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  • Quantum advantage with shallow circuits
    Science (IF 41.058) Pub Date : 2018-10-19
    Sergey Bravyi, David Gosset, Robert König

    Quantum effects can enhance information-processing capabilities and speed up the solution of certain computational problems. Whether a quantum advantage can be rigorously proven in some setting or demonstrated experimentally using near-term devices is the subject of active debate. We show that parallel quantum algorithms running in a constant time period are strictly more powerful than their classical counterparts; they are provably better at solving certain linear algebra problems associated with binary quadratic forms. Our work gives an unconditional proof of a computational quantum advantage and simultaneously pinpoints its origin: It is a consequence of quantum nonlocality. The proposed quantum algorithm is a suitable candidate for near-future experimental realizations, as it requires only constant-depth quantum circuits with nearest-neighbor gates on a two-dimensional grid of qubits (quantum bits).

    更新日期:2018-10-19
  • Chiral Lewis acids integrated with single-walled carbon nanotubes for asymmetric catalysis in water
    Science (IF 41.058) Pub Date : 2018-10-19
    Taku Kitanosono, Pengyu Xu, Shū Kobayashi

    The development of highly reactive and stereoselective catalytic systems is required not only to improve existing synthetic methods but also to invent distinct chemical reactions. Herein, a homogenized combination of nickel-based Lewis acid–surfactant-combined catalysts and single-walled carbon nanotubes is shown to exhibit substantial activity in water. In addition to the enhanced reactivity, stereoselective performance and long-term stability were demonstrated in asymmetric conjugate addition reactions of aldoximes to furnish chiral nitrones in high yields with excellent selectivities. The practical and straightforward application of the designed catalysts in water provides an expedient, environmentally benign, and highly efficient pathway to access optically active compounds.

    更新日期:2018-10-19
  • Hierarchically porous polymer coatings for highly efficient passive daytime radiative cooling
    Science (IF 41.058) Pub Date : 2018-10-19
    Jyotirmoy Mandal, Yanke Fu, Adam C. Overvig, Mingxin Jia, Kerui Sun, Norman N. Shi, Hua Zhou, Xianghui Xiao, Nanfang Yu, Yuan Yang

    Passive daytime radiative cooling (PDRC) involves spontaneously cooling a surface by reflecting sunlight and radiating heat to the cold outer space. Current PDRC designs are promising alternatives to electrical cooling but are either inefficient or have limited applicability. We present a simple, inexpensive, and scalable phase inversion–based method for fabricating hierarchically porous poly(vinylidene fluoride-co-hexafluoropropene) [P(VdF-HFP)HP] coatings with excellent PDRC capability. High, substrate-independent hemispherical solar reflectances (0.96 ± 0.03) and long-wave infrared emittances (0.97 ± 0.02) allow for subambient temperature drops of ~6°C and cooling powers of ~96 watts per square meter (W m−2) under solar intensities of 890 and 750 W m−2, respectively. The performance equals or surpasses those of state-of-the-art PDRC designs, and the technique offers a paint-like simplicity.

    更新日期:2018-10-19
  • Aptamer–field-effect transistors overcome Debye length limitations for small-molecule sensing
    Science (IF 41.058) Pub Date : 2018-10-19
    Nako Nakatsuka, Kyung-Ae Yang, John M. Abendroth, Kevin M. Cheung, Xiaobin Xu, Hongyan Yang, Chuanzhen Zhao, Bowen Zhu, You Seung Rim, Yang Yang, Paul S. Weiss, Milan N. Stojanović, Anne M. Andrews

    Detection of analytes by means of field-effect transistors bearing ligand-specific receptors is fundamentally limited by the shielding created by the electrical double layer (the “Debye length” limitation). We detected small molecules under physiological high–ionic strength conditions by modifying printed ultrathin metal-oxide field-effect transistor arrays with deoxyribonucleotide aptamers selected to bind their targets adaptively. Target-induced conformational changes of negatively charged aptamer phosphodiester backbones in close proximity to semiconductor channels gated conductance in physiological buffers, resulting in highly sensitive detection. Sensing of charged and electroneutral targets (serotonin, dopamine, glucose, and sphingosine-1-phosphate) was enabled by specifically isolated aptameric stem-loop receptors.

    更新日期:2018-10-19
  • A family of finite-temperature electronic phase transitions in graphene multilayers
    Science (IF 41.058) Pub Date : 2018-10-19
    Youngwoo Nam, Dong-Keun Ki, David Soler-Delgado, Alberto F. Morpurgo

    Suspended Bernal-stacked graphene multilayers up to an unexpectedly large thickness exhibit a broken-symmetry ground state whose origin remains to be understood. We show that a finite-temperature second-order phase transition occurs in multilayers whose critical temperature (Tc) increases from 12 kelvins (K) in bilayers to 100 K in heptalayers. A comparison of the data with a phenomenological model inspired by a mean-field approach suggests that the transition is associated with the appearance of a self-consistent valley- and spin-dependent staggered potential that changes sign from one layer to the next, appearing at Tc and increasing upon cooling. The systematic evolution with thickness of several measured quantities imposes constraints on any microscopic theory aiming to analyze the nature of electronic correlations in this system.

    更新日期:2018-10-19
  • Shear properties of Earth’s inner core constrained by a detection of J waves in global correlation wavefield
    Science (IF 41.058) Pub Date : 2018-10-19
    Hrvoje Tkalčić, Thanh-Son Phạm

    Seismic J waves, shear waves that traverse Earth’s inner core, provide direct constraints on the inner core’s solidity and shear properties. However, these waves have been elusive in the direct seismic wavefield because of their small amplitudes. We devised a new method to detect J waves in the earthquake coda correlation wavefield. They manifest through the similarity with other compressional core-sensitive signals. The inner core is solid, but relatively soft, with shear-wave speeds and shear moduli of 3.42 ± 0.02 kilometers per second and 149.0 ± 1.6 gigapascals (GPa) near the inner core boundary and 3.58 ± 0.02 kilometers per second and 167.4 ± 1.6 GPa in Earth’s center. The values are 2.5% lower than the widely used Preliminary Earth Reference Model. This provides new constraints on the dynamical interpretation of Earth’s inner core.

    更新日期:2018-10-19
  • Evidence for Majorana bound states in an iron-based superconductor
    Science (IF 41.058) Pub Date : 2018-10-19
    Dongfei Wang, Lingyuan Kong, Peng Fan, Hui Chen, Shiyu Zhu, Wenyao Liu, Lu Cao, Yujie Sun, Shixuan Du, John Schneeloch, Ruidan Zhong, Genda Gu, Liang Fu, Hong Ding, Hong-Jun Gao

    The search for Majorana bound states (MBSs) has been fueled by the prospect of using their non-Abelian statistics for robust quantum computation. Two-dimensional superconducting topological materials have been predicted to host MBSs as zero-energy modes in vortex cores. By using scanning tunneling spectroscopy on the superconducting Dirac surface state of the iron-based superconductor FeTe0.55Se0.45, we observed a sharp zero-bias peak inside a vortex core that does not split when moving away from the vortex center. The evolution of the peak under varying magnetic field, temperature, and tunneling barrier is consistent with the tunneling to a nearly pure MBS, separated from nontopological bound states. This observation offers a potential platform for realizing and manipulating MBSs at a relatively high temperature.

    更新日期:2018-10-19
  • Hyperfine interaction of individual atoms on a surface
    Science (IF 41.058) Pub Date : 2018-10-19
    Philip Willke, Yujeong Bae, Kai Yang, Jose L. Lado, Alejandro Ferrón, Taeyoung Choi, Arzhang Ardavan, Joaquín Fernández-Rossier, Andreas J. Heinrich, Christopher P. Lutz

    Taking advantage of nuclear spins for electronic structure analysis, magnetic resonance imaging, and quantum devices hinges on knowledge and control of the surrounding atomic-scale environment. We measured and manipulated the hyperfine interaction of individual iron and titanium atoms placed on a magnesium oxide surface by using spin-polarized scanning tunneling microscopy in combination with single-atom electron spin resonance. Using atom manipulation to move single atoms, we found that the hyperfine interaction strongly depended on the binding configuration of the atom. We could extract atom- and position-dependent information about the electronic ground state, the state mixing with neighboring atoms, and properties of the nuclear spin. Thus, the hyperfine spectrum becomes a powerful probe of the chemical environment of individual atoms and nanostructures.

    更新日期:2018-10-19
  • Supracellular contraction at the rear of neural crest cell groups drives collective chemotaxis
    Science (IF 41.058) Pub Date : 2018-10-19
    Adam Shellard, András Szabó, Xavier Trepat, Roberto Mayor

    Collective cell chemotaxis, the directed migration of cell groups along gradients of soluble chemical cues, underlies various developmental and pathological processes. We use neural crest cells, a migratory embryonic stem cell population whose behavior has been likened to malignant invasion, to study collective chemotaxis in vivo. Studying Xenopus and zebrafish, we have shown that the neural crest exhibits a tensile actomyosin ring at the edge of the migratory cell group that contracts in a supracellular fashion. This contractility is polarized during collective cell chemotaxis: It is inhibited at the front but persists at the rear of the cell cluster. The differential contractility drives directed collective cell migration ex vivo and in vivo through the intercalation of rear cells. Thus, in neural crest cells, collective chemotaxis works by rear-wheel drive.

    更新日期:2018-10-19
  • The opium poppy genome and morphinan production
    Science (IF 41.058) Pub Date : 2018-10-19
    Li Guo, Thilo Winzer, Xiaofei Yang, Yi Li, Zemin Ning, Zhesi He, Roxana Teodor, Ying Lu, Tim A. Bowser, Ian A. Graham, Kai Ye

    Morphinan-based painkillers are derived from opium poppy (Papaver somniferum L.). We report a draft of the opium poppy genome, with 2.72 gigabases assembled into 11 chromosomes with contig N50 and scaffold N50 of 1.77 and 204 megabases, respectively. Synteny analysis suggests a whole-genome duplication at ~7.8 million years ago and ancient segmental or whole-genome duplication(s) that occurred before the Papaveraceae-Ranunculaceae divergence 110 million years ago. Syntenic blocks representative of phthalideisoquinoline and morphinan components of a benzylisoquinoline alkaloid cluster of 15 genes provide insight into how this cluster evolved. Paralog analysis identified P450 and oxidoreductase genes that combined to form the STORR gene fusion essential for morphinan biosynthesis in opium poppy. Thus, gene duplication, rearrangement, and fusion events have led to evolution of specialized metabolic products in opium poppy.

    更新日期:2018-10-19
  • Realizing private and practical pharmacological collaboration
    Science (IF 41.058) Pub Date : 2018-10-19
    Brian Hie, Hyunghoon Cho, Bonnie Berger

    Although combining data from multiple entities could power life-saving breakthroughs, open sharing of pharmacological data is generally not viable because of data privacy and intellectual property concerns. To this end, we leverage modern cryptographic tools to introduce a computational protocol for securely training a predictive model of drug–target interactions (DTIs) on a pooled dataset that overcomes barriers to data sharing by provably ensuring the confidentiality of all underlying drugs, targets, and observed interactions. Our protocol runs within days on a real dataset of more than 1 million interactions and is more accurate than state-of-the-art DTI prediction methods. Using our protocol, we discover previously unidentified DTIs that we experimentally validated via targeted assays. Our work lays a foundation for more effective and cooperative biomedical research.

    更新日期:2018-10-19
  • DNGR-1 in dendritic cells limits tissue damage by dampening neutrophil recruitment
    Science (IF 41.058) Pub Date : 2018-10-19
    Carlos del Fresno, Paula Saz-Leal, Michel Enamorado, Stefanie K. Wculek, Sarai Martínez-Cano, Noelia Blanco-Menéndez, Oliver Schulz, Mattia Gallizioli, Francesc Miró-Mur, Eva Cano, Anna Planas, David Sancho

    Host injury triggers feedback mechanisms that limit tissue damage. Conventional type 1 dendritic cells (cDC1s) express dendritic cell natural killer lectin group receptor-1 (DNGR-1), encoded by the gene Clec9a, which senses tissue damage and favors cross-presentation of dead-cell material to CD8+ T cells. Here we find that DNGR-1 additionally reduces host-damaging inflammatory responses induced by sterile and infectious tissue injury in mice. DNGR-1 deficiency leads to exacerbated caerulein-induced necrotizing pancreatitis and increased pathology during systemic Candida albicans infection without affecting fungal burden. This effect is B and T cell–independent and attributable to increased neutrophilia in DNGR-1–deficient settings. Mechanistically, DNGR-1 engagement activates SHP-1 and inhibits MIP-2 (encoded by Cxcl2) production by cDC1s during Candida infection. This consequently restrains neutrophil recruitment and promotes disease tolerance. Thus, DNGR-1–mediated sensing of injury by cDC1s serves as a rheostat for the control of tissue damage, innate immunity, and immunopathology.

    更新日期:2018-10-19
  • Generation of human oogonia from induced pluripotent stem cells in vitro
    Science (IF 41.058) Pub Date : 2018-10-19
    Chika Yamashiro, Kotaro Sasaki, Yukihiro Yabuta, Yoji Kojima, Tomonori Nakamura, Ikuhiro Okamoto, Shihori Yokobayashi, Yusuke Murase, Yukiko Ishikura, Kenjiro Shirane, Hiroyuki Sasaki, Takuya Yamamoto, Mitinori Saitou

    Human in vitro gametogenesis may transform reproductive medicine. Human pluripotent stem cells (hPSCs) have been induced into primordial germ cell–like cells (hPGCLCs); however, further differentiation to a mature germ cell has not been achieved. Here, we show that hPGCLCs differentiate progressively into oogonia-like cells during a long-term in vitro culture (approximately 4 months) in xenogeneic reconstituted ovaries with mouse embryonic ovarian somatic cells. The hPGCLC-derived oogonia display hallmarks of epigenetic reprogramming—genome-wide DNA demethylation, imprint erasure, and extinguishment of aberrant DNA methylation in hPSCs—and acquire an immediate precursory state for meiotic recombination. Furthermore, the inactive X chromosome shows a progressive demethylation and reactivation, albeit partially. These findings establish the germline competence of hPSCs and provide a critical step toward human in vitro gametogenesis.

    更新日期:2018-10-19
  • Structure of the human voltage-gated sodium channel Nav1.4 in complex with β1
    Science (IF 41.058) Pub Date : 2018-10-19
    Xiaojing Pan, Zhangqiang Li, Qiang Zhou, Huaizong Shen, Kun Wu, Xiaoshuang Huang, Jiaofeng Chen, Juanrong Zhang, Xuechen Zhu, Jianlin Lei, Wei Xiong, Haipeng Gong, Bailong Xiao, Nieng Yan

    Voltage-gated sodium (Nav) channels, which are responsible for action potential generation, are implicated in many human diseases. Despite decades of rigorous characterization, the lack of a structure of any human Nav channel has hampered mechanistic understanding. Here, we report the cryo–electron microscopy structure of the human Nav1.4-β1 complex at 3.2-Å resolution. Accurate model building was made for the pore domain, the voltage-sensing domains, and the β1 subunit, providing insight into the molecular basis for Na+ permeation and kinetic asymmetry of the four repeats. Structural analysis of reported functional residues and disease mutations corroborates an allosteric blocking mechanism for fast inactivation of Nav channels. The structure provides a path toward mechanistic investigation of Nav channels and drug discovery for Nav channelopathies.

    更新日期:2018-10-19
  • Structural basis for the modulation of voltage-gated sodium channels by animal toxins
    Science (IF 41.058) Pub Date : 2018-10-19
    Huaizong Shen, Zhangqiang Li, Yan Jiang, Xiaojing Pan, Jianping Wu, Ben Cristofori-Armstrong, Jennifer J. Smith, Yanni K. Y. Chin, Jianlin Lei, Qiang Zhou, Glenn F. King, Nieng Yan

    Animal toxins that modulate the activity of voltage-gated sodium (Nav) channels are broadly divided into two categories—pore blockers and gating modifiers. The pore blockers tetrodotoxin (TTX) and saxitoxin (STX) are responsible for puffer fish and shellfish poisoning in humans, respectively. Here, we present structures of the insect Nav channel NavPaS bound to a gating modifier toxin Dc1a at 2.8 angstrom-resolution and in the presence of TTX or STX at 2.6-Å and 3.2-Å resolution, respectively. Dc1a inserts into the cleft between VSDII and the pore of NavPaS, making key contacts with both domains. The structures with bound TTX or STX reveal the molecular details for the specific blockade of Na+ access to the selectivity filter from the extracellular side by these guanidinium toxins. The structures shed light on structure-based development of Nav channel drugs.

    更新日期:2018-10-19
  • Landscapes that work for biodiversity and people
    Science (IF 41.058) Pub Date : 2018-10-19
    C. Kremen, A. M. Merenlender

    How can we manage farmlands, forests, and rangelands to respond to the triple challenge of the Anthropocene—biodiversity loss, climate change, and unsustainable land use? When managed by using biodiversity-based techniques such as agroforestry, silvopasture, diversified farming, and ecosystem-based forest management, these socioeconomic systems can help maintain biodiversity and provide habitat connectivity, thereby complementing protected areas and providing greater resilience to climate change. Simultaneously, the use of these management techniques can improve yields and profitability more sustainably, enhancing livelihoods and food security. This approach to “working lands conservation” can create landscapes that work for nature and people. However, many socioeconomic challenges impede the uptake of biodiversity-based land management practices. Although improving voluntary incentives, market instruments, environmental regulations, and governance is essential to support working lands conservation, it is community action, social movements, and broad coalitions among citizens, businesses, nonprofits, and government agencies that have the power to transform how we manage land and protect the environment.

    更新日期:2018-10-19
  • Quantum internet: A vision for the road ahead
    Science (IF 41.058) Pub Date : 2018-10-19
    Stephanie Wehner, David Elkouss, Ronald Hanson

    The internet—a vast network that enables simultaneous long-range classical communication—has had a revolutionary impact on our world. The vision of a quantum internet is to fundamentally enhance internet technology by enabling quantum communication between any two points on Earth. Such a quantum internet may operate in parallel to the internet that we have today and connect quantum processors in order to achieve capabilities that are provably impossible by using only classical means. Here, we propose stages of development toward a full-blown quantum internet and highlight experimental and theoretical progress needed to attain them.

    更新日期:2018-10-19
  • Relationship of gender differences in preferences to economic development and gender equality
    Science (IF 41.058) Pub Date : 2018-10-19
    Armin Falk, Johannes Hermle

    Preferences concerning time, risk, and social interactions systematically shape human behavior and contribute to differential economic and social outcomes between women and men. We present a global investigation of gender differences in six fundamental preferences. Our data consist of measures of willingness to take risks, patience, altruism, positive and negative reciprocity, and trust for 80,000 individuals in 76 representative country samples. Gender differences in preferences were positively related to economic development and gender equality. This finding suggests that greater availability of and gender-equal access to material and social resources favor the manifestation of gender-differentiated preferences across countries.

    更新日期:2018-10-19
  • Programmed DNA destruction by miniature CRISPR-Cas14 enzymes
    Science (IF 41.058) Pub Date : 2018-10-18
    Lucas B. Harrington, David Burstein, Janice S. Chen, David Paez-Espino, Enbo Ma, Isaac P. Witte, Joshua C. Cofsky, Nikos C. Kyrpides, Jillian F. Banfield, Jennifer A. Doudna

    CRISPR-Cas systems provide microbes with adaptive immunity to infectious nucleic acids and are widely employed as genome editing tools. These tools utilize RNA-guided Cas proteins whose large size (950–1400 amino acids) has been considered essential to their specific DNA- or RNA-targeting activities. Here we present a set of CRISPR-Cas systems from uncultivated archaea that contain Cas14, a family of exceptionally compact RNA-guided nucleases (400–700 amino acids). Despite their small size, Cas14 proteins are capable of targeted single-stranded DNA (ssDNA) cleavage without restrictive sequence requirements. Moreover, target recognition by Cas14 triggers non-specific cutting of ssDNA molecules, an activity that enables high-fidelity SNP genotyping (Cas14-DETECTR). Metagenomic data show that multiple CRISPR-Cas14 systems evolved independently and suggest a potential evolutionary origin of single-effector CRISPR-based adaptive immunity.

    更新日期:2018-10-19
  • Magnetic hysteresis up to 80 kelvin in a dysprosium metallocene single-molecule magnet
    Science (IF 41.058) Pub Date : 2018-10-18
    Fu-Sheng Guo, Benjamin M. Day, Yan-Cong Chen, Ming-Liang Tong, Akseli Mansikkamäki, Richard A. Layfield

    Single-molecule magnets (SMMs) containing only one metal center may represent the lower size limit for molecule-based magnetic information storage materials. Their current drawback is that all SMMs require liquid-helium cooling to show magnetic memory effects. We now report a chemical strategy to access the dysprosium metallocene cation [(CpiPr5)Dy(Cp*)]+ (CpiPr5 = penta-iso-propylcyclopentadienyl, Cp* = pentamethylcyclopentadienyl), which displays magnetic hysteresis above liquid-nitrogen temperatures. An effective energy barrier to reversal of the magnetization of Ueff = 1,541 cm–1 is also measured. The magnetic blocking temperature of TB = 80 K for this cation overcomes an essential barrier towards the development of nanomagnet devices that function at practical temperatures.

    更新日期:2018-10-19
  • Somatic mutant clones colonize the human esophagus with age
    Science (IF 41.058) Pub Date : 2018-10-18
    Iñigo Martincorena, Joanna C. Fowler, Agnieszka Wabik, Andrew R. J. Lawson, Federico Abascal, Michael W. J. Hall, Alex Cagan, Kasumi Murai, Krishnaa Mahbubani, Michael R. Stratton, Rebecca C. Fitzgerald, Penny A. Handford, Peter J. Campbell, Kourosh Saeb-Parsy, Philip H. Jones

    The extent to which cells in normal tissues accumulate mutations throughout life is poorly understood. Some mutant cells expand into clones that can be detected by genome sequencing. We mapped mutant clones in normal esophageal epithelium from nine donors (age range, 20 to 75 years). Somatic mutations accumulated with age and were caused mainly by intrinsic mutational processes. We found strong positive selection of clones carrying mutations in 14 cancer genes, with tens to hundreds of clones per square centimeter. In middle-aged and elderly donors, clones with cancer-associated mutations covered much of the epithelium, with NOTCH1 and TP53 mutations affecting 12 to 80% and 2 to 37% of cells, respectively. Unexpectedly, the prevalence of NOTCH1 mutations in normal esophagus was several times higher than in esophageal cancers. These findings have implications for our understanding of cancer and aging.

    更新日期:2018-10-19
  • Colossal grain growth yields single-crystal metal foils by contact-free annealing
    Science (IF 41.058) Pub Date : 2018-10-18
    Sunghwan Jin, Ming Huang, Youngwoo Kwon, Leining Zhang, Bao-Wen Li, Sangjun Oh, Jichen Dong, Da Luo, Mandakini Biswal, Benjamin V. Cunning, Pavel V. Bakharev, Inyong Moon, Won Jong Yoo, Dulce C. Camacho-Mojica, Yong-Jin Kim, Sun Hwa Lee, Bin Wang, Won Kyung Seong, Manav Saxena, Feng Ding, Hyung-Joon Shin, Rodney S. Ruoff

    Single-crystal metals have unique properties due to the absence of grain boundaries and strong anisotropy. Commercial single-crystal metals are usually synthesized by bulk crystal growth or by deposition of thin films onto substrates, and they are expensive and small. We prepare extremely large single-crystal metal foils by ‘contact-free annealing’ from commercial polycrystalline foils. The colossal grain growth (up to 32 cm2) is achieved by minimizing contact stresses, resulting in a preferred in-plane and out-of-plane crystal orientation, and is driven by surface energy minimization during the rotation of the crystal lattice followed by ‘consumption’ of neighboring grains. Industrial scale production of single-crystal metal foils is possible from this discovery.

    更新日期:2018-10-19
  • Neuronal specification in space and time
    Science (IF 41.058) Pub Date : 2018-10-12
    Isabel Holguera, Claude Desplan

    To understand how neurons assemble to form functional circuits, it is necessary to obtain a detailed knowledge of their diversity and to define the developmental specification programs that give rise to this diversity. Invertebrates and vertebrates appear to share common developmental principles of neuronal specification in which cascades of transcription factors temporally pattern progenitors, while spatial cues modify the outcomes of this temporal patterning. Here, we highlight these conserved mechanisms and describe how they are used in distinct neural structures. We present the questions that remain for a better understanding of neuronal specification. Single-cell RNA profiling approaches will potentially shed light on these questions, allowing not only the characterization of neuronal diversity in adult brains, but also the investigation of the developmental trajectories leading to the generation and maintenance of this diversity.

    更新日期:2018-10-12
  • Glia as architects of central nervous system formation and function
    Science (IF 41.058) Pub Date : 2018-10-12
    Nicola J. Allen, David A. Lyons

    Glia constitute roughly half of the cells of the central nervous system (CNS) but were long-considered to be static bystanders to its formation and function. Here we provide an overview of how the diverse and dynamic functions of glial cells orchestrate essentially all aspects of nervous system formation and function. Radial glia, astrocytes, oligodendrocyte progenitor cells, oligodendrocytes, and microglia each influence nervous system development, from neuronal birth, migration, axon specification, and growth through circuit assembly and synaptogenesis. As neural circuits mature, distinct glia fulfill key roles in synaptic communication, plasticity, homeostasis, and network-level activity through dynamic monitoring and alteration of CNS structure and function. Continued elucidation of glial cell biology, and the dynamic interactions of neurons and glia, will enrich our understanding of nervous system formation, health, and function.

    更新日期:2018-10-12
  • Microglia and early brain development: An intimate journey
    Science (IF 41.058) Pub Date : 2018-10-12
    Morgane S. Thion, Florent Ginhoux, Sonia Garel

    Cross-talk between the nervous and immune systems has been well described in the context of adult physiology and disease. Recent advances in our understanding of immune cell ontogeny have revealed a notable interplay between neurons and microglia during the prenatal and postnatal emergence of functional circuits. This Review focuses on the brain, where the early symbiotic relationship between microglia and neuronal cells critically regulates wiring, contributes to sex-specific differences in neural circuits, and relays crucial information from the periphery, including signals derived from the microbiota. These observations underscore the importance of studying neurodevelopment as part of a broader framework that considers nervous system interactions with microglia in a whole-body context.

    更新日期:2018-10-12
  • Homology, neocortex, and the evolution of developmental mechanisms
    Science (IF 41.058) Pub Date : 2018-10-12
    Steven D. Briscoe, Clifton W. Ragsdale

    The six-layered neocortex of the mammalian pallium has no clear homolog in birds or non-avian reptiles. Recent research indicates that although these extant amniotes possess a variety of divergent and nonhomologous pallial structures, they share a conserved set of neuronal cell types and circuitries. These findings suggest a principle of brain evolution: that natural selection preferentially preserves the integrity of information-processing pathways, whereas other levels of biological organization, such as the three-dimensional architectures of neuronal assemblies, are less constrained. We review the similarities of pallial neuronal cell types in amniotes, delineate candidate gene regulatory networks for their cellular identities, and propose a model of developmental evolution for the divergence of amniote pallial structures.

    更新日期:2018-10-12
  • A hot and fast ultra-stripped supernova that likely formed a compact neutron star binary
    Science (IF 41.058) Pub Date : 2018-10-12
    K. De, M. M. Kasliwal, E. O. Ofek, T. J. Moriya, J. Burke, Y. Cao, S. B. Cenko, G. B. Doran, G. E. Duggan, R. P. Fender, C. Fransson, A. Gal-Yam, A. Horesh, S. R. Kulkarni, R. R. Laher, R. Lunnan, I. Manulis, F. Masci, P. A. Mazzali, P. E. Nugent, D. A. Perley, T. Petrushevska, A. L. Piro, C. Rumsey, J. Sollerman, M. Sullivan, F. Taddia

    Compact neutron star binary systems are produced from binary massive stars through stellar evolution involving up to two supernova explosions. The final stages in the formation of these systems have not been directly observed. We report the discovery of iPTF 14gqr (SN 2014ft), a type Ic supernova with a fast-evolving light curve indicating an extremely low ejecta mass (≈0.2 solar masses) and low kinetic energy (≈2 × 1050 ergs). Early photometry and spectroscopy reveal evidence of shock cooling of an extended helium-rich envelope, likely ejected in an intense pre-explosion mass-loss episode of the progenitor. Taken together, we interpret iPTF 14gqr as evidence for ultra-stripped supernovae that form neutron stars in compact binary systems.

    更新日期:2018-10-12
  • Genome hypermobility by lateral transduction
    Science (IF 41.058) Pub Date : 2018-10-12
    John Chen, Nuria Quiles-Puchalt, Yin Ning Chiang, Rodrigo Bacigalupe, Alfred Fillol-Salom, Melissa Su Juan Chee, J. Ross Fitzgerald, José R. Penadés

    Genetic transduction is a major evolutionary force that underlies bacterial adaptation. Here we report that the temperate bacteriophages of Staphylococcus aureus engage in a distinct form of transduction we term lateral transduction. Staphylococcal prophages do not follow the previously described excision-replication-packaging pathway but instead excise late in their lytic program. Here, DNA packaging initiates in situ from integrated prophages, and large metameric spans including several hundred kilobases of the S. aureus genome are packaged in phage heads at very high frequency. In situ replication before DNA packaging creates multiple prophage genomes so that lateral-transducing particles form during normal phage maturation, transforming parts of the S. aureus chromosome into hypermobile regions of gene transfer.

    更新日期:2018-10-12
  • Entropy-driven stability of chiral single-walled carbon nanotubes
    Science (IF 41.058) Pub Date : 2018-10-12
    Yann Magnin, Hakim Amara, François Ducastelle, Annick Loiseau, Christophe Bichara

    Single-walled carbon nanotubes are hollow cylinders that can grow centimeters long via carbon incorporation at the interface with a catalyst. They display semiconducting or metallic characteristics, depending on their helicity, which is determined during their growth. To support the quest for a selective synthesis, we develop a thermodynamic model that relates the tube-catalyst interfacial energies, temperature, and the resulting tube chirality. We show that nanotubes can grow chiral because of the configurational entropy of their nanometer-sized edge, thus explaining experimentally observed temperature evolutions of chiral distributions. Taking the chemical nature of the catalyst into account through interfacial energies, we derive structural maps and phase diagrams that will guide a rational choice of a catalyst and growth parameters toward a better selectivity.

    更新日期:2018-10-12
  • Confined acids catalyze asymmetric single aldolizations of acetaldehyde enolates
    Science (IF 41.058) Pub Date : 2018-10-12
    Lucas Schreyer, Philip S. J. Kaib, Vijay N. Wakchaure, Carla Obradors, Roberta Properzi, Sunggi Lee, Benjamin List

    Reactions that form a product with the same reactive functionality as that of one of the starting compounds frequently end in oligomerization. As a salient example, selective aldol coupling of the smallest, though arguably most useful, enolizable aldehyde, acetaldehyde, with just one partner substrate has proven to be extremely challenging. Here, we report a highly enantioselective Mukaiyama aldol reaction with the simple triethylsilyl (TES) and tert-butyldimethylsilyl (TBS) enolates of acetaldehyde and various aliphatic and aromatic acceptor aldehydes. The reaction is catalyzed by recently developed, strongly acidic imidodiphosphorimidates (IDPi), which, like enzymes, display a confined active site but, like small-molecule catalysts, have a broad substrate scope. The process is scalable, fast, efficient (0.5 to 1.5 mole % catalyst loading), and greatly simplifies access to highly valuable silylated acetaldehyde aldols.

    更新日期:2018-10-12
  • Key-and-lock commodity self-healing copolymers
    Science (IF 41.058) Pub Date : 2018-10-12
    Marek W. Urban, Dmitriy Davydovich, Ying Yang, Tugba Demir, Yunzhi Zhang, Leah Casabianca

    Self-healing materials are notable for their ability to recover from physical or chemical damage. We report that commodity copolymers, such as poly(methyl methacrylate)/n-butyl acrylate [p(MMA/nBA)] and their derivatives, can self-heal upon mechanical damage. This behavior occurs in a narrow compositional range for copolymer topologies that are preferentially alternating with a random component (alternating/random) and is attributed to favorable interchain van der Waals forces forming key-and-lock interchain junctions. The use of van der Waals forces instead of supramolecular or covalent rebonding or encapsulated reactants eliminates chemical and physical alterations and enables multiple recovery upon mechanical damage without external intervention. Unlike other self-healing approaches, perturbation of ubiquitous van der Waals forces upon mechanical damage is energetically unfavorable for interdigitated alternating/random copolymer motifs that facilitate self-healing under ambient conditions.

    更新日期:2018-10-12
  • Ketyl radical reactivity via atom transfer catalysis
    Science (IF 41.058) Pub Date : 2018-10-12
    Lu Wang, Jeremy M. Lear, Sean M. Rafferty, Stacy C. Fosu, David A. Nagib

    Single-electron reduction of a carbonyl to a ketyl enables access to a polarity-reversed platform of reactivity for this cornerstone functional group. However, the synthetic utility of the ketyl radical is hindered by the strong reductants necessary for its generation, which also limit its reactivity to net reductive mechanisms. We report a strategy for net redox-neutral generation and reaction of ketyl radicals. The in situ conversion of aldehydes to α-acetoxy iodides lowers their reduction potential by more than 1 volt, allowing for milder access to the corresponding ketyl radicals and an oxidative termination event. Upon subjecting these iodides to a dimanganese decacarbonyl precatalyst and visible light irradiation, an atom transfer radical addition (ATRA) mechanism affords a broad scope of vinyl iodide products with high Z-selectivity.

    更新日期:2018-10-12
  • Electrical generation and detection of spin waves in a quantum Hall ferromagnet
    Science (IF 41.058) Pub Date : 2018-10-12
    Di S. Wei, Toeno van der Sar, Seung Hwan Lee, Kenji Watanabe, Takashi Taniguchi, Bertrand I. Halperin, Amir Yacoby

    Spin waves are collective excitations of magnetic systems. An attractive setting for studying long-lived spin-wave physics is the quantum Hall (QH) ferromagnet, which forms spontaneously in clean two-dimensional electron systems at low temperature and in a perpendicular magnetic field. We used out-of-equilibrium occupation of QH edge channels in graphene to excite and detect spin waves in magnetically ordered QH states. Our experiments provide direct evidence for long-distance spin-wave propagation through different ferromagnetic phases in the N = 0 Landau level, as well as across the insulating canted antiferromagnetic phase. Our results will enable experimental investigation of the fundamental magnetic properties of these exotic two-dimensional electron systems.

    更新日期:2018-10-12
  • Systemic control of legume susceptibility to rhizobial infection by a mobile microRNA
    Science (IF 41.058) Pub Date : 2018-10-12
    Daniela Tsikou, Zhe Yan, Dennis B. Holt, Nikolaj B. Abel, Dugald E. Reid, Lene H. Madsen, Hemal Bhasin, Moritz Sexauer, Jens Stougaard, Katharina Markmann

    Nitrogen-fixing root nodules on legumes result from two developmental processes, bacterial infection and nodule organogenesis. To balance symbiosis and plant growth, legume hosts restrict nodule numbers through an inducible autoregulatory process. Here, we present a mechanism where repression of a negative regulator ensures symbiotic susceptibility of uninfected roots of the host Lotus japonicus. We show that microRNA miR2111 undergoes shoot-to-root translocation to control rhizobial infection through posttranscriptional regulation of the symbiosis suppressor TOO MUCH LOVE in roots. miR2111 maintains a susceptible default status in uninfected hosts and functions as an activator of symbiosis downstream of LOTUS HISTIDINE KINASE1–mediated cytokinin perception in roots and HYPERNODULATION ABERRANT ROOT FORMATION1, a shoot factor in autoregulation. The miR2111-TML node ensures activation of feedback regulation to balance infection and nodulation events.

    更新日期:2018-10-12
  • Systematic discovery of natural CRISPR-Cas12a inhibitors
    Science (IF 41.058) Pub Date : 2018-10-12
    Kyle E. Watters, Christof Fellmann, Hua B. Bai, Shawn M. Ren, Jennifer A. Doudna

    Cas12a (Cpf1) is a CRISPR-associated nuclease with broad utility for synthetic genome engineering, agricultural genomics, and biomedical applications. Although bacteria harboring CRISPR-Cas9 or CRISPR-Cas3 adaptive immune systems sometimes acquire mobile genetic elements encoding anti-CRISPR proteins that inhibit Cas9, Cas3, or the DNA-binding Cascade complex, no such inhibitors have been found for CRISPR-Cas12a. Here we use a comprehensive bioinformatic and experimental screening approach to identify three different inhibitors that block or diminish CRISPR-Cas12a–mediated genome editing in human cells. We also find a widespread connection between CRISPR self-targeting and inhibitor prevalence in prokaryotic genomes, suggesting a straightforward path to the discovery of many more anti-CRISPRs from the microbial world.

    更新日期:2018-10-12
  • Discovery of widespread type I and type V CRISPR-Cas inhibitors
    Science (IF 41.058) Pub Date : 2018-10-12
    Nicole D. Marino, Jenny Y. Zhang, Adair L. Borges, Alexander A. Sousa, Lina M. Leon, Benjamin J. Rauch, Russell T. Walton, Joel D. Berry, J. Keith Joung, Benjamin P. Kleinstiver, Joseph Bondy-Denomy

    Bacterial CRISPR-Cas systems protect their host from bacteriophages and other mobile genetic elements. Mobile elements, in turn, encode various anti-CRISPR (Acr) proteins to inhibit the immune function of CRISPR-Cas. To date, Acr proteins have been discovered for type I (subtypes I-D, I-E, and I-F) and type II (II-A and II-C) but not other CRISPR systems. Here, we report the discovery of 12 acr genes, including inhibitors of type V-A and I-C CRISPR systems. AcrVA1 inhibits a broad spectrum of Cas12a (Cpf1) orthologs—including MbCas12a, Mb3Cas12a, AsCas12a, and LbCas12a—when assayed in human cells. The acr genes reported here provide useful biotechnological tools and mark the discovery of acr loci in many bacteria and phages.

    更新日期:2018-10-12
  • Pan-tumor genomic biomarkers for PD-1 checkpoint blockade–based immunotherapy
    Science (IF 41.058) Pub Date : 2018-10-12
    Razvan Cristescu, Robin Mogg, Mark Ayers, Andrew Albright, Erin Murphy, Jennifer Yearley, Xinwei Sher, Xiao Qiao Liu, Hongchao Lu, Michael Nebozhyn, Chunsheng Zhang, Jared K. Lunceford, Andrew Joe, Jonathan Cheng, Andrea L. Webber, Nageatte Ibrahim, Elizabeth R. Plimack, Patrick A. Ott, Tanguy Y. Seiwert, Antoni Ribas, Terrill K. McClanahan, Joanne E. Tomassini, Andrey Loboda, David Kaufman

    Programmed cell death protein–1 (PD-1) and programmed cell death ligand–1 (PD-L1) checkpoint blockade immunotherapy elicits durable antitumor effects in multiple cancers, yet not all patients respond. We report the evaluation of >300 patient samples across 22 tumor types from four KEYNOTE clinical trials. Tumor mutational burden (TMB) and a T cell–inflamed gene expression profile (GEP) exhibited joint predictive utility in identifying responders and nonresponders to the PD-1 antibody pembrolizumab. TMB and GEP were independently predictive of response and demonstrated low correlation, suggesting that they capture distinct features of neoantigenicity and T cell activation. Analysis of The Cancer Genome Atlas database showed TMB and GEP to have a low correlation, and analysis by joint stratification revealed biomarker-defined patterns of targetable-resistance biology. These biomarkers may have utility in clinical trial design by guiding rational selection of anti–PD-1 monotherapy and combination immunotherapy regimens.

    更新日期:2018-10-12
  • Thyroid hormone signaling specifies cone subtypes in human retinal organoids
    Science (IF 41.058) Pub Date : 2018-10-12
    Kiara C. Eldred, Sarah E. Hadyniak, Katarzyna A. Hussey, Boris Brenerman, Ping-Wu Zhang, Xitiz Chamling, Valentin M. Sluch, Derek S. Welsbie, Samer Hattar, James Taylor, Karl Wahlin, Donald J. Zack, Robert J. Johnston

    The mechanisms underlying specification of neuronal subtypes within the human nervous system are largely unknown. The blue (S), green (M), and red (L) cones of the retina enable high-acuity daytime and color vision. To determine the mechanism that controls S versus L/M fates, we studied the differentiation of human retinal organoids. Organoids and retinas have similar distributions, expression profiles, and morphologies of cone subtypes. S cones are specified first, followed by L/M cones, and thyroid hormone signaling controls this temporal switch. Dynamic expression of thyroid hormone–degrading and –activating proteins within the retina ensures low signaling early to specify S cones and high signaling late to produce L/M cones. This work establishes organoids as a model for determining mechanisms of human development with promising utility for therapeutics and vision repair.

    更新日期:2018-10-12
  • Structure and dynamics of the yeast SWR1-nucleosome complex
    Science (IF 41.058) Pub Date : 2018-10-12
    Oliver Willhoft, Mohamed Ghoneim, Chia-Liang Lin, Eugene Y. D. Chua, Martin Wilkinson, Yuriy Chaban, Rafael Ayala, Elizabeth A. McCormack, Lorraine Ocloo, David S. Rueda, Dale B. Wigley

    The yeast SWR1 complex exchanges histone H2A in nucleosomes with Htz1 (H2A.Z in humans). The cryo–electron microscopy structure of the SWR1 complex bound to a nucleosome at 3.6-angstrom resolution reveals details of the intricate interactions between components of the SWR1 complex and its nucleosome substrate. Interactions between the Swr1 motor domains and the DNA wrap at superhelical location 2 distort the DNA, causing a bulge with concomitant translocation of the DNA by one base pair, coupled to conformational changes of the histone core. Furthermore, partial unwrapping of the DNA from the histone core takes place upon binding of nucleosomes to SWR1 complex. The unwrapping, as monitored by single-molecule data, is stabilized and has its dynamics altered by adenosine triphosphate binding but does not require hydrolysis.

    更新日期:2018-10-12
  • Dimerization quality control ensures neuronal development and survival
    Science (IF 41.058) Pub Date : 2018-10-12
    Elijah L. Mena, Rachel A. S. Kjolby, Robert A. Saxton, Achim Werner, Brandon G. Lew, John M. Boyle, Richard Harland, Michael Rape

    Aberrant complex formation by recurrent interaction modules, such as BTB domains, leucine zippers, or coiled coils, can disrupt signal transduction, yet whether cells detect and eliminate complexes of irregular composition is unknown. By searching for regulators of the BTB family, we discovered a quality control pathway that ensures functional dimerization [dimerization quality control (DQC)]. Key to this network is the E3 ligase SCFFBXL17, which selectively binds and ubiquitylates BTB dimers of aberrant composition to trigger their clearance by proteasomal degradation. Underscoring the physiological importance of DQC, SCFFBXL17 is required for the differentiation, function, and survival of neural crest and neuronal cells. We conclude that metazoan organisms actively monitor BTB dimerization, and we predict that distinct E3 ligases similarly control complex formation by other recurrent domains.

    更新日期:2018-10-12
  • Substrate-engaged 26S proteasome structures reveal mechanisms for ATP-hydrolysis–driven translocation
    Science (IF 41.058) Pub Date : 2018-10-11
    Andres H. de la Peña, Ellen A. Goodall, Stephanie N. Gates, Gabriel C. Lander, A. Martin

    The 26S proteasome is the primary eukaryotic degradation machine and thus critically involved in numerous cellular processes. The hetero-hexameric ATPase motor of the proteasome unfolds and translocates targeted protein substrates into the open gate of a proteolytic core, while a proteasomal deubiquitinase concomitantly removes substrate-attached ubiquitin chains. However, the mechanisms by which ATP hydrolysis drives the conformational changes responsible for these processes have remained elusive. Here we present the cryo-EM structures of four distinct conformational states of the actively ATP-hydrolyzing, substrate-engaged 26S proteasome. These structures reveal how mechanical substrate translocation accelerates deubiquitination, and how ATP-binding, hydrolysis, and phosphate-release events are coordinated within the AAA+ motor to induce conformational changes and propel the substrate through the central pore.

    更新日期:2018-10-12
  • Identity inference of genomic data using long-range familial searches
    Science (IF 41.058) Pub Date : 2018-10-11
    Yaniv Erlich, Tal Shor, Itsik Pe’er, Shai Carmi

    Consumer genomics databases have reached the scale of millions of individuals. Recently, law enforcement authorities have exploited some of these databases to identify suspects via distant familial relatives. Using genomic data of 1.28 million individuals tested with consumer genomics, we investigated the power of this technique. We project that about 60% of the searches for individuals of European-descent will result in a third cousin or closer match, which can allow their identification using demographic identifiers. Moreover, the technique could implicate nearly any US-individual of European-descent in the near future. We demonstrate that the technique can also identify research participants of a public sequencing project. Based on these results, we propose a potential mitigation strategy and policy implications to human subject research.

    更新日期:2018-10-12
  • In vivo modeling of human neuron dynamics and Down syndrome
    Science (IF 41.058) Pub Date : 2018-10-11
    Raquel Real, Manuel Peter, Antonio Trabalza, Shabana Khan, Mark A. Smith, Joana Dopp, Samuel J. Barnes, Ayiba Momoh, Alessio Strano, Emanuela Volpi, Graham Knott, Frederick J. Livesey, Vincenzo De Paola

    Harnessing the potential of human stem cells for modelling the physiology and diseases of cortical circuitry requires monitoring cellular dynamics in vivo. Here, we show that human iPSC–derived cortical neurons transplanted in the adult mouse cortex consistently organized in large (up to ~100 mm3) vascularized neuron-glia territories with complex cytoarchitecture. Longitudinal imaging of >4000 grafted developing human neurons revealed that neuronal arbors refined via branch-specific retraction; human synaptic networks substantially restructured over 4 months, with balanced rates of synapse formation and elimination; and oscillatory population activity mirrored the patterns of fetal neural networks. Finally, we found increased synaptic stability and reduced oscillations in transplants from two individuals with Down syndrome, demonstrating the potential of in vivo imaging in human tissue grafts for patient-specific modelling of cortical development, physiology, and pathogenesis.

    更新日期:2018-10-12
  • Controlled crack propagation for atomic precision handling of wafer-scale two-dimensional materials
    Science (IF 41.058) Pub Date : 2018-10-11
    Jaewoo Shim, Sang-Hoon Bae, Wei Kong, Doyoon Lee, Kuan Qiao, Daniel Nezich, Yong Ju Park, Ruike Zhao, Suresh Sundaram, Xin Li, Hanwool Yeon, Chanyeol Choi, Hyun Kum, Ruoyu Yue, Guanyu Zhou, Yunbo Ou, Kyusang Lee, Jagadeesh Moodera, Xuanhe Zhao, Jong-Hyun Ahn, Christopher Hinkle, Abdallah Ougazzaden, Jeehwan Kim

    Although flakes of two-dimensional (2D) heterostructures at micrometer scale can be formed with adhesive-tape methods, isolation of 2D flakes into monolayers is extremely time-consuming as it is a trial-and-error process. Controlling the number of 2D layers through direct growth also presents difficulty because of the high nucleation barrier on 2D materials. We demonstrate a layer-resolved 2D material splitting technique that permits the high-throughput production of multiple monolayers of wafer-scale (5 centimeter diameter) 2D materials by splitting single stacks of thick 2D materials grown on a single wafer. Wafer-scale uniformity of h-BN, WS2, WSe2, MoS2, and MoSe2 monolayers was verified by photoluminescence (PL) response and by substantial retention of electronic conductivity. We fabricated wafer-scale van der Waals heterostructures, including field-effect transistors, with single-atom thickness resolution.

    更新日期:2018-10-12
  • Methylammonium-free, high-performance and stable perovskite solar cells on a planar architecture
    Science (IF 41.058) Pub Date : 2018-10-11
    Silver-Hamill Turren-Cruz, Anders Hagfeldt, Michael Saliba

    Currently, perovskite solar cells (PSCs) with high performances >20% contain Br, causing a suboptimal bandgap, and the thermally unstable methylammonium (MA) molecule. Avoiding Br and especially MA can, therefore, result in more optimal bandgaps and stable perovskites. We show that inorganic cation tuning, using Rb and Cs, enables highly crystalline formamidinium-based perovskites without Br or MA. On a conventional, planar device architecture, using polymeric interlayers at the electron and hole transporting interface, we demonstrate an efficiency of 20.35% (stabilized), one of the highest for MA-free perovskites, with a drastically improved stability reached without the stabilizing influence of mesoporous interlayers. The perovskite is not heated beyond 100°C. Going MA-free is a new direction for perovskites that are inherently stable and compatible with tandems or flexible substrates which are the main routes commercializing PSCs.

    更新日期:2018-10-12
  • Observation of the topological Anderson insulator in disordered atomic wires
    Science (IF 41.058) Pub Date : 2018-10-11
    Eric J. Meier, Fangzhao Alex An, Alexandre Dauphin, Maria Maffei, Pietro Massignan, Taylor L. Hughes, Bryce Gadway

    Topology and disorder have a rich combined influence on quantum transport. In order to probe their interplay, we synthesized one-dimensional chiral symmetric wires with controllable disorder via spectroscopic Hamiltonian engineering, based on the laser-driven coupling of discrete momentum states of ultracold atoms. Measuring the bulk evolution of a topological indicator following a sudden quench, we observed the topological Anderson insulator phase, in which added disorder drives the band structure of a wire from topologically trivial to non-trivial. In addition, we observed the robustness of topologically non-trivial wires to weak disorder and measured the transition to a trivial phase in the presence of strong disorder. Atomic interactions in this quantum simulation platform may enable realizations of strongly interacting topological fluids.

    更新日期:2018-10-12
  • Single-cell analysis uncovers convergence of cell identities during axolotl limb regeneration
    Science (IF 41.058) Pub Date : 2018-10-09
    Tobias Gerber, Prayag Murawala, Dunja Knapp, Wouter Masselink, Maritta Schuez, Sarah Hermann, Malgorzata Gac-Santel, Sergej Nowoshilow, Jorge Kageyama, Shahryar Khattak, Joshua D. Currie, J. Gray Camp, Elly M. Tanaka, Barbara Treutlein

    Amputation of the axolotl forelimb results in the formation of a blastema, a transient tissue where progenitor cells accumulate prior to limb regeneration. However, the molecular understanding of blastema formation had previously suffered from the inability to identify and isolate blastema precursor cells in the adult tissue. Here we use a combination of Cre-loxP reporter lineage tracking and single-cell (sc) RNA-seq to molecularly track mature connective tissue (CT) cell heterogeneity and its transition to a limb blastema state. We uncover a multi-phasic molecular program where CT cell types found in the uninjured adult limb revert to a relatively homogenous progenitor state that recapitulates an embryonic limb bud-like phenotype including multipotency within the CT lineage. Together, our data illuminates molecular and cellular reprogramming during complex organ regeneration in a vertebrate.

    更新日期:2018-10-09
  • Glacial lake outburst floods as drivers of fluvial erosion in the Himalaya
    Science (IF 41.058) Pub Date : 2018-10-05
    Kristen L. Cook, Christoff Andermann, Florent Gimbert, Basanta Raj Adhikari, Niels Hovius

    Himalayan rivers are frequently hit by catastrophic floods that are caused by the failure of glacial lake and landslide dams; however, the dynamics and long-term impacts of such floods remain poorly understood. We present a comprehensive set of observations that capture the July 2016 glacial lake outburst flood (GLOF) in the Bhotekoshi/Sunkoshi River of Nepal. Seismic records of the flood provide new insights into GLOF mechanics and their ability to mobilize large boulders that otherwise prevent channel erosion. Because of this boulder mobilization, GLOF impacts far exceed those of the annual summer monsoon, and GLOFs may dominate fluvial erosion and channel-hillslope coupling many tens of kilometers downstream of glaciated areas. Long-term valley evolution in these regions may therefore be driven by GLOF frequency and magnitude, rather than by precipitation.

    更新日期:2018-10-04
  • Slab2, a comprehensive subduction zone geometry model
    Science (IF 41.058) Pub Date : 2018-10-05
    Gavin P. Hayes, Ginevra L. Moore, Daniel E. Portner, Mike Hearne, Hanna Flamme, Maria Furtney, Gregory M. Smoczyk

    Subduction zones are home to the most seismically active faults on the planet. The shallow megathrust interfaces of subduction zones host Earth’s largest earthquakes and are likely the only faults capable of magnitude 9+ ruptures. Despite these facts, our knowledge of subduction zone geometry—which likely plays a key role in determining the spatial extent and ultimately the size of subduction zone earthquakes—is incomplete. We calculated the three-dimensional geometries of all seismically active global subduction zones. The resulting model, called Slab2, provides a uniform geometrical analysis of all currently subducting slabs.

    更新日期:2018-10-04
  • Rapid change of superconductivity and electron-phonon coupling through critical doping in Bi-2212
    Science (IF 41.058) Pub Date : 2018-10-05
    Y. He, M. Hashimoto, D. Song, S.-D. Chen, J. He, I. M. Vishik, B. Moritz, D.-H. Lee, N. Nagaosa, J. Zaanen, T. P. Devereaux, Y. Yoshida, H. Eisaki, D. H. Lu, Z.-X. Shen

    Electron-boson coupling plays a key role in superconductivity for many systems. However, in copper-based high–critical temperature (Tc) superconductors, its relation to superconductivity remains controversial despite strong spectroscopic fingerprints. In this study, we used angle-resolved photoemission spectroscopy to find a pronounced correlation between the superconducting gap and the bosonic coupling strength near the Brillouin zone boundary in Bi2Sr2CaCu2O8+δ. The bosonic coupling strength rapidly increases from the overdoped Fermi liquid regime to the optimally doped strange metal, concomitant with the quadrupled superconducting gap and the doubled gap-to-Tc ratio across the pseudogap boundary. This synchronized lattice and electronic response suggests that the effects of electronic interaction and the electron-phonon coupling (EPC) reinforce each other in a positive-feedback loop upon entering the strange-metal regime, which in turn drives a stronger superconductivity.

    更新日期:2018-10-04
  • Quantum oscillations of electrical resistivity in an insulator
    Science (IF 41.058) Pub Date : 2018-10-05
    Z. Xiang, Y. Kasahara, T. Asaba, B. Lawson, C. Tinsman, Lu Chen, K. Sugimoto, S. Kawaguchi, Y. Sato, G. Li, S. Yao, Y. L. Chen, F. Iga, John Singleton, Y. Matsuda, Lu Li

    In metals, orbital motions of conduction electrons on the Fermi surface are quantized in magnetic fields, which is manifested by quantum oscillations in electrical resistivity. This Landau quantization is generally absent in insulators. Here, we report a notable exception in an insulator—ytterbium dodecaboride (YbB12). The resistivity of YbB12, which is of a much larger magnitude than the resistivity in metals, exhibits distinct quantum oscillations. These unconventional oscillations arise from the insulating bulk, even though the temperature dependence of the oscillation amplitude follows the conventional Fermi liquid theory of metals with a large effective mass. Quantum oscillations in the magnetic torque are also observed, albeit with a lighter effective mass.

    更新日期:2018-10-04
  • Quantifying hot carrier and thermal contributions in plasmonic photocatalysis
    Science (IF 41.058) Pub Date : 2018-10-05
    Linan Zhou, Dayne F. Swearer, Chao Zhang, Hossein Robatjazi, Hangqi Zhao, Luke Henderson, Liangliang Dong, Phillip Christopher, Emily A. Carter, Peter Nordlander, Naomi J. Halas

    Photocatalysis based on optically active, “plasmonic” metal nanoparticles has emerged as a promising approach to facilitate light-driven chemical conversions under far milder conditions than thermal catalysis. However, an understanding of the relation between thermal and electronic excitations has been lacking. We report the substantial light-induced reduction of the thermal activation barrier for ammonia decomposition on a plasmonic photocatalyst. We introduce the concept of a light-dependent activation barrier to account for the effect of light illumination on electronic and thermal excitations in a single unified picture. This framework provides insight into the specific role of hot carriers in plasmon-mediated photochemistry, which is critically important for designing energy-efficient plasmonic photocatalysts.

    更新日期:2018-10-04
  • Rapid Pliocene adaptive radiation of modern kangaroos
    Science (IF 41.058) Pub Date : 2018-10-05
    Aidan M. C. Couzens, Gavin J. Prideaux

    Differentiating between ancient and younger, more rapidly evolved clades is important for determining paleoenvironmental drivers of diversification. Australia possesses many aridity-adapted lineages, the origins of which have been closely linked to late Miocene continental aridification. Using dental macrowear and molar crown height measurements, spanning the past 25 million years, we show that the most iconic Australian terrestrial mammals, “true” kangaroos (Macropodini), adaptively radiated in response to mid-Pliocene grassland expansion rather than Miocene aridity. In contrast, low-crowned, short-faced kangaroos radiated into predominantly browsing niches as the late Cenozoic became more arid, contradicting the view that this was an interval of global browser decline. Our results implicate warm-to-cool climatic oscillations as a trigger for adaptive radiation and refute arguments attributing Pleistocene megafaunal extinction to aridity-forced dietary change.

    更新日期:2018-10-04
  • Urbanization and humidity shape the intensity of influenza epidemics in U.S. cities
    Science (IF 41.058) Pub Date : 2018-10-05
    Benjamin D. Dalziel, Stephen Kissler, Julia R. Gog, Cecile Viboud, Ottar N. Bjørnstad, C. Jessica E. Metcalf, Bryan T. Grenfell

    Influenza epidemics vary in intensity from year to year, driven by climatic conditions and by viral antigenic evolution. However, important spatial variation remains unexplained. Here we show predictable differences in influenza incidence among cities, driven by population size and structure. Weekly incidence data from 603 cities in the United States reveal that epidemics in smaller cities are focused on shorter periods of the influenza season, whereas in larger cities, incidence is more diffuse. Base transmission potential estimated from city-level incidence data is positively correlated with population size and with spatiotemporal organization in population density, indicating a milder response to climate forcing in metropolises. This suggests that urban centers incubate critical chains of transmission outside of peak climatic conditions, altering the spatiotemporal geometry of herd immunity.

    更新日期:2018-10-04
  • Impacts of species richness on productivity in a large-scale subtropical forest experiment
    Science (IF 41.058) Pub Date : 2018-10-05
    Yuanyuan Huang, Yuxin Chen, Nadia Castro-Izaguirre, Martin Baruffol, Matteo Brezzi, Anne Lang, Ying Li, Werner Härdtle, Goddert von Oheimb, Xuefei Yang, Xiaojuan Liu, Kequan Pei, Sabine Both, Bo Yang, David Eichenberg, Thorsten Assmann, Jürgen Bauhus, Thorsten Behrens, François Buscot, Xiao-Yong Chen, Douglas Chesters, Bing-Yang Ding, Walter Durka, Alexandra Erfmeier, Jingyun Fang, Markus Fischer, Liang-Dong Guo, Dali Guo, Jessica L. M. Gutknecht, Jin-Sheng He, Chun-Ling He, Andy Hector, Lydia Hönig, Ren-Yong Hu, Alexandra-Maria Klein, Peter Kühn, Yu Liang, Shan Li, Stefan Michalski, Michael Scherer-Lorenzen, Karsten Schmidt, Thomas Scholten, Andreas Schuldt, Xuezheng Shi, Man-Zhi Tan, Zhiyao Tang, Stefan Trogisch, Zhengwen Wang, Erik Welk, Christian Wirth, Tesfaye Wubet, Wenhua Xiang, Mingjian Yu, Xiao-Dong Yu, Jiayong Zhang, Shouren Zhang, Naili Zhang, Hong-Zhang Zhou, Chao-Dong Zhu, Li Zhu, Helge Bruelheide, Keping Ma, Pascal A. Niklaus, Bernhard Schmid

    Biodiversity experiments have shown that species loss reduces ecosystem functioning in grassland. To test whether this result can be extrapolated to forests, the main contributors to terrestrial primary productivity, requires large-scale experiments. We manipulated tree species richness by planting more than 150,000 trees in plots with 1 to 16 species. Simulating multiple extinction scenarios, we found that richness strongly increased stand-level productivity. After 8 years, 16-species mixtures had accumulated over twice the amount of carbon found in average monocultures and similar amounts as those of two commercial monocultures. Species richness effects were strongly associated with functional and phylogenetic diversity. A shrub addition treatment reduced tree productivity, but this reduction was smaller at high shrub species richness. Our results encourage multispecies afforestation strategies to restore biodiversity and mitigate climate change.

    更新日期:2018-10-04
  • The role of education interventions in improving economic rationality
    Science (IF 41.058) Pub Date : 2018-10-05
    Hyuncheol Bryant Kim, Syngjoo Choi, Booyuel Kim, Cristian Pop-Eleches

    Schooling rewards people with labor market returns and nonpecuniary benefits in other realms of life. However, there is no experimental evidence showing that education interventions improve individual economic rationality. We examine this hypothesis by studying a randomized 1-year financial support program for education in Malawi that reduced absence and dropout rates and increased scores on a qualification exam of female secondary school students. We measure economic rationality 4 years after the intervention by using lab-in-the-field experiments to create scores of consistency with utility maximization that are derived from revealed preference theory. We find that students assigned to the intervention had higher scores of rationality. The results remain robust after controlling for changes in cognitive and noncognitive skills. Our results suggest that education enhances the quality of economic decision-making.

    更新日期:2018-10-04
  • Gene editing restores dystrophin expression in a canine model of Duchenne muscular dystrophy
    Science (IF 41.058) Pub Date : 2018-10-05
    Leonela Amoasii, John C. W. Hildyard, Hui Li, Efrain Sanchez-Ortiz, Alex Mireault, Daniel Caballero, Rachel Harron, Thaleia-Rengina Stathopoulou, Claire Massey, John M. Shelton, Rhonda Bassel-Duby, Richard J. Piercy, Eric N. Olson

    Mutations in the gene encoding dystrophin, a protein that maintains muscle integrity and function, cause Duchenne muscular dystrophy (DMD). The deltaE50-MD dog model of DMD harbors a mutation corresponding to a mutational “hotspot” in the human DMD gene. We used adeno-associated viruses to deliver CRISPR gene editing components to four dogs and examined dystrophin protein expression 6 weeks after intramuscular delivery (n = 2) or 8 weeks after systemic delivery (n = 2). After systemic delivery in skeletal muscle, dystrophin was restored to levels ranging from 3 to 90% of normal, depending on muscle type. In cardiac muscle, dystrophin levels in the dog receiving the highest dose reached 92% of normal. The treated dogs also showed improved muscle histology. These large-animal data support the concept that, with further development, gene editing approaches may prove clinically useful for the treatment of DMD.

    更新日期:2018-10-04
  • Reprogramming normal human epithelial tissues to a common, lethal neuroendocrine cancer lineage
    Science (IF 41.058) Pub Date : 2018-10-05
    Jung Wook Park, John K. Lee, Katherine M. Sheu, Liang Wang, Nikolas G. Balanis, Kim Nguyen, Bryan A. Smith, Chen Cheng, Brandon L. Tsai, Donghui Cheng, Jiaoti Huang, Siavash K. Kurdistani, Thomas G. Graeber, Owen N. Witte

    The use of potent therapies inhibiting critical oncogenic pathways active in epithelial cancers has led to multiple resistance mechanisms, including the development of highly aggressive, small cell neuroendocrine carcinoma (SCNC). SCNC patients have a dismal prognosis due in part to a limited understanding of the molecular mechanisms driving this malignancy and the lack of effective treatments. Here, we demonstrate that a common set of defined oncogenic drivers reproducibly reprograms normal human prostate and lung epithelial cells to small cell prostate cancer (SCPC) and small cell lung cancer (SCLC), respectively. We identify shared active transcription factor binding regions in the reprogrammed prostate and lung SCNCs by integrative analyses of epigenetic and transcriptional landscapes. These results suggest that neuroendocrine cancers arising from distinct epithelial tissues may share common vulnerabilities that could be exploited for the development of drugs targeting SCNCs.

    更新日期:2018-10-04
  • A radiation belt of energetic protons located between Saturn and its rings
    Science (IF 41.058) Pub Date : 2018-10-05
    E. Roussos, P. Kollmann, N. Krupp, A. Kotova, L. Regoli, C. Paranicas, D. G. Mitchell, S. M. Krimigis, D. Hamilton, P. Brandt, J. Carbary, S. Christon, K. Dialynas, I. Dandouras, M. E. Hill, W. H. Ip, G. H. Jones, S. Livi, B. H. Mauk, B. Palmaerts, E. C. Roelof, A. Rymer, N. Sergis, H. T. Smith

    Saturn has a sufficiently strong dipole magnetic field to trap high-energy charged particles and form radiation belts, which have been observed outside its rings. Whether stable radiation belts exist near the planet and inward of the rings was previously unknown. The Cassini spacecraft’s Magnetosphere Imaging Instrument obtained measurements of a radiation belt that lies just above Saturn’s dense atmosphere and is decoupled from the rest of the magnetosphere by the planet’s A- to C-rings. The belt extends across the D-ring and comprises protons produced through cosmic ray albedo neutron decay and multiple charge-exchange reactions. These protons are lost to atmospheric neutrals and D-ring dust. Strong proton depletions that map onto features on the D-ring indicate a highly structured and diverse dust environment near Saturn.

    更新日期:2018-10-04
  • The low-frequency source of Saturn’s kilometric radiation
    Science (IF 41.058) Pub Date : 2018-10-05
    L. Lamy, P. Zarka, B. Cecconi, R. Prangé, W. S. Kurth, G. Hospodarsky, A. Persoon, M. Morooka, J.-E. Wahlund, G. J. Hunt

    Understanding how auroral radio emissions are produced by magnetized bodies requires in situ measurements within their source region. Saturn’s kilometric radiation (SKR) has been widely used as a remote proxy of Saturn’s magnetosphere. We present wave and plasma measurements from the Cassini spacecraft during its ring-grazing high-inclination orbits, which passed three times through the high-altitude SKR emission region. Northern dawn-side, narrow-banded radio sources were encountered at frequencies of 10 to 20 kilohertz, within regions of upward currents mapping to the ultraviolet auroral oval. The kilometric waves were produced on the extraordinary mode by the cyclotron maser instability from 6– to 12–kilo–electron volt electron beams and radiated quasi-perpendicularly to the auroral magnetic field lines. The SKR low-frequency sources appear to be strongly controlled by time-variable magnetospheric electron densities.

    更新日期:2018-10-04
Some contents have been Reproduced with permission of the American Chemical Society.
Some contents have been Reproduced by permission of The Royal Society of Chemistry.
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