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  • Lineage tracing on transcriptional landscapes links state to fate during differentiation
    Science (IF 41.037) Pub Date : 2020-01-24
    Caleb Weinreb, Alejo Rodriguez-Fraticelli, Fernando D. Camargo, Allon M. Klein

    A challenge in biology is to associate molecular differences among progenitor cells with their capacity to generate mature cell types. Here, we use expressed DNA barcodes to clonally trace transcriptomes over time and applied this to study fate determination in hematopoiesis. We identify states of primed fate potential and locate them on a continuous transcriptional landscape. We identify two routes of monocyte differentiation that leave an imprint on mature cells. Yet analysis of sister cells also reveals cells to have intrinsic fate biases not detectable by single-cell RNA sequencing. Finally, we benchmark computational methods of dynamic inference from single-cell snapshots, showing that fate choice occurs earlier than is detected by state-of the-art algorithms, and that cells progress steadily through pseudotime with precise and consistent dynamics.

    更新日期:2020-01-26
  • Learning from the past and considering the future of chemicals in the environment
    Science (IF 41.037) Pub Date : 2020-01-24
    Andrew C. Johnson, Xiaowei Jin, Norihide Nakada, John P. Sumpter

    Knowledge of the hazards and associated risks from chemicals discharged to the environment has grown considerably over the past 40 years. This improving awareness stems from advances in our ability to measure chemicals at low environmental concentrations, recognition of a range of effects on organisms, and a worldwide growth in expertise. Environmental scientists and companies have learned from the experiences of the past; in theory, the next generation of chemicals will cause less acute toxicity and be less environmentally persistent and bioaccumulative. However, researchers still struggle to establish whether the nonlethal effects associated with some modern chemicals and substances will have serious consequences for wildlife. Obtaining the resources to address issues associated with chemicals in the environment remains a challenge.

    更新日期:2020-01-24
  • Tracking complex mixtures of chemicals in our changing environment
    Science (IF 41.037) Pub Date : 2020-01-24
    Beate I. Escher, Heather M. Stapleton, Emma L. Schymanski

    Chemicals have improved our quality of life, but the resulting environmental pollution has the potential to cause detrimental effects on humans and the environment. People and biota are chronically exposed to thousands of chemicals from various environmental sources through multiple pathways. Environmental chemists and toxicologists have moved beyond detecting and quantifying single chemicals to characterizing complex mixtures of chemicals in indoor and outdoor environments and biological matrices. We highlight analytical and bioanalytical approaches to isolating, characterizing, and tracking groups of chemicals of concern in complex matrices. Techniques that combine chemical analysis and bioassays have the potential to facilitate the identification of mixtures of chemicals that pose a combined risk.

    更新日期:2020-01-24
  • The exposome and health: Where chemistry meets biology
    Science (IF 41.037) Pub Date : 2020-01-24
    Roel Vermeulen, Emma L. Schymanski, Albert-László Barabási, Gary W. Miller

    Despite extensive evidence showing that exposure to specific chemicals can lead to disease, current research approaches and regulatory policies fail to address the chemical complexity of our world. To safeguard current and future generations from the increasing number of chemicals polluting our environment, a systematic and agnostic approach is needed. The “exposome” concept strives to capture the diversity and range of exposures to synthetic chemicals, dietary constituents, psychosocial stressors, and physical factors, as well as their corresponding biological responses. Technological advances such as high-resolution mass spectrometry and network science have allowed us to take the first steps toward a comprehensive assessment of the exposome. Given the increased recognition of the dominant role that nongenetic factors play in disease, an effort to characterize the exposome at a scale comparable to that of the human genome is warranted.

    更新日期:2020-01-24
  • Designing for a green chemistry future
    Science (IF 41.037) Pub Date : 2020-01-24
    Julie B. Zimmerman, Paul T. Anastas, Hanno C. Erythropel, Walter Leitner

    The material basis of a sustainable society will depend on chemical products and processes that are designed following principles that make them conducive to life. Important inherent properties of molecules need to be considered from the earliest stage—the design stage—to address whether compounds and processes are depleting versus renewable, toxic versus benign, and persistent versus readily degradable. Products, feedstocks, and manufacturing processes will need to integrate the principles of green chemistry and green engineering under an expanded definition of performance that includes sustainability considerations. This transformation will require the best of the traditions of science and innovation coupled with new emerging systems thinking and systems design that begins at the molecular level and results in a positive impact on the global scale.

    更新日期:2020-01-24
  • Single-cell transcriptional diversity is a hallmark of developmental potential
    Science (IF 41.037) Pub Date : 2020-01-24
    Gunsagar S. Gulati, Shaheen S. Sikandar, Daniel J. Wesche, Anoop Manjunath, Anjan Bharadwaj, Mark J. Berger, Francisco Ilagan, Angera H. Kuo, Robert W. Hsieh, Shang Cai, Maider Zabala, Ferenc A. Scheeren, Neethan A. Lobo, Dalong Qian, Feiqiao B. Yu, Frederick M. Dirbas, Michael F. Clarke, Aaron M. Newman

    Single-cell RNA sequencing (scRNA-seq) is a powerful approach for reconstructing cellular differentiation trajectories. However, inferring both the state and direction of differentiation is challenging. Here, we demonstrate a simple, yet robust, determinant of developmental potential—the number of expressed genes per cell—and leverage this measure of transcriptional diversity to develop a computational framework (CytoTRACE) for predicting differentiation states from scRNA-seq data. When applied to diverse tissue types and organisms, CytoTRACE outperformed previous methods and nearly 19,000 annotated gene sets for resolving 52 experimentally determined developmental trajectories. Additionally, it facilitated the identification of quiescent stem cells and revealed genes that contribute to breast tumorigenesis. This study thus establishes a key RNA-based feature of developmental potential and a platform for delineation of cellular hierarchies.

    更新日期:2020-01-24
  • Attosecond coherent manipulation of electrons in tunneling microscopy
    Science (IF 41.037) Pub Date : 2020-01-24
    M. Garg, K. Kern

    Nanoelectronic devices operating in the quantum regime require coherent manipulation and control over electrons at atomic length and time scales. We demonstrate coherent control over electrons in a tunnel junction of a scanning tunneling microscope by means of precise tuning of the carrier-envelope phase of two-cycle long (<6-femtosecond) optical pulses. We explore photon and field-driven tunneling, two different regimes of interaction of optical pulses with the tunnel junction, and demonstrate a transition from one regime to the other. Our results show that it is possible to induce, track, and control electronic current at atomic scales with subfemtosecond resolution, providing a route to develop petahertz coherent nanoelectronics and microscopy.

    更新日期:2020-01-24
  • A type Ia supernova at the heart of superluminous transient SN 2006gy
    Science (IF 41.037) Pub Date : 2020-01-24
    Anders Jerkstrand, Keiichi Maeda, Koji S. Kawabata

    Superluminous supernovae radiate up to 100 times more energy than normal supernovae. The origin of this energy and the nature of the stellar progenitors of these transients are poorly understood. We identify neutral iron lines in the spectrum of one such supernova, SN 2006gy, and show that they require a large mass of iron (≳0.3 solar masses) expanding at 1500 kilometers per second. By modeling a standard type Ia supernova hitting a shell of circumstellar material, we produce a light curve and late-time iron-dominated spectrum that match the observations of SN 2006gy. In such a scenario, common envelope evolution of a progenitor binary system can synchronize envelope ejection and supernova explosion and may explain these bright transients.

    更新日期:2020-01-24
  • Rational construction of a scalable heterostructured nanorod megalibrary
    Science (IF 41.037) Pub Date : 2020-01-24
    Benjamin C. Steimle, Julie L. Fenton, Raymond E. Schaak

    Integrating multiple materials in arbitrary arrangements within nanoparticles is a prerequisite for advancing many applications. Strategies to synthesize heterostructured nanoparticles are emerging, but they are limited in complexity, scope, and scalability. We introduce two design guidelines, based on interfacial reactivity and crystal structure relations, that enable the rational synthesis of a heterostructured nanorod megalibrary. We define synthetically feasible pathways to 65,520 distinct multicomponent metal sulfide nanorods having as many as 6 materials, 8 segments, and 11 internal interfaces by applying up to seven sequential cation-exchange reactions to copper sulfide nanorod precursors. We experimentally observe 113 individual heterostructured nanorods and demonstrate the scalable production of three samples. Previously unimaginable complexity in heterostructured nanorods is now routinely achievable with simple benchtop chemistry and standard laboratory glassware.

    更新日期:2020-01-24
  • Entanglement-based single-shot detection of a single magnon with a superconducting qubit
    Science (IF 41.037) Pub Date : 2020-01-24
    Dany Lachance-Quirion, Samuel Piotr Wolski, Yutaka Tabuchi, Shingo Kono, Koji Usami, Yasunobu Nakamura

    The recent development of hybrid systems based on superconducting circuits provides the possibility of engineering quantum sensors that exploit different degrees of freedom. Quantum magnonics, which aims to control and read out quanta of collective spin excitations in magnetically ordered systems, provides opportunities for advances in both the study of magnetism and the development of quantum technologies. Using a superconducting qubit as a quantum sensor, we report the detection of a single magnon in a millimeter-sized ferrimagnetic crystal with a quantum efficiency of up to 0.71. The detection is based on the entanglement between a magnetostatic mode and the qubit, followed by a single-shot measurement of the qubit state. This proof-of-principle experiment establishes the single-photon detector counterpart for magnonics.

    更新日期:2020-01-24
  • Visualizing H2O molecules reacting at TiO2 active sites with transmission electron microscopy
    Science (IF 41.037) Pub Date : 2020-01-24
    Wentao Yuan, Beien Zhu, Xiao-Yan Li, Thomas W. Hansen, Yang Ou, Ke Fang, Hangsheng Yang, Ze Zhang, Jakob B. Wagner, Yi Gao, Yong Wang

    Imaging a reaction taking place at the molecular level could provide direct information for understanding the catalytic reaction mechanism. We used in situ environmental transmission electron microscopy and a nanocrystalline anatase titanium dioxide (001) surface with (1 × 4) reconstruction as a catalyst, which provided highly ordered four-coordinated titanium “active rows” to realize real-time monitoring of water molecules dissociating and reacting on the catalyst surface. The twin-protrusion configuration of adsorbed water was observed. During the water–gas shift reaction, dynamic changes in these structures were visualized on these active rows at the molecular level.

    更新日期:2020-01-24
  • A two-way molecular dialogue between embryo and endosperm is required for seed development
    Science (IF 41.037) Pub Date : 2020-01-24
    N. M. Doll, S. Royek, S. Fujita, S. Okuda, S. Chamot, A. Stintzi, T. Widiez, M. Hothorn, A. Schaller, N. Geldner, G. Ingram

    The plant embryonic cuticle is a hydrophobic barrier deposited de novo by the embryo during seed development. At germination, it protects the seedling from water loss and is, thus, critical for survival. Embryonic cuticle formation is controlled by a signaling pathway involving the ABNORMAL LEAF SHAPE1 subtilase and the two GASSHO receptor-like kinases. We show that a sulfated peptide, TWISTED SEED1 (TWS1), acts as a GASSHO ligand. Cuticle surveillance depends on the action of the subtilase, which, unlike the TWS1 precursor and the GASSHO receptors, is not produced in the embryo but in the neighboring endosperm. Subtilase-mediated processing of the embryo-derived TWS1 precursor releases the active peptide, triggering GASSHO-dependent cuticle reinforcement in the embryo. Thus, a bidirectional molecular dialogue between embryo and endosperm safeguards cuticle integrity before germination.

    更新日期:2020-01-24
  • Four glial cells regulate ER stress resistance and longevity via neuropeptide signaling in C. elegans
    Science (IF 41.037) Pub Date : 2020-01-24
    Ashley E. Frakes, Melissa G. Metcalf, Sarah U. Tronnes, Raz Bar-Ziv, Jenni Durieux, Holly K. Gildea, Nazineen Kandahari, Samira Monshietehadi, Andrew Dillin

    The ability of the nervous system to sense cellular stress and coordinate protein homeostasis is essential for organismal health. Unfortunately, stress responses that mitigate disturbances in proteostasis, such as the unfolded protein response of the endoplasmic reticulum (UPRER), become defunct with age. In this work, we expressed the constitutively active UPRER transcription factor, XBP-1s, in a subset of astrocyte-like glia, which extended the life span in Caenorhabditis elegans. Glial XBP-1s initiated a robust cell nonautonomous activation of the UPRER in distal cells and rendered animals more resistant to protein aggregation and chronic ER stress. Mutants deficient in neuropeptide processing and secretion suppressed glial cell nonautonomous induction of the UPRER and life-span extension. Thus, astrocyte-like glial cells play a role in regulating organismal ER stress resistance and longevity.

    更新日期:2020-01-24
  • A common hub for sleep and motor control in the substantia nigra
    Science (IF 41.037) Pub Date : 2020-01-24
    Danqian Liu, Weifu Li, Chenyan Ma, Weitong Zheng, Yuanyuan Yao, Chak Foon Tso, Peng Zhong, Xi Chen, Jun Ho Song, Woochul Choi, Se-Bum Paik, Hua Han, Yang Dan

    The arousal state of the brain covaries with the motor state of the animal. How these state changes are coordinated remains unclear. We discovered that sleep–wake brain states and motor behaviors are coregulated by shared neurons in the substantia nigra pars reticulata (SNr). Analysis of mouse home-cage behavior identified four states with different levels of brain arousal and motor activity: locomotion, nonlocomotor movement, quiet wakefulness, and sleep; transitions occurred not randomly but primarily between neighboring states. The glutamic acid decarboxylase 2 but not the parvalbumin subset of SNr γ-aminobutyric acid (GABA)–releasing (GABAergic) neurons was preferentially active in states of low motor activity and arousal. Their activation or inactivation biased the direction of natural behavioral transitions and promoted or suppressed sleep, respectively. These GABAergic neurons integrate wide-ranging inputs and innervate multiple arousal-promoting and motor-control circuits through extensive collateral projections.

    更新日期:2020-01-24
  • An RNA vaccine drives expansion and efficacy of claudin-CAR-T cells against solid tumors
    Science (IF 41.037) Pub Date : 2020-01-24
    Katharina Reinhard, Benjamin Rengstl, Petra Oehm, Kristina Michel, Arne Billmeier, Nina Hayduk, Oliver Klein, Kathrin Kuna, Yasmina Ouchan, Stefan Wöll, Elmar Christ, David Weber, Martin Suchan, Thomas Bukur, Matthias Birtel, Veronika Jahndel, Karolina Mroz, Kathleen Hobohm, Lena Kranz, Mustafa Diken, Klaus Kühlcke, Özlem Türeci, Ugur Sahin

    Chimeric antigen receptor (CAR)–T cells have shown efficacy in patients with B cell malignancies. Yet, their application for solid tumors has challenges that include limited cancer-specific targets and nonpersistence of adoptively transferred CAR-T cells. Here, we introduce the developmentally regulated tight junction protein claudin 6 (CLDN6) as a CAR target in solid tumors and a strategy to overcome inefficient CAR-T cell stimulation in vivo. We demonstrate that a nanoparticulate RNA vaccine, designed for body-wide delivery of the CAR antigen into lymphoid compartments, stimulates adoptively transferred CAR-T cells. Presentation of the natively folded target on resident antigen-presenting cells promotes cognate and selective expansion of CAR-T cells. Improved engraftment of CAR-T cells and regression of large tumors in difficult-to-treat mouse models was achieved at subtherapeutic CAR-T cell doses.

    更新日期:2020-01-24
  • A tensile ring drives tissue flows to shape the gastrulating amniote embryo
    Science (IF 41.037) Pub Date : 2020-01-24
    Mehdi Saadaoui, Didier Rocancourt, Julian Roussel, Francis Corson, Jerome Gros

    Tissue morphogenesis is driven by local cellular deformations that are powered by contractile actomyosin networks. How localized forces are transmitted across tissues to shape them at a mesoscopic scale is still unclear. Analyzing gastrulation in entire avian embryos, we show that it is driven by the graded contraction of a large-scale supracellular actomyosin ring at the margin between the embryonic and extraembryonic territories. The propagation of these forces is enabled by a fluid-like response of the epithelial embryonic disk, which depends on cell division. A simple model of fluid motion entrained by a tensile ring quantitatively captures the vortex-like “polonaise” movements that accompany the formation of the primitive streak. The geometry of the early embryo thus arises from the transmission of active forces generated along its boundary.

    更新日期:2020-01-24
  • Total synthesis reveals atypical atropisomerism in a small-molecule natural product, tryptorubin A
    Science (IF 41.037) Pub Date : 2020-01-24
    Solomon H. Reisberg, Yang Gao, Allison S. Walker, Eric J. N. Helfrich, Jon Clardy, Phil S. Baran

    Molecular shape defines function in both biological and material settings, and chemists have developed an ever-increasing vernacular to describe these shapes. Noncanonical atropisomers—shape-defined molecules that are formally topologically trivial but are interconvertible only by complex, nonphysical multibond torsions—form a unique subset of atropisomers that differ from both canonical atropisomers (e.g., binaphthyls) and topoisomers (i.e., molecules that have identical connectivity but nonidentical molecular graphs). Small molecules, in contrast to biomacromolecules, are not expected to exhibit such ambiguous shapes. Using total synthesis, we found that the peptidic alkaloid tryptorubin A can be one of two noncanonical atropisomers. We then devised a synthetic strategy that drives the atropospecific synthesis of a noncanonical atrop-defined small molecule.

    更新日期:2020-01-24
  • Phase separation provides a mechanism to reduce noise in cells
    Science (IF 41.037) Pub Date : 2020-01-24
    A. Klosin, F. Oltsch, T. Harmon, A. Honigmann, F. Jülicher, A. A. Hyman, C. Zechner

    Expression of proteins inside cells is noisy, causing variability in protein concentration among identical cells. A central problem in cellular control is how cells cope with this inherent noise. Compartmentalization of proteins through phase separation has been suggested as a potential mechanism to reduce noise, but systematic studies to support this idea have been missing. In this study, we used a physical model that links noise in protein concentration to theory of phase separation to show that liquid droplets can effectively reduce noise. We provide experimental support for noise reduction by phase separation using engineered proteins that form liquid-like compartments in mammalian cells. Thus, phase separation can play an important role in biological signal processing and control.

    更新日期:2020-01-24
  • Chromatin accessibility dynamics in a model of human forebrain development
    Science (IF 41.037) Pub Date : 2020-01-24
    Alexandro E. Trevino, Nasa Sinnott-Armstrong, Jimena Andersen, Se-Jin Yoon, Nina Huber, Jonathan K. Pritchard, Howard Y. Chang, William J. Greenleaf, Sergiu P. Pașca

    Forebrain development is characterized by highly synchronized cellular processes, which, if perturbed, can cause disease. To chart the regulatory activity underlying these events, we generated a map of accessible chromatin in human three-dimensional forebrain organoids. To capture corticogenesis, we sampled glial and neuronal lineages from dorsal or ventral forebrain organoids over 20 months in vitro. Active chromatin regions identified in human primary brain tissue were observed in organoids at different developmental stages. We used this resource to map genetic risk for disease and to explore evolutionary conservation. Moreover, we integrated chromatin accessibility with transcriptomics to identify putative enhancer-gene linkages and transcription factors that regulate human corticogenesis. Overall, this platform brings insights into gene-regulatory dynamics at previously inaccessible stages of human forebrain development, including signatures of neuropsychiatric disorders.

    更新日期:2020-01-24
  • Quantum anomalous Hall effect in intrinsic magnetic topological insulator MnBi2Te4
    Science (IF 41.037) Pub Date : 2020-01-23
    Yujun Deng, Yijun Yu, Meng Zhu Shi, Zhongxun Guo, Zihan Xu, Jing Wang, Xian Hui Chen, Yuanbo Zhang

    In a magnetic topological insulator, nontrivial band topology conspires with magnetic order to produce exotic states of matter such as quantum anomalous Hall (QAH) insulators and axion insulators. Here, we probe quantum transport in MnBi2Te4 thin flake—a topological insulator with intrinsic magnetic order. In this layered van der Waals crystal, the ferromagnetic layers couple anti-parallel to each other; atomically thin MnBi2Te4, however, becomes ferromagnetic when the sample has an odd number of septuple layers. We observe zero-field QAH effect in a five-septuple-layer specimen at 1.4 Kelvin; an external magnetic field further raises the quantization temperature up to 6.5 Kelvin by aligning all layers ferromagnetically. The results establish MnBi2Te4 as an ideal arena for further exploring various topological phenomena with a spontaneously broken time-reversal symmetry.

    更新日期:2020-01-24
  • On impact and volcanism across the Cretaceous-Paleogene boundary
    Science (IF 41.037) Pub Date : 2020-01-17
    Pincelli M. Hull, André Bornemann, Donald E. Penman, Michael J. Henehan, Richard D. Norris, Paul A. Wilson, Peter Blum, Laia Alegret, Sietske J. Batenburg, Paul R. Bown, Timothy J. Bralower, Cecile Cournede, Alexander Deutsch, Barbara Donner, Oliver Friedrich, Sofie Jehle, Hojung Kim, Dick Kroon, Peter C. Lippert, Dominik Loroch, Iris Moebius, Kazuyoshi Moriya, Daniel J. Peppe, Gregory E. Ravizza, Ursula Röhl, Jonathan D. Schueth, Julio Sepúlveda, Philip F. Sexton, Elizabeth C. Sibert, Kasia K. Śliwińska, Roger E. Summons, Ellen Thomas, Thomas Westerhold, Jessica H. Whiteside, Tatsuhiko Yamaguchi, James C. Zachos

    The cause of the end-Cretaceous mass extinction is vigorously debated, owing to the occurrence of a very large bolide impact and flood basalt volcanism near the boundary. Disentangling their relative importance is complicated by uncertainty regarding kill mechanisms and the relative timing of volcanogenic outgassing, impact, and extinction. We used carbon cycle modeling and paleotemperature records to constrain the timing of volcanogenic outgassing. We found support for major outgassing beginning and ending distinctly before the impact, with only the impact coinciding with mass extinction and biologically amplified carbon cycle change. Our models show that these extinction-related carbon cycle changes would have allowed the ocean to absorb massive amounts of carbon dioxide, thus limiting the global warming otherwise expected from postextinction volcanism.

    更新日期:2020-01-17
  • A high-resolution summary of Cambrian to Early Triassic marine invertebrate biodiversity
    Science (IF 41.037) Pub Date : 2020-01-17
    Jun-xuan Fan, Shu-zhong Shen, Douglas H. Erwin, Peter M. Sadler, Norman MacLeod, Qiu-ming Cheng, Xu-dong Hou, Jiao Yang, Xiang-dong Wang, Yue Wang, Hua Zhang, Xu Chen, Guo-xiang Li, Yi-chun Zhang, Yu-kun Shi, Dong-xun Yuan, Qing Chen, Lin-na Zhang, Chao Li, Ying-ying Zhao

    One great challenge in understanding the history of life is resolving the influence of environmental change on biodiversity. Simulated annealing and genetic algorithms were used to synthesize data from 11,000 marine fossil species, collected from more than 3000 stratigraphic sections, to generate a new Cambrian to Triassic biodiversity curve with an imputed temporal resolution of 26 ± 14.9 thousand years. This increased resolution clarifies the timing of known diversification and extinction events. Comparative analysis suggests that partial pressure of carbon dioxide (Pco2) is the only environmental factor that seems to display a secular pattern similar to that of biodiversity, but this similarity was not confirmed when autocorrelation within that time series was analyzed by detrending. These results demonstrate that fossil data can provide the temporal and taxonomic resolutions necessary to test (paleo)biological hypotheses at a level of detail approaching those of long-term ecological analyses.

    更新日期:2020-01-17
  • Decay of the coronal magnetic field can release sufficient energy to power a solar flare
    Science (IF 41.037) Pub Date : 2020-01-17
    Gregory D. Fleishman, Dale E. Gary, Bin Chen, Natsuha Kuroda, Sijie Yu, Gelu M. Nita

    Solar flares are powered by a rapid release of energy in the solar corona, thought to be produced by the decay of the coronal magnetic field strength. Direct quantitative measurements of the evolving magnetic field strength are required to test this. We report microwave observations of a solar flare, showing spatial and temporal changes in the coronal magnetic field. The field decays at a rate of ~5 Gauss per second for 2 minutes, as measured within a flare subvolume of ~1028 cubic centimeters. This fast rate of decay implies a sufficiently strong electric field to account for the particle acceleration that produces the microwave emission. The decrease in stored magnetic energy is enough to power the solar flare, including the associated eruption, particle acceleration, and plasma heating.

    更新日期:2020-01-17
  • Nitromethane as a nitrogen donor in Schmidt-type formation of amides and nitriles
    Science (IF 41.037) Pub Date : 2020-01-17
    Jianzhong Liu, Cheng Zhang, Ziyao Zhang, Xiaojin Wen, Xiaodong Dou, Jialiang Wei, Xu Qiu, Song Song, Ning Jiao

    The Schmidt reaction has been an efficient and widely used synthetic approach to amides and nitriles since its discovery in 1923. However, its application often entails the use of volatile, potentially explosive, and highly toxic azide reagents. Here, we report a sequence whereby triflic anhydride and formic and acetic acids activate the bulk chemical nitromethane to serve as a nitrogen donor in place of azides in Schmidt-like reactions. This protocol further expands the substrate scope to alkynes and simple alkyl benzenes for the preparation of amides and nitriles.

    更新日期:2020-01-17
  • Singular charge fluctuations at a magnetic quantum critical point
    Science (IF 41.037) Pub Date : 2020-01-17
    L. Prochaska, X. Li, D. C. MacFarland, A. M. Andrews, M. Bonta, E. F. Bianco, S. Yazdi, W. Schrenk, H. Detz, A. Limbeck, Q. Si, E. Ringe, G. Strasser, J. Kono, S. Paschen

    Strange metal behavior is ubiquitous in correlated materials, ranging from cuprate superconductors to bilayer graphene, and may arise from physics beyond the quantum fluctuations of a Landau order parameter. In quantum-critical heavy-fermion antiferromagnets, such physics may be realized as critical Kondo entanglement of spin and charge and probed with optical conductivity. We present terahertz time-domain transmission spectroscopy on molecular beam epitaxy–grown thin films of YbRh2Si2, a model strange-metal compound. We observed frequency over temperature scaling of the optical conductivity as a hallmark of beyond-Landau quantum criticality. Our discovery suggests that critical charge fluctuations play a central role in the strange metal behavior, elucidating one of the long-standing mysteries of correlated quantum matter.

    更新日期:2020-01-17
  • Subwavelength dielectric resonators for nonlinear nanophotonics
    Science (IF 41.037) Pub Date : 2020-01-17
    Kirill Koshelev, Sergey Kruk, Elizaveta Melik-Gaykazyan, Jae-Hyuck Choi, Andrey Bogdanov, Hong-Gyu Park, Yuri Kivshar

    Subwavelength optical resonators made of high-index dielectric materials provide efficient ways to manipulate light at the nanoscale through mode interferences and enhancement of both electric and magnetic fields. Such Mie-resonant dielectric structures have low absorption, and their functionalities are limited predominantly by radiative losses. We implement a new physical mechanism for suppressing radiative losses of individual nanoscale resonators to engineer special modes with high quality factors: optical bound states in the continuum (BICs). We demonstrate that an individual subwavelength dielectric resonator hosting a BIC mode can boost nonlinear effects increasing second-harmonic generation efficiency. Our work suggests a route to use subwavelength high-index dielectric resonators for a strong enhancement of light–matter interactions with applications to nonlinear optics, nanoscale lasers, quantum photonics, and sensors.

    更新日期:2020-01-17
  • How flight feathers stick together to form a continuous morphing wing
    Science (IF 41.037) Pub Date : 2020-01-17
    Laura Y. Matloff, Eric Chang, Teresa J. Feo, Lindsie Jeffries, Amanda K. Stowers, Cole Thomson, David Lentink

    Variable feather overlap enables birds to morph their wings, unlike aircraft. They accomplish this feat by means of elastic compliance of connective tissue, which passively redistributes the overlapping flight feathers when the skeleton moves to morph the wing planform. Distinctive microstructures form “directional Velcro,” such that when adjacent feathers slide apart during extension, thousands of lobate cilia on the underlapping feathers lock probabilistically with hooked rami of overlapping feathers to prevent gaps. These structures unlock automatically during flexion. Using a feathered biohybrid aerial robot, we demonstrate how both passive mechanisms make morphing wings robust to turbulence. We found that the hooked microstructures fasten feathers across bird species except silent fliers, whose feathers also lack the associated Velcro-like noise. These findings could inspire innovative directional fasteners and morphing aircraft.

    更新日期:2020-01-17
  • Stormy water on Mars: The distribution and saturation of atmospheric water during the dusty season
    Science (IF 41.037) Pub Date : 2020-01-17
    Anna A. Fedorova, Franck Montmessin, Oleg Korablev, Mikhail Luginin, Alexander Trokhimovskiy, Denis A. Belyaev, Nikolay I. Ignatiev, Franck Lefèvre, Juan Alday, Patrick G. J. Irwin, Kevin S. Olsen, Jean-Loup Bertaux, Ehouarn Millour, Anni Määttänen, Alexey Shakun, Alexey V. Grigoriev, Andrey Patrakeev, Svyatoslav Korsa, Nikita Kokonkov, Lucio Baggio, Francois Forget, Colin F. Wilson

    The loss of water from Mars to space is thought to result from the transport of water to the upper atmosphere, where it is dissociated to hydrogen and escapes the planet. Recent observations have suggested large, rapid seasonal intrusions of water into the upper atmosphere, boosting the hydrogen abundance. We use the Atmospheric Chemistry Suite on the ExoMars Trace Gas Orbiter to characterize the water distribution by altitude. Water profiles during the 2018–2019 southern spring and summer stormy seasons show that high-altitude water is preferentially supplied close to perihelion, and supersaturation occurs even when clouds are present. This implies that the potential for water to escape from Mars is higher than previously thought.

    更新日期:2020-01-17
  • Lipid-gated monovalent ion fluxes regulate endocytic traffic and support immune surveillance
    Science (IF 41.037) Pub Date : 2020-01-17
    Spencer A. Freeman, Stefan Uderhardt, Amra Saric, Richard F. Collins, Catherine M. Buckley, Sivakami Mylvaganam, Parastoo Boroumand, Jonathan Plumb, Ronald N. Germain, Dejian Ren, Sergio Grinstein

    Despite ongoing (macro)pinocytosis of extracellular fluid, the volume of the endocytic pathway remains unchanged. To investigate the underlying mechanism, we used high-resolution video imaging to analyze the fate of macropinosomes formed by macrophages in vitro and in situ. Na+, the primary cationic osmolyte internalized, exited endocytic vacuoles via two-pore channels, accompanied by parallel efflux of Cl− and osmotically coupled water. The resulting shrinkage caused crenation of the membrane, which fostered recruitment of curvature-sensing proteins. These proteins stabilized tubules and promoted their elongation, driving vacuolar remodeling, receptor recycling, and resolution of the organelles. Failure to resolve internalized fluid impairs the tissue surveillance activity of resident macrophages. Thus, osmotically driven increases in the surface-to-volume ratio of endomembranes promote traffic between compartments and help to ensure tissue homeostasis.

    更新日期:2020-01-17
  • Integrated hearing and chewing modules decoupled in a Cretaceous stem therian mammal
    Science (IF 41.037) Pub Date : 2020-01-17
    Fangyuan Mao, Yaoming Hu, Chuankui Li, Yuanqing Wang, Morgan Hill Chase, Andrew K. Smith, Jin Meng

    On the basis of multiple skeletal specimens from Liaoning, China, we report a new genus and species of Cretaceous stem therian mammal that displays decoupling of hearing and chewing apparatuses and functions. The auditory bones, including the surangular, have no bone contact with the ossified Meckel’s cartilage; the latter is loosely lodged on the medial rear of the dentary. This configuration probably represents the initial morphological stage of the definitive mammalian middle ear. Evidence shows that hearing and chewing apparatuses have evolved in a modular fashion. Starting as an integrated complex in non-mammaliaform cynodonts, the two modules, regulated by similar developmental and genetic mechanisms, eventually decoupled during the evolution of mammals, allowing further improvement for more efficient hearing and mastication.

    更新日期:2020-01-17
  • Phonon hydrodynamics and ultrahigh–room-temperature thermal conductivity in thin graphite
    Science (IF 41.037) Pub Date : 2020-01-17
    Yo Machida, Nayuta Matsumoto, Takayuki Isono, Kamran Behnia

    Allotropes of carbon, such as diamond and graphene, are among the best conductors of heat. We monitored the evolution of thermal conductivity in thin graphite as a function of temperature and thickness and found an intimate link between high conductivity, thickness, and phonon hydrodynamics. The room-temperature in-plane thermal conductivity of 8.5-micrometer-thick graphite was 4300 watts per meter-kelvin—a value well above that for diamond and slightly larger than in isotopically purified graphene. Warming enhances thermal diffusivity across a wide temperature range, supporting partially hydrodynamic phonon flow. The enhancement of thermal conductivity that we observed with decreasing thickness points to a correlation between the out-of-plane momentum of phonons and the fraction of momentum-relaxing collisions. We argue that this is due to the extreme phonon dispersion anisotropy in graphite.

    更新日期:2020-01-17
  • Fluorination of arylboronic esters enabled by bismuth redox catalysis
    Science (IF 41.037) Pub Date : 2020-01-17
    Oriol Planas, Feng Wang, Markus Leutzsch, Josep Cornella

    Bismuth catalysis has traditionally relied on the Lewis acidic properties of the element in a fixed oxidation state. In this paper, we report a series of bismuth complexes that can undergo oxidative addition, reductive elimination, and transmetallation in a manner akin to transition metals. Rational ligand optimization featuring a sulfoximine moiety produced an active catalyst for the fluorination of aryl boronic esters through a bismuth (III)/bismuth (V) redox cycle. Crystallographic characterization of the different bismuth species involved, together with a mechanistic investigation of the carbon-fluorine bond-forming event, identified the crucial features that were combined to implement the full catalytic cycle.

    更新日期:2020-01-17
  • VISTA is a checkpoint regulator for naïve T cell quiescence and peripheral tolerance
    Science (IF 41.037) Pub Date : 2020-01-17
    Mohamed A. ElTanbouly, Yanding Zhao, Elizabeth Nowak, Jiannan Li, Evelien Schaafsma, Isabelle Le Mercier, Sabrina Ceeraz, J. Louise Lines, Changwei Peng, Catherine Carriere, Xin Huang, Maria Day, Brent Koehn, Sam W. Lee, Milagros Silva Morales, Kristin A. Hogquist, Stephen C. Jameson, Daniel Mueller, Jay Rothstein, Bruce R. Blazar, Chao Cheng, Randolph J. Noelle

    Negative checkpoint regulators (NCRs) temper the T cell immune response to self-antigens and limit the development of autoimmunity. Unlike all other NCRs that are expressed on activated T lymphocytes, V-type immunoglobulin domain-containing suppressor of T cell activation (VISTA) is expressed on naïve T cells. We report an unexpected heterogeneity within the naïve T cell compartment in mice, where loss of VISTA disrupted the major quiescent naïve T cell subset and enhanced self-reactivity. Agonistic VISTA engagement increased T cell tolerance by promoting antigen-induced peripheral T cell deletion. Although a critical player in naïve T cell homeostasis, the ability of VISTA to restrain naïve T cell responses was lost under inflammatory conditions. VISTA is therefore a distinctive NCR of naïve T cells that is critical for steady-state maintenance of quiescence and peripheral tolerance.

    更新日期:2020-01-17
  • Quantum spin liquids
    Science (IF 41.037) Pub Date : 2020-01-17
    C. Broholm, R. J. Cava, S. A. Kivelson, D. G. Nocera, M. R. Norman, T. Senthil

    Spin liquids are quantum phases of matter with a variety of unusual features arising from their topological character, including “fractionalization”—elementary excitations that behave as fractions of an electron. Although there is not yet universally accepted experimental evidence that establishes that any single material has a spin liquid ground state, in the past few years a number of materials have been shown to exhibit distinctive properties that are expected of a quantum spin liquid. Here, we review theoretical and experimental progress in this area.

    更新日期:2020-01-17
  • Correlative three-dimensional super-resolution and block-face electron microscopy of whole vitreously frozen cells
    Science (IF 41.037) Pub Date : 2020-01-17
    David P. Hoffman, Gleb Shtengel, C. Shan Xu, Kirby R. Campbell, Melanie Freeman, Lei Wang, Daniel E. Milkie, H. Amalia Pasolli, Nirmala Iyer, John A. Bogovic, Daniel R. Stabley, Abbas Shirinifard, Song Pang, David Peale, Kathy Schaefer, Wim Pomp, Chi-Lun Chang, Jennifer Lippincott-Schwartz, Tom Kirchhausen, David J. Solecki, Eric Betzig, Harald F. Hess

    Within cells, the spatial compartmentalization of thousands of distinct proteins serves a multitude of diverse biochemical needs. Correlative super-resolution (SR) fluorescence and electron microscopy (EM) can elucidate protein spatial relationships to global ultrastructure, but has suffered from tradeoffs of structure preservation, fluorescence retention, resolution, and field of view. We developed a platform for three-dimensional cryogenic SR and focused ion beam–milled block-face EM across entire vitreously frozen cells. The approach preserves ultrastructure while enabling independent SR and EM workflow optimization. We discovered unexpected protein-ultrastructure relationships in mammalian cells including intranuclear vesicles containing endoplasmic reticulum–associated proteins, web-like adhesions between cultured neurons, and chromatin domains subclassified on the basis of transcriptional activity. Our findings illustrate the value of a comprehensive multimodal view of ultrastructural variability across whole cells.

    更新日期:2020-01-17
  • N6-methyladenosine of chromosome-associated regulatory RNA regulates chromatin state and transcription
    Science (IF 41.037) Pub Date : 2020-01-16
    Jun Liu, Xiaoyang Dou, Chuanyuan Chen, Chuan Chen, Chang Liu, Meng Michelle Xu, Siqi Zhao, Bin Shen, Yawei Gao, Dali Han, Chuan He

    N6-methyladenosine (m6A) regulates stability and translation of messenger RNA (mRNA) in various biological processes. Here, we showed that knockout of the m6A writer Mettl3 or a nuclear reader Ythdc1 in mouse embryonic stem cells increases chromatin accessibility and activates transcription in an m6A-dependent manner. We found that METTL3 deposits m6A modifications on chromosome-associated regulatory RNAs (carRNAs), including promoter-associated RNAs, enhancer RNAs and repeats RNAs. YTHDC1 facilitates decay of a subset of these m6A-modified RNAs, especially LINE1 elements, through the NEXT-mediated nuclear degradation. Reducing m6A methylation by METTL3 depletion or site-specific m6A demethylation of selected carRNAs elevates the levels of carRNAs and promotes open chromatin state and downstream transcription. Collectively, our results revealed that m6A on carRNAs can globally tune chromatin state and transcription.

    更新日期:2020-01-17
  • Dermal sheath contraction powers stem cell niche relocation during hair cycle regression
    Science (IF 41.037) Pub Date : 2020-01-10
    Nicholas Heitman, Rachel Sennett, Ka-Wai Mok, Nivedita Saxena, Devika Srivastava, Pieter Martino, Laura Grisanti, Zichen Wang, Avi Ma’ayan, Panteleimon Rompolas, Michael Rendl

    Tissue homeostasis requires the balance of growth by cell production and regression through cell loss. In the hair cycle, during follicle regression, the niche traverses the skin through an unknown mechanism to reach the stem cell reservoir and trigger new growth. Here, we identify the dermal sheath that lines the follicle as the key driver of tissue regression and niche relocation through the smooth muscle contractile machinery that generates centripetal constriction force. We reveal that the calcium-calmodulin–myosin light chain kinase pathway controls sheath contraction. When this pathway is blocked, sheath contraction is inhibited, impeding follicle regression and niche relocation. Thus, our study identifies the dermal sheath as smooth muscle that drives follicle regression for reuniting niche and stem cells in order to regenerate tissue structure during homeostasis.

    更新日期:2020-01-10
  • A lost world in Wallacea: Description of a montane archipelagic avifauna
    Science (IF 41.037) Pub Date : 2020-01-10
    Frank E. Rheindt, Dewi M. Prawiradilaga, Hidayat Ashari, Suparno, Chyi Yin Gwee, Geraldine W. X. Lee, Meng Yue Wu, Nathaniel S. R. Ng

    Birds are the best-known animal class, with only about five or six new species descriptions per year since 1999. Integrating genomic and phenotypic research with arduous fieldwork in remote regions, we describe five new songbird species and five new subspecies from a small area near Sulawesi, Indonesia, all collected in a single 6-week expedition. Two factors contributed to the description of this large number of species from such a small geographic area: (i) Knowledge of Quaternary Period land connections helped pinpoint isolated islands likely to harbor substantial endemism and (ii) studying accounts of historic collectors such as Alfred Wallace facilitated the identification of undercollected islands. Our findings suggest that humans’ understanding of biogeographically complex regions such as Wallacea remains incomplete.

    更新日期:2020-01-10
  • Observation of hydrogen trapping at dislocations, grain boundaries, and precipitates
    Science (IF 41.037) Pub Date : 2020-01-10
    Yi-Sheng Chen, Hongzhou Lu, Jiangtao Liang, Alexander Rosenthal, Hongwei Liu, Glenn Sneddon, Ingrid McCarroll, Zhengzhi Zhao, Wei Li, Aimin Guo, Julie M. Cairney

    Hydrogen embrittlement of high-strength steel is an obstacle for using these steels in sustainable energy production. Hydrogen embrittlement involves hydrogen-defect interactions at multiple-length scales. However, the challenge of measuring the precise location of hydrogen atoms limits our understanding. Thermal desorption spectroscopy can identify hydrogen retention or trapping, but data cannot be easily linked to the relative contributions of different microstructural features. We used cryo-transfer atom probe tomography to observe hydrogen at specific microstructural features in steels. Direct observation of hydrogen at carbon-rich dislocations and grain boundaries provides validation for embrittlement models. Hydrogen observed at an incoherent interface between niobium carbides and the surrounding steel provides direct evidence that these incoherent boundaries can act as trapping sites. This information is vital for designing embrittlement-resistant steels.

    更新日期:2020-01-10
  • Observation of an isomerizing double-well quantum system in the condensed phase
    Science (IF 41.037) Pub Date : 2020-01-10
    Jascha A. Lau, Arnab Choudhury, Li Chen, Dirk Schwarzer, Varun B. Verma, Alec M. Wodtke

    Molecular isomerization fundamentally involves quantum states bound within a potential energy function with multiple minima. For isolated gas-phase molecules, eigenstates well above the isomerization saddle points have been characterized. However, to observe the quantum nature of isomerization, systems in which transitions between the eigenstates occur—such as condensed-phase systems—must be studied. Efforts to resolve quantum states with spectroscopic tools are typically unsuccessful for such systems. An exception is CO adsorbed on NaCl(100), which is bound with the well-known OC–Na+ structure. We observe an unexpected upside-down isomer (CO–Na+) produced by infrared laser excitation and obtain well-resolved infrared fluorescence spectra from highly energetic vibrational states of both orientational isomers. This distinctive condensed-phase system is ideally suited to spectroscopic investigations of the quantum nature of isomerization.

    更新日期:2020-01-10
  • Observation of the fastest chemical processes in the radiolysis of water
    Science (IF 41.037) Pub Date : 2020-01-10
    Z.-H. Loh, G. Doumy, C. Arnold, L. Kjellsson, S. H. Southworth, A. Al Haddad, Y. Kumagai, M.-F. Tu, P. J. Ho, A. M. March, R. D. Schaller, M. S. Bin Mohd Yusof, T. Debnath, M. Simon, R. Welsch, L. Inhester, K. Khalili, K. Nanda, A. I. Krylov, S. Moeller, G. Coslovich, J. Koralek, M. P. Minitti, W. F. Schlotter, J.-E. Rubensson, R. Santra, L. Young

    Elementary processes associated with ionization of liquid water provide a framework for understanding radiation-matter interactions in chemistry and biology. Although numerous studies have been conducted on the dynamics of the hydrated electron, its partner arising from ionization of liquid water, H2O+, remains elusive. We used tunable femtosecond soft x-ray pulses from an x-ray free electron laser to reveal the dynamics of the valence hole created by strong-field ionization and to track the primary proton transfer reaction giving rise to the formation of OH. The isolated resonance associated with the valence hole (H2O+/OH) enabled straightforward detection. Molecular dynamics simulations revealed that the x-ray spectra are sensitive to structural dynamics at the ionization site. We found signatures of hydrated-electron dynamics in the x-ray spectrum.

    更新日期:2020-01-10
  • A terrestrial gamma-ray flash and ionospheric ultraviolet emissions powered by lightning
    Science (IF 41.037) Pub Date : 2020-01-10
    Torsten Neubert, Nikolai Østgaard, Victor Reglero, Olivier Chanrion, Matthias Heumesser, Krystallia Dimitriadou, Freddy Christiansen, Carl Budtz-Jørgensen, Irfan Kuvvetli, Ib Lundgaard Rasmussen, Andrey Mezentsev, Martino Marisaldi, Kjetil Ullaland, Georgi Genov, Shiming Yang, Pavlo Kochkin, Javier Navarro-Gonzalez, Paul H. Connell, Chris J. Eyles

    Terrestrial gamma-ray flashes (TGFs) are transient gamma-ray emissions from thunderstorms, generated by electrons accelerated to relativistic energies in electric fields. Elves are ultraviolet and optical emissions excited in the lower ionosphere by electromagnetic waves radiated from lightning current pulses. We observed a TGF and an associated elve using the Atmosphere-Space Interactions Monitor on the International Space Station. The TGF occurred at the onset of a lightning current pulse that generated an elve, in the early stage of a lightning flash. Our measurements suggest that the current onset is fast and has a high amplitude—a prerequisite for elves—and that the TGF is generated in the electric fields associated with the lightning leader.

    更新日期:2020-01-10
  • Time-resolved observation of spin-charge deconfinement in fermionic Hubbard chains
    Science (IF 41.037) Pub Date : 2020-01-10
    Jayadev Vijayan, Pimonpan Sompet, Guillaume Salomon, Joannis Koepsell, Sarah Hirthe, Annabelle Bohrdt, Fabian Grusdt, Immanuel Bloch, Christian Gross

    Elementary particles carry several quantum numbers, such as charge and spin. However, in an ensemble of strongly interacting particles, the emerging degrees of freedom can fundamentally differ from those of the individual constituents. For example, one-dimensional systems are described by independent quasiparticles carrying either spin (spinon) or charge (holon). Here, we report on the dynamical deconfinement of spin and charge excitations in real space after the removal of a particle in Fermi-Hubbard chains of ultracold atoms. Using space- and time-resolved quantum gas microscopy, we tracked the evolution of the excitations through their signatures in spin and charge correlations. By evaluating multipoint correlators, we quantified the spatial separation of the excitations in the context of fractionalization into single spinons and holons at finite temperatures.

    更新日期:2020-01-10
  • Nearly quantized conductance plateau of vortex zero mode in an iron-based superconductor
    Science (IF 41.037) Pub Date : 2020-01-10
    Shiyu Zhu, Lingyuan Kong, Lu Cao, Hui Chen, Michał Papaj, Shixuan Du, Yuqing Xing, Wenyao Liu, Dongfei Wang, Chengmin Shen, Fazhi Yang, John Schneeloch, Ruidan Zhong, Genda Gu, Liang Fu, Yu-Yang Zhang, Hong Ding, Hong-Jun Gao

    Majorana zero modes (MZMs) are spatially localized, zero-energy fractional quasiparticles with non-Abelian braiding statistics that hold promise for topological quantum computing. Owing to the particle-antiparticle equivalence, MZMs exhibit quantized conductance at low temperature. By using variable-tunnel–coupled scanning tunneling spectroscopy, we studied tunneling conductance of vortex bound states on FeTe0.55Se0.45 superconductors. We report observations of conductance plateaus as a function of tunnel coupling for zero-energy vortex bound states with values close to or even reaching the 2e2/h quantum conductance (where e is the electron charge and h is Planck’s constant). By contrast, no plateaus were observed on either finite energy vortex bound states or in the continuum of electronic states outside the superconducting gap. This behavior of the zero-mode conductance supports the existence of MZMs in FeTe0.55Se0.45.

    更新日期:2020-01-10
  • Hydrophobic zeolite modification for in situ peroxide formation in methane oxidation to methanol
    Science (IF 41.037) Pub Date : 2020-01-10
    Zhu Jin, Liang Wang, Erik Zuidema, Kartick Mondal, Ming Zhang, Jian Zhang, Chengtao Wang, Xiangju Meng, Hengquan Yang, Carl Mesters, Feng-Shou Xiao

    Selective partial oxidation of methane to methanol suffers from low efficiency. Here, we report a heterogeneous catalyst system for enhanced methanol productivity in methane oxidation by in situ generated hydrogen peroxide at mild temperature (70°C). The catalyst was synthesized by fixation of AuPd alloy nanoparticles within aluminosilicate zeolite crystals, followed by modification of the external surface of the zeolite with organosilanes. The silanes appear to allow diffusion of hydrogen, oxygen, and methane to the catalyst active sites, while confining the generated peroxide there to enhance its reaction probability. At 17.3% conversion of methane, methanol selectivity reached 92%, corresponding to methanol productivity up to 91.6 millimoles per gram of AuPd per hour.

    更新日期:2020-01-10
  • Programmed cell death along the midline axis patterns ipsilaterality in gastrulation
    Science (IF 41.037) Pub Date : 2020-01-10
    Lisandro Maya-Ramos, Takashi Mikawa

    Bilateral symmetry is the predominant body plan in the animal kingdom. Cells on the left and right sides remain compartmentalized on their ipsilateral side throughout life, but with occasional variation, as evidenced by gynandromorphs and human disorders. How this evolutionarily conserved body plan is programmed remains a fundamental yet unanswered question. Here, we show that germ-layer patterning in avian gastrulation is ipsilateral despite cells undergoing highly invasive mesenchymal transformation and cell migration. Contralateral invasion is suppressed by extracellular matrix (ECM) and programmed cell death (PCD) along the embryonic midline. Ipsilateral gastrulation was lost by midline ECM and PCD inhibition but restored with exogenously induced PCD. Our data support ipsilaterality as an integral component of bilaterality and highlight a positive functional role of PCD in development.

    更新日期:2020-01-10
  • Effect of tolerance on the evolution of antibiotic resistance under drug combinations
    Science (IF 41.037) Pub Date : 2020-01-10
    Jiafeng Liu, Orit Gefen, Irine Ronin, Maskit Bar-Meir, Nathalie Q. Balaban

    Drug combinations are widely used in clinical practice to prevent the evolution of resistance. However, little is known about the effect of tolerance, a different mode of survival, on the efficacy of drug combinations for preventing the evolution of resistance. In this work, we monitored Staphylococcus aureus strains evolving in patients under treatment. We detected the rapid emergence of tolerance mutations, followed by the emergence of resistance, despite the combination treatment. Evolution experiments on the clinical strains in vitro revealed a new way by which tolerance promotes the evolution of resistance under combination treatments. Further experiments under different antibiotic classes reveal the generality of the effect. We conclude that tolerance is an important factor to consider in designing combination treatments that prevent the evolution of resistance.

    更新日期:2020-01-10
  • Glucose-dependent control of leucine metabolism by leucyl-tRNA synthetase 1
    Science (IF 41.037) Pub Date : 2020-01-10
    Ina Yoon, Miso Nam, Hoi Kyoung Kim, Hee-Sun Moon, Sungmin Kim, Jayun Jang, Ji Ae Song, Seung Jae Jeong, Sang Bum Kim, Seongmin Cho, YounHa Kim, Jihye Lee, Won Suk Yang, Hee Chan Yoo, Kibum Kim, Min-Sun Kim, Aerin Yang, Kyukwang Cho, Hee-Sung Park, Geum-Sook Hwang, Kwang Yeon Hwang, Jung Min Han, Jong Hyun Kim, Sunghoon Kim

    Despite the importance of glucose and amino acids for energy metabolism, interactions between the two nutrients are not well understood. We provide evidence for a role of leucyl-tRNA synthetase 1 (LARS1) in glucose-dependent control of leucine usage. Upon glucose starvation, LARS1 was phosphorylated by Unc-51 like autophagy activating kinase 1 (ULK1) at the residues crucial for leucine binding. The phosphorylated LARS1 showed decreased leucine binding, which may inhibit protein synthesis and help save energy. Leucine that is not used for anabolic processes may be available for catabolic pathway energy generation. The LARS1-mediated changes in leucine utilization might help support cell survival under glucose deprivation. Thus, depending on glucose availability, LARS1 may help regulate whether leucine is used for protein synthesis or energy production.

    更新日期:2020-01-10
  • Age control of the first appearance datum for Javanese Homo erectus in the Sangiran area
    Science (IF 41.037) Pub Date : 2020-01-10
    Shuji Matsu’ura, Megumi Kondo, Tohru Danhara, Shuhei Sakata, Hideki Iwano, Takafumi Hirata, Iwan Kurniawan, Erick Setiyabudi, Yoshihiro Takeshita, Masayuki Hyodo, Ikuko Kitaba, Masafumi Sudo, Yugo Danhara, Fachroel Aziz

    The chronology of the World Heritage Site of Sangiran in Indonesia is crucial for the understanding of human dispersals and settlement in Asia in the Early Pleistocene (before 780,000 years ago). It has been controversial, however, especially regarding the timing of the earliest hominin migration into the Sangiran region. We use a method of combining fission-track and uranium-lead dating and present key ages to calibrate the lower (older) Sangiran hominin-bearing horizons. We conclude that the first appearance datum for the Sangiran hominins is most likely ~1.3 million years ago and less than 1.5 million years ago, which is markedly later than the dates that have been widely accepted for the past two decades.

    更新日期:2020-01-10
  • Ultrahigh thermal conductivity in isotope-enriched cubic boron nitride
    Science (IF 41.037) Pub Date : 2020-01-09
    Ke Chen, Bai Song, Navaneetha K. Ravichandran, Qiye Zheng, Xi Chen, Hwijong Lee, Haoran Sun, Sheng Li, Geethal Amila Gamage, Fei Tian, Zhiwei Ding, Qichen Song, Akash Rai, Hanlin Wu, Pawan Koirala, Aaron J. Schmidt, Kenji Watanabe, Bing Lv, Zhifeng Ren, Li Shi, David G. Cahill, Takashi Taniguchi, David Broido, Gang Chen

    Materials with high thermal conductivity (κ) are of technological importance and fundamental interest. We grew cubic boron nitride (cBN) crystals with controlled abundance of boron isotopes and measured κ over 1600 Wm−1 K−1 at room temperature in samples with enriched 10B or 11B. In comparison, we found the isotope enhancement of κ is considerably lower for boron phosphide and boron arsenide as the identical isotopic mass disorder becomes increasingly invisible to phonons. The ultrahigh κ in conjunction with its wide bandgap (6.2 eV) makes cBN a promising material for microelectronics thermal management, high-power electronics, and optoelectronics applications.

    更新日期:2020-01-10
  • Butyrophilin 2A1 is essential for phosphoantigen reactivity by γδ T cells
    Science (IF 41.037) Pub Date : 2020-01-09
    Marc Rigau, Simone Ostrouska, Thomas S. Fulford, Darryl N. Johnson, Katherine Woods, Zheng Ruan, Hamish E.G. McWilliam, Christopher Hudson, Candani Tutuka, Adam K. Wheatley, Stephen J. Kent, Jose A. Villadangos, Bhupinder Pal, Christian Kurts, Jason Simmonds, Matthias Pelzing, Andrew D. Nash, Andrew Hammet, Anne M. Verhagen, Gino Vairo, Eugene Maraskovsky, Con Panousis, Nicholas A. Gherardin, Jonathan Cebon, Dale I. Godfrey, Andreas Behren, Adam P. Uldrich

    Gamma delta (γδ) T cells are essential to protective immunity. In humans, most γδ T cells express Vγ9Vδ2+ T cell receptors (TCRs) that respond to phosphoantigens (pAg) produced by cellular pathogens and overexpressed by cancers. However, the molecular targets recognized by these γδTCRs are unknown. Here, we identify butyrophilin 2A1 (BTN2A1) as a key ligand that binds to the Vγ9+ TCR γ-chain. BTN2A1 associates with another butyrophilin, BTN3A1, which act together to initiate responses to pAg. Furthermore, binding of a second ligand, possibly BTN3A1, to a separate TCR domain incorporating Vδ2 is also required. This unique mode of Ag-dependent T cell activation advances our understanding of diseases involving pAg recognition and creates opportunities for the development of γδ T cell-based immunotherapies.

    更新日期:2020-01-10
  • Oriented attachment induces fivefold twins by forming and decomposing high-energy grain boundaries
    Science (IF 41.037) Pub Date : 2020-01-03
    Miao Song, Gang Zhou, Ning Lu, Jaewon Lee, Elias Nakouzi, Hao Wang, Dongsheng Li

    Natural and synthetic nanoparticles composed of fivefold twinned crystal domains have distinct properties. The formation mechanism of these fivefold twinned nanoparticles is poorly understood. We used in situ high-resolution transmission electron microscopy combined with molecular dynamics simulations to demonstrate that fivefold twinning occurs through repeated oriented attachment of ~3-nanometer gold, platinum, and palladium nanoparticles. We discovered two different mechanisms for forming fivefold twinned nanoparticles that are driven by the accumulation and elimination of strain. This was accompanied by decomposition of grain boundaries and the formation of a special class of twins with a net strain of zero. These observations allowed us to develop a quantitative picture of the twinning process. The mechanisms provide guidance for controlling twin structures and morphologies across a wide range of materials.

    更新日期:2020-01-04
  • Massively multiplex chemical transcriptomics at single-cell resolution
    Science (IF 41.037) Pub Date : 2020-01-03
    Sanjay R. Srivatsan, José L. McFaline-Figueroa, Vijay Ramani, Lauren Saunders, Junyue Cao, Jonathan Packer, Hannah A. Pliner, Dana L. Jackson, Riza M. Daza, Lena Christiansen, Fan Zhang, Frank Steemers, Jay Shendure, Cole Trapnell

    High-throughput chemical screens typically use coarse assays such as cell survival, limiting what can be learned about mechanisms of action, off-target effects, and heterogeneous responses. Here, we introduce “sci-Plex,” which uses “nuclear hashing” to quantify global transcriptional responses to thousands of independent perturbations at single-cell resolution. As a proof of concept, we applied sci-Plex to screen three cancer cell lines exposed to 188 compounds. In total, we profiled ~650,000 single-cell transcriptomes across ~5000 independent samples in one experiment. Our results reveal substantial intercellular heterogeneity in response to specific compounds, commonalities in response to families of compounds, and insight into differential properties within families. In particular, our results with histone deacetylase inhibitors support the view that chromatin acts as an important reservoir of acetate in cancer cells.

    更新日期:2020-01-04
  • A Kelch13-defined endocytosis pathway mediates artemisinin resistance in malaria parasites
    Science (IF 41.037) Pub Date : 2020-01-03
    Jakob Birnbaum, Sarah Scharf, Sabine Schmidt, Ernst Jonscher, Wieteke Anna Maria Hoeijmakers, Sven Flemming, Christa Geeke Toenhake, Marius Schmitt, Ricarda Sabitzki, Bärbel Bergmann, Ulrike Fröhlke, Paolo Mesén-Ramírez, Alexandra Blancke Soares, Hendrik Herrmann, Richárd Bártfai, Tobias Spielmann

    Artemisinin and its derivatives (ARTs) are the frontline drugs against malaria, but resistance is jeopardizing their effectiveness. ART resistance is mediated by mutations in the parasite’s Kelch13 protein, but Kelch13 function and its role in resistance remain unclear. In this study, we identified proteins located at a Kelch13-defined compartment. Inactivation of eight of these proteins, including Kelch13, rendered parasites resistant to ART, revealing a pathway critical for resistance. Functional analysis showed that these proteins are required for endocytosis of hemoglobin from the host cell. Parasites with inactivated Kelch13 or a resistance-conferring Kelch13 mutation displayed reduced hemoglobin endocytosis. ARTs are activated by degradation products of hemoglobin. Hence, reduced activity of Kelch13 and its interactors diminishes hemoglobin endocytosis and thereby ART activation, resulting in parasite resistance.

    更新日期:2020-01-04
  • A single photonic cavity with two independent physical synthetic dimensions
    Science (IF 41.037) Pub Date : 2020-01-03
    Avik Dutt, Qian Lin, Luqi Yuan, Momchil Minkov, Meng Xiao, Shanhui Fan

    The concept of synthetic dimensions has generated interest in many branches of science, ranging from ultracold atomic physics to photonics, as it provides a versatile platform for realizing effective gauge potentials and topological physics. Previous experiments have augmented the real-space dimensionality by one additional physical synthetic dimension. In this study, we endow a single ring resonator with two independent physical synthetic dimensions. Our system consists of a temporally modulated ring resonator with spatial coupling between the clockwise and counterclockwise modes, creating a synthetic Hall ladder along the frequency and pseudospin degrees of freedom for photons propagating in the ring. We observe a wide variety of physics, including effective spin-orbit coupling, magnetic fields, spin-momentum locking, a Meissner-to-vortex phase transition, and signatures of topological chiral one-way edge currents, completely in synthetic dimensions. Our experiments demonstrate that higher-dimensional physics can be studied in simple systems by leveraging the concept of multiple simultaneous synthetic dimensions.

    更新日期:2020-01-04
  • Absence of evidence for chiral Majorana modes in quantum anomalous Hall-superconductor devices
    Science (IF 41.037) Pub Date : 2020-01-03
    Morteza Kayyalha, Di Xiao, Ruoxi Zhang, Jaeho Shin, Jue Jiang, Fei Wang, Yi-Fan Zhao, Run Xiao, Ling Zhang, Kajetan M. Fijalkowski, Pankaj Mandal, Martin Winnerlein, Charles Gould, Qi Li, Laurens W. Molenkamp, Moses H. W. Chan, Nitin Samarth, Cui-Zu Chang

    A quantum anomalous Hall (QAH) insulator coupled to an s-wave superconductor is predicted to harbor chiral Majorana modes. A recent experiment interprets the half-quantized two-terminal conductance plateau as evidence for these modes in a millimeter-size QAH-niobium hybrid device. However, non-Majorana mechanisms can also generate similar signatures, especially in disordered samples. Here, we studied similar hybrid devices with a well-controlled and transparent interface between the superconductor and the QAH insulator. When the devices are in the QAH state with well-aligned magnetization, the two-terminal conductance is always half-quantized. Our experiment provides a comprehensive understanding of the superconducting proximity effect observed in QAH-superconductor hybrid devices and shows that the half-quantized conductance plateau is unlikely to be induced by chiral Majorana fermions in samples with a highly transparent interface.

    更新日期:2020-01-04
  • Atomic manipulation of the gap in Bi2Sr2CaCu2O8+x
    Science (IF 41.037) Pub Date : 2020-01-03
    F. Massee, Y. K. Huang, M. Aprili

    Single-atom manipulation within doped correlated electron systems could help disentangle the influence of dopants, structural defects, and crystallographic characteristics on local electronic states. Unfortunately, the high diffusion barrier in these materials prevents conventional manipulation techniques. Here, we demonstrate the possibility to reversibly manipulate select sites in the optimally doped high-temperature superconductor Bi2Sr2CaCu2O8+x using the local electric field of the tip of a scanning tunneling microscope. We show that upon shifting individual Bi atoms at the surface, the spectral gap associated with superconductivity is seen to reversibly change by as much as 15 milli–electron volts (on average ~5% of the total gap size). Our toy model, which captures all observed characteristics, suggests that the electric field induces lateral movement of local pairing potentials in the CuO2 plane.

    更新日期:2020-01-04
  • Topological mechanics of knots and tangles
    Science (IF 41.037) Pub Date : 2020-01-03
    Vishal P. Patil, Joseph D. Sandt, Mathias Kolle, Jörn Dunkel

    Knots play a fundamental role in the dynamics of biological and physical systems, from DNA to turbulent plasmas, as well as in climbing, weaving, sailing, and surgery. Despite having been studied for centuries, the subtle interplay between topology and mechanics in elastic knots remains poorly understood. Here, we combined optomechanical experiments with theory and simulations to analyze knotted fibers that change their color under mechanical deformations. Exploiting an analogy with long-range ferromagnetic spin systems, we identified simple topological counting rules to predict the relative mechanical stability of knots and tangles, in agreement with simulations and experiments for commonly used climbing and sailing bends. Our results highlight the importance of twist and writhe in unknotting processes, providing guidance for the control of systems with complex entanglements.

    更新日期:2020-01-04
  • Electrostatic control of photoisomerization pathways in proteins
    Science (IF 41.037) Pub Date : 2020-01-03
    Matthew G. Romei, Chi-Yun Lin, Irimpan I. Mathews, Steven G. Boxer

    Rotation around a specific bond after photoexcitation is central to vision and emerging opportunities in optogenetics, super-resolution microscopy, and photoactive molecular devices. Competing roles for steric and electrostatic effects that govern bond-specific photoisomerization have been widely discussed, the latter originating from chromophore charge transfer upon excitation. We systematically altered the electrostatic properties of the green fluorescent protein chromophore in a photoswitchable variant, Dronpa2, using amber suppression to introduce electron-donating and electron-withdrawing groups to the phenolate ring. Through analysis of the absorption (color), fluorescence quantum yield, and energy barriers to ground- and excited-state isomerization, we evaluate the contributions of sterics and electrostatics quantitatively and demonstrate how electrostatic effects bias the pathway of chromophore photoisomerization, leading to a generalized framework to guide protein design.

    更新日期:2020-01-04
  • On-chip integrated laser-driven particle accelerator
    Science (IF 41.037) Pub Date : 2020-01-03
    Neil V. Sapra, Ki Youl Yang, Dries Vercruysse, Kenneth J. Leedle, Dylan S. Black, R. Joel England, Logan Su, Rahul Trivedi, Yu Miao, Olav Solgaard, Robert L. Byer, Jelena Vučkovicć

    Particle accelerators represent an indispensable tool in science and industry. However, the size and cost of conventional radio-frequency accelerators limit the utility and reach of this technology. Dielectric laser accelerators (DLAs) provide a compact and cost-effective solution to this problem by driving accelerator nanostructures with visible or near-infrared pulsed lasers, resulting in a 104 reduction of scale. Current implementations of DLAs rely on free-space lasers directly incident on the accelerating structures, limiting the scalability and integrability of this technology. We present an experimental demonstration of a waveguide-integrated DLA that was designed using a photonic inverse-design approach. By comparing the measured electron energy spectra with particle-tracking simulations, we infer a maximum energy gain of 0.915 kilo–electron volts over 30 micrometers, corresponding to an acceleration gradient of 30.5 mega–electron volts per meter. On-chip acceleration provides the possibility for a completely integrated mega–electron volt-scale DLA.

    更新日期:2020-01-04
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