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  • Feasibility of blood testing combined with PET-CT to screen for cancer and guide intervention.
    Science (IF 41.845) Pub Date : 2020-07-03
    Anne Marie Lennon,Adam H Buchanan,Isaac Kinde,Andrew Warren,Ashley Honushefsky,Ariella T Cohain,David H Ledbetter,Fred Sanfilippo,Kathleen Sheridan,Dillenia Rosica,Christian S Adonizio,Hee Jung Hwang,Kamel Lahouel,Joshua D Cohen,Christopher Douville,Aalpen A Patel,Leonardo N Hagmann,David D Rolston,Nirav Malani,Shibin Zhou,Chetan Bettegowda,David L Diehl,Bobbi Urban,Christopher D Still,Lisa Kann,Julie

    Cancer treatments are often more successful when the disease is detected early. We evaluated the feasibility and safety of multicancer blood testing coupled with positron emission tomography–computed tomography (PET-CT) imaging to detect cancer in a prospective, interventional study of 10,006 women not previously known to have cancer. Positive blood tests were independently confirmed by a diagnostic

    更新日期:2020-07-02
  • Sharing vitamins: Cobamides unveil microbial interactions
    Science (IF 41.845) Pub Date : 2020-07-03
    Olga M. Sokolovskaya, Amanda N. Shelton, Michiko E. Taga

    Microbial communities are essential to fundamental processes on Earth. Underlying the compositions and functions of these communities are nutritional interdependencies among individual species. One class of nutrients, cobamides (the family of enzyme cofactors that includes vitamin B12), is widely used for a variety of microbial metabolic functions, but these structurally diverse cofactors are synthesized

    更新日期:2020-07-02
  • Number of HIV-1 founder variants is determined by the recency of the source partner infection
    Science (IF 41.845) Pub Date : 2020-07-03
    Ch. Julián Villabona-Arenas, Matthew Hall, Katrina A. Lythgoe, Stephen G. Gaffney, Roland R. Regoes, Stéphane Hué, Katherine E. Atkins

    During sexual transmission, the high genetic diversity of HIV-1 within an individual is frequently reduced to one founder variant that initiates infection. Understanding the drivers of this bottleneck is crucial to developing effective infection control strategies. Little is known about the importance of the source partner during this bottleneck. To test the hypothesis that the source partner affects

    更新日期:2020-07-02
  • A piperidinium salt stabilizes efficient metal-halide perovskite solar cells
    Science (IF 41.845) Pub Date : 2020-07-03
    Yen-Hung Lin, Nobuya Sakai, Peimei Da, Jiaying Wu, Harry C. Sansom, Alexandra J. Ramadan, Suhas Mahesh, Junliang Liu, Robert D. J. Oliver, Jongchul Lim, Lee Aspitarte, Kshama Sharma, P. K. Madhu, Anna B. Morales‐Vilches, Pabitra K. Nayak, Sai Bai, Feng Gao, Chris R. M. Grovenor, Michael B. Johnston, John G. Labram, James R. Durrant, James M. Ball, Bernard Wenger, Bernd Stannowski, Henry J. Snaith

    Longevity has been a long-standing concern for hybrid perovskite photovoltaics. We demonstrate high-resilience positive-intrinsic-negative perovskite solar cells by incorporating a piperidinium-based ionic compound into the formamidinium-cesium lead-trihalide perovskite absorber. With the bandgap tuned to be well suited for perovskite-on-silicon tandem cells, this piperidinium additive enhances the

    更新日期:2020-07-02
  • C(sp3)–H functionalizations of light hydrocarbons using decatungstate photocatalysis in flow
    Science (IF 41.845) Pub Date : 2020-07-03
    Gabriele Laudadio, Yuchao Deng, Klaas van der Wal, Davide Ravelli, Manuel Nuño, Maurizio Fagnoni, Duncan Guthrie, Yuhan Sun, Timothy Noël

    Direct activation of gaseous hydrocarbons remains a major challenge for the chemistry community. Because of the intrinsic inertness of these compounds, harsh reaction conditions are typically required to enable C(sp3)–H bond cleavage, barring potential applications in synthetic organic chemistry. Here, we report a general and mild strategy to activate C(sp3)–H bonds in methane, ethane, propane, and

    更新日期:2020-07-02
  • An ideal Josephson junction in an ultracold two-dimensional Fermi gas
    Science (IF 41.845) Pub Date : 2020-07-03
    Niclas Luick, Lennart Sobirey, Markus Bohlen, Vijay Pal Singh, Ludwig Mathey, Thomas Lompe, Henning Moritz

    The role of reduced dimensionality in high-temperature superconductors is still under debate. Recently, ultracold atoms have emerged as an ideal model system to study such strongly correlated two-dimensional (2D) systems. Here, we report on the realization of a Josephson junction in an ultracold 2D Fermi gas. We measure the frequency of Josephson oscillations as a function of the phase difference across

    更新日期:2020-07-02
  • Strongly correlated superfluid order parameters from dc Josephson supercurrents
    Science (IF 41.845) Pub Date : 2020-07-03
    W. J. Kwon, G. Del Pace, R. Panza, M. Inguscio, W. Zwerger, M. Zaccanti, F. Scazza, G. Roati

    The direct-current (dc) Josephson effect provides a phase-sensitive tool for investigating superfluid order parameters. We report on the observation of dc Josephson supercurrents in strongly interacting fermionic superfluids across a tunneling barrier in the absence of any applied potential difference. For sufficiently strong barriers, we observed a sinusoidal current-phase relation, in agreement with

    更新日期:2020-07-02
  • Ultrahigh capacitive energy density in ion-bombarded relaxor ferroelectric films
    Science (IF 41.845) Pub Date : 2020-07-03
    Jieun Kim, Sahar Saremi, Megha Acharya, Gabriel Velarde, Eric Parsonnet, Patrick Donahue, Alexander Qualls, David Garcia, Lane W. Martin

    Dielectric capacitors can store and release electric energy at ultrafast rates and are extensively studied for applications in electronics and electric power systems. Among various candidates, thin films based on relaxor ferroelectrics, a special kind of ferroelectric with nanometer-sized domains, have attracted special attention because of their high energy densities and efficiencies. We show that

    更新日期:2020-07-02
  • Rapid development of an inactivated vaccine candidate for SARS-CoV-2.
    Science (IF 41.845) Pub Date : 2020-07-03
    Qiang Gao,Linlin Bao,Haiyan Mao,Lin Wang,Kangwei Xu,Minnan Yang,Yajing Li,Ling Zhu,Nan Wang,Zhe Lv,Hong Gao,Xiaoqin Ge,Biao Kan,Yaling Hu,Jiangning Liu,Fang Cai,Deyu Jiang,Yanhui Yin,Chengfeng Qin,Jing Li,Xuejie Gong,Xiuyu Lou,Wen Shi,Dongdong Wu,Hengming Zhang,Lang Zhu,Wei Deng,Yurong Li,Jinxing Lu,Changgui Li,Xiangxi Wang,Weidong Yin,Yanjun Zhang,Chuan Qin

    The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in an unprecedented public health crisis. Because of the novelty of the virus, there are currently no SARS-CoV-2–specific treatments or vaccines available. Therefore, rapid development of effective vaccines against SARS-CoV-2 are urgently needed. Here, we developed a

    更新日期:2020-07-02
  • Cell position fates and collective fountain flow in bacterial biofilms revealed by light-sheet microscopy.
    Science (IF 41.845) Pub Date : 2020-07-03
    Boyang Qin,Chenyi Fei,Andrew A Bridges,Ameya A Mashruwala,Howard A Stone,Ned S Wingreen,Bonnie L Bassler

    Bacterial biofilms represent a basic form of multicellular organization that confers survival advantages to constituent cells. The sequential stages of cell ordering during biofilm development have been studied in the pathogen and model biofilm-former Vibrio cholerae. It is unknown how spatial trajectories of individual cells and the collective motions of many cells drive biofilm expansion. We developed

    更新日期:2020-07-02
  • Thermal bottlenecks in the life cycle define climate vulnerability of fish
    Science (IF 41.845) Pub Date : 2020-07-03
    Flemming T. Dahlke, Sylke Wohlrab, Martin Butzin, Hans-Otto Pörtner

    Species’ vulnerability to climate change depends on the most temperature-sensitive life stages, but for major animal groups such as fish, life cycle bottlenecks are often not clearly defined. We used observational, experimental, and phylogenetic data to assess stage-specific thermal tolerance metrics for 694 marine and freshwater fish species from all climate zones. Our analysis shows that spawning

    更新日期:2020-07-02
  • The histone H3-H4 tetramer is a copper reductase enzyme
    Science (IF 41.845) Pub Date : 2020-07-03
    Narsis Attar, Oscar A. Campos, Maria Vogelauer, Chen Cheng, Yong Xue, Stefan Schmollinger, Lukasz Salwinski, Nathan V. Mallipeddi, Brandon A. Boone, Linda Yen, Sichen Yang, Shannon Zikovich, Jade Dardine, Michael F. Carey, Sabeeha S. Merchant, Siavash K. Kurdistani

    Eukaryotic histone H3-H4 tetramers contain a putative copper (Cu2+) binding site at the H3-H3′ dimerization interface with unknown function. The coincident emergence of eukaryotes with global oxygenation, which challenged cellular copper utilization, raised the possibility that histones may function in cellular copper homeostasis. We report that the recombinant Xenopus laevis H3-H4 tetramer is an oxidoreductase

    更新日期:2020-07-02
  • A phage-encoded anti-CRISPR enables complete evasion of type VI-A CRISPR-Cas immunity.
    Science (IF 41.845) Pub Date : 2020-07-03
    Alexander J Meeske,Ning Jia,Alice K Cassel,Albina Kozlova,Jingqiu Liao,Martin Wiedmann,Dinshaw J Patel,Luciano A Marraffini

    The CRISPR RNA (crRNA)–guided nuclease Cas13 recognizes complementary viral transcripts to trigger the degradation of both host and viral RNA during the type VI CRISPR-Cas antiviral response. However, how viruses can counteract this immunity is not known. We describe a listeriaphage (ϕLS46) encoding an anti-CRISPR protein (AcrVIA1) that inactivates the type VI-A CRISPR system of Listeria seeligeri

    更新日期:2020-07-02
  • SARS-CoV-2 productively infects human gut enterocytes.
    Science (IF 41.845) Pub Date : 2020-07-03
    Mart M Lamers,Joep Beumer,Jelte van der Vaart,Kèvin Knoops,Jens Puschhof,Tim I Breugem,Raimond B G Ravelli,J Paul van Schayck,Anna Z Mykytyn,Hans Q Duimel,Elly van Donselaar,Samra Riesebosch,Helma J H Kuijpers,Debby Schippers,Willine J van de Wetering,Miranda de Graaf,Marion Koopmans,Edwin Cuppen,Peter J Peters,Bart L Haagmans,Hans Clevers

    Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can cause coronavirus disease 2019 (COVID-19), an influenza-like disease that is primarily thought to infect the lungs with transmission through the respiratory route. However, clinical evidence suggests that the intestine may present another viral target organ. Indeed, the SARS-CoV-2 receptor angiotensin-converting enzyme 2 (ACE2) is highly

    更新日期:2020-07-02
  • Scale-free ferroelectricity induced by flat phonon bands in HfO2
    Science (IF 41.845) Pub Date : 2020-07-02
    Hyun-Jae Lee, Minseong Lee, Kyoungjun Lee, Jinhyeong Jo, Hyemi Yang, Yungyeom Kim, Seung Chul Chae, Umesh Waghmare, Jun Hee Lee

    Discovery of robust yet reversibly switchable electric dipoles at reduced dimensions is critical in advancing nanoelectronics devices. Energy bands flat in momentum space generate robust localized states that are activated independently of each other. We determined flat bands exist and induce robust yet independently switchable dipoles exhibiting a unique ferroelectricity in HfO2. Flat polar phonon

    更新日期:2020-07-02
  • Covalent surface modifications and superconductivity of two-dimensional metal carbide MXenes
    Science (IF 41.845) Pub Date : 2020-07-02
    Vladislav Kamysbayev, Alexander S. Filatov, Huicheng Hu, Xue Rui, Francisco Lagunas, Di Wang, Robert F. Klie, Dmitri V. Talapin

    Versatile chemical transformations of surface functional groups in 2D transition-metal carbides (MXenes) open up a new design space for this broad class of functional materials. We introduce a general strategy to install and remove surface groups by performing substitution and elimination reactions in molten inorganic salts. Successful synthesis of MXenes with O, NH, S, Cl, Se, Br, and Te surface terminations

    更新日期:2020-07-02
  • Primary exposure to SARS-CoV-2 protects against reinfection in rhesus macaques
    Science (IF 41.845) Pub Date : 2020-07-02
    Wei Deng, Linlin Bao, Jiangning Liu, Chong Xiao, Jiayi Liu, Jing Xue, Qi Lv, Feifei Qi, Hong Gao, Pin Yu, Yanfeng Xu, Yajin Qu, Fengdi Li, Zhiguang Xiang, Haisheng Yu, Shuran Gong, Mingya Liu, Guanpeng Wang, Shunyi Wang, Zhiqi Song, Ying Liu, Wenjie Zhao, Yunlin Han, Linna Zhao, Xing Liu, Qiang Wei, Chuan Qin

    Coronavirus disease 2019 (COVID-19), which is caused by infection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has become a global pandemic. It currently remains unclear whether convalescing patients have a risk of reinfection. We generated a rhesus macaque model of SARS-CoV-2 infection that was characterized by interstitial pneumonia and systemic viral dissemination mainly

    更新日期:2020-07-02
  • Accelerating water dissociation in bipolar membranes and for electrocatalysis
    Science (IF 41.845) Pub Date : 2020-07-02
    Sebastian Z. Oener, Marc J. Foster, Shannon W. Boettcher

    Catalyzing water dissociation (WD) into protons and hydroxide ions is important both for fabricating bipolar membranes (BPMs) that can couple different pH environments into a single electrochemical device, and for accelerating electrocatalytic reactions that consume protons in neutral-to-alkaline media. We designed a BPM electrolyzer to quantitatively measure WD kinetics and show that, for metal nanoparticles

    更新日期:2020-07-02
  • Architecture and function of human uromodulin filaments in urinary tract infections
    Science (IF 41.845) Pub Date : 2020-07-02
    Gregor L. Weiss, Jessica J. Stanisich, Maximilian M. Sauer, Chia-Wei Lin, Jonathan Eras, Dawid S. Zyla, Johannes Trück, Olivier Devuyst, Markus Aebi, Martin Pilhofer, Rudi Glockshuber

    Uromodulin is the most abundant protein in human urine and forms filaments that antagonize the adhesion of uropathogens; however, filament structure and mechanism of protection remain poorly understood. We used cryo-electron tomography to show that the uromodulin filament consists of a zigzag-shaped backbone with laterally protruding arms. N-glycosylation mapping and biophysical assays revealed that

    更新日期:2020-07-02
  • Exploring whole-genome duplicate gene retention with complex genetic interaction analysis
    Science (IF 41.845) Pub Date : 2020-06-26
    Elena Kuzmin, Benjamin VanderSluis, Alex N. Nguyen Ba, Wen Wang, Elizabeth N. Koch, Matej Usaj, Anton Khmelinskii, Mojca Mattiazzi Usaj, Jolanda van Leeuwen, Oren Kraus, Amy Tresenrider, Michael Pryszlak, Ming-Che Hu, Brenda Varriano, Michael Costanzo, Michael Knop, Alan Moses, Chad L. Myers, Brenda J. Andrews, Charles Boone

    Whole-genome duplication has played a central role in the genome evolution of many organisms, including the human genome. Most duplicated genes are eliminated, and factors that influence the retention of persisting duplicates remain poorly understood. We describe a systematic complex genetic interaction analysis with yeast paralogs derived from the whole-genome duplication event. Mapping of digenic

    更新日期:2020-06-26
  • Flexible recruitment of memory-based choice representations by the human medial frontal cortex
    Science (IF 41.845) Pub Date : 2020-06-26
    Juri Minxha, Ralph Adolphs, Stefano Fusi, Adam N. Mamelak, Ueli Rutishauser

    Decision-making in complex environments relies on flexibly using prior experience. This process depends on the medial frontal cortex (MFC) and the medial temporal lobe, but it remains unknown how these structures implement selective memory retrieval. We recorded single neurons in the MFC, amygdala, and hippocampus while human subjects switched between making recognition memory–based and categorization-based

    更新日期:2020-06-26
  • Muscle and neuronal guidepost-like cells facilitate planarian visual system regeneration
    Science (IF 41.845) Pub Date : 2020-06-26
    M. Lucila Scimone, Kutay D. Atabay, Christopher T. Fincher, Ashley R. Bonneau, Dayan J. Li, Peter W. Reddien

    Neuronal circuits damaged or lost after injury can be regenerated in some adult organisms, but the mechanisms enabling this process are largely unknown. We used the planarian Schmidtea mediterranea to study visual system regeneration after injury. We identify a rare population of muscle cells tightly associated with photoreceptor axons at stereotyped positions in both uninjured and regenerating animals

    更新日期:2020-06-26
  • Structural basis for inhibition of the RNA-dependent RNA polymerase from SARS-CoV-2 by remdesivir.
    Science (IF 41.845) Pub Date : 2020-06-26
    Wanchao Yin,Chunyou Mao,Xiaodong Luan,Dan-Dan Shen,Qingya Shen,Haixia Su,Xiaoxi Wang,Fulai Zhou,Wenfeng Zhao,Minqi Gao,Shenghai Chang,Yuan-Chao Xie,Guanghui Tian,He-Wei Jiang,Sheng-Ce Tao,Jingshan Shen,Yi Jiang,Hualiang Jiang,Yechun Xu,Shuyang Zhang,Yan Zhang,H Eric Xu

    The pandemic of coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has become a global crisis. Replication of SARS-CoV-2 requires the viral RNA-dependent RNA polymerase (RdRp) enzyme, a target of the antiviral drug remdesivir. Here we report the cryo–electron microscopy structure of the SARS-CoV-2 RdRp, both in the apo form at 2.8-angstrom resolution

    更新日期:2020-06-26
  • Arctic-adapted dogs emerged at the Pleistocene–Holocene transition
    Science (IF 41.845) Pub Date : 2020-06-26
    Mikkel-Holger S. Sinding, Shyam Gopalakrishnan, Jazmín Ramos-Madrigal, Marc de Manuel, Vladimir V. Pitulko, Lukas Kuderna, Tatiana R. Feuerborn, Laurent A. F. Frantz, Filipe G. Vieira, Jonas Niemann, Jose A. Samaniego Castruita, Christian Carøe, Emilie U. Andersen-Ranberg, Peter D. Jordan, Elena Y. Pavlova, Pavel A. Nikolskiy, Aleksei K. Kasparov, Varvara V. Ivanova, Eske Willerslev, Pontus Skoglund

    Although sled dogs are one of the most specialized groups of dogs, their origin and evolution has received much less attention than many other dog groups. We applied a genomic approach to investigate their spatiotemporal emergence by sequencing the genomes of 10 modern Greenland sled dogs, an ~9500-year-old Siberian dog associated with archaeological evidence for sled technology, and an ~33,000-year-old

    更新日期:2020-06-26
  • Quieting a noisy antenna reproduces photosynthetic light-harvesting spectra
    Science (IF 41.845) Pub Date : 2020-06-26
    Trevor B. Arp, Jed Kistner-Morris, Vivek Aji, Richard J. Cogdell, Rienk van Grondelle, Nathaniel M. Gabor

    Photosynthesis achieves near unity light-harvesting quantum efficiency yet it remains unknown whether there exists a fundamental organizing principle giving rise to robust light harvesting in the presence of dynamic light conditions and noisy physiological environments. Here, we present a noise-canceling network model that relates noisy physiological conditions, power conversion efficiency, and the

    更新日期:2020-06-26
  • Metalens-array–based high-dimensional and multiphoton quantum source
    Science (IF 41.845) Pub Date : 2020-06-26
    Lin Li, Zexuan Liu, Xifeng Ren, Shuming Wang, Vin-Cent Su, Mu-Ku Chen, Cheng Hung Chu, Hsin Yu Kuo, Biheng Liu, Wenbo Zang, Guangcan Guo, Lijian Zhang, Zhenlin Wang, Shining Zhu, Din Ping Tsai

    The development of two-dimensional metasurfaces has shown great potential in quantum-optical technologies because of the excellent flexibility in light-field manipulation. By integrating a metalens array with a nonlinear crystal, we demonstrate a 100-path spontaneous parametric down-conversion photon-pair source in a 10 × 10 array, which shows promise for high-dimensional entanglement and multiphoton-state

    更新日期:2020-06-26
  • Changes in contact patterns shape the dynamics of the COVID-19 outbreak in China.
    Science (IF 41.845) Pub Date : 2020-06-26
    Juanjuan Zhang,Maria Litvinova,Yuxia Liang,Yan Wang,Wei Wang,Shanlu Zhao,Qianhui Wu,Stefano Merler,Cécile Viboud,Alessandro Vespignani,Marco Ajelli,Hongjie Yu

    Intense nonpharmaceutical interventions were put in place in China to stop transmission of the novel coronavirus disease 2019 (COVID-19). As transmission intensifies in other countries, the interplay between age, contact patterns, social distancing, susceptibility to infection, and COVID-19 dynamics remains unclear. To answer these questions, we analyze contact survey data for Wuhan and Shanghai before

    更新日期:2020-06-26
  • A multiplanet system of super-Earths orbiting the brightest red dwarf star GJ 887
    Science (IF 41.845) Pub Date : 2020-06-26
    S. V. Jeffers, S. Dreizler, J. R. Barnes, C. A. Haswell, R. P. Nelson, E. Rodríguez, M. J. López-González, N. Morales, R. Luque, M. Zechmeister, S. S. Vogt, J. S. Jenkins, E. Palle, Z. M. Berdi ñas, G. A. L. Coleman, M. R. Díaz, I. Ribas, H. R. A. Jones, R. P. Butler, C. G. Tinney, J. Bailey, B. D. Carter, S. O’Toole, R. A. Wittenmyer, J. D. Crane, F. Feng, S. A. Shectman, J. Teske, A. Reiners, P.

    The closet exoplanets to the Sun provide opportunities for detailed characterization of planets outside the Solar System. We report the discovery, using radial velocity measurements, of a compact multiplanet system of super-Earth exoplanets orbiting the nearby red dwarf star GJ 887. The two planets have orbital periods of 9.3 and 21.8 days. Assuming an Earth-like albedo, the equilibrium temperature

    更新日期:2020-06-26
  • Micelle-directed chiral seeded growth on anisotropic gold nanocrystals
    Science (IF 41.845) Pub Date : 2020-06-26
    Guillermo González-Rubio, Jesús Mosquera, Vished Kumar, Adrián Pedrazo-Tardajos, Pablo Llombart, Diego M. Solís, Ivan Lobato, Eva G. Noya, Andrés Guerrero-Martínez, José M. Taboada, Fernando Obelleiro, Luis G. MacDowell, Sara Bals, Luis M. Liz-Marzán

    Surfactant-assisted seeded growth of metal nanoparticles (NPs) can be engineered to produce anisotropic gold nanocrystals with high chiroptical activity through the templating effect of chiral micelles formed in the presence of dissymmetric cosurfactants. Mixed micelles adsorb on gold nanorods, forming quasihelical patterns that direct seeded growth into NPs with pronounced morphological and optical

    更新日期:2020-06-26
  • Meridional flow in the Sun’s convection zone is a single cell in each hemisphere
    Science (IF 41.845) Pub Date : 2020-06-26
    Laurent Gizon, Robert H. Cameron, Majid Pourabdian, Zhi-Chao Liang, Damien Fournier, Aaron C. Birch, Chris S. Hanson

    The Sun’s magnetic field is generated by subsurface motions of the convecting plasma. The latitude at which the magnetic field emerges through the solar surface (as sunspots) drifts toward the equator over the course of the 11-year solar cycle. We use helioseismology to infer the meridional flow (in the latitudinal and radial directions) over two solar cycles covering 1996–2019. Two data sources are

    更新日期:2020-06-26
  • Mass-resolved electronic circular dichroism ion spectroscopy
    Science (IF 41.845) Pub Date : 2020-06-26
    Steven Daly, Frédéric Rosu, Valérie Gabelica

    DNA and proteins are chiral: Their three-dimensional structures cannot be superimposed with their mirror images. Circular dichroism spectroscopy is widely used to characterize chiral compounds, but data interpretation is difficult in the case of mixtures. We recorded the electronic circular dichroism spectra of DNA helices separated in a mass spectrometer. We studied guanine-rich strands having various

    更新日期:2020-06-26
  • Mechanisms of OCT4-SOX2 motif readout on nucleosomes.
    Science (IF 41.845) Pub Date : 2020-06-26
    Alicia K Michael,Ralph S Grand,Luke Isbel,Simone Cavadini,Zuzanna Kozicka,Georg Kempf,Richard D Bunker,Andreas D Schenk,Alexandra Graff-Meyer,Ganesh R Pathare,Joscha Weiss,Syota Matsumoto,Lukas Burger,Dirk Schübeler,Nicolas H Thomä

    Transcription factors (TFs) regulate gene expression through chromatin where nucleosomes restrict DNA access. To study how TFs bind nucleosome-occupied motifs, we focused on the reprogramming factors OCT4 and SOX2 in mouse embryonic stem cells. We determined TF engagement throughout a nucleosome at base-pair resolution in vitro, enabling structure determination by cryo–electron microscopy at two preferred

    更新日期:2020-06-26
  • Cryo-EM structure of the human cohesin-NIPBL-DNA complex.
    Science (IF 41.845) Pub Date : 2020-06-26
    Zhubing Shi,Haishan Gao,Xiao-Chen Bai,Hongtao Yu

    As a ring-shaped adenosine triphosphatase (ATPase) machine, cohesin organizes the eukaryotic genome by extruding DNA loops and mediates sister chromatid cohesion by topologically entrapping DNA. How cohesin executes these fundamental DNA transactions is not understood. Using cryo–electron microscopy (cryo-EM), we determined the structure of human cohesin bound to its loader NIPBL and DNA at medium

    更新日期:2020-06-26
  • Single-molecule regulatory architectures captured by chromatin fiber sequencing
    Science (IF 41.845) Pub Date : 2020-06-26
    Andrew B. Stergachis, Brian M. Debo, Eric Haugen, L. Stirling Churchman, John A. Stamatoyannopoulos

    Gene regulation is chiefly determined at the level of individual linear chromatin molecules, yet our current understanding of cis-regulatory architectures derives from fragmented sampling of large numbers of disparate molecules. We developed an approach for precisely stenciling the structure of individual chromatin fibers onto their composite DNA templates using nonspecific DNA N6-adenine methyltransferases

    更新日期:2020-06-26
  • Rational synthesis of atomically precise graphene nanoribbons directly on metal oxide surfaces
    Science (IF 41.845) Pub Date : 2020-06-25
    M. Kolmer, A.K. Steiner, I. Izydorczyk, W. Ko, M. Engelund, M. Szymonski, A.-P. Li, K. Amsharov

    Atomically precise graphene nanoribbons (GNRs) attract great interest because of their highly tunable electronic, optical, and transport properties. However, on-surface synthesis of GNRs is typically based on metal-surface assisted chemical reactions, where metallic substrates strongly screen their designer electronic properties and limit further applications. Here, we present an on-surface synthesis

    更新日期:2020-06-26
  • Structural insight into precursor ribosomal RNA processing by ribonuclease MRP
    Science (IF 41.845) Pub Date : 2020-06-25
    Pengfei Lan, Bin Zhou, Ming Tan, Shaobai Li, Mi Cao, Jian Wu, Ming Lei

    Ribonuclease (RNase) MRP is a conserved eukaryotic ribonucleoprotein complex that plays essential roles in pre-ribosomal RNA (pre-rRNA) processing and cell cycle regulation. In contrast to RNase P, which selectively cleaves tRNA-like substrates, it has remained a mystery how RNase MRP recognizes its diverse substrates. To address this question, we determined cryo-EM structures of Saccharomyces cerevisiae

    更新日期:2020-06-26
  • Estimating the burden of SARS-CoV-2 in France.
    Science (IF 41.845) Pub Date : 2020-06-25
    Henrik Salje,Cécile Tran Kiem,Noémie Lefrancq,Noémie Courtejoie,Paolo Bosetti,Juliette Paireau,Alessio Andronico,Nathanaël Hozé,Jehanne Richet,Claire-Lise Dubost,Yann Le Strat,Justin Lessler,Daniel Levy-Bruhl,Arnaud Fontanet,Lulla Opatowski,Pierre-Yves Boelle,Simon Cauchemez

    France has been heavily affected by the SARS-CoV-2 epidemic and went into lockdown on the 17 March 2020. Using models applied to hospital and death data, we estimate the impact of the lockdown and current population immunity. We find 3.6% of infected individuals are hospitalized and 0.7% die, ranging from 0.001% in those <20 years of age (ya) to 10.1% in those >80ya. Across all ages, men are more likely

    更新日期:2020-06-26
  • A mathematical model reveals the influence of population heterogeneity on herd immunity to SARS-CoV-2
    Science (IF 41.845) Pub Date : 2020-06-23
    Tom Britton, Frank Ball, Pieter Trapman

    Despite various levels of preventive measures, in 2020 many countries have suffered severely from the coronavirus 2019 (COVID-19) pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus. We show that population heterogeneity can significantly impact disease-induced immunity as the proportion infected in groups with the highest contact rates is greater than in groups

    更新日期:2020-06-24
  • A neutralizing human antibody binds to the N-terminal domain of the Spike protein of SARS-CoV-2.
    Science (IF 41.845) Pub Date : 2020-06-22
    Xiangyang Chi,Renhong Yan,Jun Zhang,Guanying Zhang,Yuanyuan Zhang,Meng Hao,Zhe Zhang,Pengfei Fan,Yunzhu Dong,Yilong Yang,Zhengshan Chen,Yingying Guo,Jinlong Zhang,Yaning Li,Xiaohong Song,Yi Chen,Lu Xia,Ling Fu,Lihua Hou,Junjie Xu,Changming Yu,Jianmin Li,Qiang Zhou,Wei Chen

    Developing therapeutics against SARS-CoV-2 could be guided by the distribution of epitopes, not only on the receptor binding domain (RBD) of the Spike (S) protein, but also across the full Spike (S) protein. We isolated and characterized monoclonal antibodies (mAbs) from ten convalescent COVID-19 patients. Three mAbs showed neutralizing activities against authentic SARS-CoV-2. An mAb, named 4A8, exhibits

    更新日期:2020-06-23
  • Climate-driven risks to the climate mitigation potential of forests.
    Science (IF 41.845) Pub Date : 2020-06-19
    William R L Anderegg,Anna T Trugman,Grayson Badgley,Christa M Anderson,Ann Bartuska,Philippe Ciais,Danny Cullenward,Christopher B Field,Jeremy Freeman,Scott J Goetz,Jeffrey A Hicke,Deborah Huntzinger,Robert B Jackson,John Nickerson,Stephen Pacala,James T Randerson

    Forests have considerable potential to help mitigate human-caused climate change and provide society with many cobenefits. However, climate-driven risks may fundamentally compromise forest carbon sinks in the 21st century. Here, we synthesize the current understanding of climate-driven risks to forest stability from fire, drought, biotic agents, and other disturbances. We review how efforts to use

    更新日期:2020-06-19
  • Meissner corpuscles and their spatially intermingled afferents underlie gentle touch perception.
    Science (IF 41.845) Pub Date : 2020-06-19
    Nicole L Neubarth,Alan J Emanuel,Yin Liu,Mark W Springel,Annie Handler,Qiyu Zhang,Brendan P Lehnert,Chong Guo,Lauren L Orefice,Amira Abdelaziz,Michelle M DeLisle,Michael Iskols,Julia Rhyins,Soo J Kim,Stuart J Cattel,Wade Regehr,Christopher D Harvey,Jan Drugowitsch,David D Ginty

    Meissner corpuscles are mechanosensory end organs that densely occupy mammalian glabrous skin. We generated mice that selectively lacked Meissner corpuscles and found them to be deficient in both perceiving the gentlest detectable forces acting on glabrous skin and fine sensorimotor control. We found that Meissner corpuscles are innervated by two mechanoreceptor subtypes that exhibit distinct responses

    更新日期:2020-06-19
  • Gas chromatography-mass spectrometry analyses of encapsulated stable perovskite solar cells.
    Science (IF 41.845) Pub Date : 2020-06-19
    Lei Shi,Martin P Bucknall,Trevor L Young,Meng Zhang,Long Hu,Jueming Bing,Da Seul Lee,Jincheol Kim,Tom Wu,Noboru Takamure,David R McKenzie,Shujuan Huang,Martin A Green,Anita W Y Ho-Baillie

    Although perovskite solar cells have produced remarkable energy conversion efficiencies, they cannot become commercially viable without improvements in durability. We used gas chromatography–mass spectrometry (GC-MS) to reveal signature volatile products of the decomposition of organic hybrid perovskites under thermal stress. In addition, we were able to use GC-MS to confirm that a low-cost polymer/glass

    更新日期:2020-06-19
  • Manipulating synthetic optogenetic odors reveals the coding logic of olfactory perception.
    Science (IF 41.845) Pub Date : 2020-06-19
    Edmund Chong,Monica Moroni,Christopher Wilson,Shy Shoham,Stefano Panzeri,Dmitry Rinberg

    How does neural activity generate perception? Finding the combinations of spatial or temporal activity features (such as neuron identity or latency) that are consequential for perception remains challenging. We trained mice to recognize synthetic odors constructed from parametrically defined patterns of optogenetic activation, then measured perceptual changes during extensive and controlled perturbations

    更新日期:2020-06-19
  • Partitioning of cancer therapeutics in nuclear condensates.
    Science (IF 41.845) Pub Date : 2020-06-19
    Isaac A Klein,Ann Boija,Lena K Afeyan,Susana Wilson Hawken,Mengyang Fan,Alessandra Dall'Agnese,Ozgur Oksuz,Jonathan E Henninger,Krishna Shrinivas,Benjamin R Sabari,Ido Sagi,Victoria E Clark,Jesse M Platt,Mrityunjoy Kar,Patrick M McCall,Alicia V Zamudio,John C Manteiga,Eliot L Coffey,Charles H Li,Nancy M Hannett,Yang Eric Guo,Tim-Michael Decker,Tong Ihn Lee,Tinghu Zhang,Jing-Ke Weng,Dylan J Taatjes

    The nucleus contains diverse phase-separated condensates that compartmentalize and concentrate biomolecules with distinct physicochemical properties. Here, we investigated whether condensates concentrate small-molecule cancer therapeutics such that their pharmacodynamic properties are altered. We found that antineoplastic drugs become concentrated in specific protein condensates in vitro and that this

    更新日期:2020-06-19
  • Structural evidence for a dynamic metallocofactor during N2 reduction by Mo-nitrogenase.
    Science (IF 41.845) Pub Date : 2020-06-19
    Wonchull Kang,Chi Chung Lee,Andrew J Jasniewski,Markus W Ribbe,Yilin Hu

    The enzyme nitrogenase uses a suite of complex metallocofactors to reduce dinitrogen (N2) to ammonia. Mechanistic details of this reaction remain sparse. We report a 1.83-angstrom crystal structure of the nitrogenase molybdenum-iron (MoFe) protein captured under physiological N2 turnover conditions. This structure reveals asymmetric displacements of the cofactor belt sulfurs (S2B or S3A and S5A) with

    更新日期:2020-06-19
  • Information arms race explains plant-herbivore chemical communication in ecological communities.
    Science (IF 41.845) Pub Date : 2020-06-19
    Pengjuan Zu,Karina Boege,Ek Del-Val,Meredith C Schuman,Philip C Stevenson,Alejandro Zaldivar-Riverón,Serguei Saavedra

    Plants emit an extraordinary diversity of chemicals that provide information about their identity and mediate their interactions with insects. However, most studies of this have focused on a few model species in controlled environments, limiting our capacity to understand plant-insect chemical communication in ecological communities. Here, by integrating information theory with ecological and evolutionary

    更新日期:2020-06-19
  • T cells with dysfunctional mitochondria induce multimorbidity and premature senescence.
    Science (IF 41.845) Pub Date : 2020-06-19
    Gabriela Desdín-Micó,Gonzalo Soto-Heredero,Juan Francisco Aranda,Jorge Oller,Elisa Carrasco,Enrique Gabandé-Rodríguez,Eva Maria Blanco,Arantzazu Alfranca,Lorena Cussó,Manuel Desco,Borja Ibañez,Arancha R Gortazar,Pablo Fernández-Marcos,Maria N Navarro,Bruno Hernaez,Antonio Alcamí,Francesc Baixauli,María Mittelbrunn

    The effect of immunometabolism on age-associated diseases remains uncertain. In this work, we show that T cells with dysfunctional mitochondria owing to mitochondrial transcription factor A (TFAM) deficiency act as accelerators of senescence. In mice, these cells instigate multiple aging-related features, including metabolic, cognitive, physical, and cardiovascular alterations, which together result

    更新日期:2020-06-19
  • Measles virus and rinderpest virus divergence dated to the sixth century BCE.
    Science (IF 41.845) Pub Date : 2020-06-19
    Ariane Düx,Sebastian Lequime,Livia Victoria Patrono,Bram Vrancken,Sengül Boral,Jan F Gogarten,Antonia Hilbig,David Horst,Kevin Merkel,Baptiste Prepoint,Sabine Santibanez,Jasmin Schlotterbeck,Marc A Suchard,Markus Ulrich,Navena Widulin,Annette Mankertz,Fabian H Leendertz,Kyle Harper,Thomas Schnalke,Philippe Lemey,Sébastien Calvignac-Spencer

    Many infectious diseases are thought to have emerged in humans after the Neolithic revolution. Although it is broadly accepted that this also applies to measles, the exact date of emergence for this disease is controversial. We sequenced the genome of a 1912 measles virus and used selection-aware molecular clock modeling to determine the divergence date of measles virus and rinderpest virus. This divergence

    更新日期:2020-06-19
  • Rapid implementation of mobile technology for real-time epidemiology of COVID-19.
    Science (IF 41.845) Pub Date : 2020-06-19
    David A Drew,Long H Nguyen,Claire J Steves,Cristina Menni,Maxim Freydin,Thomas Varsavsky,Carole H Sudre,M Jorge Cardoso,Sebastien Ourselin,Jonathan Wolf,Tim D Spector,Andrew T Chan,

    The rapid pace of the coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) presents challenges to the robust collection of population-scale data to address this global health crisis. We established the COronavirus Pandemic Epidemiology (COPE) Consortium to unite scientists with expertise in big data research and epidemiology to develop

    更新日期:2020-06-19
  • 3D fault architecture controls the dynamism of earthquake swarms.
    Science (IF 41.845) Pub Date : 2020-06-19
    Zachary E Ross,Elizabeth S Cochran,Daniel T Trugman,Jonathan D Smith

    The vibrant evolutionary patterns made by earthquake swarms are incompatible with standard, effectively two-dimensional (2D) models for general fault architecture. We leverage advances in earthquake monitoring with a deep-learning algorithm to image a fault zone hosting a 4-year-long swarm in southern California. We infer that fluids are naturally injected into the fault zone from below and diffuse

    更新日期:2020-06-19
  • Microfluidic electrochemistry for single-electron transfer redox-neutral reactions.
    Science (IF 41.845) Pub Date : 2020-06-19
    Yiming Mo,Zhaohong Lu,Girish Rughoobur,Prashant Patil,Neil Gershenfeld,Akintunde I Akinwande,Stephen L Buchwald,Klavs F Jensen

    Electrochemistry offers opportunities to promote single-electron transfer (SET) redox-neutral chemistries similar to those recently discovered using visible-light photocatalysis but without the use of an expensive photocatalyst. Herein, we introduce a microfluidic redox-neutral electrochemistry (μRN-eChem) platform that has broad applicability to SET chemistry, including radical-radical cross-coupling

    更新日期:2020-06-19
  • Making ultrastrong steel tough by grain-boundary delamination.
    Science (IF 41.845) Pub Date : 2020-06-19
    L Liu,Qin Yu,Z Wang,Jon Ell,M X Huang,Robert O Ritchie

    Developing ultrahigh-strength steels that are ductile, fracture resistant, and cost effective would be attractive for a variety of structural applications. We show that improved fracture resistance in a steel with an ultrahigh yield strength of nearly 2 gigapascals can be achieved by activating delamination toughening coupled with transformation-induced plasticity. Delamination toughening associated

    更新日期:2020-06-19
  • Landscape-scale forest loss as a catalyst of population and biodiversity change.
    Science (IF 41.845) Pub Date : 2020-06-19
    Gergana N Daskalova,Isla H Myers-Smith,Anne D Bjorkman,Shane A Blowes,Sarah R Supp,Anne E Magurran,Maria Dornelas

    Global biodiversity assessments have highlighted land-use change as a key driver of biodiversity change. However, there is little empirical evidence of how habitat transformations such as forest loss and gain are reshaping biodiversity over time. We quantified how change in forest cover has influenced temporal shifts in populations and ecological assemblages from 6090 globally distributed time series

    更新日期:2020-06-19
  • Different genetic barriers for resistance to HA stem antibodies in influenza H3 and H1 viruses.
    Science (IF 41.845) Pub Date : 2020-06-19
    Nicholas C Wu,Andrew J Thompson,Juhye M Lee,Wen Su,Britni M Arlian,Jia Xie,Richard A Lerner,Hui-Ling Yen,Jesse D Bloom,Ian A Wilson

    The discovery and characterization of broadly neutralizing human antibodies (bnAbs) to the highly conserved stem region of influenza hemagglutinin (HA) have contributed to considerations of a universal influenza vaccine. However, the potential for resistance to stem bnAbs also needs to be more thoroughly evaluated. Using deep mutational scanning, with a focus on epitope residues, we found that the

    更新日期:2020-06-19
  • Structure-based design of antiviral drug candidates targeting the SARS-CoV-2 main protease.
    Science (IF 41.845) Pub Date : 2020-06-19
    Wenhao Dai,Bing Zhang,Xia-Ming Jiang,Haixia Su,Jian Li,Yao Zhao,Xiong Xie,Zhenming Jin,Jingjing Peng,Fengjiang Liu,Chunpu Li,You Li,Fang Bai,Haofeng Wang,Xi Cheng,Xiaobo Cen,Shulei Hu,Xiuna Yang,Jiang Wang,Xiang Liu,Gengfu Xiao,Hualiang Jiang,Zihe Rao,Lei-Ke Zhang,Yechun Xu,Haitao Yang,Hong Liu

    SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) is the etiological agent responsible for the global COVID-19 (coronavirus disease 2019) outbreak. The main protease of SARS-CoV-2, Mpro, is a key enzyme that plays a pivotal role in mediating viral replication and transcription. We designed and synthesized two lead compounds (11a and 11b) targeting Mpro. Both exhibited excellent inhibitory

    更新日期:2020-06-19
  • Human-specific ARHGAP11B increases size and folding of primate neocortex in the fetal marmoset.
    Science (IF 41.845) Pub Date : 2020-06-18
    Michael Heide,Christiane Haffner,Ayako Murayama,Yoko Kurotaki,Haruka Shinohara,Hideyuki Okano,Erika Sasaki,Wieland B Huttner

    The neocortex has expanded during mammalian evolution. Overexpression studies in developing mouse and ferret neocortex have implicated the human-specific gene ARHGAP11B in neocortical expansion, but the relevance for primate evolution has been unclear. Here, we provide functional evidence that ARHGAP11B causes expansion of the primate neocortex. ARHGAP11B expressed in fetal neocortex of the common

    更新日期:2020-06-19
  • Direct reversible decarboxylation from stable organic acids in dimethylformamide solution.
    Science (IF 41.845) Pub Date : 2020-06-18
    Duanyang Kong,Patrick J Moon,Erica K J Lui,Odey Bsharat,Rylan J Lundgren

    Many classical and emerging methodologies in organic chemistry rely on CO2 extrusion to generate reactive intermediates for bond-forming events. Synthetic reactions that involve the microscopic reverse, the carboxylation of reactive intermediates, have conventionally been undertaken using very different conditions. We report that chemically stable C(sp3) carboxylates, such as arylacetic acids and malonate

    更新日期:2020-06-19
  • Cooling and entangling ultracold atoms in optical lattices.
    Science (IF 41.845) Pub Date : 2020-06-18
    Bing Yang,Hui Sun,Chun-Jiong Huang,Han-Yi Wang,Youjin Deng,Han-Ning Dai,Zhen-Sheng Yuan,Jian-Wei Pan

    Scalable, coherent many-body systems can enable the realization of previously unexplored quantum phases and have a potential to exponentially speed up information processing. Here we report the cooling of a quantum simulator with ten thousand atoms and mass production of high-fidelity entangled pairs. In a two-dimensional plane, we cool Mott-insulator samples by immersing them into removable superfluid

    更新日期:2020-06-19
  • Unexpected air pollution with marked emission reductions during the COVID-19 outbreak in China.
    Science (IF 41.845) Pub Date : 2020-06-17
    Tianhao Le,Yuan Wang,Lang Liu,Jiani Yang,Yuk L Yung,Guohui Li,John H Seinfeld

    The absence of motor vehicle traffic and suspended manufacturing during the COVID-19 pandemic in China produced a unique experiment to assess the efficiency of air pollution mitigation. Up to 90% reduction of certain emissions during the city-lockdown period can be identified from satellite and ground-based observations. Unexpectedly, extreme particulate matter levels simultaneously occurred in northern

    更新日期:2020-06-18
  • Potent neutralizing antibodies from COVID-19 patients define multiple targets of vulnerability.
    Science (IF 41.845) Pub Date : 2020-06-15
    Philip J M Brouwer,Tom G Caniels,Karlijn van der Straten,Jonne L Snitselaar,Yoann Aldon,Sandhya Bangaru,Jonathan L Torres,Nisreen M A Okba,Mathieu Claireaux,Gius Kerster,Arthur E H Bentlage,Marlies M van Haaren,Denise Guerra,Judith A Burger,Edith E Schermer,Kirsten D Verheul,Niels van der Velde,Alex van der Kooi,Jelle van Schooten,Mariëlle J van Breemen,Tom P L Bijl,Kwinten Sliepen,Aafke Aartse,Ronald

    The rapid spread of SARS-CoV-2 has a significant impact on global health, travel and economy. Therefore, preventative and therapeutic measures are urgently needed. Here, we isolated monoclonal antibodies from three convalescent COVID-19 patients using a SARS-CoV-2 stabilized prefusion spike protein. These antibodies had low levels of somatic hypermutation and showed a strong enrichment in VH1-69, VH3-30-3

    更新日期:2020-06-15
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