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  • Controlled hydroxylations of diterpenoids allow for plant chemical defense without autotoxicity
    Science (IF 41.845) Pub Date : 2021-01-15
    Jiancai Li, Rayko Halitschke, Dapeng Li, Christian Paetz, Haichao Su, Sven Heiling, Shuqing Xu, Ian T. Baldwin

    Many plant specialized metabolites function in herbivore defense, and abrogating particular steps in their biosynthetic pathways frequently causes autotoxicity. However, the molecular mechanisms underlying their defense and autotoxicity remain unclear. Here, we show that silencing two cytochrome P450s involved in diterpene biosynthesis in the wild tobacco Nicotiana attenuata causes severe autotoxicity

    更新日期:2021-01-15
  • Formation of α clusters in dilute neutron-rich matter
    Science (IF 41.845) Pub Date : 2021-01-15
    Junki Tanaka, Zaihong Yang, Stefan Typel, Satoshi Adachi, Shiwei Bai, Patrik van Beek, Didier Beaumel, Yuki Fujikawa, Jiaxing Han, Sebastian Heil, Siwei Huang, Azusa Inoue, Ying Jiang, Marco Knösel, Nobuyuki Kobayashi, Yuki Kubota, Wei Liu, Jianling Lou, Yukie Maeda, Yohei Matsuda, Kenjiro Miki, Shoken Nakamura, Kazuyuki Ogata, Valerii Panin, Heiko Scheit, Fabia Schindler, Philipp Schrock, Dmytro Symochko

    The surface of neutron-rich heavy nuclei, with a neutron skin created by excess neutrons, provides an important terrestrial model system to study dilute neutron-rich matter. By using quasi-free α cluster–knockout reactions, we obtained direct experimental evidence for the formation of α clusters at the surface of neutron-rich tin isotopes. The observed monotonous decrease of the reaction cross sections

    更新日期:2021-01-15
  • Senolysis by glutaminolysis inhibition ameliorates various age-associated disorders
    Science (IF 41.845) Pub Date : 2021-01-15
    Yoshikazu Johmura, Takehiro Yamanaka, Satotaka Omori, Teh-Wei Wang, Yuki Sugiura, Masaki Matsumoto, Narumi Suzuki, Soichiro Kumamoto, Kiyoshi Yamaguchi, Seira Hatakeyama, Tomoyo Takami, Rui Yamaguchi, Eigo Shimizu, Kazutaka Ikeda, Nobuyuki Okahashi, Ryuta Mikawa, Makoto Suematsu, Makoto Arita, Masataka Sugimoto, Keiichi I. Nakayama, Yoichi Furukawa, Seiya Imoto, Makoto Nakanishi

    Removal of senescent cells (senolysis) has been proposed to be beneficial for improving age-associated pathologies, but the molecular pathways for such senolytic activity have not yet emerged. Here, we identified glutaminase 1 (GLS1) as an essential gene for the survival of human senescent cells. The intracellular pH in senescent cells was lowered by lysosomal membrane damage, and this lowered pH induced

    更新日期:2021-01-15
  • GPER1 is required to protect fetal health from maternal inflammation
    Science (IF 41.845) Pub Date : 2021-01-15
    Alfred T. Harding, Marisa A. Goff, Heather M. Froggatt, Jean K. Lim, Nicholas S. Heaton

    Type I interferon (IFN) signaling in fetal tissues causes developmental abnormalities and fetal demise. Although pathogens that infect fetal tissues can induce birth defects through the local production of type I IFN, it remains unknown why systemic IFN generated during maternal infections only rarely causes fetal developmental defects. Here, we report that activation of the guanine nucleotide–binding

    更新日期:2021-01-15
  • Plant roots sense soil compaction through restricted ethylene diffusion
    Science (IF 41.845) Pub Date : 2021-01-15
    Bipin K. Pandey, Guoqiang Huang, Rahul Bhosale, Sjon Hartman, Craig J. Sturrock, Lottie Jose, Olivier C. Martin, Michal Karady, Laurentius A. C. J. Voesenek, Karin Ljung, Jonathan P. Lynch, Kathleen M. Brown, William R. Whalley, Sacha J. Mooney, Dabing Zhang, Malcolm J. Bennett

    Soil compaction represents a major challenge for modern agriculture. Compaction is intuitively thought to reduce root growth by limiting the ability of roots to penetrate harder soils. We report that root growth in compacted soil is instead actively suppressed by the volatile hormone ethylene. We found that mutant Arabidopsis and rice roots that were insensitive to ethylene penetrated compacted soil

    更新日期:2021-01-15
  • Driving energetically unfavorable dehydrogenation dynamics with plasmonics
    Science (IF 41.845) Pub Date : 2021-01-15
    Katherine Sytwu, Michal Vadai, Fariah Hayee, Daniel K. Angell, Alan Dai, Jefferson Dixon, Jennifer A. Dionne

    Nanoparticle surface structure and geometry generally dictate where chemical transformations occur, with higher chemical activity at sites with lower activation energies. Here, we show how optical excitation of plasmons enables spatially modified phase transformations, activating otherwise energetically unfavorable sites. We have designed a crossed-bar Au-PdHx antenna-reactor system that localizes

    更新日期:2021-01-15
  • Learning the language of viral evolution and escape
    Science (IF 41.845) Pub Date : 2021-01-15
    Brian Hie, Ellen D. Zhong, Bonnie Berger, Bryan Bryson

    The ability for viruses to mutate and evade the human immune system and cause infection, called viral escape, remains an obstacle to antiviral and vaccine development. Understanding the complex rules that govern escape could inform therapeutic design. We modeled viral escape with machine learning algorithms originally developed for human natural language. We identified escape mutations as those that

    更新日期:2021-01-15
  • Three-quarters attack rate of SARS-CoV-2 in the Brazilian Amazon during a largely unmitigated epidemic
    Science (IF 41.845) Pub Date : 2021-01-15
    Lewis F. Buss, Carlos A. Prete, Claudia M. M. Abrahim, Alfredo Mendrone, Tassila Salomon, Cesar de Almeida-Neto, Rafael F. O. França, Maria C. Belotti, Maria P. S. S. Carvalho, Allyson G. Costa, Myuki A. E. Crispim, Suzete C. Ferreira, Nelson A. Fraiji, Susie Gurzenda, Charles Whittaker, Leonardo T. Kamaura, Pedro L. Takecian, Pedro da Silva Peixoto, Marcio K. Oikawa, Anna S. Nishiya, Vanderson Rocha

    Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spread rapidly in Manaus, the capital of Amazonas state in northern Brazil. The attack rate there is an estimate of the final size of the largely unmitigated epidemic that occurred in Manaus. We use a convenience sample of blood donors to show that by June 2020, 1 month after the epidemic peak in Manaus, 44% of the population had detectable

    更新日期:2021-01-15
  • Local convergence of behavior across species
    Science (IF 41.845) Pub Date : 2021-01-15
    Toman Barsbai, Dieter Lukas, Andreas Pondorfer

    Behavior is a way for organisms to respond flexibly to the environmental conditions they encounter. Our own species exhibits large behavioral flexibility and occurs in all terrestrial habitats, sharing these environments with many other species. It remains unclear to what extent a shared environment constrains behavior and whether these constraints apply similarly across species. Here, we show that

    更新日期:2021-01-15
  • Topological pumping of a 1D dipolar gas into strongly correlated prethermal states
    Science (IF 41.845) Pub Date : 2021-01-15
    Wil Kao, Kuan-Yu Li, Kuan-Yu Lin, Sarang Gopalakrishnan, Benjamin L. Lev

    Long-lived excited states of interacting quantum systems that retain quantum correlations and evade thermalization are of great fundamental interest. We create nonthermal states in a bosonic one-dimensional (1D) quantum gas of dysprosium by stabilizing a super-Tonks-Girardeau gas against collapse and thermalization with repulsive long-range dipolar interactions. Stiffness and energy-per-particle measurements

    更新日期:2021-01-15
  • Cryo-EM structure of the B cell co-receptor CD19 bound to the tetraspanin CD81
    Science (IF 41.845) Pub Date : 2021-01-15
    Katherine J. Susa, Shaun Rawson, Andrew C. Kruse, Stephen C. Blacklow

    Signaling through the CD19-CD81 co-receptor complex, in combination with the B cell receptor, is a critical determinant of B cell development and activation. It is unknown how CD81 engages CD19 to enable co-receptor function. Here, we report a 3.8-angstrom structure of the CD19-CD81 complex bound to a therapeutic antigen-binding fragment, determined by cryo–electron microscopy (cryo-EM). The structure

    更新日期:2021-01-15
  • Structure of a transcribing RNA polymerase II–U1 snRNP complex
    Science (IF 41.845) Pub Date : 2021-01-15
    Suyang Zhang, Shintaro Aibara, Seychelle M. Vos, Dmitry E. Agafonov, Reinhard Lührmann, Patrick Cramer

    To initiate cotranscriptional splicing, RNA polymerase II (Pol II) recruits the U1 small nuclear ribonucleoprotein particle (U1 snRNP) to nascent precursor messenger RNA (pre-mRNA). Here, we report the cryo–electron microscopy structure of a mammalian transcribing Pol II–U1 snRNP complex. The structure reveals that Pol II and U1 snRNP interact directly. This interaction positions the pre-mRNA 5′ splice

    更新日期:2021-01-15
  • Noncanonical transnitrosylation network contributes to synapse loss in Alzheimer’s disease
    Science (IF 41.845) Pub Date : 2021-01-15
    Tomohiro Nakamura, Chang-ki Oh, Lujian Liao, Xu Zhang, Kevin M. Lopez, Daniel Gibbs, Amanda K. Deal, Henry R. Scott, Brian Spencer, Eliezer Masliah, Robert A. Rissman, John R. Yates, Stuart A. Lipton

    Here we describe mechanistically distinct enzymes (a kinase, a guanosine triphosphatase, and a ubiquitin protein hydrolase) that function in disparate biochemical pathways and can also act in concert to mediate a series of redox reactions. Each enzyme manifests a second, noncanonical function—transnitrosylation—that triggers a pathological biochemical cascade in mouse models and in humans with Alzheimer’s

    更新日期:2021-01-15
  • Transmission heterogeneities, kinetics, and controllability of SARS-CoV-2
    Science (IF 41.845) Pub Date : 2021-01-15
    Kaiyuan Sun, Wei Wang, Lidong Gao, Yan Wang, Kaiwei Luo, Lingshuang Ren, Zhifei Zhan, Xinghui Chen, Shanlu Zhao, Yiwei Huang, Qianlai Sun, Ziyan Liu, Maria Litvinova, Alessandro Vespignani, Marco Ajelli, Cécile Viboud, Hongjie Yu

    A long-standing question in infectious disease dynamics concerns the role of transmission heterogeneities, which are driven by demography, behavior, and interventions. On the basis of detailed patient and contact-tracing data in Hunan, China, we find that 80% of secondary infections traced back to 15% of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) primary infections, which indicates

    更新日期:2021-01-15
  • Aberrant type 1 immunity drives susceptibility to mucosal fungal infections
    Science (IF 41.845) Pub Date : 2021-01-15
    Timothy J. Break, Vasileios Oikonomou, Nicolas Dutzan, Jigar V. Desai, Marc Swidergall, Tilo Freiwald, Daniel Chauss, Oliver J. Harrison, Julie Alejo, Drake W. Williams, Stefania Pittaluga, Chyi-Chia R. Lee, Nicolas Bouladoux, Muthulekha Swamydas, Kevin W. Hoffman, Teresa Greenwell-Wild, Vincent M. Bruno, Lindsey B. Rosen, Wint Lwin, Andy Renteria, Sergio M. Pontejo, John P. Shannon, Ian A. Myles,

    Human monogenic disorders have revealed the critical contribution of type 17 responses in mucosal fungal surveillance. We unexpectedly found that in certain settings, enhanced type 1 immunity rather than defective type 17 responses can promote mucosal fungal infection susceptibility. Notably, in mice and humans with AIRE deficiency, an autoimmune disease characterized by selective susceptibility to

    更新日期:2021-01-15
  • Phylodynamics for cell biologists
    Science (IF 41.845) Pub Date : 2021-01-15
    T. Stadler, O. G. Pybus, M. P. H. Stumpf

    Multicellular organisms are composed of cells connected by ancestry and descent from progenitor cells. The dynamics of cell birth, death, and inheritance within an organism give rise to the fundamental processes of development, differentiation, and cancer. Technical advances in molecular biology now allow us to study cellular composition, ancestry, and evolution at the resolution of individual cells

    更新日期:2021-01-15
  • A structure of human Scap bound to Insig-2 suggests how their interaction is regulated by sterols
    Science (IF 41.845) Pub Date : 2021-01-14
    Renhong Yan, Pingping Cao, Wenqi Song, Hongwu Qian, Ximing Du, Hudson W. Coates, Xin Zhao, Yaning Li, Shuai Gao, Xin Gong, Ximing Liu, Jianhua Sui, Jianlin Lei, Hongyuan Yang, Andrew J. Brown, Qiang Zhou, Chuangye Yan, Nieng Yan

    The SREBP pathway controls cellular homeostasis of sterols. The key players in this pathway, Scap and Insig-1/2, are membrane-embedded sterol sensors. 25-hydroxycholesterol (25HC)-dependent association of Scap and Insigs acts as the master switch for the SREBP pathway. Here, we present cryo-EM analysis of the human Scap and Insig-2 complex in the presence of 25HC, with the transmembrane (TM) domains

    更新日期:2021-01-15
  • Widespread haploid-biased gene expression enables sperm-level natural selection
    Science (IF 41.845) Pub Date : 2021-01-14
    Kunal Bhutani, Katherine Stansifer, Simina Ticau, Lazar Bojic, Alexandra-Chloé Villani, Joanna Slisz, Claudia M. Cremers, Christian Roy, Jerry Donovan, Brian Fiske, Robin C. Friedman

    Sperm are haploid, but must be functionally equivalent to distribute alleles equally among progeny. Accordingly, gene products are shared through spermatid cytoplasmic bridges which erase phenotypic differences between individual haploid sperm. Here, we show that a large class of mammalian genes are not completely shared across these bridges. We term these genes “genoinformative markers” (GIMs) and

    更新日期:2021-01-15
  • Mosaic nanoparticles elicit cross-reactive immune responses to zoonotic coronaviruses in mice
    Science (IF 41.845) Pub Date : 2021-01-12
    Alexander A. Cohen, Priyanthi N. P. Gnanapragasam, Yu E. Lee, Pauline R. Hoffman, Susan Ou, Leesa M. Kakutani, Jennifer R. Keeffe, Hung-Jen Wu, Mark Howarth, Anthony P. West, Christopher O. Barnes, Michel C. Nussenzweig, Pamela J. Bjorkman

    Protection against SARS-CoV-2 and SARS-related emergent zoonotic coronaviruses is urgently needed. We made homotypic nanoparticles displaying the receptor-binding domain (RBD) of SARS-CoV-2 or co-displaying SARS-CoV-2 RBD along with RBDs from animal betacoronaviruses that represent threats to humans (mosaic nanoparticles; 4-8 distinct RBDs). Mice immunized with RBD-nanoparticles, but not soluble antigen

    更新日期:2021-01-13
  • Immunological characteristics govern the transition of COVID-19 to endemicity
    Science (IF 41.845) Pub Date : 2021-01-12
    Jennie S. Lavine, Ottar N. Bjornstad, Rustom Antia

    We are currently faced with the question of how the CoV-2 severity may change in the years ahead. Our analysis of immunological and epidemiological data on endemic human coronaviruses (HCoVs) shows that infection-blocking immunity wanes rapidly, but disease-reducing immunity is long-lived. Our model, incorporating these components of immunity, recapitulates both the current severity of CoV-2 and the

    更新日期:2021-01-13
  • Structure-guided multivalent nanobodies block SARS-CoV-2 infection and suppress mutational escape
    Science (IF 41.845) Pub Date : 2021-01-12
    Paul-Albert Koenig, Hrishikesh Das, Hejun Liu, Beate M. Kümmerer, Florian N. Gohr, Lea-Marie Jenster, Lisa D. J. Schiffelers, Yonas M. Tesfamariam, Miki Uchima, Jennifer D. Wuerth, Karl Gatterdam, Natalia Ruetalo, Maria H. Christensen, Caroline I. Fandrey, Sabine Normann, Jan M. P. Tödtmann, Steffen Pritzl, Leo Hanke, Jannik Boos, Meng Yuan, Xueyong Zhu, Jonathan L. Schmid-Burgk, Hiroki Kato, Michael

    The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic continues to spread with devastating consequences. For passive immunization efforts, nanobodies have size and cost advantages over conventional antibodies. Here, we generated four neutralizing nanobodies that target the receptor-binding domain of the SARS-CoV-2 spike protein. We defined two distinct binding epitopes using x-ray

    更新日期:2021-01-13
  • Establishment and lineage dynamics of the SARS-CoV-2 epidemic in the UK
    Science (IF 41.845) Pub Date : 2021-01-08
    Louis du Plessis, John T. McCrone, Alexander E. Zarebski, Verity Hill, Christopher Ruis, Bernardo Gutierrez, Jayna Raghwani, Jordan Ashworth, Rachel Colquhoun, Thomas R. Connor, Nuno R. Faria, Ben Jackson, Nicholas J. Loman, Áine O’Toole, Samuel M. Nicholls, Kris V. Parag, Emily Scher, Tetyana I. Vasylyeva, Erik M. Volz, Alexander Watts, Isaac I. Bogoch, Kamran Khan, COVID-19 Genomics UK (COG-UK) Consortium†

    The UK’s COVID-19 epidemic during early 2020 was one of world’s largest and unusually well represented by virus genomic sampling. Here we reveal the fine-scale genetic lineage structure of this epidemic through analysis of 50,887 SARS-CoV-2 genomes, including 26,181 from the UK sampled throughout the country’s first wave of infection. Using large-scale phylogenetic analyses, combined with epidemiological

    更新日期:2021-01-10
  • RNA stabilization by a poly(A) tail 3ʹ-end binding pocket and other modes of poly(A)-RNA interaction
    Science (IF 41.845) Pub Date : 2021-01-07
    Seyed-Fakhreddin Torabi, Anand T. Vaidya, Kazimierz T. Tycowski, Suzanne J. DeGregorio, Jimin Wang, Mei-Di Shu, Thomas A. Steitz, Joan A. Steitz

    Poly(A) tail addition to the 3ʹ end of a wide range of RNAs is a highly conserved modification that plays a central role in cellular RNA function. Elements for nuclear expression (ENEs) are cis-acting RNA elements that stabilize poly(A) tails by sequestering them in RNA triplex structures. A 2.89-Å resolution crystal structure of a double ENE from a rice hAT transposon mRNA complexed with poly(A)28

    更新日期:2021-01-08
  • Characterization of a common progenitor pool of the epicardium and myocardium
    Science (IF 41.845) Pub Date : 2021-01-07
    Richard C. V. Tyser, Ximena Ibarra-Soria, Katie McDole, Satish A. Jayaram, Jonathan Godwin, Teun A. H. van den Brand, Antonio M. A. Miranda, Antonio Scialdone, Philipp J. Keller, John C. Marioni, Shankar Srinivas

    The mammalian heart is derived from multiple cell lineages; however, our understanding of when and how the diverse cardiac cell types arise is limited. We mapped the origin of the embryonic mouse heart at single-cell resolution using a combination of transcriptomic, imaging, and genetic lineage labeling approaches. This provided a transcriptional and anatomic definition of cardiac progenitor types

    更新日期:2021-01-08
  • A noninflammatory mRNA vaccine for treatment of experimental autoimmune encephalomyelitis
    Science (IF 41.845) Pub Date : 2021-01-08
    Christina Krienke, Laura Kolb, Elif Diken, Michael Streuber, Sarah Kirchhoff, Thomas Bukur, Özlem Akilli-Öztürk, Lena M. Kranz, Hendrik Berger, Jutta Petschenka, Mustafa Diken, Sebastian Kreiter, Nir Yogev, Ari Waisman, Katalin Karikó, Özlem Türeci, Ugur Sahin

    The ability to control autoreactive T cells without inducing systemic immune suppression is the major goal for treatment of autoimmune diseases. The key challenge is the safe and efficient delivery of pharmaceutically well-defined antigens in a noninflammatory context. Here, we show that systemic delivery of nanoparticle-formulated 1 methylpseudouridine-modified messenger RNA (m1Ψ mRNA) coding for

    更新日期:2021-01-07
  • Anterior cingulate inputs to nucleus accumbens control the social transfer of pain and analgesia
    Science (IF 41.845) Pub Date : 2021-01-08
    Monique L. Smith, Naoyuki Asada, Robert C. Malenka

    Empathy is an essential component of social communication that involves experiencing others’ sensory and emotional states. We observed that a brief social interaction with a mouse experiencing pain or morphine analgesia resulted in the transfer of these experiences to its social partner. Optogenetic manipulations demonstrated that the anterior cingulate cortex (ACC) and its projections to the nucleus

    更新日期:2021-01-07
  • Crossover from hydrogen to chemical bonding
    Science (IF 41.845) Pub Date : 2021-01-08
    Bogdan Dereka, Qi Yu, Nicholas H. C. Lewis, William B. Carpenter, Joel M. Bowman, Andrei Tokmakoff

    Hydrogen bonds (H-bonds) can be interpreted as a classical electrostatic interaction or as a covalent chemical bond if the interaction is strong enough. As a result, short strong H-bonds exist at an intersection between qualitatively different bonding descriptions, with few experimental methods to understand this dichotomy. The [F-H-F]− ion represents a bare short H-bond, whose distinctive vibrational

    更新日期:2021-01-07
  • Carbonaceous chondrite meteorites experienced fluid flow within the past million years
    Science (IF 41.845) Pub Date : 2021-01-08
    Simon Turner, Lucy McGee, Munir Humayun, John Creech, Brigitte Zanda

    Carbonaceous chondritic meteorites are primordial Solar System materials and a source of water delivery to Earth. Fluid flow on the parent bodies of these meteorites is known to have occurred very early in Solar System history (first <4 million years). We analyze short-lived uranium isotopes in carbonaceous chondrites, finding excesses of 234-uranium over 238-uranium and 238-uranium over 230-thorium

    更新日期:2021-01-07
  • Lithium pollution of a white dwarf records the accretion of an extrasolar planetesimal
    Science (IF 41.845) Pub Date : 2021-01-08
    B. C. Kaiser, J. C. Clemens, S. Blouin, P. Dufour, R. J. Hegedus, J. S. Reding, A. Bédard

    Tidal disruption and subsequent accretion of planetesimals by white dwarfs can reveal the elemental abundances of rocky bodies in exoplanetary systems. Those abundances provide information on the composition of the nebula from which the systems formed, which is analogous to how meteorite abundances inform our understanding of the early Solar System. We report the detection of lithium, sodium, potassium

    更新日期:2021-01-07
  • Transmission of SARS-CoV-2 on mink farms between humans and mink and back to humans
    Science (IF 41.845) Pub Date : 2021-01-08
    Bas B. Oude Munnink, Reina S. Sikkema, David F. Nieuwenhuijse, Robert Jan Molenaar, Emmanuelle Munger, Richard Molenkamp, Arco van der Spek, Paulien Tolsma, Ariene Rietveld, Miranda Brouwer, Noortje Bouwmeester-Vincken, Frank Harders, Renate Hakze-van der Honing, Marjolein C. A. Wegdam-Blans, Ruth J. Bouwstra, Corine GeurtsvanKessel, Annemiek A. van der Eijk, Francisca C. Velkers, Lidwien A. M. Smit

    Animal experiments have shown that nonhuman primates, cats, ferrets, hamsters, rabbits, and bats can be infected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In addition, SARS-CoV-2 RNA has been detected in felids, mink, and dogs in the field. Here, we describe an in-depth investigation using whole-genome sequencing of outbreaks on 16 mink farms and the humans living or working

    更新日期:2021-01-07
  • Microbial sulfate reduction and organic sulfur formation in sinking marine particles
    Science (IF 41.845) Pub Date : 2021-01-08
    M. R. Raven, R. G. Keil, S. M. Webb

    Climate change is driving an expansion of marine oxygen-deficient zones, which may alter the global cycles of carbon, sulfur, nitrogen, and trace metals. Currently, however, we lack a full mechanistic understanding of how oxygen deficiency affects organic carbon cycling and burial. Here, we show that cryptic microbial sulfate reduction occurs in sinking particles from the eastern tropical North Pacific

    更新日期:2021-01-07
  • Pre–T cell receptors topologically sample self-ligands during thymocyte β-selection
    Science (IF 41.845) Pub Date : 2021-01-08
    Xiaolong Li, Réka Mizsei, Kemin Tan, Robert J. Mallis, Jonathan S. Duke-Cohan, Aoi Akitsu, Paul W. Tetteh, Abhinav Dubey, Wonmuk Hwang, Gerhard Wagner, Matthew J. Lang, Haribabu Arthanari, Jia-huai Wang, Ellis L. Reinherz

    Self-discrimination, a critical but ill-defined molecular process programmed during thymocyte development, requires myriad pre–T cell receptors (preTCRs) and αβTCRs. Using x-ray crystallography, we show how a preTCR applies the concave β-sheet surface of its single variable domain (Vβ) to “horizontally” grab the protruding MHC α2-helix. By contrast, αβTCRs purpose all six complementarity-determining

    更新日期:2021-01-07
  • A ubiquitous tire rubber–derived chemical induces acute mortality in coho salmon
    Science (IF 41.845) Pub Date : 2021-01-08
    Zhenyu Tian, Haoqi Zhao, Katherine T. Peter, Melissa Gonzalez, Jill Wetzel, Christopher Wu, Ximin Hu, Jasmine Prat, Emma Mudrock, Rachel Hettinger, Allan E. Cortina, Rajshree Ghosh Biswas, Flávio Vinicius Crizóstomo Kock, Ronald Soong, Amy Jenne, Bowen Du, Fan Hou, Huan He, Rachel Lundeen, Alicia Gilbreath, Rebecca Sutton, Nathaniel L. Scholz, Jay W. Davis, Michael C. Dodd, Andre Simpson, Jenifer K

    In U.S. Pacific Northwest coho salmon (Oncorhynchus kisutch), stormwater exposure annually causes unexplained acute mortality when adult salmon migrate to urban creeks to reproduce. By investigating this phenomenon, we identified a highly toxic quinone transformation product of N-(1,3-dimethylbutyl)-N′-phenyl-p-phenylenediamine (6PPD), a globally ubiquitous tire rubber antioxidant. Retrospective analysis

    更新日期:2021-01-07
  • A broadly protective antibody that targets the flavivirus NS1 protein
    Science (IF 41.845) Pub Date : 2021-01-08
    Naphak Modhiran, Hao Song, Lidong Liu, Cheryl Bletchly, Lou Brillault, Alberto A. Amarilla, Xiaoying Xu, Jianxun Qi, Yan Chai, Stacey T. M. Cheung, Renee Traves, Yin Xiang Setoh, Summa Bibby, Connor A. P. Scott, Morgan E. Freney, Natalee D. Newton, Alexander A. Khromykh, Keith J. Chappell, David A. Muller, Katryn J. Stacey, Michael J. Landsberg, Yi Shi, George F. Gao, Paul R. Young, Daniel Watterson

    There are no approved flaviviral therapies and the development of vaccines against flaviruses has the potential of being undermined by antibody-dependent enhancement (ADE). The flavivirus nonstructural protein 1 (NS1) is a promising vaccine antigen with low ADE risk but has yet to be explored as a broad-spectrum therapeutic antibody target. Here, we provide the structural basis of NS1 antibody cross-reactivity

    更新日期:2021-01-07
  • Structural basis for antibody inhibition of flavivirus NS1–triggered endothelial dysfunction
    Science (IF 41.845) Pub Date : 2021-01-08
    Scott B. Biering, David L. Akey, Marcus P. Wong, W. Clay Brown, Nicholas T. N. Lo, Henry Puerta-Guardo, Francielle Tramontini Gomes de Sousa, Chunling Wang, Jamie R. Konwerski, Diego A. Espinosa, Nicholas J. Bockhaus, Dustin R. Glasner, Jeffrey Li, Sophie F. Blanc, Evan Y. Juan, Stephen J. Elledge, Michael J. Mina, P. Robert Beatty, Janet L. Smith, Eva Harris

    Medically important flaviviruses cause diverse disease pathologies and collectively are responsible for a major global disease burden. A contributing factor to pathogenesis is secreted flavivirus nonstructural protein 1 (NS1). Despite demonstrated protection by NS1-specific antibodies against lethal flavivirus challenge, the structural and mechanistic basis remains unknown. Here, we present three crystal

    更新日期:2021-01-07
  • Coordination between microbiota and root endodermis supports plant mineral nutrient homeostasis
    Science (IF 41.845) Pub Date : 2021-01-08
    Isai Salas-González, Guilhem Reyt, Paulina Flis, Valéria Custódio, David Gopaulchan, Niokhor Bakhoum, Tristan P. Dew, Kiran Suresh, Rochus Benni Franke, Jeffery L. Dangl, David E. Salt, Gabriel Castrillo

    Plant roots and animal guts have evolved specialized cell layers to control mineral nutrient homeostasis. These layers must tolerate the resident microbiota while keeping homeostatic integrity. Whether and how the root diffusion barriers in the endodermis, which are critical for the mineral nutrient balance of plants, coordinate with the microbiota is unknown. We demonstrate that genes controlling

    更新日期:2021-01-07
  • Recapitulation of HIV-1 Env-antibody coevolution in macaques leading to neutralization breadth
    Science (IF 41.845) Pub Date : 2021-01-08
    Ryan S. Roark, Hui Li, Wilton B. Williams, Hema Chug, Rosemarie D. Mason, Jason Gorman, Shuyi Wang, Fang-Hua Lee, Juliette Rando, Mattia Bonsignori, Kwan-Ki Hwang, Kevin O. Saunders, Kevin Wiehe, M. Anthony Moody, Peter T. Hraber, Kshitij Wagh, Elena E. Giorgi, Ronnie M. Russell, Frederic Bibollet-Ruche, Weimin Liu, Jesse Connell, Andrew G. Smith, Julia DeVoto, Alexander I. Murphy, Jessica Smith, Wenge

    Neutralizing antibodies elicited by HIV-1 coevolve with viral envelope proteins (Env) in distinctive patterns, in some cases acquiring substantial breadth. We report that primary HIV-1 envelope proteins—when expressed by simian-human immunodeficiency viruses in rhesus macaques—elicited patterns of Env-antibody coevolution very similar to those in humans, including conserved immunogenetic, structural

    更新日期:2021-01-07
  • Tubulin glycylation controls axonemal dynein activity, flagellar beat, and male fertility
    Science (IF 41.845) Pub Date : 2021-01-08
    Sudarshan Gadadhar, Gonzalo Alvarez Viar, Jan Niklas Hansen, An Gong, Aleksandr Kostarev, Côme Ialy-Radio, Sophie Leboucher, Marjorie Whitfield, Ahmed Ziyyat, Aminata Touré, Luis Alvarez, Gaia Pigino, Carsten Janke

    Posttranslational modifications of the microtubule cytoskeleton have emerged as key regulators of cellular functions, and their perturbations have been linked to a growing number of human pathologies. Tubulin glycylation modifies microtubules specifically in cilia and flagella, but its functional and mechanistic roles remain unclear. In this study, we generated a mouse model entirely lacking tubulin

    更新日期:2021-01-07
  • Making sense of neural development by comparing wiring strategies for seeing and hearing
    Science (IF 41.845) Pub Date : 2021-01-08
    A. A. Sitko, L. V. Goodrich

    The ability to perceive and interact with the world depends on a diverse array of neural circuits specialized for carrying out specific computations. Each circuit is assembled using a relatively limited number of molecules and common developmental steps, from cell fate specification to activity-dependent synaptic refinement. Given this shared toolkit, how do individual circuits acquire their characteristic

    更新日期:2021-01-07
  • Mechanism of spliceosome remodeling by the ATPase/helicase Prp2 and its coactivator Spp2
    Science (IF 41.845) Pub Date : 2021-01-08
    Rui Bai, Ruixue Wan, Chuangye Yan, Qi Jia, Jianlin Lei, Yigong Shi

    Spliceosome remodeling, executed by conserved adenosine triphosphatase (ATPase)/helicases including Prp2, enables precursor messenger RNA (pre-mRNA) splicing. However, the structural basis for the function of the ATPase/helicases remains poorly understood. Here, we report atomic structures of Prp2 in isolation, Prp2 complexed with its coactivator Spp2, and Prp2-loaded activated spliceosome and the

    更新日期:2021-01-07
  • Immunological memory to SARS-CoV-2 assessed for up to 8 months after infection
    Science (IF 41.845) Pub Date : 2021-01-07
    Jennifer M. Dan, Jose Mateus, Yu Kato, Kathryn M. Hastie, Esther Dawen Yu, Caterina E. Faliti, Alba Grifoni, Sydney I. Ramirez, Sonya Haupt, April Frazier, Catherine Nakao, Vamseedhar Rayaprolu, Stephen A. Rawlings, Bjoern Peters, Florian Krammer, Viviana Simon, Erica Ollmann Saphire, Davey M. Smith, Daniela Weiskopf, Alessandro Sette, Shane Crotty

    Understanding immune memory to SARS-CoV-2 is critical for improving diagnostics and vaccines, and for assessing the likely future course of the COVID-19 pandemic. We analyzed multiple compartments of circulating immune memory to SARS-CoV-2 in 254 samples from 188 COVID-19 cases, including 43 samples at ≥ 6 months post-infection. IgG to the Spike protein was relatively stable over 6+ months. Spike-specific

    更新日期:2021-01-07
  • A rechargeable zinc-air battery based on zinc peroxide chemistry
    Science (IF 41.845) Pub Date : 2021-01-01
    Wei Sun, Fei Wang, Bao Zhang, Mengyi Zhang, Verena Küpers, Xiao Ji, Claudia Theile, Peter Bieker, Kang Xu, Chunsheng Wang, Martin Winter

    Rechargeable alkaline zinc-air batteries promise high energy density and safety but suffer from the sluggish 4 electron (e−)/oxygen (O2) chemistry that requires participation of water and from the electrochemical irreversibility originating from parasitic reactions caused by caustic electrolytes and atmospheric carbon dioxide. Here, we report a zinc-O2/zinc peroxide (ZnO2) chemistry that proceeds through

    更新日期:2020-12-31
  • Airway stem cells sense hypoxia and differentiate into protective solitary neuroendocrine cells
    Science (IF 41.845) Pub Date : 2021-01-01
    Manjunatha Shivaraju, Udbhav K. Chitta, Robert M. H. Grange, Isha H. Jain, Diane Capen, Lan Liao, Jianming Xu, Fumito Ichinose, Warren M. Zapol, Vamsi K. Mootha, Jayaraj Rajagopal

    Neuroendocrine (NE) cells are epithelial cells that possess many of the characteristics of neurons, including the presence of secretory vesicles and the ability to sense environmental stimuli. The normal physiologic functions of solitary airway NE cells remain a mystery. We show that mouse and human airway basal stem cells sense hypoxia. Hypoxia triggers the direct differentiation of these stem cells

    更新日期:2020-12-31
  • Interactions between nascent proteins translated by adjacent ribosomes drive homomer assembly
    Science (IF 41.845) Pub Date : 2021-01-01
    Matilde Bertolini, Kai Fenzl, Ilia Kats, Florian Wruck, Frank Tippmann, Jaro Schmitt, Josef Johannes Auburger, Sander Tans, Bernd Bukau, Günter Kramer

    Accurate assembly of newly synthesized proteins into functional oligomers is crucial for cell activity. In this study, we investigated whether direct interaction of two nascent proteins, emerging from nearby ribosomes (co-co assembly), constitutes a general mechanism for oligomer formation. We used proteome-wide screening to detect nascent chain–connected ribosome pairs and identified hundreds of homomer

    更新日期:2020-12-31
  • A tripartite mechanism catalyzes Mad2-Cdc20 assembly at unattached kinetochores
    Science (IF 41.845) Pub Date : 2021-01-01
    Pablo Lara-Gonzalez, Taekyung Kim, Karen Oegema, Kevin Corbett, Arshad Desai

    During cell division, kinetochores couple chromosomes to spindle microtubules. To protect against chromosome gain or loss, kinetochores lacking microtubule attachment locally catalyze association of the checkpoint proteins Cdc20 and Mad2, which is the key event in the formation of a diffusible checkpoint complex that prevents mitotic exit. We elucidated the mechanism of kinetochore-catalyzed Mad2-Cdc20

    更新日期:2020-12-31
  • CDC20 assists its catalytic incorporation in the mitotic checkpoint complex
    Science (IF 41.845) Pub Date : 2021-01-01
    Valentina Piano, Amal Alex, Patricia Stege, Stefano Maffini, Gerardo A. Stoppiello, Pim J. Huis in ’t Veld, Ingrid R. Vetter, Andrea Musacchio

    Open (O) and closed (C) topologies of HORMA-domain proteins are respectively associated with inactive and active states of fundamental cellular pathways. The HORMA protein O-MAD2 converts to C-MAD2 upon binding CDC20. This is rate limiting for assembly of the mitotic checkpoint complex (MCC), the effector of a checkpoint required for mitotic fidelity. A catalyst assembled at kinetochores accelerates

    更新日期:2020-12-31
  • Nanoscale control of internal inhomogeneity enhances water transport in desalination membranes
    Science (IF 41.845) Pub Date : 2021-01-01
    Tyler E. Culp, Biswajit Khara, Kaitlyn P. Brickey, Michael Geitner, Tawanda J. Zimudzi, Jeffrey D. Wilbur, Steven D. Jons, Abhishek Roy, Mou Paul, Baskar Ganapathysubramanian, Andrew L. Zydney, Manish Kumar, Enrique D. Gomez

    Biological membranes can achieve remarkably high permeabilities, while maintaining ideal selectivities, by relying on well-defined internal nanoscale structures in the form of membrane proteins. Here, we apply such design strategies to desalination membranes. A series of polyamide desalination membranes—which were synthesized in an industrial-scale manufacturing line and varied in processing conditions

    更新日期:2020-12-31
  • Achieving large uniform tensile elasticity in microfabricated diamond
    Science (IF 41.845) Pub Date : 2021-01-01
    Chaoqun Dang, Jyh-Pin Chou, Bing Dai, Chang-Ti Chou, Yang Yang, Rong Fan, Weitong Lin, Fanling Meng, Alice Hu, Jiaqi Zhu, Jiecai Han, Andrew M. Minor, Ju Li, Yang Lu

    Diamond is not only the hardest material in nature, but is also an extreme electronic material with an ultrawide bandgap, exceptional carrier mobilities, and thermal conductivity. Straining diamond can push such extreme figures of merit for device applications. We microfabricated single-crystalline diamond bridge structures with ~1 micrometer length by ~100 nanometer width and achieved sample-wide

    更新日期:2020-12-31
  • Seroprevalence of anti–SARS-CoV-2 IgG antibodies in Kenyan blood donors
    Science (IF 41.845) Pub Date : 2021-01-01
    Sophie Uyoga, Ifedayo M. O. Adetifa, Henry K. Karanja, James Nyagwange, James Tuju, Perpetual Wanjiku, Rashid Aman, Mercy Mwangangi, Patrick Amoth, Kadondi Kasera, Wangari Ng’ang’a, Charles Rombo, Christine Yegon, Khamisi Kithi, Elizabeth Odhiambo, Thomas Rotich, Irene Orgut, Sammy Kihara, Mark Otiende, Christian Bottomley, Zonia N. Mupe, Eunice W. Kagucia, Katherine E. Gallagher, Anthony Etyang, Shirine

    The spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in Africa is poorly described. The first case of SARS-CoV-2 in Kenya was reported on 12 March 2020, and an overwhelming number of cases and deaths were expected, but by 31 July 2020, there were only 20,636 cases and 341 deaths. However, the extent of SARS-CoV-2 exposure in the community remains unknown. We determined the prevalence

    更新日期:2020-12-31
  • Aerosol invigoration of atmospheric convection through increases in humidity
    Science (IF 41.845) Pub Date : 2021-01-01
    Tristan H. Abbott, Timothy W. Cronin

    Cloud-aerosol interactions remain a major obstacle to understanding climate and severe weather. Observations suggest that aerosols enhance tropical thunderstorm activity; past research, motivated by the importance of understanding aerosol impacts on clouds, has proposed several mechanisms that could explain that observed link. We find that high-resolution atmospheric simulations can reproduce the observed

    更新日期:2020-12-31
  • Evolution of fold switching in a metamorphic protein
    Science (IF 41.845) Pub Date : 2021-01-01
    Acacia F. Dishman, Robert C. Tyler, Jamie C. Fox, Andrew B. Kleist, Kenneth E. Prehoda, M. Madan Babu, Francis C. Peterson, Brian F. Volkman

    Metamorphic proteins switch between different folds, defying the protein folding paradigm. It is unclear how fold switching arises during evolution. With ancestral reconstruction and nuclear magnetic resonance, we studied the evolution of the metamorphic human protein XCL1, which has two distinct folds with different functions, making it an unusual member of the chemokine family, whose members generally

    更新日期:2020-12-31
  • Low rattling: A predictive principle for self-organization in active collectives
    Science (IF 41.845) Pub Date : 2021-01-01
    Pavel Chvykov, Thomas A. Berrueta, Akash Vardhan, William Savoie, Alexander Samland, Todd D. Murphey, Kurt Wiesenfeld, Daniel I. Goldman, Jeremy L. England

    Self-organization is frequently observed in active collectives as varied as ant rafts and molecular motor assemblies. General principles describing self-organization away from equilibrium have been challenging to identify. We offer a unifying framework that models the behavior of complex systems as largely random while capturing their configuration-dependent response to external forcing. This allows

    更新日期:2020-12-31
  • Clocks, cancer, and chronochemotherapy
    Science (IF 41.845) Pub Date : 2021-01-01
    Aziz Sancar, Russell N. Van Gelder

    The circadian clock coordinates daily rhythmicity of biochemical, physiologic, and behavioral functions in humans. Gene expression, cell division, and DNA repair are modulated by the clock, which gives rise to the hypothesis that clock dysfunction may predispose individuals to cancer. Although the results of many epidemiologic and animal studies are consistent with there being a role for the clock

    更新日期:2020-12-31
  • Steps toward translocation-independent RNA polymerase inactivation by terminator ATPase ρ
    Science (IF 41.845) Pub Date : 2021-01-01
    Nelly Said, Tarek Hilal, Nicholas D. Sunday, Ajay Khatri, Jörg Bürger, Thorsten Mielke, Georgiy A. Belogurov, Bernhard Loll, Ranjan Sen, Irina Artsimovitch, Markus C. Wahl

    Factor-dependent transcription termination mechanisms are poorly understood. We determined a series of cryo–electron microscopy structures portraying the hexameric adenosine triphosphatase (ATPase) ρ on a pathway to terminating NusA/NusG-modified elongation complexes. An open ρ ring contacts NusA, NusG, and multiple regions of RNA polymerase, trapping and locally unwinding proximal upstream DNA. NusA

    更新日期:2020-12-31
  • Structural basis of antagonizing the vitamin K catalytic cycle for anticoagulation
    Science (IF 41.845) Pub Date : 2021-01-01
    Shixuan Liu, Shuang Li, Guomin Shen, Narayanasami Sukumar, Andrzej M. Krezel, Weikai Li

    Vitamin K antagonists are widely used anticoagulants that target vitamin K epoxide reductases (VKOR), a family of integral membrane enzymes. To elucidate their catalytic cycle and inhibitory mechanism, we report 11 x-ray crystal structures of human VKOR and pufferfish VKOR-like, with substrates and antagonists in different redox states. Substrates entering the active site in a partially oxidized state

    更新日期:2020-12-31
  • QRICH1 dictates the outcome of ER stress through transcriptional control of proteostasis
    Science (IF 41.845) Pub Date : 2021-01-01
    Kwontae You, Lingfei Wang, Chih-Hung Chou, Kai Liu, Toru Nakata, Alok Jaiswal, Junmei Yao, Ariel Lefkovith, Abdifatah Omar, Jacqueline G. Perrigoue, Jennifer E. Towne, Aviv Regev, Daniel B. Graham, Ramnik J. Xavier

    Tissue homeostasis is perturbed in a diversity of inflammatory pathologies. These changes can elicit endoplasmic reticulum (ER) stress, protein misfolding, and cell death. ER stress triggers the unfolded protein response (UPR), which can promote recovery of ER proteostasis and cell survival or trigger programmed cell death. Here, we leveraged single-cell RNA sequencing to define dynamic transcriptional

    更新日期:2020-12-31
  • In situ genome sequencing resolves DNA sequence and structure in intact biological samples
    Science (IF 41.845) Pub Date : 2020-12-31
    Andrew C. Payne, Zachary D. Chiang, Paul L. Reginato, Sarah M. Mangiameli, Evan M. Murray, Chun-Chen Yao, Styliani Markoulaki, Andrew S. Earl, Ajay S. Labade, Rudolf Jaenisch, George M. Church, Edward S. Boyden, Jason D. Buenrostro, Fei Chen

    Understanding genome organization requires integration of DNA sequence and 3D spatial context, however, existing genome-wide methods lack either base-pair sequence resolution or direct spatial localization. Here, we describe in situ genome sequencing (IGS), a method for simultaneously sequencing and imaging genomes within intact biological samples. We applied IGS to human fibroblasts and early mouse

    更新日期:2020-12-31
  • Afucosylated IgG characterizes enveloped viral responses and correlates with COVID-19 severity
    Science (IF 41.845) Pub Date : 2020-12-23
    Mads Delbo Larsen, Erik L. de Graaf, Myrthe E. Sonneveld, H. Rosina Plomp, Jan Nouta, Willianne Hoepel, Hung-Jen Chen, Federica Linty, Remco Visser, Maximilian Brinkhaus, Tonći Šuštić, Steven W. de Taeye, Arthur E. H. Bentlage, Suvi Toivonen, Carolien A. M. Koeleman, Susanna Sainio, Neeltje A. Kootstra, Philip J.M. Brouwer, Chiara Elisabeth Geyer, Ninotska I. L. Derksen, Gertjan Wolbink, Menno de Winther

    IgG antibodies are crucial for protection against invading pathogens. A highly conserved N-linked glycan within the IgG-Fc tail, essential for IgG function, shows variable composition in humans. Afucosylated IgG variants are already used in anti-cancer therapeutic antibodies for their elevated activity through Fc receptors (FcγRIIIa). Here, we report that afucosylated IgG (~6% of total IgG in humans)

    更新日期:2020-12-24
  • Relativistic kinematics of a magnetic soliton
    Science (IF 41.845) Pub Date : 2020-12-18
    Lucas Caretta, Se-Hyeok Oh, Takian Fakhrul, Dong-Kyu Lee, Byung Hun Lee, Se Kwon Kim, Caroline A. Ross, Kyung-Jin Lee, Geoffrey S. D. Beach

    A tenet of special relativity is that no particle can exceed the speed of light. In certain magnetic materials, the maximum magnon group velocity serves as an analogous relativistic limit for the speed of magnetic solitons. Here, we drive domain walls to this limit in a low-dissipation magnetic insulator using pure spin currents from the spin Hall effect. We achieve record current-driven velocities

    更新日期:2020-12-18
  • How directed evolution reshapes the energy landscape in an enzyme to boost catalysis
    Science (IF 41.845) Pub Date : 2020-12-18
    Renee Otten, Ricardo A. P. Pádua, H. Adrian Bunzel, Vy Nguyen, Warintra Pitsawong, MacKenzie Patterson, Shuo Sui, Sarah L. Perry, Aina E. Cohen, Donald Hilvert, Dorothee Kern

    The advent of biocatalysts designed computationally and optimized by laboratory evolution provides an opportunity to explore molecular strategies for augmenting catalytic function. Applying a suite of nuclear magnetic resonance, crystallography, and stopped-flow techniques to an enzyme designed for an elementary proton transfer reaction, we show how directed evolution gradually altered the conformational

    更新日期:2020-12-18
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