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  • Maintenance of neural stem cell positional identity by mixed-lineage leukemia 1
    Science (IF 41.037) Pub Date : 2020-04-03
    Ryan N. Delgado, Benjamin Mansky, Sajad Hamid Ahanger, Changqing Lu, Rebecca E. Andersen, Yali Dou, Arturo Alvarez-Buylla, Daniel A. Lim

    Neural stem cells (NSCs) in the developing and postnatal brain have distinct positional identities that dictate the types of neurons they generate. Although morphogens initially establish NSC positional identity in the neural tube, it is unclear how such regional differences are maintained as the forebrain grows much larger and more anatomically complex. We found that the maintenance of NSC positional

    更新日期:2020-04-03
  • Endoplasmic reticulum–associated degradation regulates mitochondrial dynamics in brown adipocytes
    Science (IF 41.037) Pub Date : 2020-04-03
    Zhangsen Zhou, Mauricio Torres, Haibo Sha, Christopher J. Halbrook, Françoise Van den Bergh, Rachel B. Reinert, Tatsuya Yamada, Siwen Wang, Yingying Luo, Allen H. Hunter, Chunqing Wang, Thomas H. Sanderson, Meilian Liu, Aaron Taylor, Hiromi Sesaki, Costas A. Lyssiotis, Jun Wu, Sander Kersten, Daniel A. Beard, Ling Qi

    The endoplasmic reticulum (ER) engages mitochondria at specialized ER domains known as mitochondria-associated membranes (MAMs). Here, we used three-dimensional high-resolution imaging to investigate the formation of pleomorphic “megamitochondria” with altered MAMs in brown adipocytes lacking the Sel1L-Hrd1 protein complex of ER-associated protein degradation (ERAD). Mice with ERAD deficiency in brown

    更新日期:2020-04-03
  • Critical differences in 3D atomic structure of individual ligand-protected nanocrystals in solution
    Science (IF 41.037) Pub Date : 2020-04-03
    Byung Hyo Kim, Junyoung Heo, Sungin Kim, Cyril F. Reboul, Hoje Chun, Dohun Kang, Hyeonhu Bae, Hyejeong Hyun, Jongwoo Lim, Hoonkyung Lee, Byungchan Han, Taeghwan Hyeon, A. Paul Alivisatos, Peter Ercius, Hans Elmlund, Jungwon Park

    Precise three-dimensional (3D) atomic structure determination of individual nanocrystals is a prerequisite for understanding and predicting their physical properties. Nanocrystals from the same synthesis batch display what are often presumed to be small but possibly important differences in size, lattice distortions, and defects, which can only be understood by structural characterization with high

    更新日期:2020-04-03
  • An artificial impact on the asteroid (162173) Ryugu formed a crater in the gravity-dominated regime
    Science (IF 41.037) Pub Date : 2020-04-03
    M. Arakawa, T. Saiki, K. Wada, K. Ogawa, T. Kadono, K. Shirai, H. Sawada, K. Ishibashi, R. Honda, N. Sakatani, Y. Iijima, C. Okamoto, H. Yano, Y. Takagi, M. Hayakawa, P. Michel, M. Jutzi, Y. Shimaki, S. Kimura, Y. Mimasu, T. Toda, H. Imamura, S. Nakazawa, H. Hayakawa, S. Sugita, T. Morota, S. Kameda, E. Tatsumi, Y. Cho, K. Yoshioka, Y. Yokota, M. Matsuoka, M. Yamada, T. Kouyama, C. Honda, Y. Tsuda

    The Hayabusa2 spacecraft investigated the small asteroid Ryugu, which has a rubble-pile structure. We describe an impact experiment on Ryugu using Hayabusa2’s Small Carry-on Impactor. The impact produced an artificial crater with a diameter >10 meters, which has a semicircular shape, an elevated rim, and a central pit. Images of the impact and resulting ejecta were recorded by the Deployable CAMera

    更新日期:2020-04-03
  • Extreme tensile strain states in La0.7Ca0.3MnO3 membranes
    Science (IF 41.037) Pub Date : 2020-04-03
    Seung Sae Hong, Mingqiang Gu, Manish Verma, Varun Harbola, Bai Yang Wang, Di Lu, Arturas Vailionis, Yasuyuki Hikita, Rossitza Pentcheva, James M. Rondinelli, Harold Y. Hwang

    A defining feature of emergent phenomena in complex oxides is the competition and cooperation between ground states. In manganites, the balance between metallic and insulating phases can be tuned by the lattice; extending the range of lattice control would enhance the ability to access other phases. We stabilized uniform extreme tensile strain in nanoscale La0.7Ca0.3MnO3 membranes, exceeding 8% uniaxially

    更新日期:2020-04-03
  • A slip law for glaciers on deformable beds
    Science (IF 41.037) Pub Date : 2020-04-03
    Lucas K. Zoet, Neal R. Iverson

    Slip of marine-terminating ice streams over beds of deformable till is responsible for most of the contribution of the West Antarctic Ice Sheet to sea level rise. Flow models of the ice sheet and till-bedded glaciers elsewhere require a law that relates slip resistance, slip velocity, and water pressure at the bed. We present results of experiments in which pressurized ice at its melting temperature

    更新日期:2020-04-03
  • De novo design of protein logic gates
    Science (IF 41.037) Pub Date : 2020-04-03
    Zibo Chen, Ryan D. Kibler, Andrew Hunt, Florian Busch, Jocelynn Pearl, Mengxuan Jia, Zachary L. VanAernum, Basile I. M. Wicky, Galen Dods, Hanna Liao, Matthew S. Wilken, Christie Ciarlo, Shon Green, Hana El-Samad, John Stamatoyannopoulos, Vicki H. Wysocki, Michael C. Jewett, Scott E. Boyken, David Baker

    The design of modular protein logic for regulating protein function at the posttranscriptional level is a challenge for synthetic biology. Here, we describe the design of two-input AND, OR, NAND, NOR, XNOR, and NOT gates built from de novo–designed proteins. These gates regulate the association of arbitrary protein units ranging from split enzymes to transcriptional machinery in vitro, in yeast and

    更新日期:2020-04-03
  • Cysteine depletion induces pancreatic tumor ferroptosis in mice
    Science (IF 41.037) Pub Date : 2020-04-03
    Michael A. Badgley, Daniel M. Kremer, H. Carlo Maurer, Kathleen E. DelGiorno, Ho-Joon Lee, Vinee Purohit, Irina R. Sagalovskiy, Alice Ma, Jonathan Kapilian, Christina E. M. Firl, Amanda R. Decker, Steve A. Sastra, Carmine F. Palermo, Leonardo R. Andrade, Peter Sajjakulnukit, Li Zhang, Zachary P. Tolstyka, Tal Hirschhorn, Candice Lamb, Tong Liu, Wei Gu, E. Scott Seeley, Everett Stone, George Georgiou

    Ferroptosis is a form of cell death that results from the catastrophic accumulation of lipid reactive oxygen species (ROS). Oncogenic signaling elevates lipid ROS production in many tumor types and is counteracted by metabolites that are derived from the amino acid cysteine. In this work, we show that the import of oxidized cysteine (cystine) via system xC– is a critical dependency of pancreatic ductal

    更新日期:2020-04-03
  • Facial expressions of emotion states and their neuronal correlates in mice
    Science (IF 41.037) Pub Date : 2020-04-03
    Nejc Dolensek, Daniel A. Gehrlach, Alexandra S. Klein, Nadine Gogolla

    Understanding the neurobiological underpinnings of emotion relies on objective readouts of the emotional state of an individual, which remains a major challenge especially in animal models. We found that mice exhibit stereotyped facial expressions in response to emotionally salient events, as well as upon targeted manipulations in emotion-relevant neuronal circuits. Facial expressions were classified

    更新日期:2020-04-03
  • A plant’s diet, surviving in a variable nutrient environment
    Science (IF 41.037) Pub Date : 2020-04-03
    Giles E. D. Oldroyd, Ottoline Leyser

    As primary producers, plants rely on a large aboveground surface area to collect carbon dioxide and sunlight and a large underground surface area to collect the water and mineral nutrients needed to support their growth and development. Accessibility of the essential nutrients nitrogen (N) and phosphorus (P) in the soil is affected by many factors that create a variable spatiotemporal landscape of

    更新日期:2020-04-03
  • Structural basis for allosteric PARP-1 retention on DNA breaks
    Science (IF 41.037) Pub Date : 2020-04-03
    Levani Zandarashvili, Marie-France Langelier, Uday Kiran Velagapudi, Mark A. Hancock, Jamin D. Steffen, Ramya Billur, Zain M. Hannan, Andrew J. Wicks, Dragomir B. Krastev, Stephen J. Pettitt, Christopher J. Lord, Tanaji T. Talele, John M. Pascal, Ben E. Black

    The success of poly(ADP-ribose) polymerase–1 (PARP-1) inhibitors (PARPi) to treat cancer relates to their ability to trap PARP-1 at the site of a DNA break. Although different forms of PARPi all target the catalytic center of the enzyme, they have variable abilities to trap PARP-1. We found that several structurally distinct PARPi drive PARP-1 allostery to promote release from a DNA break. Other inhibitors

    更新日期:2020-04-03
  • Contemporaneity of Australopithecus, Paranthropus, and early Homo erectus in South Africa
    Science (IF 41.037) Pub Date : 2020-04-03
    Andy I. R. Herries, Jesse M. Martin, A. B. Leece, Justin W. Adams, Giovanni Boschian, Renaud Joannes-Boyau, Tara R. Edwards, Tom Mallett, Jason Massey, Ashleigh Murszewski, Simon Neubauer, Robyn Pickering, David S. Strait, Brian J. Armstrong, Stephanie Baker, Matthew V. Caruana, Tim Denham, John Hellstrom, Jacopo Moggi-Cecchi, Simon Mokobane, Paul Penzo-Kajewski, Douglass S. Rovinsky, Gary T. Schwartz

    Understanding the extinction of Australopithecus and origins of Paranthropus and Homo in South Africa has been hampered by the perceived complex geological context of hominin fossils, poor chronological resolution, and a lack of well-preserved early Homo specimens. We describe, date, and contextualize the discovery of two hominin crania from Drimolen Main Quarry in South Africa. At ~2.04 million to

    更新日期:2020-04-03
  • Temporal integration of mitogen history in mother cells controls proliferation of daughter cells
    Science (IF 41.037) Pub Date : 2020-04-02
    Mingwei Min, Yao Rong, Chengzhe Tian, Sabrina Spencer

    Multi-cellular organisms use mitogens to regulate cell proliferation, yet how fluctuating mitogenic signals are converted into proliferation-quiescence decisions is poorly understood. Here we combine live-cell imaging with temporally controlled perturbations to determine the timescale and mechanisms underlying the system. Contrary to the textbook model that cells only sense mitogen availability in

    更新日期:2020-04-03
  • Evolving epidemiology of poliovirus serotype 2 following withdrawal of the type 2 oral poliovirus vaccine
    Science (IF 41.037) Pub Date : 2020-03-31
    G. R. Macklin, K. M. O’Reilly, N. C. Grassly, W. J. Edmunds, O. Mach, R. Santhana Gopala Krishnan, A. Voorman, J. F. Vertefeuille, J. Abdelwahab, N. Gumede, A. Goel, S. Sosler, J. Sever, A. S. Bandyopadhyay, M. A. Pallansch, R. Nandy, P. Mkanda, O. M. Diop, R. W. Sutter

    While there have been no cases of type-2 wild poliovirus for over 20 years, transmission of type-2 vaccine-derived poliovirus (VDPV2) and associated paralytic cases in several continents represent a threat to eradication. The withdrawal of the type-2 component of oral poliovirus vaccine (OPV2) was implemented in April 2016 to stop VDPV2 emergence and secure eradication of all poliovirus type 2. Globally

    更新日期:2020-04-01
  • Quantifying SARS-CoV-2 transmission suggests epidemic control with digital contact tracing
    Science (IF 41.037) Pub Date : 2020-03-31
    Luca Ferretti, Chris Wymant, Michelle Kendall, Lele Zhao, Anel Nurtay, Lucie Abeler-Dörner, Michael Parker, David Bonsall, Christophe Fraser

    The newly emergent human virus SARS-CoV-2 is resulting in high fatality rates and incapacitated health systems. Preventing further transmission is a priority. We analyzed key parameters of epidemic spread to estimate the contribution of different transmission routes and determine requirements for case isolation and contact-tracing needed to stop the epidemic. We conclude that viral spread is too fast

    更新日期:2020-03-31
  • An investigation of transmission control measures during the first 50 days of the COVID-19 epidemic in China
    Science (IF 41.037) Pub Date : 2020-03-31
    Huaiyu Tian, Yonghong Liu, Yidan Li, Chieh-Hsi Wu, Bin Chen, Moritz U. G. Kraemer, Bingying Li, Jun Cai, Bo Xu, Qiqi Yang, Ben Wang, Peng Yang, Yujun Cui, Yimeng Song, Pai Zheng, Quanyi Wang, Ottar N. Bjornstad, Ruifu Yang, Bryan T. Grenfell, Oliver G. Pybus, Christopher Dye

    Responding to an outbreak of a novel coronavirus (agent of COVID-19) in December 2019, China banned travel to and from Wuhan city on 23 January and implemented a national emergency response. We investigated the spread and control of COVID-19 using a unique data set including case reports, human movement and public health interventions. The Wuhan shutdown was associated with the delayed arrival of COVID-19

    更新日期:2020-03-31
  • Structural basis for the recognition of SARS-CoV-2 by full-length human ACE2
    Science (IF 41.037) Pub Date : 2020-03-27
    Renhong Yan, Yuanyuan Zhang, Yaning Li, Lu Xia, Yingying Guo, Qiang Zhou

    Angiotensin-converting enzyme 2 (ACE2) is the cellular receptor for severe acute respiratory syndrome–coronavirus (SARS-CoV) and the new coronavirus (SARS-CoV-2) that is causing the serious coronavirus disease 2019 (COVID-19) epidemic. Here, we present cryo–electron microscopy structures of full-length human ACE2 in the presence of the neutral amino acid transporter B0AT1 with or without the receptor

    更新日期:2020-03-27
  • The evolutionary dynamics and fitness landscape of clonal hematopoiesis
    Science (IF 41.037) Pub Date : 2020-03-27
    Caroline J. Watson, A. L. Papula, Gladys Y. P. Poon, Wing H. Wong, Andrew L. Young, Todd E. Druley, Daniel S. Fisher, Jamie R. Blundell

    Somatic mutations acquired in healthy tissues as we age are major determinants of cancer risk. Whether variants confer a fitness advantage or rise to detectable frequencies by chance remains largely unknown. Blood sequencing data from ~50,000 individuals reveal how mutation, genetic drift, and fitness shape the genetic diversity of healthy blood (clonal hematopoiesis). We show that positive selection

    更新日期:2020-03-27
  • Type-II Ising pairing in few-layer stanene.
    Science (IF 41.037) Pub Date : 2020-03-12
    Joseph Falson,Yong Xu,Menghan Liao,Yunyi Zang,Kejing Zhu,Chong Wang,Zetao Zhang,Hongchao Liu,Wenhui Duan,Ke He,Haiwen Liu,Jurgen H Smet,Ding Zhang,Qi-Kun Xue

    Spin-orbit coupling has proven indispensable in realizing topological materials and more recently Ising pairing in two-dimensional superconductors. This pairing mechanism relies on inversion symmetry breaking and sustains anomalously large in-plane polarizing magnetic fields whose upper limit is predicted to diverge at low temperatures. Here we show that the recently discovered superconductor few-layer

    更新日期:2020-03-27
  • Frequency-comb spectroscopy on pure quantum states of a single molecular ion
    Science (IF 41.037) Pub Date : 2020-03-27
    C. W. Chou, A. L. Collopy, C. Kurz, Y. Lin, M. E. Harding, P. N. Plessow, T. Fortier, S. Diddams, D. Leibfried, D. R. Leibrandt

    Spectroscopy is a powerful tool for studying molecules and is commonly performed on large thermal molecular ensembles that are perturbed by motional shifts and interactions with the environment and one another, resulting in convoluted spectra and limited resolution. Here, we use quantum-logic techniques to prepare a trapped molecular ion in a single quantum state, drive terahertz rotational transitions

    更新日期:2020-03-27
  • Observation of dynamical fermionization
    Science (IF 41.037) Pub Date : 2020-03-27
    Joshua M. Wilson, Neel Malvania, Yuan Le, Yicheng Zhang, Marcos Rigol, David S. Weiss

    The wave function of a Tonks-Girardeau (T-G) gas of strongly interacting bosons in one dimension maps onto the absolute value of the wave function of a noninteracting Fermi gas. Although this fermionization makes many aspects of the two gases identical, their equilibrium momentum distributions are quite different. We observed dynamical fermionization, where the momentum distribution of a T-G gas evolves

    更新日期:2020-03-27
  • The dark matter interpretation of the 3.5-keV line is inconsistent with blank-sky observations
    Science (IF 41.037) Pub Date : 2020-03-27
    Christopher Dessert, Nicholas L. Rodd, Benjamin R. Safdi

    Observations of nearby galaxies and galaxy clusters have reported an unexpected x-ray emission line around 3.5 kilo–electron volts (keV). Proposals to explain this line include decaying dark matter—in particular, that the decay of sterile neutrinos with a mass around 7 keV could match the available data. If this interpretation is correct, the 3.5-keV line should also be emitted by dark matter in the

    更新日期:2020-03-27
  • Deregulation of ribosomal protein expression and translation promotes breast cancer metastasis.
    Science (IF 41.037) Pub Date : 2020-03-27
    Richard Y Ebright,Sooncheol Lee,Ben S Wittner,Kira L Niederhoffer,Benjamin T Nicholson,Aditya Bardia,Samuel Truesdell,Devon F Wiley,Benjamin Wesley,Selena Li,Andy Mai,Nicola Aceto,Nicole Vincent-Jordan,Annamaria Szabolcs,Brian Chirn,Johannes Kreuzer,Valentine Comaills,Mark Kalinich,Wilhelm Haas,David T Ting,Mehmet Toner,Shobha Vasudevan,Daniel A Haber,Shyamala Maheswaran,Douglas S Micalizzi

    Circulating tumor cells (CTCs) are shed into the bloodstream from primary tumors, but only a small subset generates metastases. We conducted an in vivo genome-wide CRISPR activation screen in breast cancer patient-derived CTCs to identify genes that promote their distant metastasis in mice. Genes coding for ribosomal proteins and regulators of translation were enriched in this screen. Overexpression

    更新日期:2020-03-27
  • Ultrahigh-field 67Zn NMR reveals short-range disorder in zeolitic imidazolate framework glasses
    Science (IF 41.037) Pub Date : 2020-03-27
    Rasmus S. K. Madsen, Ang Qiao, Jishnu Sen, Ivan Hung, Kuizhi Chen, Zhehong Gan, Sabyasachi Sen, Yuanzheng Yue

    The structure of melt-quenched zeolitic imidazole framework (ZIF) glasses can provide insights into their glass-formation mechanism. We directly detected short-range disorder in ZIF glasses using ultrahigh-field zinc-67 solid-state nuclear magnetic resonance spectroscopy. Two distinct Zn sites characteristic of the parent crystals transformed upon melting into a single tetrahedral site with a broad

    更新日期:2020-03-27
  • No consistent ENSO response to volcanic forcing over the last millennium
    Science (IF 41.037) Pub Date : 2020-03-27
    Sylvia G. Dee, Kim M. Cobb, Julien Emile-Geay, Toby R. Ault, R. Lawrence Edwards, Hai Cheng, Christopher D. Charles

    The El Niño–Southern Oscillation (ENSO) shapes global climate patterns yet its sensitivity to external climate forcing remains uncertain. Modeling studies suggest that ENSO is sensitive to sulfate aerosol forcing associated with explosive volcanism but observational support for this effect remains ambiguous. Here, we used absolutely dated fossil corals from the central tropical Pacific to gauge ENSO’s

    更新日期:2020-03-27
  • Peptide signaling for drought-induced tomato flower drop
    Science (IF 41.037) Pub Date : 2020-03-27
    S. Reichardt, H.-P. Piepho, A. Stintzi, A. Schaller

    The premature abscission of flowers and fruits limits crop yield under environmental stress. Drought-induced flower drop in tomato plants was found to be regulated by phytosulfokine (PSK), a peptide hormone previously known for its growth-promoting and immune-modulating activities. PSK formation in response to drought stress depends on phytaspase 2, a subtilisin-like protease of the phytaspase subtype

    更新日期:2020-03-27
  • Interglacial instability of North Atlantic Deep Water ventilation
    Science (IF 41.037) Pub Date : 2020-03-27
    Eirik Vinje Galaasen, Ulysses S. Ninnemann, Augustin Kessler, Nil Irvalı, Yair Rosenthal, Jerry Tjiputra, Nathaëlle Bouttes, Didier M. Roche, Helga (Kikki) F. Kleiven, David A. Hodell

    Disrupting North Atlantic Deep Water (NADW) ventilation is a key concern in climate projections. We use (sub)centennially resolved bottom water δ13C records that span the interglacials of the last 0.5 million years to assess the frequency of and the climatic backgrounds capable of triggering large NADW reductions. Episodes of reduced NADW in the deep Atlantic, similar in magnitude to glacial events

    更新日期:2020-03-27
  • Flux-induced topological superconductivity in full-shell nanowires
    Science (IF 41.037) Pub Date : 2020-03-27
    S. Vaitiekėnas, G. W. Winkler, B. van Heck, T. Karzig, M.-T. Deng, K. Flensberg, L. I. Glazman, C. Nayak, P. Krogstrup, R. M. Lutchyn, C. M. Marcus

    Hybrid semiconductor-superconductor nanowires have emerged as a promising platform for realizing topological superconductivity (TSC). Here, we present a route to TSC using magnetic flux applied to a full superconducting shell surrounding a semiconducting nanowire core. Tunneling into the core reveals a hard induced gap near zero applied flux, corresponding to zero phase winding, and a gapped region

    更新日期:2020-03-27
  • Last Interglacial Iberian Neandertals as fisher-hunter-gatherers
    Science (IF 41.037) Pub Date : 2020-03-27
    J. Zilhão, D. E. Angelucci, M. Araújo Igreja, L. J. Arnold, E. Badal, P. Callapez, J. L. Cardoso, F. d’Errico, J. Daura, M. Demuro, M. Deschamps, C. Dupont, S. Gabriel, D. L. Hoffmann, P. Legoinha, H. Matias, A. M. Monge Soares, M. Nabais, P. Portela, A. Queffelec, F. Rodrigues, P. Souto

    Marine food–reliant subsistence systems such as those in the African Middle Stone Age (MSA) were not thought to exist in Europe until the much later Mesolithic. Whether this apparent lag reflects taphonomic biases or behavioral distinctions between archaic and modern humans remains much debated. Figueira Brava cave, in the Arrábida range (Portugal), provides an exceptionally well preserved record of

    更新日期:2020-03-27
  • The historical roots of economic development
    Science (IF 41.037) Pub Date : 2020-03-27
    Nathan Nunn

    This article reviews an emerging area of research within economics that seeks to better understand contemporary economic outcomes by taking a historical perspective. The field has established that many of the contemporary differences in comparative economic development have their roots in the distant past. The insights gained from this literature are not only of academic importance but also useful

    更新日期:2020-03-27
  • Topological funneling of light
    Science (IF 41.037) Pub Date : 2020-03-26
    Sebastian Weidemann, Mark Kremer, Tobias Helbig, Tobias Hofmann, Alexander Stegmaier, Martin Greiter, Ronny Thomale, Alexander Szameit

    Dissipation is a general feature of non-Hermitian systems. But rather than being an unavoidable nuisance, non-Hermiticity can be precisely controlled and, hence, used for sophisticated applications such as optical sensors with enhanced sensitivity. In our work, we implement a non-Hermitian photonic mesh lattice by tailoring the anisotropy of the inter-site coupling. The appearance of an interface results

    更新日期:2020-03-27
  • Transcription polymerase–catalyzed emergence of novel RNA replicons
    Science (IF 41.037) Pub Date : 2020-03-26
    Nimit Jain, Lucas R. Blauch, Michal R. Szymanski, Rhiju Das, Sindy K. Y. Tang, Y. Whitney Yin, Andrew Z. Fire

    Transcription polymerases can exhibit an unusual mode of regenerating certain RNA templates from RNA, yielding systems that can replicate and evolve with RNA as information carrier. Two classes of pathogenic RNAs (Hepatitis delta virus in animals and viroids in plants) are copied by host transcription polymerases. Using in vitro RNA replication by the transcription polymerase of T7 bacteriophage as

    更新日期:2020-03-27
  • Unconstrained genome targeting with near-PAMless engineered CRISPR-Cas9 variants
    Science (IF 41.037) Pub Date : 2020-03-26
    Russell T. Walton, Kathleen A. Christie, Madelynn N. Whittaker, Benjamin P. Kleinstiver

    Manipulation of DNA by CRISPR-Cas enzymes requires the recognition of a protospacer adjacent motif (PAM), limiting target site recognition to a subset of sequences. To remove this constraint, we engineered variants of Streptococcus pyogenes Cas9 (SpCas9) to eliminate the NGG PAM requirement. We developed a variant named SpG capable of targeting an expanded set of NGN PAMs, and further optimized this

    更新日期:2020-03-27
  • Structure of a trapped radical transfer pathway within a ribonucleotide reductase holocomplex
    Science (IF 41.037) Pub Date : 2020-03-26
    Gyunghoon Kang, Alexander T. Taguchi, JoAnne Stubbe, Catherine L. Drennan

    Ribonucleotide reductases (RNRs) are a diverse family of enzymes that are alone capable of generating 2′-deoxynucleotides de novo and are thus critical in DNA biosynthesis and repair. The nucleotide reduction reaction in all RNRs requires the generation of a transient active site thiyl radical, and in class I RNRs this process involves a long-range radical transfer between two subunits, α and β. Due

    更新日期:2020-03-27
  • Efficient, stable silicon tandem cells enabled by anion-engineered wide-bandgap perovskites
    Science (IF 41.037) Pub Date : 2020-03-26
    Daehan Kim, Hee Joon Jung, Ik Jae Park, Bryon W. Larson, Sean P. Dunfield, Chuanxiao Xiao, Jekyung Kim, Jinhui Tong, Passarut Boonmongkolras, Su Geun Ji, Fei Zhang, Seong Ryul Pae, Minkyu Kim, Seok Beom Kang, Vinayak Dravid, Joseph J. Berry, Jin Young Kim, Kai Zhu, Dong Hoe Kim, Byungha Shin

    Maximizing the power conversion efficiency (PCE) of perovskite-silicon tandem solar cells that can exceed the Shockley-Queisser single-cell limit requires a high performing, stable perovskite top cell with a wide band gap. We developed a stable perovskite solar cell with a band gap of ~1.7 electron volt that retained over 80% of its initial PCE of 20.7% after 1000 hours of continuous illumination.

    更新日期:2020-03-27
  • The effect of human mobility and control measures on the COVID-19 epidemic in China
    Science (IF 41.037) Pub Date : 2020-03-25
    Moritz U. G. Kraemer, Chia-Hung Yang, Bernardo Gutierrez, Chieh-Hsi Wu, Brennan Klein, David M. Pigott, Open COVID-19 Data Working Group†, Louis du Plessis, Nuno R. Faria, Ruoran Li, William P. Hanage, John S. Brownstein, Maylis Layan, Alessandro Vespignani, Huaiyu Tian, Christopher Dye, Oliver G. Pybus, Samuel V. Scarpino

    The ongoing COVID-19 outbreak expanded rapidly throughout China. Major behavioral, clinical, and state interventions have been undertaken to mitigate the epidemic and prevent the persistence of the virus in human populations in China and worldwide. It remains unclear how these unprecedented interventions, including travel restrictions, affected COVID-19 spread in China. We use real-time mobility data

    更新日期:2020-03-26
  • Substantial undocumented infection facilitates the rapid dissemination of novel coronavirus (SARS-CoV2)
    Science (IF 41.037) Pub Date : 2020-03-25
    Ruiyun Li, Sen Pei, Bin Chen, Yimeng Song, Tao Zhang, Wan Yang, Jeffrey Shaman

    Estimation of the prevalence and contagiousness of undocumented novel coronavirus (SARS-CoV2) infections is critical for understanding the overall prevalence and pandemic potential of this disease. Here we use observations of reported infection within China, in conjunction with mobility data, a networked dynamic metapopulation model and Bayesian inference, to infer critical epidemiological characteristics

    更新日期:2020-03-26
  • Crystal structure of SARS-CoV-2 main protease provides a basis for design of improved α-ketoamide inhibitors
    Science (IF 41.037) Pub Date : 2020-03-23
    Linlin Zhang, Daizong Lin, Xinyuanyuan Sun, Ute Curth, Christian Drosten, Lucie Sauerhering, Stephan Becker, Katharina Rox, Rolf Hilgenfeld

    The COVID-19 pandemic caused by SARS-CoV-2 is a global health emergency. An attractive drug target among coronaviruses is the main protease (Mpro, 3CLpro), due to its essential role in processing the polyproteins that are translated from the viral RNA. We report the X-ray structures of the unliganded SARS-CoV-2 Mpro and its complex with an α-ketoamide inhibitor. This was derived from a previously designed

    更新日期:2020-03-24
  • History, mass loss, structure, and dynamic behavior of the Antarctic Ice Sheet
    Science (IF 41.037) Pub Date : 2020-03-20
    Robin E. Bell, Helene Seroussi

    Antarctica contains most of Earth’s fresh water stored in two large ice sheets. The more stable East Antarctic Ice Sheet is larger and older, rests on higher topography, and hides entire mountain ranges and ancient lakes. The less stable West Antarctic Ice Sheet is smaller and younger and was formed on what was once a shallow sea. Recent observations made with several independent satellite measurements

    更新日期:2020-03-20
  • The Southern Ocean and its interaction with the Antarctic Ice Sheet
    Science (IF 41.037) Pub Date : 2020-03-20
    David M. Holland, Keith W. Nicholls, Aurora Basinski

    The Southern Ocean exerts a major influence on the mass balance of the Antarctic Ice Sheet, either indirectly, by its influence on air temperatures and winds, or directly, mostly through its effects on ice shelves. How much melting the ocean causes depends on the temperature of the water, which in turn is controlled by the combination of the thermal structure of the surrounding ocean and local ocean

    更新日期:2020-03-20
  • The uncertain future of the Antarctic Ice Sheet
    Science (IF 41.037) Pub Date : 2020-03-20
    Frank Pattyn, Mathieu Morlighem

    The Antarctic Ice Sheet is losing mass at an accelerating pace, and ice loss will likely continue over the coming decades and centuries. Some regions of the ice sheet may reach a tipping point, potentially leading to rates of sea level rise at least an order of magnitude larger than those observed now, owing to strong positive feedbacks in the ice-climate system. How fast and how much Antarctica will

    更新日期:2020-03-20
  • Electrical power generation from moderate-temperature radiative thermal sources.
    Science (IF 41.037) Pub Date : 2020-02-20
    Paul S Davids,Jared Kirsch,Andrew Starbuck,Robert Jarecki,Joshua Shank,David Peters

    Moderate-temperature thermal sources (100-400°C) that radiate waste heat are often the by-product of mechanical work, chemical or nuclear reactions, or information processing. We demonstrate conversion of thermal radiation into electrical power using a bipolar grating-coupled complimentary metal-oxide-silicon (CMOS) tunnel diode. A two-step photon-assisted tunneling charge pumping mechanism results

    更新日期:2020-03-20
  • Structural basis of Gs and Gi recognition by the human glucagon receptor
    Science (IF 41.037) Pub Date : 2020-03-20
    Anna Qiao, Shuo Han, Xinmei Li, Zhixin Li, Peishen Zhao, Antao Dai, Rulve Chang, Linhua Tai, Qiuxiang Tan, Xiaojing Chu, Limin Ma, Thor Seneca Thorsen, Steffen Reedtz-Runge, Dehua Yang, Ming-Wei Wang, Patrick M. Sexton, Denise Wootten, Fei Sun, Qiang Zhao, Beili Wu

    Class B G protein–coupled receptors, an important class of therapeutic targets, signal mainly through the Gs class of heterotrimeric G proteins, although they do display some promiscuity in G protein binding. Using cryo–electron microscopy, we determined the structures of the human glucagon receptor (GCGR) bound to glucagon and distinct classes of heterotrimeric G proteins, Gs or Gi1. These two structures

    更新日期:2020-03-20
  • Resolving spatial and energetic distributions of trap states in metal halide perovskite solar cells
    Science (IF 41.037) Pub Date : 2020-03-20
    Zhenyi Ni, Chunxiong Bao, Ye Liu, Qi Jiang, Wu-Qiang Wu, Shangshang Chen, Xuezeng Dai, Bo Chen, Barry Hartweg, Zhengshan Yu, Zachary Holman, Jinsong Huang

    We report the profiling of spatial and energetic distributions of trap states in metal halide perovskite single-crystalline and polycrystalline solar cells. The trap densities in single crystals varied by five orders of magnitude, with a lowest value of 2 × 1011 per cubic centimeter and most of the deep traps located at crystal surfaces. The charge trap densities of all depths of the interfaces of

    更新日期:2020-03-20
  • Latitudinal effect of vegetation on erosion rates identified along western South America
    Science (IF 41.037) Pub Date : 2020-03-20
    J. Starke, T. A. Ehlers, M. Schaller

    Vegetation influences erosion by stabilizing hillslopes and accelerating weathering, thereby providing a link between the biosphere and Earth’s surface. Previous studies investigating vegetation effects on erosion have proved challenging owing to poorly understood interactions between vegetation and other factors, such as precipitation and surface processes. We address these complexities along 3500

    更新日期:2020-03-20
  • Dopamine promotes cognitive effort by biasing the benefits versus costs of cognitive work
    Science (IF 41.037) Pub Date : 2020-03-20
    A. Westbrook, R. van den Bosch, J. I. Määttä, L. Hofmans, D. Papadopetraki, R. Cools, M. J. Frank

    Stimulants such as methylphenidate are increasingly used for cognitive enhancement but precise mechanisms are unknown. We found that methylphenidate boosts willingness to expend cognitive effort by altering the benefit-to-cost ratio of cognitive work. Willingness to expend effort was greater for participants with higher striatal dopamine synthesis capacity, whereas methylphenidate and sulpiride, a

    更新日期:2020-03-20
  • Golgi-derived PI(4)P-containing vesicles drive late steps of mitochondrial division
    Science (IF 41.037) Pub Date : 2020-03-20
    Shun Nagashima, Luis-Carlos Tábara, Lisa Tilokani, Vincent Paupe, Hanish Anand, Joe H. Pogson, Rodolfo Zunino, Heidi M. McBride, Julien Prudent

    Mitochondrial plasticity is a key regulator of cell fate decisions. Mitochondrial division involves Dynamin-related protein-1 (Drp1) oligomerization, which constricts membranes at endoplasmic reticulum (ER) contact sites. The mechanisms driving the final steps of mitochondrial division are still unclear. Here, we found that microdomains of phosphatidylinositol 4-phosphate [PI(4)P] on trans-Golgi network

    更新日期:2020-03-20
  • Genetically targeted chemical assembly of functional materials in living cells, tissues, and animals
    Science (IF 41.037) Pub Date : 2020-03-20
    Jia Liu, Yoon Seok Kim, Claire E. Richardson, Ariane Tom, Charu Ramakrishnan, Fikri Birey, Toru Katsumata, Shucheng Chen, Cheng Wang, Xiao Wang, Lydia-Marie Joubert, Yuenwen Jiang, Huiliang Wang, Lief E. Fenno, Jeffrey B.-H. Tok, Sergiu P. Pașca, Kang Shen, Zhenan Bao, Karl Deisseroth

    The structural and functional complexity of multicellular biological systems, such as the brain, are beyond the reach of human design or assembly capabilities. Cells in living organisms may be recruited to construct synthetic materials or structures if treated as anatomically defined compartments for specific chemistry, harnessing biology for the assembly of complex functional structures. By integrating

    更新日期:2020-03-20
  • Female toads engaging in adaptive hybridization prefer high-quality heterospecifics as mates
    Science (IF 41.037) Pub Date : 2020-03-20
    Catherine Chen, Karin S. Pfennig

    Hybridization—interbreeding between species—is generally thought to occur randomly between members of two species. Contrary to expectation, female plains spadefoot toads (Spea bombifrons) can increase their evolutionary fitness by preferentially mating with high-quality males of another species, the Mexican spadefoot toad (Spea multiplicata). Aspects of Mexican spadefoot males’ mating calls predict

    更新日期:2020-03-20
  • cFLIPL protects macrophages from LPS-induced pyroptosis via inhibition of complex II formation
    Science (IF 41.037) Pub Date : 2020-03-20
    Hayley I. Muendlein, David Jetton, Wilson M. Connolly, Keith P. Eidell, Zoie Magri, Irina Smirnova, Alexander Poltorak

    Cell death and inflammation are interdependent host responses to infection. During pyroptotic cell death, interleukin-1β (IL-1β) release occurs through caspase-1 and caspase-11–mediated gasdermin D pore formation. In vivo, responses to lipopolysaccharide (LPS) result in IL-1β secretion. In vitro, however, murine macrophages require a second “danger signal” for the inflammasome-driven maturation of

    更新日期:2020-03-20
  • A sustainable wood biorefinery for low-carbon footprint chemicals production.
    Science (IF 41.037) Pub Date : 2020-02-13
    Yuhe Liao,Steven-Friso Koelewijn,Gil Van den Bossche,Joost Van Aelst,Sander Van den Bosch,Tom Renders,Kranti Navare,Thomas Nicolaï,Korneel Van Aelst,Maarten Maesen,Hironori Matsushima,Johan Thevelein,Karel Van Acker,Bert Lagrain,Danny Verboekend,Bert F Sels

    Profitability and sustainability of future biorefineries are dependent on efficient feedstock utilization. It is essential to valorize lignin when using wood. We have developed an integrated biorefinery that converts 78 wt.% of birch into xylochemicals. Reductive catalytic fractionation of wood gives a carbohydrate pulp amenable to bioethanol production and a lignin oil. After extraction of lignin

    更新日期:2020-03-20
  • Insights into human genetic variation and population history from 929 diverse genomes
    Science (IF 41.037) Pub Date : 2020-03-20
    Anders Bergström, Shane A. McCarthy, Ruoyun Hui, Mohamed A. Almarri, Qasim Ayub, Petr Danecek, Yuan Chen, Sabine Felkel, Pille Hallast, Jack Kamm, Hélène Blanché, Jean-François Deleuze, Howard Cann, Swapan Mallick, David Reich, Manjinder S. Sandhu, Pontus Skoglund, Aylwyn Scally, Yali Xue, Richard Durbin, Chris Tyler-Smith

    Genome sequences from diverse human groups are needed to understand the structure of genetic variation in our species and the history of, and relationships between, different populations. We present 929 high-coverage genome sequences from 54 diverse human populations, 26 of which are physically phased using linked-read sequencing. Analyses of these genomes reveal an excess of previously undocumented

    更新日期:2020-03-20
  • The genetic architecture of the human cerebral cortex
    Science (IF 41.037) Pub Date : 2020-03-20
    Katrina L. Grasby, Neda Jahanshad, Jodie N. Painter, Lucía Colodro-Conde, Janita Bralten, Derrek P. Hibar, Penelope A. Lind, Fabrizio Pizzagalli, Christopher R. K. Ching, Mary Agnes B. McMahon, Natalia Shatokhina, Leo C. P. Zsembik, Sophia I. Thomopoulos, Alyssa H. Zhu, Lachlan T. Strike, Ingrid Agartz, Saud Alhusaini, Marcio A. A. Almeida, Dag Alnæs, Inge K. Amlien, Micael Andersson, Tyler Ard, Nicola

    The cerebral cortex underlies our complex cognitive capabilities, yet little is known about the specific genetic loci that influence human cortical structure. To identify genetic variants that affect cortical structure, we conducted a genome-wide association meta-analysis of brain magnetic resonance imaging data from 51,665 individuals. We analyzed the surface area and average thickness of the whole

    更新日期:2020-03-20
  • Selective targeting of BD1 and BD2 of the BET proteins in cancer and immuno-inflammation
    Science (IF 41.037) Pub Date : 2020-03-19
    Omer Gilan, Inmaculada Rioja, Kathy Knezevic, Matthew J. Bell, Miriam M. Yeung, Nicola R. Harker, Enid Y. N. Lam, Chun-wa Chung, Paul Bamborough, Massimo Petretich, Marjeta Urh, Stephen J. Atkinson, Anna K. Bassil, Emma J. Roberts, Dane Vassiliadis, Marian L. Burr, Alex G. S. Preston, Christopher Wellaway, Thilo Werner, James R. Gray, Anne-Marie Michon, Thomas Gobbetti, Vinod Kumar, Peter E. Soden

    The two tandem bromodomains of the BET proteins enable chromatin binding to facilitate transcription. Drugs that inhibit both bromodomains equally have shown efficacy in certain malignant and inflammatory conditions. To explore the individual functional contributions of the first (BD1) and second (BD2) bromodomains in biology and therapy, we developed selective BD1 and BD2 inhibitors. We found that

    更新日期:2020-03-20
  • Quantum-nondemolition state detection and spectroscopy of single trapped molecules.
    Science (IF 41.037) Pub Date : 2020-03-13
    Mudit Sinhal,Ziv Meir,Kaveh Najafian,Gregor Hegi,Stefan Willitsch

    Trapped atoms and ions, which are among the best-controlled quantum systems, find widespread applications in quantum science. For molecules, a similar degree of control is currently lacking owing to their complex energy-level structure. Quantum-logic protocols in which atomic ions serve as probes for molecular ions are a promising route for achieving this level of control, especially for homonuclear

    更新日期:2020-03-12
  • Realization of the kagome spin ice state in a frustrated intermetallic compound.
    Science (IF 41.037) Pub Date : 2020-03-13
    Kan Zhao,Hao Deng,Hua Chen,Kate A Ross,Vaclav Petříček,Gerrit Günther,Margarita Russina,Vladimir Hutanu,Philipp Gegenwart

    Spin ices are exotic phases of matter characterized by frustrated spins obeying local "ice rules," in analogy with the electric dipoles in water ice. In two dimensions, one can similarly define ice rules for in-plane Ising-like spins arranged on a kagome lattice. These ice rules require each triangle plaquette to have a single monopole and can lead to different types of orders and excitations. Using

    更新日期:2020-03-12
  • Structure of CD20 in complex with the therapeutic monoclonal antibody rituximab.
    Science (IF 41.037) Pub Date : 2020-02-20
    Lionel Rougé,Nancy Chiang,Micah Steffek,Christine Kugel,Tristan I Croll,Christine Tam,Alberto Estevez,Christopher P Arthur,Christopher M Koth,Claudio Ciferri,Edward Kraft,Jian Payandeh,Gerald Nakamura,James T Koerber,Alexis Rohou

    Cluster of Differentiation 20 (CD20) is a B cell membrane protein that is targeted by monoclonal antibodies for the treatment of malignancies and auto-immune disorders, but whose structure and function are unknown. Rituximab (RTX) has been in clinical use for two decades, but how it activates complement to kill B cells remains poorly understood. We obtained a structure of CD20 in complex with RTX,

    更新日期:2020-03-12
  • Cryo-EM structure of a neuronal functional amyloid implicated in memory persistence in Drosophila.
    Science (IF 41.037) Pub Date : 2020-03-13
    Ruben Hervas,Michael J Rau,Younshim Park,Wenjuan Zhang,Alexey G Murzin,James A J Fitzpatrick,Sjors H W Scheres,Kausik Si

    How long-lived memories withstand molecular turnover is a fundamental question. Aggregates of a prion-like RNA-binding protein, cytoplasmic polyadenylation element-binding (CPEB) protein, is a putative substrate of long-lasting memories. We isolated aggregated Drosophila CPEB, Orb2, from adult heads and determined its activity and atomic structure, at 2.6-angstrom resolution, using cryo-electron microscopy

    更新日期:2020-03-12
  • Persistent influence of obliquity on ice age terminations since the Middle Pleistocene transition.
    Science (IF 41.037) Pub Date : 2020-03-13
    Petra Bajo,Russell N Drysdale,Jon D Woodhead,John C Hellstrom,David Hodell,Patrizia Ferretti,Antje H L Voelker,Giovanni Zanchetta,Teresa Rodrigues,Eric Wolff,Jonathan Tyler,Silvia Frisia,Christoph Spötl,Anthony E Fallick

    Radiometric dating of glacial terminations over the past 640,000 years suggests pacing by Earth's climatic precession, with each glacial-interglacial period spanning four or five cycles of ~20,000 years. However, the lack of firm age estimates for older Pleistocene terminations confounds attempts to test the persistence of precession forcing. We combine an Italian speleothem record anchored by a uranium-lead

    更新日期:2020-03-12
  • Structure of V-ATPase from the mammalian brain.
    Science (IF 41.037) Pub Date : 2020-03-13
    Yazan M Abbas,Di Wu,Stephanie A Bueler,Carol V Robinson,John L Rubinstein

    In neurons, the loading of neurotransmitters into synaptic vesicles uses energy from proton-pumping vesicular- or vacuolar-type adenosine triphosphatases (V-ATPases). These membrane protein complexes possess numerous subunit isoforms, which complicates their analysis. We isolated homogeneous rat brain V-ATPase through its interaction with SidK, a Legionella pneumophila effector protein. Cryo-electron

    更新日期:2020-03-12
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