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  • Revealing hidden spin-momentum locking in a high-temperature cuprate superconductor
    Science (IF 41.058) Pub Date : 2018-12-14
    Kenneth Gotlieb, Chiu-Yun Lin, Maksym Serbyn, Wentao Zhang, Christopher L. Smallwood, Christopher Jozwiak, Hiroshi Eisaki, Zahid Hussain, Ashvin Vishwanath, Alessandra Lanzara

    Cuprate superconductors have long been thought of as having strong electronic correlations but negligible spin-orbit coupling. Using spin- and angle-resolved photoemission spectroscopy, we discovered that one of the most studied cuprate superconductors, Bi2212, has a nontrivial spin texture with a spin-momentum locking that circles the Brillouin zone center and a spin-layer locking that allows states of opposite spin to be localized in different parts of the unit cell. Our findings pose challenges for the vast majority of models of cuprates, such as the Hubbard model and its variants, where spin-orbit interaction has been mostly neglected, and open the intriguing question of how the high-temperature superconducting state emerges in the presence of this nontrivial spin texture.

    更新日期:2018-12-14
  • Ultralow-loading platinum-cobalt fuel cell catalysts derived from imidazolate frameworks
    Science (IF 41.058) Pub Date : 2018-12-14
    Lina Chong, Jianguo Wen, Joseph Kubal, Fatih G. Sen, Jianxin Zou, Jeffery Greeley, Maria Chan, Heather Barkholtz, Wenjiang Ding, Di-Jia Liu

    Achieving high catalytic performance with the lowest possible amount of platinum is critical for fuel cell cost reduction. Here we describe a method of preparing highly active yet stable electrocatalysts containing ultralow-loading platinum content by using cobalt or bimetallic cobalt and zinc zeolitic imidazolate frameworks as precursors. Synergistic catalysis between strained platinum-cobalt core-shell nanoparticles over a platinum-group metal (PGM)–free catalytic substrate led to excellent fuel cell performance under 1 atmosphere of O2 or air at both high-voltage and high-current domains. Two catalysts achieved oxygen reduction reaction (ORR) mass activities of 1.08 amperes per milligram of platinum (A mgPt−1) and 1.77 A mgPt−1 and retained 64% and 15% of initial values after 30,000 voltage cycles in a fuel cell. Computational modeling reveals that the interaction between platinum-cobalt nanoparticles and PGM-free sites improves ORR activity and durability.

    更新日期:2018-12-14
  • 3D nanofabrication by volumetric deposition and controlled shrinkage of patterned scaffolds
    Science (IF 41.058) Pub Date : 2018-12-14
    Daniel Oran, Samuel G. Rodriques, Ruixuan Gao, Shoh Asano, Mark A. Skylar-Scott, Fei Chen, Paul W. Tillberg, Adam H. Marblestone, Edward S. Boyden

    Lithographic nanofabrication is often limited to successive fabrication of two-dimensional (2D) layers. We present a strategy for the direct assembly of 3D nanomaterials consisting of metals, semiconductors, and biomolecules arranged in virtually any 3D geometry. We used hydrogels as scaffolds for volumetric deposition of materials at defined points in space. We then optically patterned these scaffolds in three dimensions, attached one or more functional materials, and then shrank and dehydrated them in a controlled way to achieve nanoscale feature sizes in a solid substrate. We demonstrate that our process, Implosion Fabrication (ImpFab), can directly write highly conductive, 3D silver nanostructures within an acrylic scaffold via volumetric silver deposition. Using ImpFab, we achieve resolutions in the tens of nanometers and complex, non–self-supporting 3D geometries of interest for optical metamaterials.

    更新日期:2018-12-14
  • Evolution of a highly active and enantiospecific metalloenzyme from short peptides
    Science (IF 41.058) Pub Date : 2018-12-14
    Sabine Studer, Douglas A. Hansen, Zbigniew L. Pianowski, Peer R. E. Mittl, Aaron Debon, Sharon L. Guffy, Bryan S. Der, Brian Kuhlman, Donald Hilvert

    Primordial sequence signatures in modern proteins imply ancestral origins tracing back to simple peptides. Although short peptides seldom adopt unique folds, metal ions might have templated their assembly into higher-order structures in early evolution and imparted useful chemical reactivity. Recapitulating such a biogenetic scenario, we have combined design and laboratory evolution to transform a zinc-binding peptide into a globular enzyme capable of accelerating ester cleavage with exacting enantiospecificity and high catalytic efficiency (kcat/KM ~ 106 M−1 s−1). The simultaneous optimization of structure and function in a naïve peptide scaffold not only illustrates a plausible enzyme evolutionary pathway from the distant past to the present but also proffers exciting future opportunities for enzyme design and engineering.

    更新日期:2018-12-14
  • Observation of the geometric phase effect in the H + HD → H2 + D reaction
    Science (IF 41.058) Pub Date : 2018-12-14
    Daofu Yuan, Yafu Guan, Wentao Chen, Hailin Zhao, Shengrui Yu, Chang Luo, Yuxin Tan, Ting Xie, Xingan Wang, Zhigang Sun, Dong H. Zhang, Xueming Yang

    Theory has established the importance of geometric phase (GP) effects in the adiabatic dynamics of molecular systems with a conical intersection connecting the ground- and excited-state potential energy surfaces, but direct observation of their manifestation in chemical reactions remains a major challenge. Here, we report a high-resolution crossed molecular beams study of the H + HD → H2 + D reaction at a collision energy slightly above the conical intersection. Velocity map ion imaging revealed fast angular oscillations in product quantum state–resolved differential cross sections in the forward scattering direction for H2 products at specific rovibrational levels. The experimental results agree with adiabatic quantum dynamical calculations only when the GP effect is included.

    更新日期:2018-12-14
  • Atmospheric 14C/12C changes during the last glacial period from Hulu Cave
    Science (IF 41.058) Pub Date : 2018-12-14
    Hai Cheng, R. Lawrence Edwards, John Southon, Katsumi Matsumoto, Joshua M. Feinberg, Ashish Sinha, Weijian Zhou, Hanying Li, Xianglei Li, Yao Xu, Shitao Chen, Ming Tan, Quan Wang, Yongjin Wang, Youfeng Ning

    Paired measurements of 14C/12C and 230Th ages from two Hulu Cave stalagmites complete a precise record of atmospheric 14C covering the full range of the 14C dating method (~54,000 years). Over the last glacial period, atmospheric 14C/12C ranges from values similar to modern values to values 1.70 times higher (42,000 to 39,000 years ago). The latter correspond to 14C ages 5200 years less than calibrated ages and correlate with the Laschamp geomagnetic excursion followed by Heinrich Stadial 4. Millennial-scale variations are largely attributable to Earth’s magnetic field changes and in part to climate-related changes in the oceanic carbon cycle. A progressive shift to lower 14C/12C values between 25,000 and 11,000 years ago is likely related, in part, to progressively increasing ocean ventilation rates.

    更新日期:2018-12-14
  • 1.9-million- and 2.4-million-year-old artifacts and stone tool–cutmarked bones from Ain Boucherit, Algeria
    Science (IF 41.058) Pub Date : 2018-12-14
    Mohamed Sahnouni, Josep M. Parés, Mathieu Duval, Isabel Cáceres, Zoheir Harichane, Jan van der Made, Alfredo Pérez-González, Salah Abdessadok, Nadia Kandi, Abdelkader Derradji, Mohamed Medig, Kamel Boulaghraif, Sileshi Semaw

    East Africa has provided the earliest known evidence for Oldowan stone artifacts and hominin-induced stone tool cutmarks dated to ~2.6 million years (Ma) ago. The ~1.8-million-year-old stone artifacts from Ain Hanech (Algeria) were considered to represent the oldest archaeological materials in North Africa. Here we report older stone artifacts and cutmarked bones excavated from two nearby deposits at Ain Boucherit estimated to ~1.9 Ma ago, and the older to ~2.4 Ma ago. Hence, the Ain Boucherit evidence shows that ancestral hominins inhabited the Mediterranean fringe in northern Africa much earlier than previously thought. The evidence strongly argues for early dispersal of stone tool manufacture and use from East Africa or a possible multiple-origin scenario of stone technology in both East and North Africa.

    更新日期:2018-12-14
  • A femtomolar-range suicide germination stimulant for the parasitic plant Striga hermonthica
    Science (IF 41.058) Pub Date : 2018-12-14
    Daisuke Uraguchi, Keiko Kuwata, Yuh Hijikata, Rie Yamaguchi, Hanae Imaizumi, Sathiyanarayanan AM, Christin Rakers, Narumi Mori, Kohki Akiyama, Stephan Irle, Peter McCourt, Toshinori Kinoshita, Takashi Ooi, Yuichiro Tsuchiya

    The parasitic plant Striga hermonthica has been causing devastating damage to the crop production in Africa. Because Striga requires host-generated strigolactones to germinate, the identification of selective and potent strigolactone agonists could help control these noxious weeds. We developed a selective agonist, sphynolactone-7, a hybrid molecule originated from chemical screening, that contains two functional modules derived from a synthetic scaffold and a core component of strigolactones. Cooperative action of these modules in the activation of a high-affinity strigolactone receptor ShHTL7 allows sphynolactone-7 to provoke Striga germination with potency in the femtomolar range. We demonstrate that sphynolactone-7 is effective for reducing Striga parasitism without impinging on host strigolactone-related processes.

    更新日期:2018-12-14
  • High-affinity allergen-specific human antibodies cloned from single IgE B cell transcriptomes
    Science (IF 41.058) Pub Date : 2018-12-14
    Derek Croote, Spyros Darmanis, Kari C. Nadeau, Stephen R. Quake

    Immunoglobulin E (IgE) antibodies protect against helminth infections but can also cause life-threatening allergic reactions. Despite their role in human health, the cells that produce these antibodies are rarely observed and remain enigmatic. We isolated single IgE B cells from individuals with food allergies and used single-cell RNA sequencing to elucidate the gene expression and splicing patterns unique to these cells. We identified a surprising example of convergent evolution in which IgE antibodies underwent identical gene rearrangements in unrelated individuals. Through the acquisition of variable region mutations, these IgE antibodies gained high affinity and unexpected cross-reactivity to the clinically important peanut allergens Ara h 2 and Ara h 3. These findings provide insight into IgE B cell transcriptomics and enable biochemical dissection of this antibody class.

    更新日期:2018-12-14
  • Multiproxy evidence highlights a complex evolutionary legacy of maize in South America
    Science (IF 41.058) Pub Date : 2018-12-14
    Logan Kistler, S. Yoshi Maezumi, Jonas Gregorio de Souza, Natalia A. S. Przelomska, Flaviane Malaquias Costa, Oliver Smith, Hope Loiselle, Jazmín Ramos-Madrigal, Nathan Wales, Eduardo Rivail Ribeiro, Ryan R. Morrison, Claudia Grimaldo, Andre P. Prous, Bernardo Arriaza, M. Thomas P. Gilbert, Fabio de Oliveira Freitas, Robin G. Allaby

    Domesticated maize evolved from wild teosinte under human influences in Mexico beginning around 9000 years before the present (yr B.P.), traversed Central America by ~7500 yr B.P., and spread into South America by ~6500 yr B.P. Landrace and archaeological maize genomes from South America suggest that the ancestral population to South American maize was brought out of the domestication center in Mexico and became isolated from the wild teosinte gene pool before traits of domesticated maize were fixed. Deeply structured lineages then evolved within South America out of this partially domesticated progenitor population. Genomic, linguistic, archaeological, and paleoecological data suggest that the southwestern Amazon was a secondary improvement center for partially domesticated maize. Multiple waves of human-mediated dispersal are responsible for the diversity and biogeography of modern South American maize.

    更新日期:2018-12-14
  • Neuron-specific signatures in the chromosomal connectome associated with schizophrenia risk
    Science (IF 41.058) Pub Date : 2018-12-14
    Prashanth Rajarajan, Tyler Borrman, Will Liao, Nadine Schrode, Erin Flaherty, Charlize Casiño, Samuel Powell, Chittampalli Yashaswini, Elizabeth A. LaMarca, Bibi Kassim, Behnam Javidfar, Sergio Espeso-Gil, Aiqun Li, Hyejung Won, Daniel H. Geschwind, Seok-Man Ho, Matthew MacDonald, Gabriel E. Hoffman, Panos Roussos, Bin Zhang, Chang-Gyu Hahn, Zhiping Weng, Kristen J. Brennand, Schahram Akbarian

    To explore the developmental reorganization of the three-dimensional genome of the brain in the context of neuropsychiatric disease, we monitored chromosomal conformations in differentiating neural progenitor cells. Neuronal and glial differentiation was associated with widespread developmental remodeling of the chromosomal contact map and included interactions anchored in common variant sequences that confer heritable risk for schizophrenia. We describe cell type–specific chromosomal connectomes composed of schizophrenia risk variants and their distal targets, which altogether show enrichment for genes that regulate neuronal connectivity and chromatin remodeling, and evidence for coordinated transcriptional regulation and proteomic interaction of the participating genes. Developmentally regulated chromosomal conformation changes at schizophrenia-relevant sequences disproportionally occurred in neurons, highlighting the existence of cell type–specific disease risk vulnerabilities in spatial genome organization.

    更新日期:2018-12-14
  • Genome-wide de novo risk score implicates promoter variation in autism spectrum disorder
    Science (IF 41.058) Pub Date : 2018-12-14
    Joon-Yong An, Kevin Lin, Lingxue Zhu, Donna M. Werling, Shan Dong, Harrison Brand, Harold Z. Wang, Xuefang Zhao, Grace B. Schwartz, Ryan L. Collins, Benjamin B. Currall, Claudia Dastmalchi, Jeanselle Dea, Clif Duhn, Michael C. Gilson, Lambertus Klei, Lindsay Liang, Eirene Markenscoff-Papadimitriou, Sirisha Pochareddy, Nadav Ahituv, Joseph D. Buxbaum, Hilary Coon, Mark J. Daly, Young Shin Kim, Gabor T. Marth, Benjamin M. Neale, Aaron R. Quinlan, John L. Rubenstein, Nenad Sestan, Matthew W. State, A. Jeremy Willsey, Michael E. Talkowski, Bernie Devlin, Kathryn Roeder, Stephan J. Sanders

    Whole-genome sequencing (WGS) has facilitated the first genome-wide evaluations of the contribution of de novo noncoding mutations to complex disorders. Using WGS, we identified 255,106 de novo mutations among sample genomes from members of 1902 quartet families in which one child, but not a sibling or their parents, was affected by autism spectrum disorder (ASD). In contrast to coding mutations, no noncoding functional annotation category, analyzed in isolation, was significantly associated with ASD. Casting noncoding variation in the context of a de novo risk score across multiple annotation categories, however, did demonstrate association with mutations localized to promoter regions. We found that the strongest driver of this promoter signal emanates from evolutionarily conserved transcription factor binding sites distal to the transcription start site. These data suggest that de novo mutations in promoter regions, characterized by evolutionary and functional signatures, contribute to ASD.

    更新日期:2018-12-14
  • Transcriptome and epigenome landscape of human cortical development modeled in organoids
    Science (IF 41.058) Pub Date : 2018-12-14
    Anahita Amiri, Gianfilippo Coppola, Soraya Scuderi, Feinan Wu, Tanmoy Roychowdhury, Fuchen Liu, Sirisha Pochareddy, Yurae Shin, Alexias Safi, Lingyun Song, Ying Zhu, André M. M. Sousa, The PsychENCODE Consortium†, Mark Gerstein, Gregory E. Crawford, Nenad Sestan, Alexej Abyzov, Flora M. Vaccarino

    Genes implicated in neuropsychiatric disorders are active in human fetal brain, yet difficult to study in a longitudinal fashion. We demonstrate that organoids from human pluripotent cells model cerebral cortical development on the molecular level before 16 weeks postconception. A multiomics analysis revealed differentially active genes and enhancers, with the greatest changes occurring at the transition from stem cells to progenitors. Networks of converging gene and enhancer modules were assembled into six and four global patterns of expression and activity across time. A pattern with progressive down-regulation was enriched with human-gained enhancers, suggesting their importance in early human brain development. A few convergent gene and enhancer modules were enriched in autism-associated genes and genomic variants in autistic children. The organoid model helps identify functional elements that may drive disease onset.

    更新日期:2018-12-14
  • Integrative functional genomic analysis of human brain development and neuropsychiatric risks
    Science (IF 41.058) Pub Date : 2018-12-14
    Mingfeng Li, Gabriel Santpere, Yuka Imamura Kawasawa, Oleg V. Evgrafov, Forrest O. Gulden, Sirisha Pochareddy, Susan M. Sunkin, Zhen Li, Yurae Shin, Ying Zhu, André M. M. Sousa, Donna M. Werling, Robert R. Kitchen, Hyo Jung Kang, Mihovil Pletikos, Jinmyung Choi, Sydney Muchnik, Xuming Xu, Daifeng Wang, Belen Lorente-Galdos, Shuang Liu, Paola Giusti-Rodríguez, Hyejung Won, Christiaan A. de Leeuw, Antonio F. Pardiñas, BrainSpan Consortium†, PsychENCODE Consortium†, PsychENCODE Developmental Subgroup†, Ming Hu, Fulai Jin, Yun Li, Michael J. Owen, Michael C. O’Donovan, James T. R. Walters, Danielle Posthuma, Pat Levitt, Daniel R. Weinberger, Thomas M. Hyde, Joel E. Kleinman, Daniel H. Geschwind, Michael J. Hawrylycz, Matthew W. State, Stephan J. Sanders, Patrick F. Sullivan, Mark B. Gerstein, Ed S. Lein, James A. Knowles, Nenad Sestan

    To broaden our understanding of human neurodevelopment, we profiled transcriptomic and epigenomic landscapes across brain regions and/or cell types for the entire span of prenatal and postnatal development. Integrative analysis revealed temporal, regional, sex, and cell type–specific dynamics. We observed a global transcriptomic cup-shaped pattern, characterized by a late fetal transition associated with sharply decreased regional differences and changes in cellular composition and maturation, followed by a reversal in childhood-adolescence, and accompanied by epigenomic reorganizations. Analysis of gene coexpression modules revealed relationships with epigenomic regulation and neurodevelopmental processes. Genes with genetic associations to brain-based traits and neuropsychiatric disorders (including MEF2C, SATB2, SOX5, TCF4, and TSHZ3) converged in a small number of modules and distinct cell types, revealing insights into neurodevelopment and the genomic basis of neuropsychiatric risks.

    更新日期:2018-12-14
  • Spatiotemporal transcriptomic divergence across human and macaque brain development
    Science (IF 41.058) Pub Date : 2018-12-14
    Ying Zhu, André M. M. Sousa, Tianliuyun Gao, Mario Skarica, Mingfeng Li, Gabriel Santpere, Paula Esteller-Cucala, David Juan, Luis Ferrández-Peral, Forrest O. Gulden, Mo Yang, Daniel J. Miller, Tomas Marques-Bonet, Yuka Imamura Kawasawa, Hongyu Zhao, Nenad Sestan

    Human nervous system development is an intricate and protracted process that requires precise spatiotemporal transcriptional regulation. We generated tissue-level and single-cell transcriptomic data from up to 16 brain regions covering prenatal and postnatal rhesus macaque development. Integrative analysis with complementary human data revealed that global intraspecies (ontogenetic) and interspecies (phylogenetic) regional transcriptomic differences exhibit concerted cup-shaped patterns, with a late fetal-to-infancy (perinatal) convergence. Prenatal neocortical transcriptomic patterns revealed transient topographic gradients, whereas postnatal patterns largely reflected functional hierarchy. Genes exhibiting heterotopic and heterochronic divergence included those transiently enriched in the prenatal prefrontal cortex or linked to autism spectrum disorder and schizophrenia. Our findings shed light on transcriptomic programs underlying the evolution of human brain development and the pathogenesis of neuropsychiatric disorders.

    更新日期:2018-12-14
  • Transcriptome-wide isoform-level dysregulation in ASD, schizophrenia, and bipolar disorder
    Science (IF 41.058) Pub Date : 2018-12-14
    Michael J. Gandal, Pan Zhang, Evi Hadjimichael, Rebecca L. Walker, Chao Chen, Shuang Liu, Hyejung Won, Harm van Bakel, Merina Varghese, Yongjun Wang, Annie W. Shieh, Jillian Haney, Sepideh Parhami, Judson Belmont, Minsoo Kim, Patricia Moran Losada, Zenab Khan, Justyna Mleczko, Yan Xia, Rujia Dai, Daifeng Wang, Yucheng T. Yang, Min Xu, Kenneth Fish, Patrick R. Hof, Jonathan Warrell, Dominic Fitzgerald, Kevin White, Andrew E. Jaffe, PsychENCODE Consortium, Mette A. Peters, Mark Gerstein, Chunyu Liu, Lilia M. Iakoucheva, Dalila Pinto, Daniel H. Geschwind

    Most genetic risk for psychiatric disease lies in regulatory regions, implicating pathogenic dysregulation of gene expression and splicing. However, comprehensive assessments of transcriptomic organization in diseased brains are limited. In this work, we integrated genotypes and RNA sequencing in brain samples from 1695 individuals with autism spectrum disorder (ASD), schizophrenia, and bipolar disorder, as well as controls. More than 25% of the transcriptome exhibits differential splicing or expression, with isoform-level changes capturing the largest disease effects and genetic enrichments. Coexpression networks isolate disease-specific neuronal alterations, as well as microglial, astrocyte, and interferon-response modules defining previously unidentified neural-immune mechanisms. We integrated genetic and genomic data to perform a transcriptome-wide association study, prioritizing disease loci likely mediated by cis effects on brain expression. This transcriptome-wide characterization of the molecular pathology across three major psychiatric disorders provides a comprehensive resource for mechanistic insight and therapeutic development.

    更新日期:2018-12-14
  • Comprehensive functional genomic resource and integrative model for the human brain
    Science (IF 41.058) Pub Date : 2018-12-14
    Daifeng Wang, Shuang Liu, Jonathan Warrell, Hyejung Won, Xu Shi, Fabio C. P. Navarro, Declan Clarke, Mengting Gu, Prashant Emani, Yucheng T. Yang, Min Xu, Michael J. Gandal, Shaoke Lou, Jing Zhang, Jonathan J. Park, Chengfei Yan, Suhn Kyong Rhie, Kasidet Manakongtreecheep, Holly Zhou, Aparna Nathan, Mette Peters, Eugenio Mattei, Dominic Fitzgerald, Tonya Brunetti, Jill Moore, Yan Jiang, Kiran Girdhar, Gabriel E. Hoffman, Selim Kalayci, Zeynep H. Gümüş, Gregory E. Crawford, PsychENCODE Consortium, Panos Roussos, Schahram Akbarian, Andrew E. Jaffe, Kevin P. White, Zhiping Weng, Nenad Sestan, Daniel H. Geschwind, James A. Knowles, Mark B. Gerstein

    Despite progress in defining genetic risk for psychiatric disorders, their molecular mechanisms remain elusive. Addressing this, the PsychENCODE Consortium has generated a comprehensive online resource for the adult brain across 1866 individuals. The PsychENCODE resource contains ~79,000 brain-active enhancers, sets of Hi-C linkages, and topologically associating domains; single-cell expression profiles for many cell types; expression quantitative-trait loci (QTLs); and further QTLs associated with chromatin, splicing, and cell-type proportions. Integration shows that varying cell-type proportions largely account for the cross-population variation in expression (with >88% reconstruction accuracy). It also allows building of a gene regulatory network, linking genome-wide association study variants to genes (e.g., 321 for schizophrenia). We embed this network into an interpretable deep-learning model, which improves disease prediction by ~6-fold versus polygenic risk scores and identifies key genes and pathways in psychiatric disorders.

    更新日期:2018-12-14
  • Structure of the posttranslational Sec protein-translocation channel complex from yeast
    Science (IF 41.058) Pub Date : 2018-12-13
    Samuel Itskanov, Eunyong Park

    The Sec61 protein-conducting channel mediates transport of many proteins, such as secretory proteins, across the endoplasmic reticulum (ER) membrane during or after translation. Posttranslational transport is enabled by two additional membrane proteins associated with the channel, Sec63 and Sec62, but its mechanism is poorly understood. We determined a structure of the Sec complex (Sec61-Sec63-Sec71-Sec72) from Saccharomyces cerevisiae by cryo-electron microscopy (cryo-EM). The structure shows that Sec63 tightly associates with Sec61 though interactions in cytosolic, transmembrane, and ER-luminal domains, prying open Sec61’s lateral gate and translocation pore and thus activating the channel for substrate engagement. Furthermore, Sec63 optimally positions binding sites for cytosolic and luminal chaperones in the complex to enable efficient polypeptide translocation. Our study provides mechanistic insights into eukaryotic posttranslational protein translocation.

    更新日期:2018-12-14
  • The Sommerfeld ground-wave limit for a molecule adsorbed at a surface
    Science (IF 41.058) Pub Date : 2018-12-13
    Li Chen, Jascha A. Lau, Dirk Schwarzer, Jörg Meyer, Varun B. Verma, Alec M. Wodtke

    Using a mid-infrared emission spectrometer based on a superconducting nanowire single-photon detector (SNSPD), we observe the dynamics of vibrational energy pooling of CO adsorbed at the surface of a NaCl crystal. After exciting a majority of the CO molecules to their first vibrationally excited state (v = 1), we observe infrared emission from states up to v = 27. Kinetic Monte Carlo simulations show that vibrational energy collects in a few CO molecules at the expense of those up to eight lattice sites away by selective excitation of NaCl’s transverse phonons. The vibrating CO molecules behave like classical oscillating dipoles, losing their energy to NaCl lattice-vibrations via the electromagnetic near-field. This is analogous to Sommerfeld’s description of the Earth’s influence on radio transmission by ground waves.

    更新日期:2018-12-14
  • Synaptotagmin-3 drives AMPA receptor endocytosis, depression of synapse strength, and forgetting
    Science (IF 41.058) Pub Date : 2018-12-13
    Ankit Awasthi, Binu Ramachandran, Saheeb Ahmed, Eva Benito, Yo Shinoda, Noam Nitzan, Alina Heukamp, Sabine Rannio, Henrik Martens, Jonas Barth, Katja Burk, Yu Tian Wang, Andre Fischer, Camin Dean

    Forgetting is important. Without it, the relative importance of acquired memories in a changing environment is lost. We discovered that Synaptotagmin-3 (Syt3) localizes to post-synaptic endocytic zones and removes AMPA receptors from synaptic plasma membranes in response to stimulation. AMPA receptor internalization, long-term-depression (LTD), and decay of long-term-potentiation (LTP) of synaptic strength required calcium-sensing by Syt3, and were abolished by Syt3 knockout. In spatial memory tasks Syt3 knockout mice learned normally, but exhibited a lack of forgetting. Disrupting Syt3:GluA2 binding in a wild-type background mimicked the lack of LTP decay and lack of forgetting, and these effects were occluded in the Syt3 knockout background. Our findings provide evidence for a molecular mechanism whereby Syt3 internalizes AMPA receptors to depress synaptic strength and promote forgetting.

    更新日期:2018-12-14
  • CRISPR-mediated activation of a promoter or enhancer rescues obesity caused by haploinsufficiency
    Science (IF 41.058) Pub Date : 2018-12-13
    Navneet Matharu, Sawitree Rattanasopha, Serena Tamura, Lenka Maliskova, Yi Wang, Adelaide Bernard, Aaron Hardin, Walter L. Eckalbar, Christian Vaisse, Nadav Ahituv

    A wide-range of human diseases result from haploinsufficiency, where the function of one of the two gene copies is lost. Here, we targeted the remaining functional copy of a haploinsufficient gene using CRISPR-mediated activation (CRISPRa) in Sim1 and Mc4r heterozygous mouse models to rescue their obesity phenotype. Transgenic-based CRISPRa targeting of the Sim1 promoter or its distant hypothalamic enhancer upregulated its expression from the endogenous functional allele in a tissue-specific manner, rescuing the obesity phenotype in Sim1 heterozygous mice. To evaluate the therapeutic potential of CRISPRa, we injected CRISPRa-rAAV into the hypothalamus, which led to reversal of the obesity phenotype in Sim1 and Mc4r haploinsufficient mice. Our results suggest that endogenous gene upregulation could be a potential strategy to treat altered gene dosage diseases.

    更新日期:2018-12-14
  • Strengthened scientific support for the Endangerment Finding for atmospheric greenhouse gases
    Science (IF 41.058) Pub Date : 2018-12-13
    Philip B. Duffy, Christopher B. Field, Noah S. Diffenbaugh, Scott C. Doney, Zoe Dutton, Sherri Goodman, Lisa Heinzerling, Solomon Hsiang, David B. Lobell, Loretta J. Mickley, Samuel Myers, Susan M. Natali, Camille Parmesan, Susan Tierney, A. Park Williams

    We assess scientific evidence that has emerged since the U.S. Environmental Protection Agency’s 2009 Endangerment Finding for six well-mixed greenhouse gases, and find that this new evidence lends increased support to the conclusion that these gases pose a danger to public health and welfare. Newly available evidence about a wide range of observed and projected impacts strengthens the association between risk of some of these impacts and anthropogenic climate change; indicates that some impacts or combinations of impacts have the potential to be more severe than previously understood; and identifies substantial risk of additional impacts through processes and pathways not considered in the endangerment finding.

    更新日期:2018-12-14
  • The 2018 rift eruption and summit collapse of Kīlauea Volcano
    Science (IF 41.058) Pub Date : 2018-12-11
    C. A. Neal, S.R. Brantley, L. Antolik, J. Babb, M. Burgess, K. Calles, M. Cappos, J. C. Chang, S. Conway, L. Desmither, P. Dotray, T. Elias, P. Fukunaga, S. Fuke, I. A. Johanson, K. Kamibayashi, J. Kauahikaua, R. L. Lee, S. Pekalib, A. Miklius, W. Million, C. J. Moniz, P. A. Nadeau, P. Okubo, C. Parcheta, M. P. Patrick, B. Shiro, D. A. Swanson, W. Tollett, F. Trusdell, E. F. Younger, M. H. Zoeller, E. K. Montgomery-Brown, K. R. Anderson, M. P. Poland, J. Ball, J. Bard, M. Coombs, H. R. Dietterich, C. Kern, W. A. Thelen, P. F. Cervelli, T. Orr, B. F. Houghton, C. Gansecki, R. Hazlett, P. Lundgren, A. K. Diefenbach, A. H. Lerner, G. Waite, P. Kelly, L. Clor, C. Werner, K. Mulliken, G. Fisher

    In 2018, Kīlauea Volcano experienced its largest lower East Rift Zone (LERZ) eruption and caldera collapse in at least 200 years. After collapse of the Pu‘u ‘Ō‘ō vent on 30 April, magma propagated downrift. Eruptive fissures opened in the LERZ on 3 May, eventually extending ~6.8 km. A 4 May earthquake (M6.9) produced ~5 m of fault slip. Lava erupted at rates exceeding 100 m3/s, eventually covering 35.5 km2. The summit magma system partially drained, producing minor explosions and near-daily collapses releasing energy equivalent to M4.7-M5.4 earthquakes. Activity declined rapidly on 4 August. Summit collapse and lava flow volume estimates are roughly equivalent—about 0.8 km3. Careful historical observation and monitoring of Kīlauea enabled successful forecasting of hazardous events.

    更新日期:2018-12-12
  • Semiconducting polymer blends that exhibit stable charge transport at high temperatures
    Science (IF 41.058) Pub Date : 2018-12-07
    Aristide Gumyusenge, Dung T. Tran, Xuyi Luo, Gregory M. Pitch, Yan Zhao, Kaelon A. Jenkins, Tim J. Dunn, Alexander L. Ayzner, Brett M. Savoie, Jianguo Mei

    Although high-temperature operation (i.e., beyond 150°C) is of great interest for many electronics applications, achieving stable carrier mobilities for organic semiconductors at elevated temperatures is fundamentally challenging. We report a general strategy to make thermally stable high-temperature semiconducting polymer blends, composed of interpenetrating semicrystalline conjugated polymers and high glass-transition temperature insulating matrices. When properly engineered, such polymer blends display a temperature-insensitive charge transport behavior with hole mobility exceeding 2.0 cm2/V·s across a wide temperature range from room temperature up to 220°C in thin-film transistors.

    更新日期:2018-12-07
  • Building two-dimensional materials one row at a time: Avoiding the nucleation barrier
    Science (IF 41.058) Pub Date : 2018-12-07
    Jiajun Chen, Enbo Zhu, Juan Liu, Shuai Zhang, Zhaoyang Lin, Xiangfeng Duan, Hendrik Heinz, Yu Huang, James J. De Yoreo

    Assembly of two-dimensional (2D) molecular arrays on surfaces produces a wide range of architectural motifs exhibiting unique properties, but little attention has been given to the mechanism by which they nucleate. Using peptides selected for their binding affinity to molybdenum disulfide, we investigated nucleation of 2D arrays by molecularly resolved in situ atomic force microscopy and compared our results to molecular dynamics simulations. The arrays assembled one row at a time, and the nuclei were ordered from the earliest stages and formed without a free energy barrier or a critical size. The results verify long-standing but unproven predictions of classical nucleation theory in one dimension while revealing key interactions underlying 2D assembly.

    更新日期:2018-12-07
  • A general reinforcement learning algorithm that masters chess, shogi, and Go through self-play
    Science (IF 41.058) Pub Date : 2018-12-07
    David Silver, Thomas Hubert, Julian Schrittwieser, Ioannis Antonoglou, Matthew Lai, Arthur Guez, Marc Lanctot, Laurent Sifre, Dharshan Kumaran, Thore Graepel, Timothy Lillicrap, Karen Simonyan, Demis Hassabis

    The game of chess is the longest-studied domain in the history of artificial intelligence. The strongest programs are based on a combination of sophisticated search techniques, domain-specific adaptations, and handcrafted evaluation functions that have been refined by human experts over several decades. By contrast, the AlphaGo Zero program recently achieved superhuman performance in the game of Go by reinforcement learning from self-play. In this paper, we generalize this approach into a single AlphaZero algorithm that can achieve superhuman performance in many challenging games. Starting from random play and given no domain knowledge except the game rules, AlphaZero convincingly defeated a world champion program in the games of chess and shogi (Japanese chess), as well as Go.

    更新日期:2018-12-07
  • Room-temperature cycling of metal fluoride electrodes: Liquid electrolytes for high-energy fluoride ion cells
    Science (IF 41.058) Pub Date : 2018-12-07
    Victoria K. Davis, Christopher M. Bates, Kaoru Omichi, Brett M. Savoie, Nebojša Momčilović, Qingmin Xu, William J. Wolf, Michael A. Webb, Keith J. Billings, Nam Hawn Chou, Selim Alayoglu, Ryan K. McKenney, Isabelle M. Darolles, Nanditha G. Nair, Adrian Hightower, Daniel Rosenberg, Musahid Ahmed, Christopher J. Brooks, Thomas F. Miller, Robert H. Grubbs, Simon C. Jones

    Fluoride ion batteries are potential “next-generation” electrochemical storage devices that offer high energy density. At present, such batteries are limited to operation at high temperatures because suitable fluoride ion–conducting electrolytes are known only in the solid state. We report a liquid fluoride ion–conducting electrolyte with high ionic conductivity, wide operating voltage, and robust chemical stability based on dry tetraalkylammonium fluoride salts in ether solvents. Pairing this liquid electrolyte with a copper–lanthanum trifluoride (Cu@LaF3) core-shell cathode, we demonstrate reversible fluorination and defluorination reactions in a fluoride ion electrochemical cell cycled at room temperature. Fluoride ion–mediated electrochemistry offers a pathway toward developing capacities beyond that of lithium ion technology.

    更新日期:2018-12-07
  • A valley valve and electron beam splitter
    Science (IF 41.058) Pub Date : 2018-12-07
    Jing Li, Rui-Xing Zhang, Zhenxi Yin, Jianxiao Zhang, Kenji Watanabe, Takashi Taniguchi, Chaoxing Liu, Jun Zhu

    Developing alternative paradigms of electronics beyond silicon technology requires the exploration of fundamentally new physical mechanisms, such as the valley-specific phenomena in hexagonal two-dimensional materials. We realize ballistic valley Hall kink states in bilayer graphene and demonstrate gate-controlled current transmission in a four-kink router device. The operations of a waveguide, a valve, and a tunable electron beam splitter are demonstrated. The valley valve exploits the valley-momentum locking of the kink states and reaches an on/off ratio of 8 at zero magnetic field. A magnetic field enables a full-range tunable coherent beam splitter. These results pave a path to building a scalable, coherent quantum transportation network based on the kink states.

    更新日期:2018-12-07
  • Photonic crystals for nano-light in moiré graphene superlattices
    Science (IF 41.058) Pub Date : 2018-12-07
    S. S. Sunku, G. X. Ni, B. Y. Jiang, H. Yoo, A. Sternbach, A. S. McLeod, T. Stauber, L. Xiong, T. Taniguchi, K. Watanabe, P. Kim, M. M. Fogler, D. N. Basov

    Graphene is an atomically thin plasmonic medium that supports highly confined plasmon polaritons, or nano-light, with very low loss. Electronic properties of graphene can be drastically altered when it is laid upon another graphene layer, resulting in a moiré superlattice. The relative twist angle between the two layers is a key tuning parameter of the interlayer coupling in thus-obtained twisted bilayer graphene (TBG). We studied the propagation of plasmon polaritons in TBG by infrared nano-imaging. We discovered that the atomic reconstruction occurring at small twist angles transforms the TBG into a natural plasmon photonic crystal for propagating nano-light. This discovery points to a pathway for controlling nano-light by exploiting quantum properties of graphene and other atomically layered van der Waals materials, eliminating the need for arduous top-down nanofabrication.

    更新日期:2018-12-07
  • Salmonella persisters undermine host immune defenses during antibiotic treatment
    Science (IF 41.058) Pub Date : 2018-12-07
    Daphne A. C. Stapels, Peter W. S. Hill, Alexander J. Westermann, Robert A. Fisher, Teresa L. Thurston, Antoine-Emmanuel Saliba, Isabelle Blommestein, Jörg Vogel, Sophie Helaine

    Many bacterial infections are hard to treat and tend to relapse, possibly due to the presence of antibiotic-tolerant persisters. In vitro, persister cells appear to be dormant. After uptake of Salmonella species by macrophages, nongrowing persisters also occur, but their physiological state is poorly understood. In this work, we show that Salmonella persisters arising during macrophage infection maintain a metabolically active state. Persisters reprogram macrophages by means of effectors secreted by the Salmonella pathogenicity island 2 type 3 secretion system. These effectors dampened proinflammatory innate immune responses and induced anti-inflammatory macrophage polarization. Such reprogramming allowed nongrowing Salmonella cells to survive for extended periods in their host. Persisters undermining host immune defenses might confer an advantage to the pathogen during relapse once antibiotic pressure is relieved.

    更新日期:2018-12-07
  • Quantifying the contribution of recessive coding variation to developmental disorders
    Science (IF 41.058) Pub Date : 2018-12-07
    Hilary C. Martin, Wendy D. Jones, Rebecca McIntyre, Gabriela Sanchez-Andrade, Mark Sanderson, James D. Stephenson, Carla P. Jones, Juliet Handsaker, Giuseppe Gallone, Michaela Bruntraeger, Jeremy F. McRae, Elena Prigmore, Patrick Short, Mari Niemi, Joanna Kaplanis, Elizabeth J. Radford, Nadia Akawi, Meena Balasubramanian, John Dean, Rachel Horton, Alice Hulbert, Diana S. Johnson, Katie Johnson, Dhavendra Kumar, Sally Ann Lynch, Sarju G. Mehta, Jenny Morton, Michael J. Parker, Miranda Splitt, Peter D. Turnpenny, Pradeep C. Vasudevan, Michael Wright, Andrew Bassett, Sebastian S. Gerety, Caroline F. Wright, David R. FitzPatrick, Helen V. Firth, Matthew E. Hurles, Jeffrey C. Barrett, on behalf of the Deciphering Developmental Disorders Study

    We estimated the genome-wide contribution of recessive coding variation in 6040 families from the Deciphering Developmental Disorders study. The proportion of cases attributable to recessive coding variants was 3.6% in patients of European ancestry, compared with 50% explained by de novo coding mutations. It was higher (31%) in patients with Pakistani ancestry, owing to elevated autozygosity. Half of this recessive burden is attributable to known genes. We identified two genes not previously associated with recessive developmental disorders, KDM5B and EIF3F, and functionally validated them with mouse and cellular models. Our results suggest that recessive coding variants account for a small fraction of currently undiagnosed nonconsanguineous individuals, and that the role of noncoding variants, incomplete penetrance, and polygenic mechanisms need further exploration.

    更新日期:2018-12-07
  • A mechanistic classification of clinical phenotypes in neuroblastoma
    Science (IF 41.058) Pub Date : 2018-12-07
    Sandra Ackermann, Maria Cartolano, Barbara Hero, Anne Welte, Yvonne Kahlert, Andrea Roderwieser, Christoph Bartenhagen, Esther Walter, Judith Gecht, Laura Kerschke, Ruth Volland, Roopika Menon, Johannes M. Heuckmann, Moritz Gartlgruber, Sabine Hartlieb, Kai-Oliver Henrich, Konstantin Okonechnikov, Janine Altmüller, Peter Nürnberg, Steve Lefever, Bram de Wilde, Frederik Sand, Fakhera Ikram, Carolina Rosswog, Janina Fischer, Jessica Theissen, Falk Hertwig, Aatur D. Singhi, Thorsten Simon, Wenzel Vogel, Sven Perner, Barbara Krug, Matthias Schmidt, Sven Rahmann, Viktor Achter, Ulrich Lang, Christian Vokuhl, Monika Ortmann, Reinhard Büttner, Angelika Eggert, Frank Speleman, Roderick J. O’Sullivan, Roman K. Thomas, Frank Berthold, Jo Vandesompele, Alexander Schramm, Frank Westermann, Johannes H. Schulte, Martin Peifer, Matthias Fischer

    Neuroblastoma is a pediatric tumor of the sympathetic nervous system. Its clinical course ranges from spontaneous tumor regression to fatal progression. To investigate the molecular features of the divergent tumor subtypes, we performed genome sequencing on 416 pretreatment neuroblastomas and assessed telomere maintenance mechanisms in 208 of these tumors. We found that patients whose tumors lacked telomere maintenance mechanisms had an excellent prognosis, whereas the prognosis of patients whose tumors harbored telomere maintenance mechanisms was substantially worse. Survival rates were lowest for neuroblastoma patients whose tumors harbored telomere maintenance mechanisms in combination with RAS and/or p53 pathway mutations. Spontaneous tumor regression occurred both in the presence and absence of these mutations in patients with telomere maintenance–negative tumors. On the basis of these data, we propose a mechanistic classification of neuroblastoma that may benefit the clinical management of patients.

    更新日期:2018-12-07
  • LZTR1 is a regulator of RAS ubiquitination and signaling
    Science (IF 41.058) Pub Date : 2018-12-07
    Johannes W. Bigenzahn, Giovanna M. Collu, Felix Kartnig, Melanie Pieraks, Gregory I. Vladimer, Leonhard X. Heinz, Vitaly Sedlyarov, Fiorella Schischlik, Astrid Fauster, Manuele Rebsamen, Katja Parapatics, Vincent A. Blomen, André C. Müller, Georg E. Winter, Robert Kralovics, Thijn R. Brummelkamp, Marek Mlodzik, Giulio Superti-Furga

    In genetic screens aimed at understanding drug resistance mechanisms in chronic myeloid leukemia cells, inactivation of the cullin 3 adapter protein-encoding leucine zipper-like transcription regulator 1 (LZTR1) gene led to enhanced mitogen-activated protein kinase (MAPK) pathway activity and reduced sensitivity to tyrosine kinase inhibitors. Knockdown of the Drosophila LZTR1 ortholog CG3711 resulted in a Ras-dependent gain-of-function phenotype. Endogenous human LZTR1 associates with the main RAS isoforms. Inactivation of LZTR1 led to decreased ubiquitination and enhanced plasma membrane localization of endogenous KRAS (V-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog). We propose that LZTR1 acts as a conserved regulator of RAS ubiquitination and MAPK pathway activation. Because LZTR1 disease mutations failed to revert loss-of-function phenotypes, our findings provide a molecular rationale for LZTR1 involvement in a variety of inherited and acquired human disorders.

    更新日期:2018-12-07
  • Mutations in LZTR1 drive human disease by dysregulating RAS ubiquitination
    Science (IF 41.058) Pub Date : 2018-12-07
    M. Steklov, S. Pandolfi, M. F. Baietti, A. Batiuk, P. Carai, P. Najm, M. Zhang, H. Jang, F. Renzi, Y. Cai, L. Abbasi Asbagh, T. Pastor, M. De Troyer, M. Simicek, E. Radaelli, H. Brems, E. Legius, J. Tavernier, K. Gevaert, F. Impens, L. Messiaen, R. Nussinov, S. Heymans, S. Eyckerman, A. A. Sablina

    The leucine zipper–like transcriptional regulator 1 (LZTR1) protein, an adaptor for cullin 3 (CUL3) ubiquitin ligase complex, is implicated in human disease, yet its mechanism of action remains unknown. We found that Lztr1 haploinsufficiency in mice recapitulates Noonan syndrome phenotypes, whereas LZTR1 loss in Schwann cells drives dedifferentiation and proliferation. By trapping LZTR1 complexes from intact mammalian cells, we identified the guanosine triphosphatase RAS as a substrate for the LZTR1-CUL3 complex. Ubiquitome analysis showed that loss of Lztr1 abrogated Ras ubiquitination at lysine-170. LZTR1-mediated ubiquitination inhibited RAS signaling by attenuating its association with the membrane. Disease-associated LZTR1 mutations disrupted either LZTR1-CUL3 complex formation or its interaction with RAS proteins. RAS regulation by LZTR1-mediated ubiquitination provides an explanation for the role of LZTR1 in human disease.

    更新日期:2018-12-07
  • A DNA methylation reader complex that enhances gene transcription
    Science (IF 41.058) Pub Date : 2018-12-07
    C. Jake Harris, Marion Scheibe, Somsakul Pop Wongpalee, Wanlu Liu, Evan M. Cornett, Robert M. Vaughan, Xueqin Li, Wei Chen, Yan Xue, Zhenhui Zhong, Linda Yen, William D. Barshop, Shima Rayatpisheh, Javier Gallego-Bartolome, Martin Groth, Zonghua Wang, James A. Wohlschlegel, Jiamu Du, Scott B. Rothbart, Falk Butter, Steven E. Jacobsen

    DNA methylation generally functions as a repressive transcriptional signal, but it is also known to activate gene expression. In either case, the downstream factors remain largely unknown. By using comparative interactomics, we isolated proteins in Arabidopsis thaliana that associate with methylated DNA. Two SU(VAR)3-9 homologs, the transcriptional antisilencing factor SUVH1, and SUVH3, were among the methyl reader candidates. SUVH1 and SUVH3 bound methylated DNA in vitro, were associated with euchromatic methylation in vivo, and formed a complex with two DNAJ domain-containing homologs, DNAJ1 and DNAJ2. Ectopic recruitment of DNAJ1 enhanced gene transcription in plants, yeast, and mammals. Thus, the SUVH proteins bind to methylated DNA and recruit the DNAJ proteins to enhance proximal gene expression, thereby counteracting the repressive effects of transposon insertion near genes.

    更新日期:2018-12-07
  • Viscous control of cellular respiration by membrane lipid composition
    Science (IF 41.058) Pub Date : 2018-12-07
    Itay Budin, Tristan de Rond, Yan Chen, Leanne Jade G. Chan, Christopher J. Petzold, Jay D. Keasling

    Lipid composition determines the physical properties of biological membranes and can vary substantially between and within organisms. We describe a specific role for the viscosity of energy-transducing membranes in cellular respiration. Engineering of fatty acid biosynthesis in Escherichia coli allowed us to titrate inner membrane viscosity across a 10-fold range by controlling the abundance of unsaturated or branched lipids. These fluidizing lipids tightly controlled respiratory metabolism, an effect that can be explained with a quantitative model of the electron transport chain (ETC) that features diffusion-coupled reactions between enzymes and electron carriers (quinones). Lipid unsaturation also modulated mitochondrial respiration in engineered budding yeast strains. Thus, diffusion in the ETC may serve as an evolutionary constraint for lipid composition in respiratory membranes.

    更新日期:2018-12-07
  • Temperature-dependent hypoxia explains biogeography and severity of end-Permian marine mass extinction
    Science (IF 41.058) Pub Date : 2018-12-07
    Justin L. Penn, Curtis Deutsch, Jonathan L. Payne, Erik A. Sperling

    Rapid climate change at the end of the Permian Period (~252 million years ago) is the hypothesized trigger for the largest mass extinction in Earth’s history. We present model simulations of the Permian/Triassic climate transition that reproduce the ocean warming and oxygen (O2) loss indicated by the geologic record. The effect of these changes on animal survival is evaluated using the Metabolic Index (Φ), a measure of scope for aerobic activity governed by organismal traits sampled in diverse modern species. Modeled loss of aerobic habitat predicts lower extinction intensity in the tropics, a pattern confirmed with a spatially explicit analysis of the marine fossil record. The combined physiological stresses of ocean warming and O2 loss can account for more than half the magnitude of the “Great Dying.”

    更新日期:2018-12-07
  • Early human dispersals within the Americas
    Science (IF 41.058) Pub Date : 2018-12-07
    J. Víctor Moreno-Mayar, Lasse Vinner, Peter de Barros Damgaard, Constanza de la Fuente, Jeffrey Chan, Jeffrey P. Spence, Morten E. Allentoft, Tharsika Vimala, Fernando Racimo, Thomaz Pinotti, Simon Rasmussen, Ashot Margaryan, Miren Iraeta Orbegozo, Dorothea Mylopotamitaki, Matthew Wooller, Clement Bataille, Lorena Becerra-Valdivia, David Chivall, Daniel Comeskey, Thibaut Devièse, Donald K. Grayson, Len George, Harold Harry, Verner Alexandersen, Charlotte Primeau, Jon Erlandson, Claudia Rodrigues-Carvalho, Silvia Reis, Murilo Q. R. Bastos, Jerome Cybulski, Carlos Vullo, Flavia Morello, Miguel Vilar, Spencer Wells, Kristian Gregersen, Kasper Lykke Hansen, Niels Lynnerup, Marta Mirazón Lahr, Kurt Kjær, André Strauss, Marta Alfonso-Durruty, Antonio Salas, Hannes Schroeder, Thomas Higham, Ripan S. Malhi, Jeffrey T. Rasic, Luiz Souza, Fabricio R. Santos, Anna-Sapfo Malaspinas, Martin Sikora, Rasmus Nielsen, Yun S. Song, David J. Meltzer, Eske Willerslev

    Studies of the peopling of the Americas have focused on the timing and number of initial migrations. Less attention has been paid to the subsequent spread of people within the Americas. We sequenced 15 ancient human genomes spanning from Alaska to Patagonia; six are ≥10,000 years old (up to ~18× coverage). All are most closely related to Native Americans, including those from an Ancient Beringian individual and two morphologically distinct “Paleoamericans.” We found evidence of rapid dispersal and early diversification that included previously unknown groups as people moved south. This resulted in multiple independent, geographically uneven migrations, including one that provides clues of a Late Pleistocene Australasian genetic signal, as well as a later Mesoamerican-related expansion. These led to complex and dynamic population histories from North to South America.

    更新日期:2018-12-07
  • Animals and the zoogeochemistry of the carbon cycle
    Science (IF 41.058) Pub Date : 2018-12-07
    Oswald J. Schmitz, Christopher C. Wilmers, Shawn J. Leroux, Christopher E. Doughty, Trisha B. Atwood, Mauro Galetti, Andrew B. Davies, Scott J. Goetz

    Predicting and managing the global carbon cycle requires scientific understanding of ecosystem processes that control carbon uptake and storage. It is generally assumed that carbon cycling is sufficiently characterized in terms of uptake and exchange between ecosystem plant and soil pools and the atmosphere. We show that animals also play an important role by mediating carbon exchange between ecosystems and the atmosphere, at times turning ecosystem carbon sources into sinks, or vice versa. Animals also move across landscapes, creating a dynamism that shapes landscape-scale variation in carbon exchange and storage. Predicting and measuring carbon cycling under such dynamism is an important scientific challenge. We explain how to link analyses of spatial ecosystem functioning, animal movement, and remote sensing of animal habitats with carbon dynamics across landscapes.

    更新日期:2018-12-07
  • Open-source discovery of chemical leads for next-generation chemoprotective antimalarials
    Science (IF 41.058) Pub Date : 2018-12-07
    Yevgeniya Antonova-Koch, Stephan Meister, Matthew Abraham, Madeline R. Luth, Sabine Ottilie, Amanda K. Lukens, Tomoyo Sakata-Kato, Manu Vanaerschot, Edward Owen, Juan Carlos Jado Rodriguez, Steven P. Maher, Jaeson Calla, David Plouffe, Yang Zhong, Kaisheng Chen, Victor Chaumeau, Amy J. Conway, Case W. McNamara, Maureen Ibanez, Kerstin Gagaring, Fernando Neria Serrano, Korina Eribez, Cullin McLean Taggard, Andrea L. Cheung, Christie Lincoln, Biniam Ambachew, Melanie Rouillier, Dionicio Siegel, François Nosten, Dennis E. Kyle, Francisco-Javier Gamo, Yingyao Zhou, Manuel Llinás, David A. Fidock, Dyann F. Wirth, Jeremy Burrows, Brice Campo, Elizabeth A. Winzeler

    To discover leads for next-generation chemoprotective antimalarial drugs, we tested more than 500,000 compounds for their ability to inhibit liver-stage development of luciferase-expressing Plasmodium spp. parasites (681 compounds showed a half-maximal inhibitory concentration of less than 1 micromolar). Cluster analysis identified potent and previously unreported scaffold families as well as other series previously associated with chemoprophylaxis. Further testing through multiple phenotypic assays that predict stage-specific and multispecies antimalarial activity distinguished compound classes that are likely to provide symptomatic relief by reducing asexual blood-stage parasitemia from those which are likely to only prevent malaria. Target identification by using functional assays, in vitro evolution, or metabolic profiling revealed 58 mitochondrial inhibitors but also many chemotypes possibly with previously unidentified mechanisms of action.

    更新日期:2018-12-07
  • Functionally diverse type V CRISPR-Cas systems
    Science (IF 41.058) Pub Date : 2018-12-06
    Winston X. Yan, Pratyusha Hunnewell, Lauren E. Alfonse, Jason M. Carte, Elise Keston-Smith, Shanmugapriya Sothiselvam, Anthony J. Garrity, Shaorong Chong, Kira S. Makarova, Eugene V. Koonin, David R. Cheng, David A. Scott

    Type V CRISPR-Cas systems are distinguished by a single RNA-guided RuvC domain-containing effector, Cas12. Although effectors of subtypes V-A (Cas12a) and V-B (Cas12b) have been studied in detail, the distinct domain architectures and diverged RuvC sequences of uncharacterized Cas12 proteins suggest unexplored functional diversity. Here, we identify and characterize Cas12c, g, h, and i. Cas12c, h, and i demonstrate RNA-guided double-stranded (ds) DNA interference activity. Cas12i exhibits markedly different efficiencies of crRNA spacer complementary and non-complementary strand cleavage resulting in predominant dsDNA nicking. Cas12g is an RNA-guided RNase with collateral RNase and single-stranded DNase activities. Our study reveals the functional diversity emerging along different routes of type V CRISPR-Cas evolution and expands the CRISPR toolbox.

    更新日期:2018-12-07
  • Commensal-specific T cell plasticity promotes rapid tissue adaptation to injury
    Science (IF 41.058) Pub Date : 2018-12-06
    Oliver J. Harrison, Jonathan L. Linehan, Han-Yu Shih, Nicolas Bouladoux, Seong-Ji Han, Margery Smelkinson, Shurjo K. Sen, Allyson L. Byrd, Michel Enamorado, Chen Yao, Samira Tamoutounour, Francois Van Laethem, Charlotte Hurabielle, Nicholas Collins, Andrea Paun, Rosalba Salcedo, John J. O’Shea, Yasmine Belkaid

    Barrier tissues are primary targets of environmental stressors and home to the largest number of antigen-experienced lymphocytes in the body, including commensal-specific T cells. Here, we show that skin-resident commensal-specific T cells harbor a paradoxical program characterized by a type-17 program associated with a poised type-2 state. Thus, in the context of injury and exposure to inflammatory mediators such as IL-18, these cells rapidly release type-2 cytokines, thereby acquiring contextual functions. Notably, such acquisition of a type-2 effector program promotes tissue repair. Aberrant type-2 responses can also be unleashed in the context of local defects in immunoregulation. Thus, commensal-specific T cells co-opt tissue residency and cell-intrinsic flexibility as a means to promote both local immunity and tissue adaptation to injury.

    更新日期:2018-12-07
  • Spectrally resolved helium absorption from the extended atmosphere of a warm Neptune-mass exoplanet
    Science (IF 41.058) Pub Date : 2018-12-06
    R. Allart, V. Bourrier, C. Lovis, D. Ehrenreich, J. J. Spake, A. Wyttenbach, L. Pino, F. Pepe, D. K. Sing, A. Lecavelier des Etangs

    Stellar heating causes atmospheres of close-in exoplanets to expand and escape. These extended atmospheres are difficult to observe because their main spectral signature—neutral hydrogen at ultraviolet wavelengths—is strongly absorbed by interstellar medium. We report the detection of the near-infrared triplet of neutral helium in the transiting warm Neptune-mass exoplanet HAT-P-11b using ground-based, high-resolution observations. The helium feature is repeatable over two independent transits, with an average absorption depth of 1.08 ± 0.05%. Interpreting absorption spectra with 3D simulations of the planet’s upper atmosphere suggests it extends beyond 5 planetary radii, with a large scale height and a helium mass loss rate ≲ 3×105 g‧s−1. A net blue-shift of the absorption might be explained by high-altitude winds flowing at 3 km‧s−1 from day to night-side.

    更新日期:2018-12-07
  • Ground-based detection of an extended helium atmosphere in the Saturn-mass exoplanet WASP-69b
    Science (IF 41.058) Pub Date : 2018-12-06
    Lisa Nortmann, Enric Pallé, Michael Salz, Jorge Sanz-Forcada, Evangelos Nagel, F. Javier Alonso-Floriano, Stefan Czesla, Fei Yan, Guo Chen, Ignas A. G. Snellen, Mathias Zechmeister, Jürgen H. M. M. Schmitt, Manuel López-Puertas, Núria Casasayas-Barris, Florian F. Bauer, Pedro J. Amado, José A. Caballero, Stefan Dreizler, Thomas Henning, Manuel Lampón, David Montes, Karan Molaverdikhani, Andreas Quirrenbach, Ansgar Reiners, Ignasi Ribas, Alejandro Sánchez-López, P. Christian Schneider, María R. Zapatero Osorio

    Hot gas giant exoplanets can lose part of their atmosphere due to strong stellar irradiation, affecting their physical and chemical evolution. Studies of atmospheric escape from exoplanets have mostly relied on space-based observations of the hydrogen Lyman-α line in the far ultraviolet which is strongly affected by interstellar absorption. Using ground-based high-resolution spectroscopy we detect excess absorption in the helium triplet at 1083 nm during the transit of the Saturn-mass exoplanet WASP-69b, at a signal-to-noise ratio of 18. We measure line blue shifts of several km s−1 and post transit absorption, which we interpret as the escape of part of the atmosphere trailing behind the planet in comet-like form.

    更新日期:2018-12-07
  • Spin transport in a Mott insulator of ultracold fermions
    Science (IF 41.058) Pub Date : 2018-12-06
    Matthew A. Nichols, Lawrence W. Cheuk, Melih Okan, Thomas R. Hartke, Enrique Mendez, T. Senthil, Ehsan Khatami, Hao Zhang, Martin W. Zwierlein

    Strongly correlated materials are expected to feature unconventional transport properties, where charge, spin, and heat conduction are potentially independent probes of the dynamics. In contrast to charge transport, the measurement of spin transport in such materials is highly challenging. Here we observe spin conduction and diffusion in a system of ultracold fermionic atoms that realizes the half-filled Fermi-Hubbard model. For strong interactions, spin diffusion is driven by super-exchange and doublon-hole-assisted tunneling, and strongly violates the quantum limit of charge diffusion. The technique developed in this work can be extended to finite doping, which can shed light on the complex interplay between spin and charge in the Hubbard model.

    更新日期:2018-12-07
  • Bad metallic transport in a cold atom Fermi-Hubbard system
    Science (IF 41.058) Pub Date : 2018-12-06
    Peter T. Brown, Debayan Mitra, Elmer Guardado-Sanchez, Reza Nourafkan, Alexis Reymbaut, Charles-David Hébert, Simon Bergeron, A.-M. S. Tremblay, Jure Kokalj, David A. Huse, Peter Schauß, Waseem S. Bakr

    Strong interactions in many-body quantum systems complicate the interpretation of charge transport in such materials. To shed light on this problem, we study transport in a clean quantum system: ultracold 6Li in a two-dimensional (2D) optical lattice, a testing ground for strong interaction physics in the Fermi-Hubbard model. We determine the diffusion constant by measuring the relaxation of an imposed density modulation and modeling its decay hydrodynamically. The diffusion constant is converted to a resistivity using the Nernst-Einstein relation. That resistivity exhibits a linear temperature dependence and shows no evidence of saturation, two characteristic signatures of a bad metal. The techniques we develop here may be applied to measurements of other transport quantities, including the optical conductivity and thermopower.

    更新日期:2018-12-07
  • Organic synthesis in a modular robotic system driven by a chemical programming language
    Science (IF 41.058) Pub Date : 2018-11-30
    Sebastian Steiner, Jakob Wolf, Stefan Glatzel, Anna Andreou, Jarosław M. Granda, Graham Keenan, Trevor Hinkley, Gerardo Aragon-Camarasa, Philip J. Kitson, Davide Angelone, Leroy Cronin

    The synthesis of complex organic compounds is largely a manual process that is often incompletely documented. To address these shortcomings, we developed an abstraction that maps commonly reported methodological instructions into discrete steps amenable to automation. These unit operations were implemented in a modular robotic platform using a chemical programming language which formalizes and controls the assembly of the molecules. We validated the concept by directing the automated system to synthesize three pharmaceutical compounds, Nytol, rufinamide, and sildenafil, without any human intervention. Yields and purities of products and intermediates were comparable to or better than those achieved manual