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  • Global upper-atmospheric heating on Jupiter by the polar aurorae
    Nature (IF 49.962) Pub Date : 2021-08-04
    O’Donoghue, J., Moore, L., Bhakyapaibul, T., Melin, H., Stallard, T., Connerney, J. E. P., Tao, C.

    Jupiter’s upper atmosphere is considerably hotter than expected from the amount of sunlight that it receives1,2,3. Processes that couple the magnetosphere to the atmosphere give rise to intense auroral emissions and enormous deposition of energy in the magnetic polar regions, so it has been presumed that redistribution of this energy could heat the rest of the planet4,5,6. Instead, most thermospheric

  • Emergent order in hydrodynamic spin lattices
    Nature (IF 49.962) Pub Date : 2021-08-04
    Sáenz, Pedro J., Pucci, Giuseppe, Turton, Sam E., Goujon, Alexis, Rosales, Rodolfo R., Dunkel, Jörn, Bush, John W. M.

    Macroscale analogues1,2,3 of microscopic spin systems offer direct insights into fundamental physical principles, thereby advancing our understanding of synchronization phenomena4 and informing the design of novel classes of chiral metamaterials5,6,7. Here we introduce hydrodynamic spin lattices (HSLs) of ‘walking’ droplets as a class of active spin systems with particle–wave coupling. HSLs reveal

  • Genetic insights into biological mechanisms governing human ovarian ageing
    Nature (IF 49.962) Pub Date : 2021-08-04
    Ruth, Katherine S., Day, Felix R., Hussain, Jazib, Martínez-Marchal, Ana, Aiken, Catherine E., Azad, Ajuna, Thompson, Deborah J., Knoblochova, Lucie, Abe, Hironori, Tarry-Adkins, Jane L., Gonzalez, Javier Martin, Fontanillas, Pierre, Claringbould, Annique, Bakker, Olivier B., Sulem, Patrick, Walters, Robin G., Terao, Chikashi, Turon, Sandra, Horikoshi, Momoko, Lin, Kuang, Onland-Moret, N. Charlotte

    Reproductive longevity is essential for fertility and influences healthy ageing in women1,2, but insights into its underlying biological mechanisms and treatments to preserve it are limited. Here we identify 290 genetic determinants of ovarian ageing, assessed using normal variation in age at natural menopause (ANM) in about 200,000 women of European ancestry. These common alleles were associated with

  • Structural insights into how Prp5 proofreads the pre-mRNA branch site
    Nature (IF 49.962) Pub Date : 2021-08-04
    Zhang, Zhenwei, Rigo, Norbert, Dybkov, Olexandr, Fourmann, Jean-Baptiste, Will, Cindy L., Kumar, Vinay, Urlaub, Henning, Stark, Holger, Lührmann, Reinhard

    During the splicing of introns from precursor messenger RNAs (pre-mRNAs), the U2 small nuclear ribonucleoprotein (snRNP) must undergo stable integration into the spliceosomal A complex—a poorly understood, multistep process that is facilitated by the DEAD-box helicase Prp5 (refs. 1,2,3,4). During this process, the U2 small nuclear RNA (snRNA) forms an RNA duplex with the pre-mRNA branch site (the U2–BS

  • Pseudogap in a crystalline insulator doped by disordered metals
    Nature (IF 49.962) Pub Date : 2021-08-04
    Ryu, Sae Hee, Huh, Minjae, Park, Do Yun, Jozwiak, Chris, Rotenberg, Eli, Bostwick, Aaron, Kim, Keun Su

    Key to our understanding of how electrons behave in crystalline solids is the band structure that connects the energy of electron waves to their wavenumber. Even in phases of matter with only short-range order (liquid or amorphous solid), the coherent part of electron waves still has a band structure. Theoretical models for the band structure of liquid metals were formulated more than five decades

  • Deficient H2A.Z deposition is associated with genesis of uterine leiomyoma
    Nature (IF 49.962) Pub Date : 2021-08-04
    Berta, Davide G., Kuisma, Heli, Välimäki, Niko, Räisänen, Maritta, Jäntti, Maija, Pasanen, Annukka, Karhu, Auli, Kaukomaa, Jaana, Taira, Aurora, Cajuso, Tatiana, Nieminen, Sanna, Penttinen, Rosa-Maria, Ahonen, Saija, Lehtonen, Rainer, Mehine, Miika, Vahteristo, Pia, Jalkanen, Jyrki, Sahu, Biswajyoti, Ravantti, Janne, Mäkinen, Netta, Rajamäki, Kristiina, Palin, Kimmo, Taipale, Jussi, Heikinheimo, Oskari

    One in four women suffers from uterine leiomyomas (ULs)—benign tumours of the uterine wall, also known as uterine fibroids—at some point in premenopausal life. ULs can cause excessive bleeding, pain and infertility1, and are a common cause of hysterectomy2. They emerge through at least three distinct genetic drivers: mutations in MED12 or FH, or genomic rearrangement of HMGA23. Here we created genome-wide

  • Satellite imaging reveals increased proportion of population exposed to floods
    Nature (IF 49.962) Pub Date : 2021-08-04
    Tellman, B., Sullivan, J. A., Kuhn, C., Kettner, A. J., Doyle, C. S., Brakenridge, G. R., Erickson, T. A., Slayback, D. A.

    Flooding affects more people than any other environmental hazard and hinders sustainable development1,2. Investing in flood adaptation strategies may reduce the loss of life and livelihood caused by floods3. Where and how floods occur and who is exposed are changing as a result of rapid urbanization4, flood mitigation infrastructure5 and increasing settlements in floodplains6. Previous estimates of

  • Structure and mechanism of blood–brain-barrier lipid transporter MFSD2A
    Nature (IF 49.962) Pub Date : 2021-08-04
    Wood, Chase A. P., Zhang, Jinru, Aydin, Deniz, Xu, Yan, Andreone, Benjamin J., Langen, Urs H., Dror, Ron O., Gu, Chenghua, Feng, Liang

    MFSD2A is a sodium-dependent lysophosphatidylcholine symporter that is responsible for the uptake of docosahexaenoic acid into the brain1,2, which is crucial for the development and performance of the brain3. Mutations that affect MFSD2A cause microcephaly syndromes4,5. The ability of MFSD2A to transport lipid is also a key mechanism that underlies its function as an inhibitor of transcytosis to regulate

  • Agrochemicals interact synergistically to increase bee mortality
    Nature (IF 49.962) Pub Date : 2021-08-04
    Siviter, Harry, Bailes, Emily J., Martin, Callum D., Oliver, Thomas R., Koricheva, Julia, Leadbeater, Ellouise, Brown, Mark J. F.

    Global concern over widely documented declines in pollinators1,2,3 has led to the identification of anthropogenic stressors that, individually, are detrimental to bee populations4,5,6,7. Synergistic interactions between these stressors could substantially amplify the environmental effect of these stressors and could therefore have important implications for policy decisions that aim to improve the

  • Quantized nonlinear Thouless pumping
    Nature (IF 49.962) Pub Date : 2021-08-04
    Jürgensen, Marius, Mukherjee, Sebabrata, Rechtsman, Mikael C.

    The topological protection of wave transport, originally observed in the context of the quantum Hall effect in two-dimensional electron gases1, has been shown to apply broadly to a range of physical platforms, including photonics2,3,4,5, ultracold atoms in optical lattices6,7,8 and others9,10,11,12. That said, the behaviour of such systems can be very different from the electronic case, particularly

  • The structural basis of odorant recognition in insect olfactory receptors
    Nature (IF 49.962) Pub Date : 2021-08-04
    del Mármol, Josefina, Yedlin, Mackenzie A., Ruta, Vanessa

    Olfactory systems must detect and discriminate amongst an enormous variety of odorants1. To contend with this challenge, diverse species have converged on a common strategy in which odorant identity is encoded through the combinatorial activation of large families of olfactory receptors1,2,3, thus allowing a finite number of receptors to detect a vast chemical world. Here we offer structural and mechanistic

  • The role of retrotransposable elements in ageing and age-associated diseases
    Nature (IF 49.962) Pub Date : 2021-08-04
    Gorbunova, Vera, Seluanov, Andrei, Mita, Paolo, McKerrow, Wilson, Fenyö, David, Boeke, Jef D., Linker, Sara B., Gage, Fred H., Kreiling, Jill A., Petrashen, Anna P., Woodham, Trenton A., Taylor, Jackson R., Helfand, Stephen L., Sedivy, John M.

    The genomes of virtually all organisms contain repetitive sequences that are generated by the activity of transposable elements (transposons). Transposons are mobile genetic elements that can move from one genomic location to another; in this process, they amplify and increase their presence in genomes, sometimes to very high copy numbers. In this Review we discuss new evidence and ideas that the activity

  • Connectomes across development reveal principles of brain maturation
    Nature (IF 49.962) Pub Date : 2021-08-04
    Witvliet, Daniel, Mulcahy, Ben, Mitchell, James K., Meirovitch, Yaron, Berger, Daniel R., Wu, Yuelong, Liu, Yufang, Koh, Wan Xian, Parvathala, Rajeev, Holmyard, Douglas, Schalek, Richard L., Shavit, Nir, Chisholm, Andrew D., Lichtman, Jeff W., Samuel, Aravinthan D. T., Zhen, Mei

    An animal’s nervous system changes as its body grows from birth to adulthood and its behaviours mature1,2,3,4,5,6,7,8. The form and extent of circuit remodelling across the connectome is unknown3,9,10,11,12,13,14,15. Here we used serial-section electron microscopy to reconstruct the full brain of eight isogenic Caenorhabditis elegans individuals across postnatal stages to investigate how it changes

  • Microbes exploit death-induced nutrient release by gut epithelial cells
    Nature (IF 49.962) Pub Date : 2021-08-04
    Anderson, Christopher J., Medina, Christopher B., Barron, Brady J., Karvelyte, Laura, Aaes, Tania Løve, Lambertz, Irina, Perry, Justin S. A., Mehrotra, Parul, Gonçalves, Amanda, Lemeire, Kelly, Blancke, Gillian, Andries, Vanessa, Ghazavi, Farzaneh, Martens, Arne, van Loo, Geert, Vereecke, Lars, Vandenabeele, Peter, Ravichandran, Kodi S.

    Regulated cell death is an integral part of life, and has broad effects on organism development and homeostasis1. Malfunctions within the regulated cell death process, including the clearance of dying cells, can manifest in diverse pathologies throughout various tissues including the gastrointestinal tract2. A long appreciated, yet elusively defined relationship exists between cell death and gastrointestinal

  • Fair algorithms for selecting citizens’ assemblies
    Nature (IF 49.962) Pub Date : 2021-08-04
    Flanigan, Bailey, Gölz, Paul, Gupta, Anupam, Hennig, Brett, Procaccia, Ariel D.

    Globally, there has been a recent surge in ‘citizens’ assemblies’1, which are a form of civic participation in which a panel of randomly selected constituents contributes to questions of policy. The random process for selecting this panel should satisfy two properties. First, it must produce a panel that is representative of the population. Second, in the spirit of democratic equality, individuals

  • Behavioral Nudges Increase COVID-19 Vaccinations
    Nature (IF 49.962) Pub Date : 2021-08-02
    Dai, Hengchen, Saccardo, Silvia, Han, Maria A., Roh, Lily, Raja, Naveen, Vangala, Sitaram, Modi, Hardikkumar, Pandya, Shital, Sloyan, Michael, Croymans, Daniel M.

    Enhancing vaccine uptake is a critical public health challenge1. Overcoming vaccine hesitancy2,3 and failure to follow-through on vaccination intentions3 requires effective communication strategies3,4. We present two sequential randomized controlled trials (RCTs) to test the impact of behavioral interventions on COVID-19 vaccine uptake. We designed text-based reminders that make vaccination salient

  • Novel bile acid biosynthetic pathways are enriched in the microbiome of centenarians
    Nature (IF 49.962) Pub Date : 2021-07-29
    Sato, Yuko, Atarashi, Koji, Plichta, Damian R., Arai, Yasumichi, Sasajima, Satoshi, Kearney, Sean M., Suda, Wataru, Takeshita, Kozue, Sasaki, Takahiro, Okamoto, Shoki, Skelly, Ashwin N., Okamura, Yuki, Vlamakis, Hera, Li, Youxian, Tanoue, Takeshi, Takei, Hajime, Nittono, Hiroshi, Narushima, Seiko, Irie, Junichiro, Itoh, Hiroshi, Moriya, Kyoji, Sugiura, Yuki, Suematsu, Makoto, Moritoki, Nobuko, Shibata

    Centenarians display decreased susceptibility to ageing-associated illness, chronic inflammation, and infectious disease1–3. Here we show that centenarians have a distinct gut microbiome enriched in microbes capable of generating unique secondary bile acids (BAs), including iso-, 3-oxo-, allo-, 3-oxoallo-, and isoallo-lithocholic acid (LCA). Among these BAs, the biosynthetic pathway for isoalloLCA

  • Rapid and stable mobilization of CD8+ T cells by SARS-CoV-2 mRNA vaccine
    Nature (IF 49.962) Pub Date : 2021-07-28
    Oberhardt, Valerie, Luxenburger, Hendrik, Kemming, Janine, Schulien, Isabel, Ciminski, Kevin, Giese, Sebastian, Csernalabics, Benedikt, Lang-Meli, Julia, Janowska, Iga, Staniek, Julian, Wild, Katharina, Basho, Kristi, Marinescu, Mircea Stefan, Fuchs, Jonas, Topfstedt, Fernando, Janda, Ales, Sogukpinar, Oezlem, Hilger, Hanna, Stete, Katarina, Emmerich, Florian, Bengsch, Bertram, Waller, Cornelius F

    SARS-CoV-2 spike mRNA vaccines1–3 mediate protection from severe disease as early as 10 days post prime vaccination3, when neutralizing antibodies are hardly detectable4–6. Vaccine-induced CD8+ T cells may thus be the main mediators of protection at this early stage7,8. The details of their induction, comparison to natural infection, and association with other arms of vaccine-induced immunity remain

  • Spectroscopic evidence for a gold-coloured metallic water solution
    Nature (IF 49.962) Pub Date : 2021-07-28
    Mason, Philip E., Schewe, H. Christian, Buttersack, Tillmann, Kostal, Vojtech, Vitek, Marco, McMullen, Ryan S., Ali, Hebatallah, Trinter, Florian, Lee, Chin, Neumark, Daniel M., Thürmer, Stephan, Seidel, Robert, Winter, Bernd, Bradforth, Stephen E., Jungwirth, Pavel

    Insulating materials can in principle be made metallic by applying pressure. In the case of pure water, this is estimated1 to require a pressure of 48 megabar, which is beyond current experimental capabilities and may only exist in the interior of large planets or stars2,3,4. Indeed, recent estimates and experiments indicate that water at pressures accessible in the laboratory will at best be superionic

  • Possible poriferan body fossils in early Neoproterozoic microbial reefs
    Nature (IF 49.962) Pub Date : 2021-07-28
    Turner, Elizabeth C.

    Molecular phylogeny indicates that metazoans (animals) emerged early in the Neoproterozoic era1, but physical evidence is lacking. The search for animal fossils from the Proterozoic eon is hampered by uncertainty about what physical characteristics to expect. Sponges are the most basic known animal type2,3; it is possible that body fossils of hitherto-undiscovered Proterozoic metazoans might resemble

  • A process-based approach to understanding and managing triggered seismicity
    Nature (IF 49.962) Pub Date : 2021-07-28
    Hager, Bradford H., Dieterich, James, Frohlich, Cliff, Juanes, Ruben, Mantica, Stefano, Shaw, John H., Bottazzi, Francesca, Caresani, Federica, Castineira, David, Cominelli, Alberto, Meda, Marco, Osculati, Lorenzo, Petroselli, Stefania, Plesch, Andreas

    There is growing concern about seismicity triggered by human activities, whereby small increases in stress bring tectonically loaded faults to failure. Examples of such activities include mining, impoundment of water, stimulation of geothermal fields, extraction of hydrocarbons and water, and the injection of water, CO2 and methane into subsurface reservoirs1. In the absence of sufficient information

  • Rewiring of the ubiquitinated proteome determines ageing in C. elegans
    Nature (IF 49.962) Pub Date : 2021-07-28
    Koyuncu, Seda, Loureiro, Rute, Lee, Hyun Ju, Wagle, Prerana, Krueger, Marcus, Vilchez, David

    Ageing is driven by a loss of cellular integrity1. Given the major role of ubiquitin modifications in cell function2, here we assess the link between ubiquitination and ageing by quantifying whole-proteome ubiquitin signatures in Caenorhabditis elegans. We find a remodelling of the ubiquitinated proteome during ageing, which is ameliorated by longevity paradigms such as dietary restriction and reduced

  • Linear-in temperature resistivity from an isotropic Planckian scattering rate
    Nature (IF 49.962) Pub Date : 2021-07-28
    Grissonnanche, Gaël, Fang, Yawen, Legros, Anaëlle, Verret, Simon, Laliberté, Francis, Collignon, Clément, Zhou, Jianshi, Graf, David, Goddard, Paul A., Taillefer, Louis, Ramshaw, B. J.

    A variety of ‘strange metals’ exhibit resistivity that decreases linearly with temperature as the temperature decreases to zero1,2,3, in contrast to conventional metals where resistivity decreases quadratically with temperature. This linear-in-temperature resistivity has been attributed to charge carriers scattering at a rate given by ħ/τ = αkBT, where α is a constant of order unity, ħ is the Planck

  • Regulated control of gene therapies by drug-induced splicing
    Nature (IF 49.962) Pub Date : 2021-07-28
    Monteys, Alex Mas, Hundley, Amiel A., Ranum, Paul T., Tecedor, Luis, Muehlmatt, Amy, Lim, Euyn, Lukashev, Dmitriy, Sivasankaran, Rajeev, Davidson, Beverly L.

    So far, gene therapies have relied on complex constructs that cannot be finely controlled1,2. Here we report a universal switch element that enables precise control of gene replacement or gene editing after exposure to a small molecule. The small-molecule inducers are currently in human use, are orally bioavailable when given to animals or humans and can reach both peripheral tissues and the brain

  • Molecular architecture of the developing mouse brain
    Nature (IF 49.962) Pub Date : 2021-07-28
    La Manno, Gioele, Siletti, Kimberly, Furlan, Alessandro, Gyllborg, Daniel, Vinsland, Elin, Mossi Albiach, Alejandro, Mattsson Langseth, Christoffer, Khven, Irina, Lederer, Alex R., Dratva, Lisa M., Johnsson, Anna, Nilsson, Mats, Lönnerberg, Peter, Linnarsson, Sten

    The mammalian brain develops through a complex interplay of spatial cues generated by diffusible morphogens, cell–cell interactions and intrinsic genetic programs that result in probably more than a thousand distinct cell types. A complete understanding of this process requires a systematic characterization of cell states over the entire spatiotemporal range of brain development. The ability of single-cell

  • Light bending and X-ray echoes from behind a supermassive black hole
    Nature (IF 49.962) Pub Date : 2021-07-28
    Wilkins, D. R., Gallo, L. C., Costantini, E., Brandt, W. N., Blandford, R. D.

    The innermost regions of accretion disks around black holes are strongly irradiated by X-rays that are emitted from a highly variable, compact corona, in the immediate vicinity of the black hole1,2,3. The X-rays that are seen reflected from the disk4, and the time delays, as variations in the X-ray emission echo or ‘reverberate’ off the disk5,6, provide a view of the environment just outside the event

  • Mechanisms of BRCA1–BARD1 nucleosome recognition and ubiquitylation
    Nature (IF 49.962) Pub Date : 2021-07-28
    Hu, Qi, Botuyan, Maria Victoria, Zhao, Debiao, Cui, Gaofeng, Mer, Elie, Mer, Georges

    The BRCA1–BARD1 tumour suppressor is an E3 ubiquitin ligase necessary for the repair of DNA double-strand breaks by homologous recombination1,2,3,4,5,6,7,8,9,10. The BRCA1–BARD1 complex localizes to damaged chromatin after DNA replication and catalyses the ubiquitylation of histone H2A and other cellular targets11,12,13,14. The molecular bases for the recruitment to double-strand breaks and target

  • Incoherent transport across the strange-metal regime of overdoped cuprates
    Nature (IF 49.962) Pub Date : 2021-07-28
    Ayres, J., Berben, M., Čulo, M., Hsu, Y.-T., van Heumen, E., Huang, Y., Zaanen, J., Kondo, T., Takeuchi, T., Cooper, J. R., Putzke, C., Friedemann, S., Carrington, A., Hussey, N. E.

    Strange metals possess highly unconventional electrical properties, such as a linear-in-temperature resistivity1,2,3,4,5,6, an inverse Hall angle that varies as temperature squared7,8,9 and a linear-in-field magnetoresistance10,11,12,13. Identifying the origin of these collective anomalies has proved fundamentally challenging, even in materials such as the hole-doped cuprates that possess a simple

  • In silico saturation mutagenesis of cancer genes
    Nature (IF 49.962) Pub Date : 2021-07-28
    Muiños, Ferran, Martínez-Jiménez, Francisco, Pich, Oriol, Gonzalez-Perez, Abel, Lopez-Bigas, Nuria

    Despite the existence of good catalogues of cancer genes1,2, identifying the specific mutations of those genes that drive tumorigenesis across tumour types is still a largely unsolved problem. As a result, most mutations identified in cancer genes across tumours are of unknown significance to tumorigenesis3. We propose that the mutations observed in thousands of tumours—natural experiments testing

  • BARD1 reads H2A lysine 15 ubiquitination to direct homologous recombination
    Nature (IF 49.962) Pub Date : 2021-07-28
    Becker, Jordan R., Clifford, Gillian, Bonnet, Clara, Groth, Anja, Wilson, Marcus D., Chapman, J. Ross

    Protein ubiquitination at sites of DNA double-strand breaks (DSBs) by RNF168 recruits BRCA1 and 53BP11,2, which are mediators of the homologous recombination and non-homologous end joining DSB repair pathways, respectively3. Non-homologous end joining relies on 53BP1 binding directly to ubiquitinated lysine 15 on H2A-type histones (H2AK15ub)4,5 (which is an RNF168-dependent modification6), but how

  • Structural basis of ketamine action on human NMDA receptors
    Nature (IF 49.962) Pub Date : 2021-07-28
    Zhang, Youyi, Ye, Fei, Zhang, Tongtong, Lv, Shiyun, Zhou, Liping, Du, Daohai, Lin, He, Guo, Fei, Luo, Cheng, Zhu, Shujia

    Ketamine is a non-competitive channel blocker of N-methyl-d-aspartate (NMDA) receptors1. A single sub-anaesthetic dose of ketamine produces rapid (within hours) and long-lasting antidepressant effects in patients who are resistant to other antidepressants2,3. Ketamine is a racemic mixture of S- and R-ketamine enantiomers, with S-ketamine isomer being the more active antidepressant4. Here we describe

  • Highly accurate protein structure prediction for the human proteome
    Nature (IF 49.962) Pub Date : 2021-07-22
    Kathryn Tunyasuvunakool, Jonas Adler, Zachary Wu, Tim Green, Michal Zielinski, Augustin Žídek, Alex Bridgland, Andrew Cowie, Clemens Meyer, Agata Laydon, Sameer Velankar, Gerard J. Kleywegt, Alex Bateman, Richard Evans, Alexander Pritzel, Michael Figurnov, Olaf Ronneberger, Russ Bates, Simon A. A. Kohl, Anna Potapenko, Andrew J. Ballard, Bernardino Romera-Paredes, Stanislav Nikolov, Rishub Jain, Ellen

    Protein structures can provide invaluable information, both for reasoning about biological processes and for enabling interventions such as structure-based drug development or targeted mutagenesis. After decades of effort, 17% of the total residues in human protein sequences are covered by an experimentally-determined structure1. Here we dramatically expand structural coverage by applying the state-of-the-art

  • Tonic prime-boost of STING signalling mediates Niemann–Pick disease type C
    Nature (IF 49.962) Pub Date : 2021-07-21
    Ting-Ting Chu, Xintao Tu, Kun Yang, Jianjun Wu, Joyce J. Repa, Nan Yan

    The classic mode of STING activation is through binding the cyclic dinucleotide 2′3′-cyclic GMP–AMP (cGAMP), produced by the DNA sensor cyclic GMP–AMP synthase (cGAS), which is important for the innate immune response to microbial infection and autoimmune disease. Modes of STING activation that are independent of cGAS are much less well understood. Here, through a spatiotemporally resolved proximity

  • EGFR activation limits the response of liver cancer to lenvatinib
    Nature (IF 49.962) Pub Date : 2021-07-21
    Haojie Jin, Yaoping Shi, Yuanyuan Lv, Shengxian Yuan, Christel F. A. Ramirez, Cor Lieftink, Liqin Wang, Siying Wang, Cun Wang, Matheus Henrique Dias, Fleur Jochems, Yuan Yang, Astrid Bosma, E. Marielle Hijmans, Marnix H. P. de Groot, Serena Vegna, Dan Cui, Yangyang Zhou, Jing Ling, Hui Wang, Yuchen Guo, Xingling Zheng, Nikita Isima, Haiqiu Wu, Chong Sun, Roderick L. Beijersbergen, Leila Akkari, Weiping

    Hepatocellular carcinoma (HCC)—the most common form of liver cancer—is an aggressive malignancy with few effective treatment options1. Lenvatinib is a small-molecule inhibitor of multiple receptor tyrosine kinases that is used for the treatment of patients with advanced HCC, but this drug has only limited clinical benefit2. Here, using a kinome-centred CRISPR–Cas9 genetic screen, we show that inhibition

  • Gut cytokines modulate olfaction through metabolic reprogramming of glia
    Nature (IF 49.962) Pub Date : 2021-07-21
    Xiaoyu Tracy Cai, Hongjie Li, Martin Borch Jensen, Elie Maksoud, Jovencio Borneo, Yuxin Liang, Stephen R. Quake, Liqun Luo, Pejmun Haghighi, Heinrich Jasper

    Infection-induced aversion against enteropathogens is a conserved sickness behaviour that can promote host survival1,2. The aetiology of this behaviour remains poorly understood, but studies in Drosophila have linked olfactory and gustatory perception to avoidance behaviours against toxic microorganisms3,4,5. Whether and how enteric infections directly influence sensory perception to induce or modulate

  • SAR1B senses leucine levels to regulate mTORC1 signalling
    Nature (IF 49.962) Pub Date : 2021-07-21
    Jie Chen, Yuhui Ou, Rong Luo, Jie Wang, Dong Wang, Jialiang Guan, Yi Li, Peixue Xia, Peng R. Chen, Ying Liu

    The mTOR complex 1 (mTORC1) controls cell growth in response to amino acid levels1. Here we report SAR1B as a leucine sensor that regulates mTORC1 signalling in response to intracellular levels of leucine. Under conditions of leucine deficiency, SAR1B inhibits mTORC1 by physically targeting its activator GATOR2. In conditions of leucine sufficiency, SAR1B binds to leucine, undergoes a conformational

  • Phenotype, specificity and avidity of antitumour CD8+ T cells in melanoma
    Nature (IF 49.962) Pub Date : 2021-07-21
    Giacomo Oliveira, Kari Stromhaug, Susan Klaeger, Tomasz Kula, Dennie T. Frederick, Phuong M. Le, Juliet Forman, Teddy Huang, Shuqiang Li, Wandi Zhang, Qikai Xu, Nicoletta Cieri, Karl R. Clauser, Sachet A. Shukla, Donna Neuberg, Sune Justesen, Gavin MacBeath, Steven A. Carr, Edward F. Fritsch, Nir Hacohen, Moshe Sade-Feldman, Kenneth J. Livak, Genevieve M. Boland, Patrick A. Ott, Derin B. Keskin, Catherine

    Interactions between T cell receptors (TCRs) and their cognate tumour antigens are central to antitumour immune responses1,2,3; however, the relationship between phenotypic characteristics and TCR properties is not well elucidated. Here we show, by linking the antigenic specificity of TCRs and the cellular phenotype of melanoma-infiltrating lymphocytes at single-cell resolution, that tumour specificity

  • Structural basis of human separase regulation by securin and CDK1–cyclin B1
    Nature (IF 49.962) Pub Date : 2021-07-21
    Jun Yu, Pierre Raia, Chloe M. Ghent, Tobias Raisch, Yashar Sadian, Simone Cavadini, Pramod M. Sabale, David Barford, Stefan Raunser, David O. Morgan, Andreas Boland

    In early mitosis, the duplicated chromosomes are held together by the ring-shaped cohesin complex1. Separation of chromosomes during anaphase is triggered by separase—a large cysteine endopeptidase that cleaves the cohesin subunit SCC1 (also known as RAD212,3,4). Separase is activated by degradation of its inhibitors, securin5 and cyclin B6, but the molecular mechanisms of separase regulation are not

  • A natively flexible 32-bit Arm microprocessor
    Nature (IF 49.962) Pub Date : 2021-07-21
    John Biggs, James Myers, Jedrzej Kufel, Emre Ozer, Simon Craske, Antony Sou, Catherine Ramsdale, Ken Williamson, Richard Price, Scott White

    Nearly 50 years ago, Intel created the world’s first commercially produced microprocessor—the 4004 (ref. 1), a modest 4-bit CPU (central processing unit) with 2,300 transistors fabricated using 10 μm process technology in silicon and capable only of simple arithmetic calculations. Since this ground-breaking achievement, there has been continuous technological development with increasing sophistication

  • Free-electron lasing at 27 nanometres based on a laser wakefield accelerator
    Nature (IF 49.962) Pub Date : 2021-07-21
    Wentao Wang, Ke Feng, Lintong Ke, Changhai Yu, Yi Xu, Rong Qi, Yu Chen, Zhiyong Qin, Zhijun Zhang, Ming Fang, Jiaqi Liu, Kangnan Jiang, Hao Wang, Cheng Wang, Xiaojun Yang, Fenxiang Wu, Yuxin Leng, Jiansheng Liu, Ruxin Li, Zhizhan Xu

    X-ray free-electron lasers can generate intense and coherent radiation at wavelengths down to the sub-ångström region1,2,3,4,5, and have become indispensable tools for applications in structural biology and chemistry, among other disciplines6. Several X-ray free-electron laser facilities are in operation2,3,4,5; however, their requirement for large, high-cost, state-of-the-art radio-frequency accelerators

  • Pauli-limit violation and re-entrant superconductivity in moiré graphene
    Nature (IF 49.962) Pub Date : 2021-07-21
    Yuan Cao, Jeong Min Park, Kenji Watanabe, Takashi Taniguchi, Pablo Jarillo-Herrero

    Moiré quantum matter has emerged as a materials platform in which correlated and topological phases can be explored with unprecedented control. Among them, magic-angle systems constructed from two or three layers of graphene have shown robust superconducting phases with unconventional characteristics1,2,3,4,5. However, direct evidence of unconventional pairing remains to be experimentally demonstrated

  • The nightside cloud-top circulation of the atmosphere of Venus
    Nature (IF 49.962) Pub Date : 2021-07-21
    Kiichi Fukuya, Takeshi Imamura, Makoto Taguchi, Tetsuya Fukuhara, Toru Kouyama, Takeshi Horinouchi, Javier Peralta, Masahiko Futaguchi, Takeru Yamada, Takao M. Sato, Atsushi Yamazaki, Shin-ya Murakami, Takehiko Satoh, Masahiro Takagi, Masato Nakamura

    Although Venus is a terrestrial planet similar to Earth, its atmospheric circulation is much different and poorly characterized1. Winds at the cloud top have been measured predominantly on the dayside. Prominent poleward drifts have been observed with dayside cloud tracking and interpreted to be caused by thermal tides and a Hadley circulation2,3,4; however, the lack of nightside measurements over

  • Layer Hall effect in a 2D topological axion antiferromagnet
    Nature (IF 49.962) Pub Date : 2021-07-21
    Anyuan Gao, Yu-Fei Liu, Chaowei Hu, Jian-Xiang Qiu, Christian Tzschaschel, Barun Ghosh, Sheng-Chin Ho, Damien Bérubé, Rui Chen, Haipeng Sun, Zhaowei Zhang, Xin-Yue Zhang, Yu-Xuan Wang, Naizhou Wang, Zumeng Huang, Claudia Felser, Amit Agarwal, Thomas Ding, Hung-Ju Tien, Austin Akey, Jules Gardener, Bahadur Singh, Kenji Watanabe, Takashi Taniguchi, Kenneth S. Burch, David C. Bell, Brian B. Zhou, Weibo

    Whereas ferromagnets have been known and used for millennia, antiferromagnets were only discovered in the 1930s1. At large scale, because of the absence of global magnetization, antiferromagnets may seem to behave like any non-magnetic material. At the microscopic level, however, the opposite alignment of spins forms a rich internal structure. In topological antiferromagnets, this internal structure

  • Extreme flow simulations reveal skeletal adaptations of deep-sea sponges
    Nature (IF 49.962) Pub Date : 2021-07-21
    Giacomo Falcucci, Giorgio Amati, Pierluigi Fanelli, Vesselin K. Krastev, Giovanni Polverino, Maurizio Porfiri, Sauro Succi

    Since its discovery1,2, the deep-sea glass sponge Euplectella aspergillum has attracted interest in its mechanical properties and beauty. Its skeletal system is composed of amorphous hydrated silica and is arranged in a highly regular and hierarchical cylindrical lattice that begets exceptional flexibility and resilience to damage3,4,5,6. Structural analyses dominate the literature, but hydrodynamic

  • A multilayered immune system through the lens of unconventional T cells
    Nature (IF 49.962) Pub Date : 2021-07-21
    Toufic Mayassi, Luis B. Barreiro, Jamie Rossjohn, Bana Jabri

    The unconventional T cell compartment encompasses a variety of cell subsets that straddle the line between innate and adaptive immunity, often reside at mucosal surfaces and can recognize a wide range of non-polymorphic ligands. Recent advances have highlighted the role of unconventional T cells in tissue homeostasis and disease. In this Review, we recast unconventional T cell subsets according to

  • Orthogonal-array dynamic molecular sieving of propylene/propane mixtures
    Nature (IF 49.962) Pub Date : 2021-07-21
    Heng Zeng, Mo Xie, Ting Wang, Rong-Jia Wei, Xiao-Jing Xie, Yifang Zhao, Weigang Lu, Dan Li

    Rigid molecular sieving materials work well for small molecules with the complete exclusion of large ones1,2,3, and molecules with matching physiochemical properties may be separated using dynamic molecular sieving materials4,5,6. Metal–organic frameworks (MOFs)7,8,9 are known for their precise control of structures and functions on a molecular level10,11,12,13,14,15. However, the rational design of

  • Cleaving arene rings for acyclic alkenylnitrile synthesis
    Nature (IF 49.962) Pub Date : 2021-07-19
    Xu Qiu, Yueqian Sang, Hao Wu, Xiao-Song Xue, Zixi Yan, Yachong Wang, Zengrui Cheng, Xiaoyang Wang, Hui Tan, Song Song, Guisheng Zhang, Xiaohui Zhang, K. N. Houk, Ning Jiao

    Synthetic chemistry is built around the formation of carbon−carbon bonds. Conversely, selective methods for C−C bond cleavage is a largely unmet challenge1–6, the solution of which will provide promising applications in synthesis, coal liquefaction, petroleum cracking, polymer degradation and biomass conversion. For example, aromatic rings are ubiquitous skeletal features in inert chemical feed stocks

  • Broad sarbecovirus neutralization by a human monoclonal antibody
    Nature (IF 49.962) Pub Date : 2021-07-19
    M. Alejandra Tortorici, Nadine Czudnochowski, Tyler N. Starr, Roberta Marzi, Alexandra C. Walls, Fabrizia Zatta, John E. Bowen, Stefano Jaconi, Julia Di Iulio, Zhaoqian Wang, Anna De Marco, Samantha K. Zepeda, Dora Pinto, Zhuoming Liu, Martina Beltramello, Istvan Bartha, Michael P. Housley, Florian A. Lempp, Laura E. Rosen, Exequiel Dellota, Hannah Kaiser, Martin Montiel-Ruiz, Jiayi Zhou, Amin Addetia

    The recent emergence of SARS-CoV-2 variants of concern (VOC)1–10 and the recurrent spillovers of coronaviruses11,12 in the human population highlight the need for broadly neutralizing antibodies that are not affected by the ongoing antigenic drift and that can prevent or treat future zoonotic infections. Here, we describe a human monoclonal antibody (mAb), designated S2X259, recognizing a highly conserved

  • Highly accurate protein structure prediction with AlphaFold
    Nature (IF 49.962) Pub Date : 2021-07-15
    John Jumper, Richard Evans, Alexander Pritzel, Tim Green, Michael Figurnov, Olaf Ronneberger, Kathryn Tunyasuvunakool, Russ Bates, Augustin Žídek, Anna Potapenko, Alex Bridgland, Clemens Meyer, Simon A. A. Kohl, Andrew J. Ballard, Andrew Cowie, Bernardino Romera-Paredes, Stanislav Nikolov, Rishub Jain, Jonas Adler, Trevor Back, Stig Petersen, David Reiman, Ellen Clancy, Michal Zielinski, Martin Steinegger

    Proteins are essential to life, and understanding their structure can facilitate a mechanistic understanding of their function. Through an enormous experimental effort1–4, the structures of around 100,000 unique proteins have been determined5, but this represents a small fraction of the billions of known protein sequences6,7. Structural coverage is bottlenecked by the months to years of painstaking

  • cGAS-like receptors sense RNA and control 3′2′-cGAMP signaling in Drosophila
    Nature (IF 49.962) Pub Date : 2021-07-14
    Kailey M. Slavik, Benjamin R. Morehouse, Adelyn E. Ragucci, Wen Zhou, Xianlong Ai, Yuqiang Chen, Lihua Li, Ziming Wei, Heike Bähre, Martin König, Roland Seifert, Amy S. Y. Lee, Hua Cai, Jean-Luc Imler, Philip J. Kranzusch

    Cyclic GMP–AMP synthase (cGAS) is a cytosolic DNA sensor that produces the second messenger 2′3′-cGAMP and controls activation of innate immunity in mammalian cells1–5. Animal genomes typically encode multiple proteins with predicted homology to cGAS6–10, but the function of these uncharacterized enzymes is unknown. Here we show that cGAS-like receptors (cGLRs) are innate immune sensors capable of

  • Two cGAS-like receptors induce antiviral immunity in Drosophila
    Nature (IF 49.962) Pub Date : 2021-07-14
    Andreas Holleufer, Kasper Grønbjerg Winther, Hans Henrik Gad, Xianlong Ai, Yuqiang Chen, Lihua Li, Ziming Wei, Huimin Deng, Jiyong Liu, Ninna Ahlmann Frederiksen, Bine Simonsen, Line Lykke Andersen, Karin Kleigrewe, Louise Dalskov, Andreas Pichlmair, Hua Cai, Jean-Luc Imler, Rune Hartmann

    In mammals, cyclic GMP-AMP (cGAMP) synthase (cGAS) produces the cyclic dinucleotide (CDN) 2'3'-cGAMP in response to cytosolic DNA and this triggers an antiviral immune response. cGAS belongs to a large family of cGAS/DncV-like nucleotidyltransferases, present in both prokaryotes1 and eukaryotes2–5. In bacteria, these enzymes synthesize a range of cyclic oligonucleotide and have recently emerged as

  • SARS-CoV-2 RBD antibodies that maximize breadth and resistance to escape
    Nature (IF 49.962) Pub Date : 2021-07-14
    Tyler N. Starr, Nadine Czudnochowski, Zhuoming Liu, Fabrizia Zatta, Young-Jun Park, Amin Addetia, Dora Pinto, Martina Beltramello, Patrick Hernandez, Allison J. Greaney, Roberta Marzi, William G. Glass, Ivy Zhang, Adam S. Dingens, John E. Bowen, M. Alejandra Tortorici, Alexandra C. Walls, Jason A. Wojcechowskyj, Anna De Marco, Laura E. Rosen, Jiayi Zhou, Martin Montiel-Ruiz, Hannah Kaiser, Josh Dillen

    An ideal anti-SARS-CoV-2 antibody would resist viral escape1–3, have activity against diverse SARS-related coronaviruses (sarbecoviruses)4–7, and be highly protective through viral neutralization8–11 and effector functions12,13. Understanding how these properties relate to each other and vary across epitopes would aid development of antibody therapeutics and guide vaccine design. Here, we comprehensively

  • A lithium-isotope perspective on the evolution of carbon and silicon cycles
    Nature (IF 49.962) Pub Date : 2021-07-14
    Boriana Kalderon-Asael, Joachim A. R. Katchinoff, Noah J. Planavsky, Ashleigh v. S. Hood, Mathieu Dellinger, Eric J. Bellefroid, David S. Jones, Axel Hofmann, Frantz Ossa Ossa, Francis A. Macdonald, Chunjiang Wang, Terry T. Isson, Jack G. Murphy, John A. Higgins, A. Joshua West, Malcolm W. Wallace, Dan Asael, Philip A. E. Pogge von Strandmann

    The evolution of the global carbon and silicon cycles is thought to have contributed to the long-term stability of Earth’s climate1,2,3. Many questions remain, however, regarding the feedback mechanisms at play, and there are limited quantitative constraints on the sources and sinks of these elements in Earth’s surface environments4,5,6,7,8,9,10,11,12. Here we argue that the lithium-isotope record

  • The 13CO-rich atmosphere of a young accreting super-Jupiter
    Nature (IF 49.962) Pub Date : 2021-07-14
    Yapeng Zhang, Ignas A. G. Snellen, Alexander J. Bohn, Paul Mollière, Christian Ginski, H. Jens Hoeijmakers, Matthew A. Kenworthy, Eric E. Mamajek, Tiffany Meshkat, Maddalena Reggiani, Frans Snik

    Isotope abundance ratios have an important role in astronomy and planetary sciences, providing insights into the origin and evolution of the Solar System, interstellar chemistry and stellar nucleosynthesis1,2. In contrast to deuterium/hydrogen ratios, carbon isotope ratios are found to be roughly constant (around 89) in the Solar System1,3, but do vary on galactic scales with a 12C/13C isotopologue

  • Exponential suppression of bit or phase errors with cyclic error correction
    Nature (IF 49.962) Pub Date : 2021-07-14

    Realizing the potential of quantum computing requires sufficiently low logical error rates1. Many applications call for error rates as low as 10−15 (refs. 2,3,4,5,6,7,8,9), but state-of-the-art quantum platforms typically have physical error rates near 10−3 (refs. 10,11,12,13,14). Quantum error correction15,16,17 promises to bridge this divide by distributing quantum logical information across many

  • Adaptive immunity induces mutualism between commensal eukaryotes
    Nature (IF 49.962) Pub Date : 2021-07-14
    Kyla S. Ost, Teresa R. O’Meara, W. Zac Stephens, Tyson Chiaro, Haoyang Zhou, Jourdan Penman, Rickesha Bell, Jason R. Catanzaro, Deguang Song, Shakti Singh, Daniel H. Call, Elizabeth Hwang-Wong, Kimberly E. Hanson, John F. Valentine, Kenneth A. Christensen, Ryan M. O’Connell, Brendan Cormack, Ashraf S. Ibrahim, Noah W. Palm, Suzanne M. Noble, June L. Round

    Pathogenic fungi reside in the intestinal microbiota but rarely cause disease. Little is known about the interactions between fungi and the immune system that promote commensalism. Here we investigate the role of adaptive immunity in promoting mutual interactions between fungi and host. We find that potentially pathogenic Candida species induce and are targeted by intestinal immunoglobulin A (IgA)

  • Acetate differentially regulates IgA reactivity to commensal bacteria
    Nature (IF 49.962) Pub Date : 2021-07-14
    Tadashi Takeuchi, Eiji Miyauchi, Takashi Kanaya, Tamotsu Kato, Yumiko Nakanishi, Takashi Watanabe, Toshimori Kitami, Takashi Taida, Takaharu Sasaki, Hiroki Negishi, Shu Shimamoto, Akinobu Matsuyama, Ikuo Kimura, Ifor R. Williams, Osamu Ohara, Hiroshi Ohno

    The balance between bacterial colonization and its containment in the intestine is indispensable for the symbiotic relationship between humans and their bacteria. One component to maintain homeostasis at the mucosal surfaces is immunoglobulin A (IgA), the most abundant immunoglobulin in mammals1,2. Several studies have revealed important characteristics of poly-reactive IgA3,4, which is produced naturally

  • Real-time optimal quantum control of mechanical motion at room temperature
    Nature (IF 49.962) Pub Date : 2021-07-14
    Lorenzo Magrini, Philipp Rosenzweig, Constanze Bach, Andreas Deutschmann-Olek, Sebastian G. Hofer, Sungkun Hong, Nikolai Kiesel, Andreas Kugi, Markus Aspelmeyer

    The ability to accurately control the dynamics of physical systems by measurement and feedback is a pillar of modern engineering1. Today, the increasing demand for applied quantum technologies requires adaptation of this level of control to individual quantum systems2,3. Achieving this in an optimal way is a challenging task that relies on both quantum-limited measurements and specifically tailored

  • Astrocytic interleukin-3 programs microglia and limits Alzheimer’s disease
    Nature (IF 49.962) Pub Date : 2021-07-14
    Cameron S. McAlpine, Joseph Park, Ana Griciuc, Eunhee Kim, Se Hoon Choi, Yoshiko Iwamoto, Máté G. Kiss, Kathleen A. Christie, Claudio Vinegoni, Wolfram C. Poller, John E. Mindur, Christopher T. Chan, Shun He, Henrike Janssen, Lai Ping Wong, Jeffrey Downey, Sumnima Singh, Atsushi Anzai, Florian Kahles, Mehdi Jorfi, Paolo Fumene Feruglio, Ruslan I. Sadreyev, Ralph Weissleder, Benjamin P. Kleinstiver

    Communication within the glial cell ecosystem is essential for neuronal and brain health1,2,3. The influence of glial cells on the accumulation and clearance of β-amyloid (Aβ) and neurofibrillary tau in the brains of individuals with Alzheimer’s disease (AD) is poorly understood, despite growing awareness that these are therapeutically important interactions4,5. Here we show, in humans and mice, that

  • Designing the next generation of proton-exchange membrane fuel cells
    Nature (IF 49.962) Pub Date : 2021-07-14
    Kui Jiao, Jin Xuan, Qing Du, Zhiming Bao, Biao Xie, Bowen Wang, Yan Zhao, Linhao Fan, Huizhi Wang, Zhongjun Hou, Sen Huo, Nigel P. Brandon, Yan Yin, Michael D. Guiver

    With the rapid growth and development of proton-exchange membrane fuel cell (PEMFC) technology, there has been increasing demand for clean and sustainable global energy applications. Of the many device-level and infrastructure challenges that need to be overcome before wide commercialization can be realized, one of the most critical ones is increasing the PEMFC power density, and ambitious goals have

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