phenomenon of sound waves that creep around the curved gallery of St Paul’s Cathedral in London1,2. These whispering-gallery waves scatter efficiently with little diffraction around an enclosure and have since found applications in ultrasonic fatigue and crack testing, and in the optical sensing of nanoparticles or molecules using silica microscale

  •   The role of charge recombination to triplet excitons in organic solar cells
    Nature (IF 49.962) Pub Date : 2021-09-29
    Alexander J. Gillett, Alberto Privitera, Rishat Dilmurat, Akchheta Karki, Deping Qian, Anton Pershin, Giacomo Londi, William K. Myers, Jaewon Lee, Jun Yuan, Seo-Jin Ko, Moritz K. Riede, Feng Gao, Guillermo C. Bazan, Akshay Rao, Thuc-Quyen Nguyen, David Beljonne, Richard H. Friend

    The use of non-fullerene acceptors (NFAs) in organic solar cells has led to power conversion efficiencies as high as 18%1. However, organic solar cells are still less efficient than inorganic solar cells, which typically have power conversion efficiencies of more than 20%2. A key reason for this difference is that organic solar cells have low open-circuit voltages relative to their optical bandgaps3

  •   Mechanism for Cas4-assisted directional spacer acquisition in CRISPR–Cas
    Nature (IF 49.962) Pub Date : 2021-09-29
    Chunyi Hu, Cristóbal Almendros, Ki Hyun Nam, Ana Rita Costa, Jochem N. A. Vink, Anna C. Haagsma, Saket R. Bagde, Stan J. J. Brouns, Ailong Ke

    Prokaryotes adapt to challenges from mobile genetic elements by integrating spacers derived from foreign DNA in the CRISPR array1. Spacer insertion is carried out by the Cas1–Cas2 integrase complex2,3,4. A substantial fraction of CRISPR–Cas systems use a Fe–S cluster containing Cas4 nuclease to ensure that spacers are acquired from DNA flanked by a protospacer adjacent motif (PAM)5,6 and inserted into

  •   Fine-root traits in the global spectrum of plant form and function
    Nature (IF 49.962) Pub Date : 2021-09-29
    Carlos P. Carmona, C. Guillermo Bueno, Aurele Toussaint, Sabrina Träger, Sandra Díaz, Mari Moora, Alison D. Munson, Meelis Pärtel, Martin Zobel, Riin Tamme

    Plant traits determine how individual plants cope with heterogeneous environments. Despite large variability in individual traits, trait coordination and trade-offs1,2 result in some trait combinations being much more widespread than others, as revealed in the global spectrum of plant form and function (GSPFF3) and the root economics space (RES4) for aboveground and fine-root traits, respectively.

  •   Structure-based classification of tauopathies
    Nature (IF 49.962) Pub Date : 2021-09-29
    Yang Shi, Wenjuan Zhang, Yang Yang, Alexey G. Murzin, Benjamin Falcon, Abhay Kotecha, Mike van Beers, Airi Tarutani, Fuyuki Kametani, Holly J. Garringer, Ruben Vidal, Grace I. Hallinan, Tammaryn Lashley, Yuko Saito, Shigeo Murayama, Mari Yoshida, Hidetomo Tanaka, Akiyoshi Kakita, Takeshi Ikeuchi, Andrew C. Robinson, David M. A. Mann, Gabor G. Kovacs, Tamas Revesz, Bernardino Ghetti, Masato Hasegawa

    The ordered assembly of tau protein into filaments characterizes several neurodegenerative diseases, which are called tauopathies. It was previously reported that, by cryo-electron microscopy, the structures of tau filaments from Alzheimer’s disease1,2, Pick’s disease3, chronic traumatic encephalopathy4 and corticobasal degeneration5 are distinct. Here we show that the structures of tau filaments

  •   Sensory processing during sleep in Drosophila melanogaster
    Nature (IF 49.962) Pub Date : 2021-09-29
    Alice S. French, Quentin Geissmann, Esteban J. Beckwith, Giorgio F. Gilestro

    During sleep, most animal species enter a state of reduced consciousness characterized by a marked sensory disconnect. Yet some processing of the external world must remain intact, given that a sleeping animal can be awoken by intense stimuli (for example, a loud noise or a bright light) or by soft but qualitatively salient stimuli (for example, the sound of a baby cooing or hearing one’s own name1

  •   Extremely anisotropic van der Waals thermal conductors
    Nature (IF 49.962) Pub Date : 2021-09-29
    Shi En Kim, Fauzia Mujid, Akash Rai, Fredrik Eriksson, Joonki Suh, Preeti Poddar, Ariana Ray, Chibeom Park, Erik Fransson, Yu Zhong, David A. Muller, Paul Erhart, David G. Cahill, Jiwoong Park

    The densification of integrated circuits requires thermal management strategies and high thermal conductivity materials1,2,3. Recent innovations include the development of materials with thermal conduction anisotropy, which can remove hotspots along the fast-axis direction and provide thermal insulation along the slow axis4,5. However, most artificially engineered thermal conductors have anisotropy

  •   The importance of lake breach floods for valley incision on early Mars
    Nature (IF 49.962) Pub Date : 2021-09-29
    Timothy A. Goudge, Alexander M. Morgan, Gaia Stucky de Quay, Caleb I. Fassett

    The surface environment of early Mars had an active hydrologic cycle, including flowing liquid water that carved river valleys1,2,3 and filled lake basins4,5,6. Over 200 of these lake basins filled with sufficient water to breach the confining topography4,6, causing catastrophic flooding and incision of outlet canyons7,8,9,10. Much past work has recognized the local importance of lake breach floods

  •   Imaging two-dimensional generalized Wigner crystals
    Nature (IF 49.962) Pub Date : 2021-09-29
    Hongyuan Li, Shaowei Li, Emma C. Regan, Danqing Wang, Wenyu Zhao, Salman Kahn, Kentaro Yumigeta, Mark Blei, Takashi Taniguchi, Kenji Watanabe, Sefaattin Tongay, Alex Zettl, Michael F. Crommie, Feng Wang

    The Wigner crystal1 has fascinated condensed matter physicists for nearly 90 years2,3,4,5,6,7,8,9,10,11,12,13,14. Signatures of two-dimensional (2D) Wigner crystals were first observed in 2D electron gases under high magnetic field2,3,4, and recently reported in transition metal dichalcogenide moiré superlattices6,7,8,9. Direct observation of the 2D Wigner crystal lattice in real space, however, has

  •   Blood and immune development in human fetal bone marrow and Down syndrome
    Nature (IF 49.962) Pub Date : 2021-09-29
    Laura Jardine, Simone Webb, Issac Goh, Mariana Quiroga Londoño, Gary Reynolds, Michael Mather, Bayanne Olabi, Emily Stephenson, Rachel A. Botting, Dave Horsfall, Justin Engelbert, Daniel Maunder, Nicole Mende, Caitlin Murnane, Emma Dann, Jim McGrath, Hamish King, Iwo Kucinski, Rachel Queen, Christopher D. Carey, Caroline Shrubsole, Elizabeth Poyner, Meghan Acres, Claire Jones, Thomas Ness, Rowen Coulthard

    Haematopoiesis in the bone marrow (BM) maintains blood and immune cell production throughout postnatal life. Haematopoiesis first emerges in human BM at 11–12 weeks after conception1,2, yet almost nothing is known about how fetal BM (FBM) evolves to meet the highly specialized needs of the fetus and newborn. Here we detail the development of FBM, including stroma, using multi-omic assessment of mRNA

  •   Circadian autophagy drives iTRF-mediated longevity
    Nature (IF 49.962) Pub Date : 2021-09-29
    Matt Ulgherait, Adil M. Midoun, Scarlet J. Park, Jared A. Gatto, Samantha J. Tener, Julia Siewert, Naomi Klickstein, Julie C. Canman, William W. Ja, Mimi Shirasu-Hiza

    Time-restricted feeding (TRF) has recently gained interest as a potential anti-ageing treatment for organisms from Drosophila to humans1,2,3,4,5. TRF restricts food intake to specific hours of the day. Because TRF controls the timing of feeding, rather than nutrient or caloric content, TRF has been hypothesized to depend on circadian-regulated functions; the underlying molecular mechanisms of its effects remain

  •   Architecture and assembly mechanism of native glycine receptors
    Nature (IF 49.962) Pub Date : 2021-09-23
    Hongtao Zhu, Eric Gouaux

    Glycine receptors (GlyRs) are pentameric, ‘Cys-loop’ receptors that form chloride-permeable channels and mediate fast inhibitory signaling throughout the central nervous system1,2. In the spinal cord and brainstem, GlyRs regulate locomotion and cause movement disorders when mutated2,3. However, the stoichiometry of native GlyRs and the mechanism by which they are assembled remain unclear, despite extensive

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