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  • Multidimensional quantum entanglement with large-scale integrated optics
    Science (IF 37.205) Pub Date : 2018-04-20
    Jianwei Wang, Stefano Paesani, Yunhong Ding, Raffaele Santagati, Paul Skrzypczyk, Alexia Salavrakos, Jordi Tura, Remigiusz Augusiak, Laura Mančinska, Davide Bacco, Damien Bonneau, Joshua W. Silverstone, Qihuang Gong, Antonio Acín, Karsten Rottwitt, Leif K. Oxenløwe, Jeremy L. O’Brien, Anthony Laing, Mark G. Thompson

    The ability to control multidimensional quantum systems is central to the development of advanced quantum technologies. We demonstrate a multidimensional integrated quantum photonic platform able to generate, control, and analyze high-dimensional entanglement. A programmable bipartite entangled system is realized with dimensions up to 15 × 15 on a large-scale silicon photonics quantum circuit. The device integrates more than 550 photonic components on a single chip, including 16 identical photon-pair sources. We verify the high precision, generality, and controllability of our multidimensional technology, and further exploit these abilities to demonstrate previously unexplored quantum applications, such as quantum randomness expansion and self-testing on multidimensional states. Our work provides an experimental platform for the development of multidimensional quantum technologies.

    更新日期:2018-04-20
  • Probing the ultimate plasmon confinement limits with a van der Waals heterostructure
    Science (IF 37.205) Pub Date : 2018-04-20
    David Alcaraz Iranzo, Sébastien Nanot, Eduardo J. C. Dias, Itai Epstein, Cheng Peng, Dmitri K. Efetov, Mark B. Lundeberg, Romain Parret, Johann Osmond, Jin-Yong Hong, Jing Kong, Dirk R. Englund, Nuno M. R. Peres, Frank H. L. Koppens

    The ability to confine light into tiny spatial dimensions is important for applications such as microscopy, sensing, and nanoscale lasers. Although plasmons offer an appealing avenue to confine light, Landau damping in metals imposes a trade-off between optical field confinement and losses. We show that a graphene-insulator-metal heterostructure can overcome that trade-off, and demonstrate plasmon confinement down to the ultimate limit of the length scale of one atom. This is achieved through far-field excitation of plasmon modes squeezed into an atomically thin hexagonal boron nitride dielectric spacer between graphene and metal rods. A theoretical model that takes into account the nonlocal optical response of both graphene and metal is used to describe the results. These ultraconfined plasmonic modes, addressed with far-field light excitation, enable a route to new regimes of ultrastrong light-matter interactions.

    更新日期:2018-04-20
  • Capillarity-induced folds fuel extreme shape changes in thin wicked membranes
    Science (IF 37.205) Pub Date : 2018-04-20
    Paul Grandgeorge, Natacha Krins, Aurélie Hourlier-Fargette, Christel Laberty-Robert, Sébastien Neukirch, Arnaud Antkowiak

    Soft deformable materials are needed for applications such as stretchable electronics, smart textiles, or soft biomedical devices. However, the design of a durable, cost-effective, or biologically compatible version of such a material remains challenging. Living animal cells routinely cope with extreme deformations by unfolding preformed membrane reservoirs available in the form of microvilli or membrane folds. We synthetically mimicked this behavior by creating nanofibrous liquid-infused tissues that spontaneously form similar reservoirs through capillarity-induced folding. By understanding the physics of membrane buckling within the liquid film, we developed proof-of-concept conformable chemical surface treatments and stretchable basic electronic circuits.

    更新日期:2018-04-20
  • Ultralarge elastic deformation of nanoscale diamond
    Science (IF 37.205) Pub Date : 2018-04-20
    Amit Banerjee, Daniel Bernoulli, Hongti Zhang, Muk-Fung Yuen, Jiabin Liu, Jichen Dong, Feng Ding, Jian Lu, Ming Dao, Wenjun Zhang, Yang Lu, Subra Suresh

    Diamonds have substantial hardness and durability, but attempting to deform diamonds usually results in brittle fracture. We demonstrate ultralarge, fully reversible elastic deformation of nanoscale (~300 nanometers) single-crystalline and polycrystalline diamond needles. For single-crystalline diamond, the maximum tensile strains (up to 9%) approached the theoretical elastic limit, and the corresponding maximum tensile stress reached ~89 to 98 gigapascals. After combining systematic computational simulations and characterization of pre- and postdeformation structural features, we ascribe the concurrent high strength and large elastic strain to the paucity of defects in the small-volume diamond nanoneedles and to the relatively smooth surfaces compared with those of microscale and larger specimens. The discovery offers the potential for new applications through optimized design of diamond nanostructure, geometry, elastic strains, and physical properties.

    更新日期:2018-04-20
  • Five-dimensional imaging of freezing emulsions with solute effects
    Science (IF 37.205) Pub Date : 2018-04-20
    Dmytro Dedovets, Cécile Monteux, Sylvain Deville

    The interaction of objects with a moving solidification front is a common feature of many industrial and natural processes such as metal processing, the growth of single crystals, the cryopreservation of cells, or the formation of sea ice. Interaction of solidification fronts with objects leads to different outcomes, from total rejection of the objects to their complete engulfment. We imaged the freezing of emulsions in five dimensions (space, time, and solute concentration) with confocal microscopy. We showed that the solute induces long-range interactions that determine the solidification microstructure. The local increase of solute concentration enhances premelting, which controls the engulfment of droplets by the front and the evolution of grain boundaries. Freezing emulsions may be a good analog of many solidification systems where objects interact with a solidification interface.

    更新日期:2018-04-20
  • Recurrences in an isolated quantum many-body system
    Science (IF 37.205) Pub Date : 2018-04-20
    Bernhard Rauer, Sebastian Erne, Thomas Schweigler, Federica Cataldini, Mohammadamin Tajik, Jörg Schmiedmayer

    The complexity of interacting quantum many-body systems leads to exceedingly long recurrence times of the initial quantum state for all but the smallest systems. For large systems, one cannot probe the full quantum state in all its details. Thus, experimentally, recurrences can only be determined on the level of the accessible observables. Realizing a commensurate spectrum of collective excitations in one-dimensional superfluids, we demonstrate recurrences of coherence and long-range order in an interacting quantum many-body system containing thousands of particles. Our findings will enable the study of the coherent dynamics of large quantum systems even after they have reached a transient thermal-like state.

    更新日期:2018-04-20
  • Body size downgrading of mammals over the late Quaternary
    Science (IF 37.205) Pub Date : 2018-04-20
    Felisa A. Smith, Rosemary E. Elliott Smith, S. Kathleen Lyons, Jonathan L. Payne

    Since the late Pleistocene, large-bodied mammals have been extirpated from much of Earth. Although all habitable continents once harbored giant mammals, the few remaining species are largely confined to Africa. This decline is coincident with the global expansion of hominins over the late Quaternary. Here, we quantify mammalian extinction selectivity, continental body size distributions, and taxonomic diversity over five time periods spanning the past 125,000 years and stretching approximately 200 years into the future. We demonstrate that size-selective extinction was already under way in the oldest interval and occurred on all continents, within all trophic modes, and across all time intervals. Moreover, the degree of selectivity was unprecedented in 65 million years of mammalian evolution. The distinctive selectivity signature implicates hominin activity as a primary driver of taxonomic losses and ecosystem homogenization. Because megafauna have a disproportionate influence on ecosystem structure and function, past and present body size downgrading is reshaping Earth’s biosphere.

    更新日期:2018-04-20
  • Synaptic transmission from subplate neurons controls radial migration of neocortical neurons
    Science (IF 37.205) Pub Date : 2018-04-20
    Chiaki Ohtaka-Maruyama, Mayumi Okamoto, Kentaro Endo, Minori Oshima, Noe Kaneko, Kei Yura, Haruo Okado, Takaki Miyata, Nobuaki Maeda

    The neocortex exhibits a six-layered structure that is formed by radial migration of excitatory neurons, for which the multipolar-to-bipolar transition of immature migrating multipolar neurons is required. Here, we report that subplate neurons, one of the first neuron types born in the neocortex, manage the multipolar-to-bipolar transition of migrating neurons. By histochemical, imaging, and microarray analyses on the mouse embryonic cortex, we found that subplate neurons extend neurites toward the ventricular side of the subplate and form transient glutamatergic synapses on the multipolar neurons just below the subplate. NMDAR (N-methyl-d-aspartate receptor)–mediated synaptic transmission from subplate neurons to multipolar neurons induces the multipolar-to-bipolar transition, leading to a change in migration mode from slow multipolar migration to faster radial glial-guided locomotion. Our data suggested that transient synapses formed on early immature neurons regulate radial migration.

    更新日期:2018-04-20
  • Unexpected reversal of C3 versus C4 grass response to elevated CO2 during a 20-year field experiment
    Science (IF 37.205) Pub Date : 2018-04-20
    Peter B. Reich, Sarah E. Hobbie, Tali D. Lee, Melissa A. Pastore

    Theory predicts and evidence shows that plant species that use the C4 photosynthetic pathway (C4 species) are less responsive to elevated carbon dioxide (eCO2) than species that use only the C3 pathway (C3 species). We document a reversal from this expected C3-C4 contrast. Over the first 12 years of a 20-year free-air CO2 enrichment experiment with 88 C3 or C4 grassland plots, we found that biomass was markedly enhanced at eCO2 relative to ambient CO2 in C3 but not C4 plots, as expected. During the subsequent 8 years, the pattern reversed: Biomass was markedly enhanced at eCO2 relative to ambient CO2 in C4 but not C3 plots. Soil net nitrogen mineralization rates, an index of soil nitrogen supply, exhibited a similar shift: eCO2 first enhanced but later depressed rates in C3 plots, with the opposite true in C4 plots, partially explaining the reversal of the eCO2 biomass response. These findings challenge the current C3-C4 eCO2 paradigm and show that even the best-supported short-term drivers of plant response to global change might not predict long-term results.

    更新日期:2018-04-20
  • Two-billion-year-old evaporites capture Earth’s great oxidation
    Science (IF 37.205) Pub Date : 2018-04-20
    C. L. Blättler, M. W. Claire, A. R. Prave, K. Kirsimäe, J. A. Higgins, P. V. Medvedev, A. E. Romashkin, D. V. Rychanchik, A. L. Zerkle, K. Paiste, T. Kreitsmann, I. L. Millar, J. A. Hayles, H. Bao, A. V. Turchyn, M. R. Warke, A. Lepland

    Major changes in atmospheric and ocean chemistry occurred in the Paleoproterozoic era (2.5 to 1.6 billion years ago). Increasing oxidation dramatically changed Earth’s surface, but few quantitative constraints exist on this important transition. This study describes the sedimentology, mineralogy, and geochemistry of a 2-billion-year-old, ~800-meter-thick evaporite succession from the Onega Basin in Russian Karelia. The deposit consists of a basal unit dominated by halite (~100 meters) followed by units dominated by anhydrite-magnesite (~500 meters) and dolomite-magnesite (~200 meters). The evaporite minerals robustly constrain marine sulfate concentrations to at least 10 millimoles per kilogram of water, representing an oxidant reservoir equivalent to more than 20% of the modern ocean-atmosphere oxidizing capacity. These results show that substantial amounts of surface oxidant accumulated during this critical transition in Earth’s oxygenation.

    更新日期:2018-04-20
  • Structure of a prehandover mammalian ribosomal SRP·SRP receptor targeting complex
    Science (IF 37.205) Pub Date : 2018-04-20
    Kan Kobayashi, Ahmad Jomaa, Jae Ho Lee, Sowmya Chandrasekar, Daniel Boehringer, Shu-ou Shan, Nenad Ban

    Signal recognition particle (SRP) targets proteins to the endoplasmic reticulum (ER). SRP recognizes the ribosome synthesizing a signal sequence and delivers it to the SRP receptor (SR) on the ER membrane followed by the transfer of the signal sequence to the translocon. Here, we present the cryo–electron microscopy structure of the mammalian translating ribosome in complex with SRP and SR in a conformation preceding signal sequence handover. The structure visualizes all eukaryotic-specific SRP and SR proteins and reveals their roles in stabilizing this conformation by forming a large protein assembly at the distal site of SRP RNA. We provide biochemical evidence that the guanosine triphosphate hydrolysis of SRP·SR is delayed at this stage, possibly to provide a time window for signal sequence handover to the translocon.

    更新日期:2018-04-20
  • Paternally inherited cis-regulatory structural variants are associated with autism
    Science (IF 37.205) Pub Date : 2018-04-20
    William M. Brandler, Danny Antaki, Madhusudan Gujral, Morgan L. Kleiber, Joe Whitney, Michelle S. Maile, Oanh Hong, Timothy R. Chapman, Shirley Tan, Prateek Tandon, Timothy Pang, Shih C. Tang, Keith K. Vaux, Yan Yang, Eoghan Harrington, Sissel Juul, Daniel J. Turner, Bhooma Thiruvahindrapuram, Gaganjot Kaur, Zhuozhi Wang, Stephen F. Kingsmore, Joseph G. Gleeson, Denis Bisson, Boyko Kakaradov, Amalio Telenti, J. Craig Venter, Roser Corominas, Claudio Toma, Bru Cormand, Isabel Rueda, Silvina Guijarro, Karen S. Messer, Caroline M. Nievergelt, Maria J. Arranz, Eric Courchesne, Karen Pierce, Alysson R. Muotri, Lilia M. Iakoucheva, Amaia Hervas, Stephen W. Scherer, Christina Corsello, Jonathan Sebat

    The genetic basis of autism spectrum disorder (ASD) is known to consist of contributions from de novo mutations in variant-intolerant genes. We hypothesize that rare inherited structural variants in cis-regulatory elements (CRE-SVs) of these genes also contribute to ASD. We investigated this by assessing the evidence for natural selection and transmission distortion of CRE-SVs in whole genomes of 9274 subjects from 2600 families affected by ASD. In a discovery cohort of 829 families, structural variants were depleted within promoters and untranslated regions, and paternally inherited CRE-SVs were preferentially transmitted to affected offspring and not to their unaffected siblings. The association of paternal CRE-SVs was replicated in an independent sample of 1771 families. Our results suggest that rare inherited noncoding variants predispose children to ASD, with differing contributions from each parent.

    更新日期:2018-04-20
  • Developmental and oncogenic programs in H3K27M gliomas dissected by single-cell RNA-seq
    Science (IF 37.205) Pub Date : 2018-04-20
    Mariella G. Filbin, Itay Tirosh, Volker Hovestadt, McKenzie L. Shaw, Leah E. Escalante, Nathan D. Mathewson, Cyril Neftel, Nelli Frank, Kristine Pelton, Christine M. Hebert, Christine Haberler, Keren Yizhak, Johannes Gojo, Kristof Egervari, Christopher Mount, Peter van Galen, Dennis M. Bonal, Quang-De Nguyen, Alexander Beck, Claire Sinai, Thomas Czech, Christian Dorfer, Liliana Goumnerova, Cinzia Lavarino, Angel M. Carcaboso, Jaume Mora, Ravindra Mylvaganam, Christina C. Luo, Andreas Peyrl, Mara Popović, Amedeo Azizi, Tracy T. Batchelor, Matthew P. Frosch, Maria Martinez-Lage, Mark W. Kieran, Pratiti Bandopadhayay, Rameen Beroukhim, Gerhard Fritsch, Gad Getz, Orit Rozenblatt-Rosen, Kai W. Wucherpfennig, David N. Louis, Michelle Monje, Irene Slavc, Keith L. Ligon, Todd R. Golub, Aviv Regev, Bradley E. Bernstein, Mario L. Suvà

    Gliomas with histone H3 lysine27-to-methionine mutations (H3K27M-glioma) arise primarily in the midline of the central nervous system of young children, suggesting a cooperation between genetics and cellular context in tumorigenesis. Although the genetics of H3K27M-glioma are well characterized, their cellular architecture remains uncharted. We performed single-cell RNA sequencing in 3321 cells from six primary H3K27M-glioma and matched models. We found that H3K27M-glioma primarily contain cells that resemble oligodendrocyte precursor cells (OPC-like), whereas more differentiated malignant cells are a minority. OPC-like cells exhibit greater proliferation and tumor-propagating potential than their more differentiated counterparts and are at least in part sustained by PDGFRA signaling. Our study characterizes oncogenic and developmental programs in H3K27M-glioma at single-cell resolution and across genetic subclones, suggesting potential therapeutic targets in this disease.

    更新日期:2018-04-20
  • MFN2 agonists reverse mitochondrial defects in preclinical models of Charcot-Marie-Tooth disease type 2A
    Science (IF 37.205) Pub Date : 2018-04-20
    Agostinho G. Rocha, Antonietta Franco, Andrzej M. Krezel, Jeanne M. Rumsey, Justin M. Alberti, William C. Knight, Nikolaos Biris, Emmanouil Zacharioudakis, James W. Janetka, Robert H. Baloh, Richard N. Kitsis, Daria Mochly-Rosen, R. Reid Townsend, Evripidis Gavathiotis, Gerald W. Dorn

    Mitofusins (MFNs) promote fusion-mediated mitochondrial content exchange and subcellular trafficking. Mutations in Mfn2 cause neurodegenerative Charcot-Marie-Tooth disease type 2A (CMT2A). We showed that MFN2 activity can be determined by Met376 and His380 interactions with Asp725 and Leu727 and controlled by PINK1 kinase–mediated phosphorylation of adjacent MFN2 Ser378. Small-molecule mimics of the peptide-peptide interface of MFN2 disrupted this interaction, allosterically activating MFN2 and promoting mitochondrial fusion. These first-in-class mitofusin agonists overcame dominant mitochondrial defects provoked in cultured neurons by CMT2A mutants MFN2 Arg94→Gln94 and MFN2 Thr105→Met105, as demonstrated by amelioration of mitochondrial dysmotility, fragmentation, depolarization, and clumping. A mitofusin agonist normalized axonal mitochondrial trafficking within sciatic nerves of MFN2 Thr105→Met105 mice, promising a therapeutic approach for CMT2A and other untreatable diseases of impaired neuronal mitochondrial dynamism and/or trafficking.

    更新日期:2018-04-20
  • Observing the cell in its native state: Imaging subcellular dynamics in multicellular organisms
    Science (IF 37.205) Pub Date : 2018-04-20
    Tsung-Li Liu, Srigokul Upadhyayula, Daniel E. Milkie, Ved Singh, Kai Wang, Ian A. Swinburne, Kishore R. Mosaliganti, Zach M. Collins, Tom W. Hiscock, Jamien Shea, Abraham Q. Kohrman, Taylor N. Medwig, Daphne Dambournet, Ryan Forster, Brian Cunniff, Yuan Ruan, Hanako Yashiro, Steffen Scholpp, Elliot M. Meyerowitz, Dirk Hockemeyer, David G. Drubin, Benjamin L. Martin, David Q. Matus, Minoru Koyama, Sean G. Megason, Tom Kirchhausen, Eric Betzig

    True physiological imaging of subcellular dynamics requires studying cells within their parent organisms, where all the environmental cues that drive gene expression, and hence the phenotypes that we actually observe, are present. A complete understanding also requires volumetric imaging of the cell and its surroundings at high spatiotemporal resolution, without inducing undue stress on either. We combined lattice light-sheet microscopy with adaptive optics to achieve, across large multicellular volumes, noninvasive aberration-free imaging of subcellular processes, including endocytosis, organelle remodeling during mitosis, and the migration of axons, immune cells, and metastatic cancer cells in vivo. The technology reveals the phenotypic diversity within cells across different organisms and developmental stages and may offer insights into how cells harness their intrinsic variability to adapt to different physiological environments.

    更新日期:2018-04-20
  • Systematic analysis of complex genetic interactions
    Science (IF 37.205) Pub Date : 2018-04-20
    Elena Kuzmin, Benjamin VanderSluis, Wen Wang, Guihong Tan, Raamesh Deshpande, Yiqun Chen, Matej Usaj, Attila Balint, Mojca Mattiazzi Usaj, Jolanda van Leeuwen, Elizabeth N. Koch, Carles Pons, Andrius J. Dagilis, Michael Pryszlak, Jason Zi Yang Wang, Julia Hanchard, Margot Riggi, Kaicong Xu, Hamed Heydari, Bryan-Joseph San Luis, Ermira Shuteriqi, Hongwei Zhu, Nydia Van Dyk, Sara Sharifpoor, Michael Costanzo, Robbie Loewith, Amy Caudy, Daniel Bolnick, Grant W. Brown, Brenda J. Andrews, Charles Boone, Chad L. Myers

    To systematically explore complex genetic interactions, we constructed ~200,000 yeast triple mutants and scored negative trigenic interactions. We selected double-mutant query genes across a broad spectrum of biological processes, spanning a range of quantitative features of the global digenic interaction network and tested for a genetic interaction with a third mutation. Trigenic interactions often occurred among functionally related genes, and essential genes were hubs on the trigenic network. Despite their functional enrichment, trigenic interactions tended to link genes in distant bioprocesses and displayed a weaker magnitude than digenic interactions. We estimate that the global trigenic interaction network is ~100 times as large as the global digenic network, highlighting the potential for complex genetic interactions to affect the biology of inheritance, including the genotype-to-phenotype relationship.

    更新日期:2018-04-20
  • Natural selection interacts with recombination to shape the evolution of hybrid genomes
    Science (IF 37.205) Pub Date : 2018-04-19
    Molly Schumer, Chenling Xu, Daniel L. Powell, Arun Durvasula, Laurits Skov, Chris Holland, John C. Blazier, Sriram Sankararaman, Peter Andolfatto, Gil G. Rosenthal, Molly Przeworski

    To investigate the consequences of hybridization between species, we studied three replicate hybrid populations that formed naturally between two swordtail fish species, estimating their fine-scale genetic map and inferring ancestry along the genomes of 690 individuals. In all three populations, ancestry from the “minor” parental species is more common in regions of high recombination and where there is linkage to fewer putative targets of selection. The same patterns are apparent in a reanalysis of human and archaic admixture. These results support models in which ancestry from the minor parental species is more likely to persist when rapidly uncoupled from alleles that are deleterious in hybrids. Our analyses further indicate that selection on swordtail hybrids stems predominantly from deleterious combinations of epistatically interacting alleles.

    更新日期:2018-04-20
  • Cell type transcriptome atlas for the planarian Schmidtea mediterranea
    Science (IF 37.205) Pub Date : 2018-04-19
    Christopher T. Fincher, Omri Wurtzel, Thom de Hoog, Kellie M. Kravarik, Peter W. Reddien

    The transcriptome of a cell dictates its unique cell-type biology. We used single-cell RNA sequencing to determine the transcriptomes for essentially every cell type of a complete animal: the regenerative planarian Schmidtea mediterranea. Planarians contain a diverse array of cell types, possess lineage progenitors for differentiated cells (including pluripotent stem cells), and constitutively express positional information, making them ideal for this undertaking. We generated data for 66,783 cells, defining transcriptomes for known and many previously unknown planarian cell types and for putative transition states between stem and differentiated cells. We also uncovered regionally expressed genes in muscle, which harbors positional information. Identifying the transcriptomes for potentially all cell types for many organisms should be readily attainable and is a powerful new approach to metazoan biology.

    更新日期:2018-04-20
  • Cell type atlas and lineage tree of a whole complex animal by single-cell transcriptomics
    Science (IF 37.205) Pub Date : 2018-04-19
    Mireya Plass, Jordi Solana, F. Alexander Wolf, Salah Ayoub, Aristotelis Misios, Petar Glažar, Benedikt Obermayer, Fabian J. Theis, Christine Kocks, Nikolaus Rajewsky

    Flatworms of the species Schmidtea mediterranea are immortal—adult animals contain a large pool of pluripotent stem cells that continuously differentiate to all adult cell types. Therefore, single-cell transcriptome profiling of adult animals should reveal mature and progenitor cells. By combining perturbation experiments, gene expression analysis, a computational method that predicts future cell states from the transcriptional changes, and a lineage reconstruction method, we placed all major cell types onto a single lineage tree that connects all cells to a single stem cell compartment. We characterize gene expression changes during differentiation and discover cell types important for regeneration. Our results demonstrate the importance of single-cell transcriptome analysis for mapping and reconstructing fundamental processes of developmental and regenerative biology at high resolution.

    更新日期:2018-04-20
  • Rapid sea level rise in the aftermath of a Neoproterozoic snowball Earth
    Science (IF 37.205) Pub Date : 2018-04-19
    P. M. Myrow, M. P. Lamb, R. C. Ewing

    Earth’s most severe climate changes occurred during global-scale snowball-Earth glaciations, which profoundly altered Earth’s atmosphere, oceans, and biosphere. Extreme rates of glacio-eustatic sea-level rise are a fundamental prediction of the snowball Earth hypothesis, but supporting geologic evidence is lacking. We use paleohydraulic analysis of wave ripples and tidal laminae of the Elatina Formation, Australia — deposited following the Marinoan glaciation ca. 635Ma — to show that water depths of 9–16m remained nearly constant for ~100yrs throughout 27m of sediment accumulation. This accumulation rate was too great to have been accommodated by subsidence, and instead indicates an extraordinarily rapid rate of sea-level rise (0.2–0.27m/yr). Our results substantiate a fundamental prediction of snowball Earth models of rapid deglaciation during the early transition to a super-greenhouse climate.

    更新日期:2018-04-20
  • Flexo-photovoltaic effect
    Science (IF 37.205) Pub Date : 2018-04-19
    Ming-Min Yang, Dong Jik Kim, Marin Alexe

    It is highly desirable to discover photovoltaic mechanisms that enable a higher efficiency of solar cells. Here, we report that the bulk photovoltaic effect, which is free from the thermodynamic Shockley-Queisser limit but usually manifested only in noncentrosymmetric (piezoelectric or ferroelectric) materials, can be realized in any semiconductor, including silicon, by mediation of flexoelectric effect. We introduce strain gradients using either an atomic force microscope or a micron-scale indentation system, creating giant photovoltaic currents from centrosymmetric single crystals of SrTiO3, TiO2, and Si. This strain-gradient-induced bulk photovoltaic effect, which we call the flexo-photovoltaic effect, functions in the absence of a p-n junction. This finding may extend present solar cell technologies by boosting the solar energy conversion efficiency from a wide pool of established semiconductors.

    更新日期:2018-04-20
  • mRNA structure determines specificity of a polyQ-driven phase separation
    Science (IF 37.205) Pub Date : 2018-04-13
    Erin M. Langdon, Yupeng Qiu, Amirhossein Ghanbari Niaki, Grace A. McLaughlin, Chase Weidmann, Therese M. Gerbich, Jean A. Smith, John M. Crutchley, Christina M. Termini, Kevin M. Weeks, Sua Myong, Amy S. Gladfelter

    RNA promotes liquid-liquid phase separation (LLPS) to build membraneless compartments in cells. How distinct molecular compositions are established and maintained in these liquid compartments is unknown. Here, we report that secondary structure allows mRNAs to self-associate and determines whether an mRNA is recruited to or excluded from liquid compartments. The polyQ-protein Whi3 induces conformational changes in RNA structure and generates distinct molecular fluctuations depending on the RNA sequence. These data support a model in which structure-based, RNA-RNA interactions promote assembly of distinct droplets and protein-driven, conformational dynamics of the RNA maintain this identity. Thus, the shape of RNA can promote the formation and coexistence of the diverse array of RNA-rich liquid compartments found in a single cell.

    更新日期:2018-04-14
  • Quantitative analysis of population-scale family trees with millions of relatives
    Science (IF 37.205) Pub Date : 2018-04-13
    Joanna Kaplanis, Assaf Gordon, Tal Shor, Omer Weissbrod, Dan Geiger, Mary Wahl, Michael Gershovits, Barak Markus, Mona Sheikh, Melissa Gymrek, Gaurav Bhatia, Daniel G. MacArthur, Alkes L. Price, Yaniv Erlich

    Family trees have vast applications in fields as diverse as genetics, anthropology, and economics. However, the collection of extended family trees is tedious and usually relies on resources with limited geographical scope and complex data usage restrictions. We collected 86 million profiles from publicly available online data shared by genealogy enthusiasts. After extensive cleaning and validation, we obtained population-scale family trees, including a single pedigree of 13 million individuals. We leveraged the data to partition the genetic architecture of human longevity and to provide insights into the geographical dispersion of families. We also report a simple digital procedure to overlay other data sets with our resource.

    更新日期:2018-04-13
  • Single-cell profiling of the developing mouse brain and spinal cord with split-pool barcoding
    Science (IF 37.205) Pub Date : 2018-04-13
    Alexander B. Rosenberg, Charles M. Roco, Richard A. Muscat, Anna Kuchina, Paul Sample, Zizhen Yao, Lucas T. Graybuck, David J. Peeler, Sumit Mukherjee, Wei Chen, Suzie H. Pun, Drew L. Sellers, Bosiljka Tasic, Georg Seelig

    To facilitate scalable profiling of single cells, we developed split-pool ligation-based transcriptome sequencing (SPLiT-seq), a single-cell RNA-seq (scRNA-seq) method that labels the cellular origin of RNA through combinatorial barcoding. SPLiT-seq is compatible with fixed cells or nuclei, allows efficient sample multiplexing, and requires no customized equipment. We used SPLiT-seq to analyze 156,049 single-nucleus transcriptomes from postnatal day 2 and 11 mouse brains and spinal cords. More than 100 cell types were identified, with gene expression patterns corresponding to cellular function, regional specificity, and stage of differentiation. Pseudotime analysis revealed transcriptional programs driving four developmental lineages, providing a snapshot of early postnatal development in the murine central nervous system. SPLiT-seq provides a path toward comprehensive single-cell transcriptomic analysis of other similarly complex multicellular systems.

    更新日期:2018-04-13
  • Observation of topological superconductivity on the surface of an iron-based superconductor
    Science (IF 37.205) Pub Date : 2018-04-13
    Peng Zhang, Koichiro Yaji, Takahiro Hashimoto, Yuichi Ota, Takeshi Kondo, Kozo Okazaki, Zhijun Wang, Jinsheng Wen, G. D. Gu, Hong Ding, Shik Shin

    Topological superconductors are predicted to host exotic Majorana states that obey non-Abelian statistics and can be used to implement a topological quantum computer. Most of the proposed topological superconductors are realized in difficult-to-fabricate heterostructures at very low temperatures. By using high-resolution spin-resolved and angle-resolved photoelectron spectroscopy, we find that the iron-based superconductor FeTe1–xSex (x = 0.45; superconducting transition temperature Tc = 14.5 kelvin) hosts Dirac-cone–type spin-helical surface states at the Fermi level; the surface states exhibit an s-wave superconducting gap below Tc. Our study shows that the surface states of FeTe0.55Se0.45 are topologically superconducting, providing a simple and possibly high-temperature platform for realizing Majorana states.

    更新日期:2018-04-13
  • Predicting reaction performance in C–N cross-coupling using machine learning
    Science (IF 37.205) Pub Date : 2018-04-13
    Derek T. Ahneman, Jesús G. Estrada, Shishi Lin, Spencer D. Dreher, Abigail G. Doyle

    Machine learning methods are becoming integral to scientific inquiry in numerous disciplines. We demonstrated that machine learning can be used to predict the performance of a synthetic reaction in multidimensional chemical space using data obtained via high-throughput experimentation. We created scripts to compute and extract atomic, molecular, and vibrational descriptors for the components of a palladium-catalyzed Buchwald-Hartwig cross-coupling of aryl halides with 4-methylaniline in the presence of various potentially inhibitory additives. Using these descriptors as inputs and reaction yield as output, we showed that a random forest algorithm provides significantly improved predictive performance over linear regression analysis. The random forest model was also successfully applied to sparse training sets and out-of-sample prediction, suggesting its value in facilitating adoption of synthetic methodology.

    更新日期:2018-04-13
  • Measurement of the fine-structure constant as a test of the Standard Model
    Science (IF 37.205) Pub Date : 2018-04-13
    Richard H. Parker, Chenghui Yu, Weicheng Zhong, Brian Estey, Holger Müller

    Measurements of the fine-structure constant α require methods from across subfields and are thus powerful tests of the consistency of theory and experiment in physics. Using the recoil frequency of cesium-133 atoms in a matter-wave interferometer, we recorded the most accurate measurement of the fine-structure constant to date: α = 1/137.035999046(27) at 2.0 × 10−10 accuracy. Using multiphoton interactions (Bragg diffraction and Bloch oscillations), we demonstrate the largest phase (12 million radians) of any Ramsey-Bordé interferometer and control systematic effects at a level of 0.12 part per billion. Comparison with Penning trap measurements of the electron gyromagnetic anomaly ge − 2 via the Standard Model of particle physics is now limited by the uncertainty in ge − 2; a 2.5σ tension rejects dark photons as the reason for the unexplained part of the muon’s magnetic moment at a 99% confidence level. Implications for dark-sector candidates and electron substructure may be a sign of physics beyond the Standard Model that warrants further investigation.

    更新日期:2018-04-13
  • A blueprint for demonstrating quantum supremacy with superconducting qubits
    Science (IF 37.205) Pub Date : 2018-04-13
    C. Neill, P. Roushan, K. Kechedzhi, S. Boixo, S. V. Isakov, V. Smelyanskiy, A. Megrant, B. Chiaro, A. Dunsworth, K. Arya, R. Barends, B. Burkett, Y. Chen, Z. Chen, A. Fowler, B. Foxen, M. Giustina, R. Graff, E. Jeffrey, T. Huang, J. Kelly, P. Klimov, E. Lucero, J. Mutus, M. Neeley, C. Quintana, D. Sank, A. Vainsencher, J. Wenner, T. C. White, H. Neven, J. M. Martinis

    A key step toward demonstrating a quantum system that can address difficult problems in physics and chemistry will be performing a computation beyond the capabilities of any classical computer, thus achieving so-called quantum supremacy. In this study, we used nine superconducting qubits to demonstrate a promising path toward quantum supremacy. By individually tuning the qubit parameters, we were able to generate thousands of distinct Hamiltonian evolutions and probe the output probabilities. The measured probabilities obey a universal distribution, consistent with uniformly sampling the full Hilbert space. As the number of qubits increases, the system continues to explore the exponentially growing number of states. Extending these results to a system of 50 qubits has the potential to address scientific questions that are beyond the capabilities of any classical computer.

    更新日期:2018-04-13
  • Bottom-up synthesis of multifunctional nanoporous graphene
    Science (IF 37.205) Pub Date : 2018-04-13
    César Moreno, Manuel Vilas-Varela, Bernhard Kretz, Aran Garcia-Lekue, Marius V. Costache, Markos Paradinas, Mirko Panighel, Gustavo Ceballos, Sergio O. Valenzuela, Diego Peña, Aitor Mugarza

    Nanosize pores can turn semimetallic graphene into a semiconductor and, from being impermeable, into the most efficient molecular-sieve membrane. However, scaling the pores down to the nanometer, while fulfilling the tight structural constraints imposed by applications, represents an enormous challenge for present top-down strategies. Here we report a bottom-up method to synthesize nanoporous graphene comprising an ordered array of pores separated by ribbons, which can be tuned down to the 1-nanometer range. The size, density, morphology, and chemical composition of the pores are defined with atomic precision by the design of the molecular precursors. Our electronic characterization further reveals a highly anisotropic electronic structure, where orthogonal one-dimensional electronic bands with an energy gap of ∼1 electron volt coexist with confined pore states, making the nanoporous graphene a highly versatile semiconductor for simultaneous sieving and electrical sensing of molecular species.

    更新日期:2018-04-13
  • Tropism for tuft cells determines immune promotion of norovirus pathogenesis
    Science (IF 37.205) Pub Date : 2018-04-13
    Craig B. Wilen, Sanghyun Lee, Leon L. Hsieh, Robert C. Orchard, Chandni Desai, Barry L. Hykes, Michael R. McAllaster, Dale R. Balce, Taylor Feehley, Jonathan R. Brestoff, Christina A. Hickey, Christine C. Yokoyama, Ya-Ting Wang, Donna A. MacDuff, Darren Kreamalmayer, Michael R. Howitt, Jessica A. Neil, Ken Cadwell, Paul M. Allen, Scott A. Handley, Menno van Lookeren Campagne, Megan T. Baldridge, Herbert W. Virgin

    Complex interactions between host immunity and the microbiome regulate norovirus infection. However, the mechanism of host immune promotion of enteric virus infection remains obscure. The cellular tropism of noroviruses is also unknown. Recently, we identified CD300lf as a murine norovirus (MNoV) receptor. In this study, we have shown that tuft cells, a rare type of intestinal epithelial cell, express CD300lf and are the target cell for MNoV in the mouse intestine. We found that type 2 cytokines, which induce tuft cell proliferation, promote MNoV infection in vivo. These cytokines can replace the effect of commensal microbiota in promoting virus infection. Our work thus provides insight into how the immune system and microbes can coordinately promote enteric viral infection.

    更新日期:2018-04-13
  • Microbial oxidation of lithospheric organic carbon in rapidly eroding tropical mountain soils
    Science (IF 37.205) Pub Date : 2018-04-13
    Jordon D. Hemingway, Robert G. Hilton, Niels Hovius, Timothy I. Eglinton, Negar Haghipour, Lukas Wacker, Meng-Chiang Chen, Valier V. Galy

    Lithospheric organic carbon (“petrogenic”; OCpetro) is oxidized during exhumation and subsequent erosion of mountain ranges. This process is a considerable source of carbon dioxide (CO2) to the atmosphere over geologic time scales, but the mechanisms that govern oxidation rates in mountain landscapes are poorly constrained. We demonstrate that, on average, 67 ± 11% of the OCpetro initially present in bedrock exhumed from the tropical, rapidly eroding Central Range of Taiwan is oxidized in soils, leading to CO2 emissions of 6.1 to 18.6 metric tons of carbon per square kilometer per year. The molecular and isotopic evolution of bulk OC and lipid biomarkers during soil formation reveals that OCpetro remineralization is microbially mediated. Rapid oxidation in mountain soils drives CO2 emission fluxes that increase with erosion rate, thereby counteracting CO2 drawdown by silicate weathering and biospheric OC burial.

    更新日期:2018-04-13
  • Photoperiodic control of seasonal growth is mediated by ABA acting on cell-cell communication
    Science (IF 37.205) Pub Date : 2018-04-13
    S. Tylewicz, A. Petterle, S. Marttila, P. Miskolczi, A. Azeez, R. K. Singh, J. Immanen, N. Mähler, T. R. Hvidsten, D. M. Eklund, J. L. Bowman, Y. Helariutta, R. P. Bhalerao

    In temperate and boreal ecosystems, seasonal cycles of growth and dormancy allow perennial plants to adapt to winter conditions. We show, in hybrid aspen trees, that photoperiodic regulation of dormancy is mechanistically distinct from autumnal growth cessation. Dormancy sets in when symplastic intercellular communication through plasmodesmata is blocked by a process dependent on the phytohormone abscisic acid. The communication blockage prevents growth-promoting signals from accessing the meristem. Thus, precocious growth is disallowed during dormancy. The dormant period, which supports robust survival of the aspen tree in winter, is due to loss of access to growth-promoting signals.

    更新日期:2018-04-13
  • Structural basis for coupling protein transport and N-glycosylation at the mammalian endoplasmic reticulum
    Science (IF 37.205) Pub Date : 2018-04-13
    Katharina Braunger, Stefan Pfeffer, Shiteshu Shrimal, Reid Gilmore, Otto Berninghausen, Elisabet C. Mandon, Thomas Becker, Friedrich Förster, Roland Beckmann

    Protein synthesis, transport, and N-glycosylation are coupled at the mammalian endoplasmic reticulum by complex formation of a ribosome, the Sec61 protein-conducting channel, and oligosaccharyltransferase (OST). Here we used different cryo–electron microscopy approaches to determine structures of native and solubilized ribosome-Sec61-OST complexes. A molecular model for the catalytic OST subunit STT3A (staurosporine and temperature sensitive 3A) revealed how it is integrated into the OST and how STT3-paralog specificity for translocon-associated OST is achieved. The OST subunit DC2 was placed at the interface between Sec61 and STT3A, where it acts as a versatile module for recruitment of STT3A-containing OST to the ribosome-Sec61 complex. This detailed structural view on the molecular architecture of the cotranslational machinery for N-glycosylation provides the basis for a mechanistic understanding of glycoprotein biogenesis at the endoplasmic reticulum.

    更新日期:2018-04-13
  • Structure of the nuclear exosome captured on a maturing preribosome
    Science (IF 37.205) Pub Date : 2018-04-13
    Jan Michael Schuller, Sebastian Falk, Lisa Fromm, Ed Hurt, Elena Conti

    The RNA exosome complex processes and degrades a wide range of transcripts, including ribosomal RNAs (rRNAs). We used cryo–electron microscopy to visualize the yeast nuclear exosome holocomplex captured on a precursor large ribosomal subunit (pre-60S) during 7S-to-5.8S rRNA processing. The cofactors of the nuclear exosome are sandwiched between the ribonuclease core complex (Exo-10) and the remodeled “foot” structure of the pre-60S particle, which harbors the 5.8S rRNA precursor. The exosome-associated helicase Mtr4 recognizes the preribosomal substrate by docking to specific sites on the 25S rRNA, captures the 3′ extension of the 5.8S rRNA, and channels it toward Exo-10. The structure elucidates how the exosome forms a structural and functional unit together with its massive pre-60S substrate to process rRNA during ribosome maturation.

    更新日期:2018-04-13
  • Germinal center antibody mutation trajectories are determined by rapid self/foreign discrimination
    Science (IF 37.205) Pub Date : 2018-04-13
    Deborah L. Burnett, David B. Langley, Peter Schofield, Jana R. Hermes, Tyani D. Chan, Jennifer Jackson, Katherine Bourne, Joanne H. Reed, Kate Patterson, Benjamin T. Porebski, Robert Brink, Daniel Christ, Christopher C. Goodnow

    Antibodies have the specificity to differentiate foreign antigens that mimic self antigens, but it remains unclear how such specificity is acquired. In a mouse model, we generated B cells displaying an antibody that cross-reacts with two related protein antigens expressed on self versus foreign cells. B cell anergy was imposed by self antigen but reversed upon challenge with high-density foreign antigen, leading to germinal center recruitment and antibody gene hypermutation. Single-cell analysis detected rapid selection for mutations that decrease self affinity and slower selection for epistatic mutations that specifically increase foreign affinity. Crystal structures revealed that these mutations exploited subtle topological differences to achieve 5000-fold preferential binding to foreign over self epitopes. Resolution of antigenic mimicry drove the optimal affinity maturation trajectory, highlighting the value of retaining self-reactive clones as substrates for protective antibody responses.

    更新日期:2018-04-13
  • MitoCPR—A surveillance pathway that protects mitochondria in response to protein import stress
    Science (IF 37.205) Pub Date : 2018-04-13
    Hilla Weidberg, Angelika Amon

    Mitochondrial functions are essential for cell viability and rely on protein import into the organelle. Various disease and stress conditions can lead to mitochondrial import defects. We found that inhibition of mitochondrial import in budding yeast activated a surveillance mechanism, mitoCPR, that improved mitochondrial import and protected mitochondria during import stress. mitoCPR induced expression of Cis1, which associated with the mitochondrial translocase to reduce the accumulation of mitochondrial precursor proteins at the mitochondrial translocase. Clearance of precursor proteins depended on the Cis1-interacting AAA+ adenosine triphosphatase Msp1 and the proteasome, suggesting that Cis1 facilitates degradation of unimported proteins. mitoCPR was required for maintaining mitochondrial functions when protein import was compromised, demonstrating the importance of mitoCPR in protecting the mitochondrial compartment.

    更新日期:2018-04-13
  • Rewritable multi-event analog recording in bacterial and mammalian cells
    Science (IF 37.205) Pub Date : 2018-04-13
    Weixin Tang, David R. Liu

    We present two CRISPR-mediated analog multi-event recording apparatus (CAMERA) systems that use base editors and Cas9 nucleases to record cellular events in bacteria and mammalian cells. The devices record signal amplitude or duration as changes in the ratio of mutually exclusive DNA sequences (CAMERA 1) or as single-base modifications (CAMERA 2). We achieved recording of multiple stimuli in bacteria or mammalian cells, including exposure to antibiotics, nutrients, viruses, light, and changes in Wnt signaling. When recording to multicopy plasmids, reliable readout requires as few as 10 to 100 cells. The order of stimuli can be recorded through an overlapping guide RNA design, and memories can be erased and re-recorded over multiple cycles. CAMERA systems serve as “cell data recorders” that write a history of endogenous or exogenous signaling events into permanent DNA sequence modifications in living cells.

    更新日期:2018-04-13
  • High-resolution cryo-EM analysis of the yeast ATP synthase in a lipid membrane
    Science (IF 37.205) Pub Date : 2018-04-12
    Anurag P. Srivastava, Min Luo, Wenchang Zhou, Jindrich Symersky, Dongyang Bai, Melissa G. Chambers, José D. Faraldo-Gómez, Maofu Liao, David M. Mueller

    Mitochondrial ATP synthase comprises a membrane embedded Fo motor that rotates to drive ATP synthesis in the F1 subunit. We used single-particle cryo-EM to obtain structures of the full complex in a lipid bilayer in the absence or presence of the inhibitor oligomycin, at 3.6 Å and 3.8 Å resolution, respectively. To limit conformational heterogeneity, we locked the rotor in a single conformation by fusing the F6 subunit of the stator with the δ-subunit of the rotor. Assembly of the enzyme with the F6-δ fusion caused a twisting of the rotor and a 9° rotation of the Fo c10-ring in the direction of ATP synthesis, relative to the structure of isolated Fo. Our cryo-EM structures show how F1 and Fo are coupled, give insight into the proton translocation pathway and show how oligomycin blocks ATP synthesis.

    更新日期:2018-04-13
  • Building one molecule from a reservoir of two atoms
    Science (IF 37.205) Pub Date : 2018-04-12
    L. R. Liu, J. D. Hood, Y. Yu, J. T. Zhang, N. R. Hutzler, T. Rosenband, K.-K. Ni

    Chemical reactions typically proceed via stochastic encounters between reactants. Going beyond this paradigm, we combine exactly two atoms into a single, controlled reaction. The experimental apparatus traps two individual laser-cooled atoms (one sodium and one cesium) in separate optical tweezers and then merges them into one optical dipole trap. Subsequently, photo-association forms an excited-state NaCs molecule. The discovery of previously unseen resonances near the molecular dissociation threshold and measurement of collision rates are enabled by the tightly trapped ultracold sample of atoms. As laser-cooling and trapping capabilities are extended to more elements, the technique will enable the study of more diverse, and eventually more complex, molecules in an isolated environment, as well as synthesis of designer molecules for qubits.

    更新日期:2018-04-13
  • RNA buffers the phase separation behavior of prion-like RNA binding proteins
    Science (IF 37.205) Pub Date : 2018-04-12
    Shovamayee Maharana, Jie Wang, Dimitrios K. Papadopoulos, Doris Richter, Andrey Pozniakovsky, Ina Poser, Marc Bickle, Sandra Rizk, Jordina Guillén-Boixet, Titus Franzmann, Marcus Jahnel, Lara Marrone, Young-Tae Chang, Jared Sterneckert, Pavel Tomancak, Anthony A. Hyman, Simon Alberti

    Prion-like RNA binding proteins (RBPs) such as TDP-43 or FUS are largely soluble in the nucleus, but form solid pathological aggregates when mislocalized to the cytoplasm. What keeps these proteins soluble in the nucleus and promotes aggregation in the cytoplasm is still unknown. We report here that RNA critically regulates the phase behavior of prion-like RBPs. Low RNA/protein ratios promote phase separation into liquid droplets, whereas high ratios prevent droplet formation in vitro. Reduction of nuclear RNA levels or genetic ablation of RNA binding causes excessive phase separation and the formation of cytotoxic solid-like assemblies in cells. We propose that the nucleus is a buffered system in which high RNA concentrations keep RBPs soluble. Changes in RNA levels or RNA binding abilities of RBPs cause aberrant phase transitions.

    更新日期:2018-04-13
  • Elastic strain engineering for ultralow mechanical dissipation
    Science (IF 37.205) Pub Date : 2018-04-12
    A. H. Ghadimi, S. A. Fedorov, N. J. Engelsen, M. J. Bereyhi, R. Schilling, D. J. Wilson, T. J. Kippenberg

    Extreme stresses can be produced in nanoscale structures, a feature which has been used to realize enhanced materials properties, such as the high mobility of silicon in modern transistors. Here we show how nanoscale stress can be used to realize exceptionally low mechanical dissipation, when combined with “soft-clamping” — a form of phononic engineering. Specifically, using a non-uniform phononic crystal pattern, we colocalize the strain and flexural motion of a free-standing Si3N4 nanobeam. Ringdown measurements at room temperature reveal string-like modes with quality (Q) factors as high as 800 million and Q × frequency exceeding 1015 Hz. These results illustrate a promising route for engineering ultra-coherent nanomechanical devices.

    更新日期:2018-04-13
  • CRMP2-binding compound, edonerpic maleate, accelerates motor function recovery from brain damage
    Science (IF 37.205) Pub Date : 2018-04-06
    Hiroki Abe, Susumu Jitsuki, Waki Nakajima, Yumi Murata, Aoi Jitsuki-Takahashi, Yuki Katsuno, Hirobumi Tada, Akane Sano, Kumiko Suyama, Nobuyuki Mochizuki, Takashi Komori, Hitoshi Masuyama, Tomohiro Okuda, Yoshio Goshima, Noriyuki Higo, Takuya Takahashi

    Brain damage such as stroke is a devastating neurological condition that may severely compromise patient quality of life. No effective medication-mediated intervention to accelerate rehabilitation has been established. We found that a small compound, edonerpic maleate, facilitated experience-driven synaptic glutamate AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic-acid) receptor delivery and resulted in the acceleration of motor function recovery after motor cortex cryoinjury in mice in a training-dependent manner through cortical reorganization. Edonerpic bound to collapsin-response-mediator-protein 2 (CRMP2) and failed to augment recovery in CRMP2-deficient mice. Edonerpic maleate enhanced motor function recovery from internal capsule hemorrhage in nonhuman primates. Thus, edonerpic maleate, a neural plasticity enhancer, could be a clinically potent small compound with which to accelerate rehabilitation after brain damage.

    更新日期:2018-04-06
  • Convergent evidence for widespread rock nitrogen sources in Earth’s surface environment
    Science (IF 37.205) Pub Date : 2018-04-06
    B. Z. Houlton, S. L. Morford, R. A. Dahlgren

    Nitrogen availability is a pivotal control on terrestrial carbon sequestration and global climate change. Historical and contemporary views assume that nitrogen enters Earth’s land-surface ecosystems from the atmosphere. Here we demonstrate that bedrock is a nitrogen source that rivals atmospheric nitrogen inputs across major sectors of the global terrestrial environment. Evidence drawn from the planet’s nitrogen balance, geochemical proxies, and our spatial weathering model reveal that ~19 to 31 teragrams of nitrogen are mobilized from near-surface rocks annually. About 11 to 18 teragrams of this nitrogen are chemically weathered in situ, thereby increasing the unmanaged (preindustrial) terrestrial nitrogen balance from 8 to 26%. These findings provide a global perspective to reconcile Earth’s nitrogen budget, with implications for nutrient-driven controls over the terrestrial carbon sink.

    更新日期:2018-04-06
  • Observation of fractional Chern insulators in a van der Waals heterostructure
    Science (IF 37.205) Pub Date : 2018-04-06
    Eric M. Spanton, Alexander A. Zibrov, Haoxin Zhou, Takashi Taniguchi, Kenji Watanabe, Michael P. Zaletel, Andrea F. Young

    Topologically ordered phases are characterized by long-range quantum entanglement and fractional statistics rather than by symmetry breaking. First observed in a fractionally filled continuum Landau level, topological order has since been proposed to arise more generally at fractional fillings of topologically nontrivial Chern bands. Here we report the observation of gapped states at fractional fillings of Harper-Hofstadter bands arising from the interplay of a magnetic field and a superlattice potential in a bilayer graphene–hexagonal boron nitride heterostructure. We observed phases at fractional filling of bands with Chern indices . Some of these phases, in and bands, are characterized by fractional Hall conductance—that is, they are known as fractional Chern insulators and constitute an example of topological order beyond Landau levels.

    更新日期:2018-04-06
  • Light-induced lattice expansion leads to high-efficiency perovskite solar cells
    Science (IF 37.205) Pub Date : 2018-04-06
    Hsinhan Tsai, Reza Asadpour, Jean-Christophe Blancon, Constantinos C. Stoumpos, Olivier Durand, Joseph W. Strzalka, Bo Chen, Rafael Verduzco, Pulickel M. Ajayan, Sergei Tretiak, Jacky Even, Muhammad Ashraf Alam, Mercouri G. Kanatzidis, Wanyi Nie, Aditya D. Mohite

    Light-induced structural dynamics plays a vital role in the physical properties, device performance, and stability of hybrid perovskite–based optoelectronic devices. We report that continuous light illumination leads to a uniform lattice expansion in hybrid perovskite thin films, which is critical for obtaining high-efficiency photovoltaic devices. Correlated, in situ structural and device characterizations reveal that light-induced lattice expansion benefits the performances of a mixed-cation pure-halide planar device, boosting the power conversion efficiency from 18.5 to 20.5%. The lattice expansion leads to the relaxation of local lattice strain, which lowers the energetic barriers at the perovskite-contact interfaces, thus improving the open circuit voltage and fill factor. The light-induced lattice expansion did not compromise the stability of these high-efficiency photovoltaic devices under continuous operation at full-spectrum 1-sun (100 milliwatts per square centimeter) illumination for more than 1500 hours.

    更新日期:2018-04-06
  • Enzymatic construction of highly strained carbocycles
    Science (IF 37.205) Pub Date : 2018-04-06
    Kai Chen, Xiongyi Huang, S. B. Jennifer Kan, Ruijie K. Zhang, Frances H. Arnold

    Small carbocycles are structurally rigid and possess high intrinsic energy due to their ring strain. These features lead to broad applications but also create challenges for their construction. We report the engineering of hemeproteins that catalyze the formation of chiral bicyclobutanes, one of the most strained four-membered systems, via successive carbene addition to unsaturated carbon-carbon bonds. Enzymes that produce cyclopropenes, putative intermediates to the bicyclobutanes, were also identified. These genetically encoded proteins are readily optimized by directed evolution, function in Escherichia coli, and act on structurally diverse substrates with high efficiency and selectivity, providing an effective route to many chiral strained structures. This biotransformation is easily performed at preparative scale, and the resulting strained carbocycles can be derivatized, opening myriad potential applications.

    更新日期:2018-04-06
  • Modular radical cross-coupling with sulfones enables access to sp3-rich (fluoro)alkylated scaffolds
    Science (IF 37.205) Pub Date : 2018-04-06
    Rohan R. Merchant, Jacob T. Edwards, Tian Qin, Monika M. Kruszyk, Cheng Bi, Guanda Che, Deng-Hui Bao, Wenhua Qiao, Lijie Sun, Michael R. Collins, Olugbeminiyi O. Fadeyi, Gary M. Gallego, James J. Mousseau, Philippe Nuhant, Phil S. Baran

    Cross-coupling chemistry is widely applied to carbon-carbon bond formation in the synthesis of medicines, agrochemicals, and other functional materials. Recently, single-electron–induced variants of this reaction class have proven particularly useful in the formation of C(sp2)–C(sp3) linkages, although certain compound classes have remained a challenge. Here, we report the use of sulfones to activate the alkyl coupling partner in nickel-catalyzed radical cross-coupling with aryl zinc reagents. This method’s tolerance of fluoroalkyl substituents proved particularly advantageous for the streamlined preparation of pharmaceutically oriented fluorinated scaffolds that previously required multiple steps, toxic reagents, and nonmodular retrosynthetic blueprints. Five specific sulfone reagents facilitate the rapid assembly of a vast set of compounds, many of which contain challenging fluorination patterns.

    更新日期:2018-04-06
  • Early emergence of cortical interneuron diversity in the mouse embryo
    Science (IF 37.205) Pub Date : 2018-04-06
    Da Mi, Zhen Li, Lynette Lim, Mingfeng Li, Monika Moissidis, Yifei Yang, Tianliuyun Gao, Tim Xiaoming Hu, Thomas Pratt, David J. Price, Nenad Sestan, Oscar Marín

    GABAergic interneurons (GABA, γ-aminobutyric acid) regulate neural-circuit activity in the mammalian cerebral cortex. These cortical interneurons are structurally and functionally diverse. Here, we use single-cell transcriptomics to study the origins of this diversity in the mouse. We identify distinct types of progenitor cells and newborn neurons in the ganglionic eminences, the embryonic proliferative regions that give rise to cortical interneurons. These embryonic precursors show temporally and spatially restricted transcriptional patterns that lead to different classes of interneurons in the adult cerebral cortex. Our findings suggest that shortly after the interneurons become postmitotic, their diversity is already patent in their diverse transcriptional programs, which subsequently guide further differentiation in the developing cortex.

    更新日期:2018-04-06
  • Environmental dynamics during the onset of the Middle Stone Age in eastern Africa
    Science (IF 37.205) Pub Date : 2018-04-06
    Richard Potts, Anna K. Behrensmeyer, J. Tyler Faith, Christian A. Tryon, Alison S. Brooks, John E. Yellen, Alan L. Deino, Rahab Kinyanjui, Jennifer B. Clark, Catherine M. Haradon, Naomi E. Levin, Hanneke J. M. Meijer, Elizabeth G. Veatch, R. Bernhart Owen, Robin W. Renaut

    Development of the African Middle Stone Age (MSA) before 300,000 years ago raises the question of how environmental change influenced the evolution of behaviors characteristic of early Homo sapiens. We used temporally well-constrained sedimentological and paleoenvironmental data to investigate environmental dynamics before and after the appearance of the early MSA in the Olorgesailie basin, Kenya. In contrast to the Acheulean archeological record in the same basin, MSA sites are associated with a markedly different faunal community, more pronounced erosion-deposition cycles, tectonic activity, and enhanced wet-dry variability. Aspects of Acheulean technology in this region imply that, as early as 615,000 years ago, greater stone material selectivity and wider resource procurement coincided with an increased pace of land-lake fluctuation, potentially anticipating the adaptability of MSA hominins.

    更新日期:2018-04-06
  • Long-distance stone transport and pigment use in the earliest Middle Stone Age
    Science (IF 37.205) Pub Date : 2018-04-06
    Alison S. Brooks, John E. Yellen, Richard Potts, Anna K. Behrensmeyer, Alan L. Deino, David E. Leslie, Stanley H. Ambrose, Jeffrey R. Ferguson, Francesco d’Errico, Andrew M. Zipkin, Scott Whittaker, Jeffrey Post, Elizabeth G. Veatch, Kimberly Foecke, Jennifer B. Clark

    Previous research suggests that the complex symbolic, technological, and socioeconomic behaviors that typify Homo sapiens had roots in the middle Pleistocene <200,000 years ago, but data bearing on human behavioral origins are limited. We present a series of excavated Middle Stone Age sites from the Olorgesailie basin, southern Kenya, dating from ≥295,000 to ~320,000 years ago by argon-40/argon-39 and uranium-series methods. Hominins at these sites made prepared cores and points, exploited iron-rich rocks to obtain red pigment, and procured stone tool materials from ≥25- to 50-kilometer distances. Associated fauna suggests a broad resource strategy that included large and small prey. These practices imply notable changes in how individuals and groups related to the landscape and to one another and provide documentation relevant to human social and cognitive evolution.

    更新日期:2018-04-06
  • Chronology of the Acheulean to Middle Stone Age transition in eastern Africa
    Science (IF 37.205) Pub Date : 2018-04-06
    Alan L. Deino, Anna K. Behrensmeyer, Alison S. Brooks, John E. Yellen, Warren D. Sharp, Richard Potts

    The origin of the Middle Stone Age (MSA) marks the transition from a highly persistent mode of stone toolmaking, the Acheulean, to a period of increasing technological innovation and cultural indicators associated with the evolution of Homo sapiens. We used argon-40/argon-39 and uranium-series dating to calibrate the chronology of Acheulean and early MSA artifact–rich sedimentary deposits in the Olorgesailie basin, southern Kenya rift. We determined the age of late Acheulean tool assemblages from 615,000 to 499,000 years ago, after which a large technological and faunal transition occurred, with a definitive MSA lacking Acheulean elements beginning most likely by ~320,000 years ago, but at least by 305,000 years ago. These results establish the oldest repository of MSA artifacts in eastern Africa.

    更新日期:2018-04-06
  • Cell cycle heterogeneity directs the timing of neural stem cell activation from quiescence
    Science (IF 37.205) Pub Date : 2018-04-06
    L. Otsuki, A. H. Brand

    Quiescent stem cells in adult tissues can be activated for homeostasis or repair. Neural stem cells (NSCs) in Drosophila are reactivated from quiescence in response to nutrition by the insulin signaling pathway. It is widely accepted that quiescent stem cells are arrested in G0. In this study, however, we demonstrate that quiescent NSCs (qNSCs) are arrested in either G2 or G0. G2-G0 heterogeneity directs NSC behavior: G2 qNSCs reactivate before G0 qNSCs. In addition, we show that the evolutionarily conserved pseudokinase Tribbles (Trbl) induces G2 NSCs to enter quiescence by promoting degradation of Cdc25String and that it subsequently maintains quiescence by inhibiting Akt activation. Insulin signaling overrides repression of Akt and silences trbl transcription, allowing NSCs to exit quiescence. Our results have implications for identifying and manipulating quiescent stem cells for regenerative purposes.

    更新日期:2018-04-06
  • Real-time imaging of DNA loop extrusion by condensin
    Science (IF 37.205) Pub Date : 2018-04-06
    Mahipal Ganji, Indra A. Shaltiel, Shveta Bisht, Eugene Kim, Ana Kalichava, Christian H. Haering, Cees Dekker

    It has been hypothesized that SMC protein complexes such as condensin and cohesin spatially organize chromosomes by extruding DNA into large loops. We directly visualized the formation and processive extension of DNA loops by yeast condensin in real time. Our findings constitute unambiguous evidence for loop extrusion. We observed that a single condensin complex is able to extrude tens of kilobase pairs of DNA at a force-dependent speed of up to 1500 base pairs per second, using the energy of adenosine triphosphate hydrolysis. Condensin-induced loop extrusion was strictly asymmetric, which demonstrates that condensin anchors onto DNA and reels it in from only one side. Active DNA loop extrusion by SMC complexes may provide the universal unifying principle for genome organization.

    更新日期:2018-04-06
  • Hepatic thrombopoietin is required for bone marrow hematopoietic stem cell maintenance
    Science (IF 37.205) Pub Date : 2018-04-06
    Matthew Decker, Juliana Leslie, Qingxue Liu, Lei Ding

    Hematopoietic stem cell (HSC) maintenance depends on extrinsic cues. Currently, only local signals arising from the bone marrow niche have been shown to maintain HSCs. However, it is not known whether systemic factors also sustain HSCs. We assessed the physiological source of thrombopoietin (TPO), a key cytokine required for maintaining HSCs. Using TpoDsRed-CreER knock-in mice, we showed that TPO is expressed by hepatocytes but not by bone marrow cells. Deletion of Tpo from hematopoietic cells, osteoblasts, or bone marrow mesenchymal stromal cells does not affect HSC number or function. However, when Tpo is deleted from hepatocytes, bone marrow HSCs are depleted. Thus, a cross-organ factor, circulating TPO made in the liver by hepatocytes, is required for bone marrow HSC maintenance. Our results demonstrate that systemic factors, in addition to the local niche, are a critical extrinsic component for HSC maintenance.

    更新日期:2018-04-06
  • Ancient genomes revisit the ancestry of domestic and Przewalski’s horses
    Science (IF 37.205) Pub Date : 2018-04-06
    Charleen Gaunitz, Antoine Fages, Kristian Hanghøj, Anders Albrechtsen, Naveed Khan, Mikkel Schubert, Andaine Seguin-Orlando, Ivy J. Owens, Sabine Felkel, Olivier Bignon-Lau, Peter de Barros Damgaard, Alissa Mittnik, Azadeh F. Mohaseb, Hossein Davoudi, Saleh Alquraishi, Ahmed H. Alfarhan, Khaled A. S. Al-Rasheid, Eric Crubézy, Norbert Benecke, Sandra Olsen, Dorcas Brown, David Anthony, Ken Massy, Vladimir Pitulko, Aleksei Kasparov, Gottfried Brem, Michael Hofreiter, Gulmira Mukhtarova, Nurbol Baimukhanov, Lembi Lõugas, Vedat Onar, Philipp W. Stockhammer, Johannes Krause, Bazartseren Boldgiv, Sainbileg Undrakhbold, Diimaajav Erdenebaatar, Sébastien Lepetz, Marjan Mashkour, Arne Ludwig, Barbara Wallner, Victor Merz, Ilja Merz, Viktor Zaibert, Eske Willerslev, Pablo Librado, Alan K. Outram, Ludovic Orlando

    The Eneolithic Botai culture of the Central Asian steppes provides the earliest archaeological evidence for horse husbandry, ~5500 years ago, but the exact nature of early horse domestication remains controversial. We generated 42 ancient-horse genomes, including 20 from Botai. Compared to 46 published ancient- and modern-horse genomes, our data indicate that Przewalski’s horses are the feral descendants of horses herded at Botai and not truly wild horses. All domestic horses dated from ~4000 years ago to present only show ~2.7% of Botai-related ancestry. This indicates that a massive genomic turnover underpins the expansion of the horse stock that gave rise to modern domesticates, which coincides with large-scale human population expansions during the Early Bronze Age.

    更新日期:2018-04-06
  • Triggered recruitment of ESCRT machinery promotes endolysosomal repair
    Science (IF 37.205) Pub Date : 2018-04-06
    Michael L. Skowyra, Paul H. Schlesinger, Teresa V. Naismith, Phyllis I. Hanson

    Endolysosomes can be damaged by diverse materials. Terminally damaged compartments are degraded by lysophagy, but pathways that repair salvageable organelles are poorly understood. Here we found that the endosomal sorting complex required for transport (ESCRT) machinery, known to mediate budding and fission on endolysosomes, also plays an essential role in their repair. ESCRTs were rapidly recruited to acutely injured endolysosomes through a pathway requiring calcium and ESCRT-activating factors that was independent of lysophagy. We used live-cell imaging to demonstrate that ESCRTs responded to small perforations in endolysosomal membranes and enabled compartments to recover from limited damage. Silica crystals that disrupted endolysosomes also triggered ESCRT recruitment. ESCRTs thus provide a defense against endolysosomal damage likely to be relevant in physiological and pathological contexts.

    更新日期:2018-04-06
  • Cryo-EM structure of a herpesvirus capsid at 3.1 Å
    Science (IF 37.205) Pub Date : 2018-04-06
    Shuai Yuan, Jialing Wang, Dongjie Zhu, Nan Wang, Qiang Gao, Wenyuan Chen, Hao Tang, Junzhi Wang, Xinzheng Zhang, Hongrong Liu, Zihe Rao, Xiangxi Wang

    Structurally and genetically, human herpesviruses are among the largest and most complex of viruses. Using cryo–electron microscopy (cryo-EM) with an optimized image reconstruction strategy, we report the herpes simplex virus type 2 (HSV-2) capsid structure at 3.1 angstroms, which is built up of about 3000 proteins organized into three types of hexons (central, peripentonal, and edge), pentons, and triplexes. Both hexons and pentons contain the major capsid protein, VP5; hexons also contain a small capsid protein, VP26; and triplexes comprise VP23 and VP19C. Acting as core organizers, VP5 proteins form extensive intermolecular networks, involving multiple disulfide bonds (about 1500 in total) and noncovalent interactions, with VP26 proteins and triplexes that underpin capsid stability and assembly. Conformational adaptations of these proteins induced by their microenvironments lead to 46 different conformers that assemble into a massive quasisymmetric shell, exemplifying the structural and functional complexity of HSV.

    更新日期:2018-04-06
  • Structure of the herpes simplex virus 1 capsid with associated tegument protein complexes
    Science (IF 37.205) Pub Date : 2018-04-06
    Xinghong Dai, Z. Hong Zhou

    Herpes simplex viruses (HSVs) rely on capsid-associated tegument complex (CATC) for long-range axonal transport of their genome-containing capsids between sites of infection and neuronal cell bodies. Here we report cryo–electron microscopy structures of the HSV-1 capsid with CATC up to 3.5-angstrom resolution and atomic models of multiple conformers of capsid proteins VP5, VP19c, VP23, and VP26 and tegument proteins pUL17, pUL25, and pUL36. Crowning every capsid vertex are five copies of heteropentameric CATC, each containing a pUL17 monomer supporting the coiled-coil helix bundle of a pUL25 dimer and a pUL36 dimer, thus positioning their flexible domains for potential involvement in nuclear capsid egress and axonal capsid transport. Notwithstanding newly discovered fold conservation between triplex proteins and bacteriophage λ protein gpD and the previously recognized bacteriophage HK97 gp5–like fold in VP5, HSV-1 capsid proteins exhibit extraordinary diversity in forms of domain insertion and conformational polymorphism, not only for interactions with tegument proteins but also for encapsulation of large genomes.

    更新日期:2018-04-06
  • Catalytic enantioselective Minisci-type addition to heteroarenes
    Science (IF 37.205) Pub Date : 2018-04-05
    Rupert S. J. Proctor, Holly J. Davis, Robert J. Phipps

    Basic heteroarenes are a ubiquitous feature of pharmaceuticals and bioactive molecules, and Minisci-type additions of radical nucleophiles are a leading method for their elaboration. Despite many Minisci-type protocols that result in the formation of stereocenters, exerting control over the absolute stereochemistry at these centers remains an unmet challenge. We report a process for addition of prochiral radicals, generated from amino acid derivatives, to pyridines and quinolines with excellent control of both enantioselectivity and regioselectivity. An enantiopure chiral Brønsted acid catalyst serves both to activate the substrate and induce asymmetry, while an iridium photocatalyst mediates the required electron transfer processes. We anticipate that this method will expedite access to enantioenriched small-molecule building blocks bearing versatile basic heterocycles.

    更新日期:2018-04-06
  • Single-cell transcriptomics of the mouse kidney reveals potential cellular targets of kidney disease
    Science (IF 37.205) Pub Date : 2018-04-05
    Jihwan Park, Rojesh Shrestha, Chengxiang Qiu, Ayano Kondo, Shizheng Huang, Max Werth, Mingyao Li, Jonathan Barasch, Katalin Suszták

    Our understanding of kidney disease pathogenesis is limited by an incomplete molecular characterization of the cell types responsible for the organ’s multiple homeostatic functions. To help fill this knowledge gap, we characterized 57,979 cells from healthy mouse kidneys using unbiased single-cell RNA sequencing. Based on gene expression patterns, we infer that inherited kidney diseases that arise from distinct genetic mutations but share the same phenotypic manifestation originate from the same cell differentiated type. We also found that the kidney collecting duct in adult mice generates a spectrum of cell types via a newly identified transitional cell. Computational cell trajectory analysis and in vivo lineage tracing revealed that intercalated cells and principal cells undergo transitions mediated by the Notch signaling pathway. In mouse and human kidney disease, these transitions were shifted toward a principal cell fate and were associated with metabolic acidosis.

    更新日期:2018-04-06
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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