Diurnal transcriptome atlas of a primate across major neural and peripheral tissues Science (IF 37.205) Pub Date : 2018-03-16 Ludovic S. Mure, Hiep D. Le, Giorgia Benegiamo, Max W. Chang, Luis Rios, Ngalla Jillani, Maina Ngotho, Thomas Kariuki, Ouria Dkhissi-Benyahya, Howard M. Cooper, Satchidananda Panda
Diurnal gene expression patterns underlie time-of-the-day–specific functional specialization of tissues. However, available circadian gene expression atlases of a few organs are largely from nocturnal vertebrates. We report the diurnal transcriptome of 64 tissues, including 22 brain regions, sampled every 2 hours over 24 hours, from the primate Papio anubis (baboon). Genomic transcription was highly rhythmic, with up to 81.7% of protein-coding genes showing daily rhythms in expression. In addition to tissue-specific gene expression, the rhythmic transcriptome imparts another layer of functional specialization. Most ubiquitously expressed genes that participate in essential cellular functions exhibit rhythmic expression in a tissue-specific manner. The peak phases of rhythmic gene expression clustered around dawn and dusk, with a “quiescent period” during early night. Our findings also unveil a different temporal organization of central and peripheral tissues between diurnal and nocturnal animals.
Phenotype risk scores identify patients with unrecognized Mendelian disease patterns Science (IF 37.205) Pub Date : 2018-03-16 Lisa Bastarache, Jacob J. Hughey, Scott Hebbring, Joy Marlo, Wanke Zhao, Wanting T. Ho, Sara L. Van Driest, Tracy L. McGregor, Jonathan D. Mosley, Quinn S. Wells, Michael Temple, Andrea H. Ramirez, Robert Carroll, Travis Osterman, Todd Edwards, Douglas Ruderfer, Digna R. Velez Edwards, Rizwan Hamid, Joy Cogan, Andrew Glazer, Wei-Qi Wei, QiPing Feng, Murray Brilliant, Zhizhuang J. Zhao, Nancy J. Cox, Dan M. Roden, Joshua C. Denny
Genetic association studies often examine features independently, potentially missing subpopulations with multiple phenotypes that share a single cause. We describe an approach that aggregates phenotypes on the basis of patterns described by Mendelian diseases. We mapped the clinical features of 1204 Mendelian diseases into phenotypes captured from the electronic health record (EHR) and summarized this evidence as phenotype risk scores (PheRSs). In an initial validation, PheRS distinguished cases and controls of five Mendelian diseases. Applying PheRS to 21,701 genotyped individuals uncovered 18 associations between rare variants and phenotypes consistent with Mendelian diseases. In 16 patients, the rare genetic variants were associated with severe outcomes such as organ transplants. PheRS can augment rare-variant interpretation and may identify subsets of patients with distinct genetic causes for common diseases.
Random heteropolymers preserve protein function in foreign environments Science (IF 37.205) Pub Date : 2018-03-16 Brian Panganiban, Baofu Qiao, Tao Jiang, Christopher DelRe, Mona M. Obadia, Trung Dac Nguyen, Anton A. A. Smith, Aaron Hall, Izaac Sit, Marquise G. Crosby, Patrick B. Dennis, Eric Drockenmuller, Monica Olvera de la Cruz, Ting Xu
The successful incorporation of active proteins into synthetic polymers could lead to a new class of materials with functions found only in living systems. However, proteins rarely function under the conditions suitable for polymer processing. On the basis of an analysis of trends in protein sequences and characteristic chemical patterns on protein surfaces, we designed four-monomer random heteropolymers to mimic intrinsically disordered proteins for protein solubilization and stabilization in non-native environments. The heteropolymers, with optimized composition and statistical monomer distribution, enable cell-free synthesis of membrane proteins with proper protein folding for transport and enzyme-containing plastics for toxin bioremediation. Controlling the statistical monomer distribution in a heteropolymer, rather than the specific monomer sequence, affords a new strategy to interface with biological systems for protein-based biomaterials.
Real-time imaging of adatom-promoted graphene growth on nickel Science (IF 37.205) Pub Date : 2018-03-16 Laerte L. Patera, Federico Bianchini, Cristina Africh, Carlo Dri, German Soldano, Marcelo M. Mariscal, Maria Peressi, Giovanni Comelli
Single adatoms are expected to participate in many processes occurring at solid surfaces, such as the growth of graphene on metals. We demonstrate, both experimentally and theoretically, the catalytic role played by single metal adatoms during the technologically relevant process of graphene growth on nickel (Ni). The catalytic action of individual Ni atoms at the edges of a growing graphene flake was directly captured by scanning tunneling microscopy imaging at the millisecond time scale, while force field molecular dynamics and density functional theory calculations rationalize the experimental observations. Our results unveil the mechanism governing the activity of a single-atom catalyst at work.
Organometallic and radical intermediates reveal mechanism of diphthamide biosynthesis Science (IF 37.205) Pub Date : 2018-03-16 Min Dong, Venkatesan Kathiresan, Michael K. Fenwick, Andrew T. Torelli, Yang Zhang, Jonathan D. Caranto, Boris Dzikovski, Ajay Sharma, Kyle M. Lancaster, Jack H. Freed, Steven E. Ealick, Brian M. Hoffman, Hening Lin
Diphthamide biosynthesis involves a carbon-carbon bond-forming reaction catalyzed by a radical S-adenosylmethionine (SAM) enzyme that cleaves a carbon-sulfur (C–S) bond in SAM to generate a 3-amino-3-carboxypropyl (ACP) radical. Using rapid freezing, we have captured an organometallic intermediate with an iron-carbon (Fe–C) bond between ACP and the enzyme’s [4Fe-4S] cluster. In the presence of the substrate protein, elongation factor 2, this intermediate converts to an organic radical, formed by addition of the ACP radical to a histidine side chain. Crystal structures of archaeal diphthamide biosynthetic radical SAM enzymes reveal that the carbon of the SAM C–S bond being cleaved is positioned near the unique cluster Fe, able to react with the cluster. Our results explain how selective C–S bond cleavage is achieved in this radical SAM enzyme.
Oklahoma's induced seismicity strongly linked to wastewater injection depth Science (IF 37.205) Pub Date : 2018-03-16 Thea Hincks, Willy Aspinall, Roger Cooke, Thomas Gernon
The sharp rise in Oklahoma seismicity since 2009 is due to wastewater injection. The role of injection depth is an open, complex issue, yet critical for hazard assessment and regulation. We developed an advanced Bayesian network to model joint conditional dependencies between spatial, operational, and seismicity parameters. We found that injection depth relative to crystalline basement most strongly correlates with seismic moment release. The joint effects of depth and volume are critical, as injection rate becomes more influential near the basement interface. Restricting injection depths to 200 to 500 meters above basement could reduce annual seismic moment release by a factor of 1.4 to 2.8. Our approach enables identification of subregions where targeted regulation may mitigate effects of induced earthquakes, aiding operators and regulators in wastewater disposal regions.
Protecting marine mammals, turtles, and birds by rebuilding global fisheries Science (IF 37.205) Pub Date : 2018-03-16 Matthew G. Burgess, Grant R. McDermott, Brandon Owashi, Lindsey E. Peavey Reeves, Tyler Clavelle, Daniel Ovando, Bryan P. Wallace, Rebecca L. Lewison, Steven D. Gaines, Christopher Costello
Reductions in global fishing pressure are needed to end overfishing of target species and maximize the value of fisheries. We ask whether such reductions would also be sufficient to protect non–target species threatened as bycatch. We compare changes in fishing pressure needed to maximize profits from 4713 target fish stocks—accounting for >75% of global catch—to changes in fishing pressure needed to reverse ongoing declines of 20 marine mammal, sea turtle, and seabird populations threatened as bycatch. We project that maximizing fishery profits would halt or reverse declines of approximately half of these threatened populations. Recovering the other populations would require substantially greater effort reductions or targeting improvements. Improving commercial fishery management could thus yield important collateral benefits for threatened bycatch species globally.
GDV1 induces sexual commitment of malaria parasites by antagonizing HP1-dependent gene silencing Science (IF 37.205) Pub Date : 2018-03-16 Michael Filarsky, Sabine A. Fraschka, Igor Niederwieser, Nicolas M. B. Brancucci, Eilidh Carrington, Elvira Carrió, Suzette Moes, Paul Jenoe, Richárd Bártfai, Till S. Voss
Malaria is caused by Plasmodium parasites that proliferate in the bloodstream. During each replication cycle, some parasites differentiate into gametocytes, the only forms able to infect the mosquito vector and transmit malaria. Sexual commitment is triggered by activation of AP2-G, the master transcriptional regulator of gametocytogenesis. Heterochromatin protein 1 (HP1)–dependent silencing of ap2-g prevents sexual conversion in proliferating parasites. In this study, we identified Plasmodium falciparum gametocyte development 1 (GDV1) as an upstream activator of sexual commitment. We found that GDV1 targeted heterochromatin and triggered HP1 eviction, thus derepressing ap2-g. Expression of GDV1 was responsive to environmental triggers of sexual conversion and controlled via a gdv1 antisense RNA. Hence, GDV1 appears to act as an effector protein that induces sexual differentiation by antagonizing HP1-dependent gene silencing.
Precursors of logical reasoning in preverbal human infants Science (IF 37.205) Pub Date : 2018-03-16 Nicoló Cesana-Arlotti, Ana Martín, Ernő Téglás, Liza Vorobyova, Ryszard Cetnarski, Luca L. Bonatti
Infants are able to entertain hypotheses about complex events and to modify them rationally when faced with inconsistent evidence. These capacities suggest that infants can use elementary logical representations to frame and prune hypotheses. By presenting scenes containing ambiguities about the identity of an object, here we show that 12- and 19-month-old infants look longer at outcomes that are inconsistent with a logical inference necessary to resolve such ambiguities. At the moment of a potential deduction, infants’ pupils dilated, and their eyes moved toward the ambiguous object when inferences could be computed, in contrast to transparent scenes not requiring inferences to identify the object. These oculomotor markers resembled those of adults inspecting similar scenes, suggesting that intuitive and stable logical structures involved in the interpretation of dynamic scenes may be part of the fabric of the human mind.
Factoring stream turbulence into global assessments of nitrogen pollution Science (IF 37.205) Pub Date : 2018-03-16 Stanley B. Grant, Morvarid Azizian, Perran Cook, Fulvio Boano, Megan A. Rippy
The discharge of excess nitrogen to streams and rivers poses an existential threat to both humans and ecosystems. A seminal study of headwater streams across the United States concluded that in-stream removal of nitrate is controlled primarily by stream chemistry and biology. Reanalysis of these data reveals that stream turbulence (in particular, turbulent mass transfer across the concentration boundary layer) imposes a previously unrecognized upper limit on the rate at which nitrate is removed from streams. The upper limit closely approximates measured nitrate removal rates in streams with low concentrations of this pollutant, a discovery that should inform stream restoration designs and efforts to assess the effects of nitrogen pollution on receiving water quality and the global nitrogen cycle.
Astrocyte-derived interleukin-33 promotes microglial synapse engulfment and neural circuit development Science (IF 37.205) Pub Date : 2018-03-16 Ilia D. Vainchtein, Gregory Chin, Frances S. Cho, Kevin W. Kelley, John G. Miller, Elliott C. Chien, Shane A. Liddelow, Phi T. Nguyen, Hiromi Nakao-Inoue, Leah C. Dorman, Omar Akil, Satoru Joshita, Ben A. Barres, Jeanne T. Paz, Ari B. Molofsky, Anna V. Molofsky
Neuronal synapse formation and remodeling are essential to central nervous system (CNS) development and are dysfunctional in neurodevelopmental diseases. Innate immune signals regulate tissue remodeling in the periphery, but how this affects CNS synapses is largely unknown. Here, we show that the interleukin-1 family cytokine interleukin-33 (IL-33) is produced by developing astrocytes and is developmentally required for normal synapse numbers and neural circuit function in the spinal cord and thalamus. We find that IL-33 signals primarily to microglia under physiologic conditions, that it promotes microglial synapse engulfment, and that it can drive microglial-dependent synapse depletion in vivo. These data reveal a cytokine-mediated mechanism required to maintain synapse homeostasis during CNS development.
Rev-erbα dynamically modulates chromatin looping to control circadian gene transcription Science (IF 37.205) Pub Date : 2018-03-16 Yong Hoon Kim, Sajid A. Marhon, Yuxiang Zhang, David J. Steger, Kyoung-Jae Won, Mitchell A. Lazar
Mammalian physiology exhibits 24-hour cyclicity due to circadian rhythms of gene expression controlled by transcription factors that constitute molecular clocks. Core clock transcription factors bind to the genome at enhancer sequences to regulate circadian gene expression, but not all binding sites are equally functional. We found that in mice, circadian gene expression in the liver is controlled by rhythmic chromatin interactions between enhancers and promoters. Rev-erbα, a core repressive transcription factor of the clock, opposes functional loop formation between Rev-erbα–regulated enhancers and circadian target gene promoters by recruitment of the NCoR-HDAC3 co-repressor complex, histone deacetylation, and eviction of the elongation factor BRD4 and the looping factor MED1. Thus, a repressive arm of the molecular clock operates by rhythmically modulating chromatin loops to control circadian gene transcription.
Lysosome activation clears aggregates and enhances quiescent neural stem cell activation during aging Science (IF 37.205) Pub Date : 2018-03-16 Dena S. Leeman, Katja Hebestreit, Tyson Ruetz, Ashley E. Webb, Andrew McKay, Elizabeth A. Pollina, Ben W. Dulken, Xiaoai Zhao, Robin W. Yeo, Theodore T. Ho, Salah Mahmoudi, Keerthana Devarajan, Emmanuelle Passegué, Thomas A. Rando, Judith Frydman, Anne Brunet
In the adult brain, the neural stem cell (NSC) pool comprises quiescent and activated populations with distinct roles. Transcriptomic analysis revealed that quiescent and activated NSCs exhibited differences in their protein homeostasis network. Whereas activated NSCs had active proteasomes, quiescent NSCs contained large lysosomes. Quiescent NSCs from young mice accumulated protein aggregates, and many of these aggregates were stored in large lysosomes. Perturbation of lysosomal activity in quiescent NSCs affected protein-aggregate accumulation and the ability of quiescent NSCs to activate. During aging, quiescent NSCs displayed defects in their lysosomes, increased accumulation of protein aggregates, and reduced ability to activate. Enhancement of the lysosome pathway in old quiescent NSCs cleared protein aggregates and ameliorated the ability of quiescent NSCs to activate, allowing them to regain a more youthful state.
Mutation dynamics and fitness effects followed in single cells Science (IF 37.205) Pub Date : 2018-03-16 Lydia Robert, Jean Ollion, Jerome Robert, Xiaohu Song, Ivan Matic, Marina Elez
Mutations have been investigated for more than a century but remain difficult to observe directly in single cells, which limits the characterization of their dynamics and fitness effects. By combining microfluidics, time-lapse imaging, and a fluorescent tag of the mismatch repair system in Escherichia coli, we visualized the emergence of mutations in single cells, revealing Poissonian dynamics. Concomitantly, we tracked the growth and life span of single cells, accumulating ~20,000 mutations genome-wide over hundreds of generations. This analysis revealed that 1% of mutations were lethal; nonlethal mutations displayed a heavy-tailed distribution of fitness effects and were dominated by quasi-neutral mutations with an average cost of 0.3%. Our approach has enabled the investigation of single-cell individuality in mutation rate, mutation fitness costs, and mutation interactions.
Topological insulator laser: Theory Science (IF 37.205) Pub Date : 2018-03-16 Gal Harari, Miguel A. Bandres, Yaakov Lumer, Mikael C. Rechtsman, Y. D. Chong, Mercedeh Khajavikhan, Demetrios N. Christodoulides, Mordechai Segev
Topological insulators are phases of matter characterized by topological edge states that propagate in a unidirectional manner that is robust to imperfections and disorder. These attributes make topological insulator systems ideal candidates for enabling applications in quantum computation and spintronics. We propose a concept that exploits topological effects in a unique way: the topological insulator laser. These are lasers whose lasing mode exhibits topologically protected transport without magnetic fields. The underlying topological properties lead to a highly efficient laser, robust to defects and disorder, with single-mode lasing even at very high gain values. The topological insulator laser alters current understanding of the interplay between disorder and lasing, and at the same time opens exciting possibilities in topological physics, such as topologically protected transport in systems with gain. On the technological side, the topological insulator laser provides a route to arrays of semiconductor lasers that operate as one single-mode high-power laser coupled efficiently into an output port.
Pleistocene North African genomes link Near Eastern and sub-Saharan African human populations Science (IF 37.205) Pub Date : 2018-03-15 Marieke van de Loosdrecht, Abdeljalil Bouzouggar, Louise Humphrey, Cosimo Posth, Nick Barton, Ayinuer Aximu-Petri, Birgit Nickel, Sarah Nagel, El Hassan Talbi, Mohammed Abdeljalil El Hajraoui, Saaïd Amzazi, Jean-Jacques Hublin, Svante Pääbo, Stephan Schiffels, Matthias Meyer, Wolfgang Haak, Choongwon Jeong, Johannes Krause
North Africa is a key region for understanding human history, but the genetic history of its people is largely unknown. We present genomic data from seven 15,000-year-old modern humans from Morocco, attributed to the Iberomaurusian culture. We find a genetic affinity with early Holocene Near Easterners, best represented by Levantine Natufians, suggesting a pre-agricultural connection between Africa and the Near East. We do not find evidence for gene flow from Paleolithic Europeans into Late Pleistocene North Africans. The Taforalt individuals derive one third of their ancestry from sub-Saharan Africans, best approximated by a mixture of genetic components preserved in present-day West and East Africans. Thus, we provide direct evidence for genetic interactions between modern humans across Africa and Eurasia in the Pleistocene.
Self-organization and progenitor targeting generate stable patterns in planarian regeneration Science (IF 37.205) Pub Date : 2018-03-15 Kutay Deniz Atabay, Samuel A. LoCascio, Thom de Hoog, Peter W. Reddien
During animal regeneration cells must organize into discrete and functional systems. We show that self-organization, along with patterning cues, govern progenitor behavior in planarian regeneration. Surgical paradigms allowed manipulation of planarian eye regeneration in predictable locations and numbers, generating alternative stable neuroanatomical states for wild-type animals with multiple functional ectopic eyes. We utilized animals with multiple ectopic eyes and eye transplantation to demonstrate that broad progenitor specification, combined with self-organization, allows anatomy maintenance during regeneration. We propose a model for regenerative progenitors involving (i) migratory targeting cues, (ii) self-organization into existing or regenerating eyes, and (iii) a broad zone, associated with coarse progenitor specification, in which eyes can be targeted by progenitors. These three properties help explain how tissues can be organized during regeneration.
Long-distance stone transport and pigment use in the earliest Middle Stone Age Science (IF 37.205) Pub Date : 2018-03-15 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 socio-economic behaviors that typify Homo sapiens had roots in the middle Pleistocene <200 ka, 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, dated ≥295 to ~320 ka by 40Ar/39Ar and U-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 ≥25-50 km distance. Associated fauna suggests a broad resource strategy that included large and small prey. These practices imply significant changes in how individuals and groups related to the landscape and one another, and provide documentation relevant to human social and cognitive evolution.
Chronology of the Acheulean to Middle Stone Age transition in eastern Africa Science (IF 37.205) Pub Date : 2018-03-15 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) denotes 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. Here we use 40Ar/39Ar and U-series dating to calibrate the chronology of Acheulean- and early MSA-rich sedimentary deposits in the Olorgesailie Basin, South Kenya Rift. We establish the age of late Acheulean tool assemblages from 615 to 499 ka, after which a large technological and faunal transition occurred, with definitive MSA lacking Acheulean elements beginning most likely by ~320 ka, but at least by 305 ka. These results establish the currently oldest repository of MSA in eastern Africa.
Environmental dynamics during the onset of the Middle Stone Age in eastern Africa Science (IF 37.205) Pub Date : 2018-03-15 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 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 thousand years ago (ka) raises the question of how environmental change influenced the evolution of behaviors characteristic of early Homo sapiens. We use 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 dramatically different faunal community, more pronounced erosion-deposition cycles, tectonic activity, and enhanced wet-dry variability. As early as 615 ka, aspects of Acheulean technology in this region imply that greater stone material selectivity and wider resource procurement coincided with an increased pace of land-lake fluctuation, potentially anticipating the adaptability of MSA hominins.
Single-cell profiling of the developing mouse brain and spinal cord with split-pool barcoding Science (IF 37.205) Pub Date : 2018-03-15 Alexander B. Rosenberg, Charles M. Roco, Richard A. Muscat, Anna Kuchina, Paul Sample, Zizhen Yao, Lucas Gray, 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. Over 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.
Single-cell Wnt signaling niches maintain stemness of alveolar type 2 cells Science (IF 37.205) Pub Date : 2018-03-09 Ahmad N. Nabhan, Douglas G. Brownfield, Pehr B. Harbury, Mark A. Krasnow, Tushar J. Desai
Alveoli, the lung’s respiratory units, are tiny sacs where oxygen enters the bloodstream. They are lined by flat alveolar type 1 (AT1) cells, which mediate gas exchange, and AT2 cells, which secrete surfactant. Rare AT2s also function as alveolar stem cells. We show that AT2 lung stem cells display active Wnt signaling, and many of them are near single, Wnt-expressing fibroblasts. Blocking Wnt secretion depletes these stem cells. Daughter cells leaving the Wnt niche transdifferentiate into AT1s: Maintaining Wnt signaling prevents transdifferentiation, whereas abrogating Wnt signaling promotes it. Injury induces AT2 autocrine Wnts, recruiting “bulk” AT2s as progenitors. Thus, individual AT2 stem cells reside in single-cell fibroblast niches providing juxtacrine Wnts that maintain them, whereas injury induces autocrine Wnts that transiently expand the progenitor pool. This simple niche maintains the gas exchange surface and is coopted in cancer.
Strong spin-photon coupling in silicon Science (IF 37.205) Pub Date : 2018-03-09 N. Samkharadze, G. Zheng, N. Kalhor, D. Brousse, A. Sammak, U. C. Mendes, A. Blais, G. Scappucci, L. M. K. Vandersypen
Long coherence times of single spins in silicon quantum dots make these systems highly attractive for quantum computation, but how to scale up spin qubit systems remains an open question. As a first step to address this issue, we demonstrate the strong coupling of a single electron spin and a single microwave photon. The electron spin is trapped in a silicon double quantum dot, and the microwave photon is stored in an on-chip high-impedance superconducting resonator. The electric field component of the cavity photon couples directly to the charge dipole of the electron in the double dot, and indirectly to the electron spin, through a strong local magnetic field gradient from a nearby micromagnet. Our results provide a route to realizing large networks of quantum dot–based spin qubit registers.
A liquid-liquid transition in supercooled aqueous solution related to the HDA-LDA transition Science (IF 37.205) Pub Date : 2018-03-09 Sander Woutersen, Bernd Ensing, Michiel Hilbers, Zuofeng Zhao, C. Austen Angell
Simulations and theory suggest that the thermodynamic anomalies of water may be related to a phase transition between two supercooled liquid states, but so far this phase transition has not been observed experimentally because of preemptive ice crystallization. We used calorimetry, infrared spectroscopy, and molecular dynamics simulations to investigate a water-rich hydrazinium trifluoroacetate solution in which the local hydrogen bond structure surrounding a water molecule resembles that in neat water at elevated pressure, but which does not crystallize upon cooling. Instead, this solution underwent a sharp, reversible phase transition between two homogeneous liquid states. The hydrogen-bond structures of these two states are similar to those established for high- and low-density amorphous (HDA and LDA) water. Such structural similarity supports theories that predict a similar sharp transition in pure water under pressure if ice crystallization could be suppressed.
Coherent, atomically thin transition-metal dichalcogenide superlattices with engineered strain Science (IF 37.205) Pub Date : 2018-03-09 Saien Xie, Lijie Tu, Yimo Han, Lujie Huang, Kibum Kang, Ka Un Lao, Preeti Poddar, Chibeom Park, David A. Muller, Robert A. DiStasio, Jiwoong Park
Epitaxy forms the basis of modern electronics and optoelectronics. We report coherent atomically thin superlattices in which different transition metal dichalcogenide monolayers—despite large lattice mismatches—are repeated and laterally integrated without dislocations within the monolayer plane. Grown by an omnidirectional epitaxy, these superlattices display fully matched lattice constants across heterointerfaces while maintaining an isotropic lattice structure and triangular symmetry. This strong epitaxial strain is precisely engineered via the nanoscale supercell dimensions, thereby enabling broad tuning of the optical properties and producing photoluminescence peak shifts as large as 250 millielectron volts. We present theoretical models to explain this coherent growth and the energetic interplay governing the ripple formation in these strained monolayers. Such coherent superlattices provide building blocks with targeted functionalities at the atomically thin limit.
Ice-VII inclusions in diamonds: Evidence for aqueous fluid in Earth’s deep mantle Science (IF 37.205) Pub Date : 2018-03-09 O. Tschauner, S. Huang, E. Greenberg, V. B. Prakapenka, C. Ma, G. R. Rossman, A. H. Shen, D. Zhang, M. Newville, A. Lanzirotti, K. Tait
Water-rich regions in Earth’s deeper mantle are suspected to play a key role in the global water budget and the mobility of heat-generating elements. We show that ice-VII occurs as inclusions in natural diamond and serves as an indicator for such water-rich regions. Ice-VII, the residue of aqueous fluid present during growth of diamond, crystallizes upon ascent of the host diamonds but remains at pressures as high as 24 gigapascals; it is now recognized as a mineral by the International Mineralogical Association. In particular, ice-VII in diamonds points toward fluid-rich locations in the upper transition zone and around the 660-kilometer boundary.
Sustained climate warming drives declining marine biological productivity Science (IF 37.205) Pub Date : 2018-03-09 J. Keith Moore, Weiwei Fu, Francois Primeau, Gregory L. Britten, Keith Lindsay, Matthew Long, Scott C. Doney, Natalie Mahowald, Forrest Hoffman, James T. Randerson
Climate change projections to the year 2100 may miss physical-biogeochemical feedbacks that emerge later from the cumulative effects of climate warming. In a coupled climate simulation to the year 2300, the westerly winds strengthen and shift poleward, surface waters warm, and sea ice disappears, leading to intense nutrient trapping in the Southern Ocean. The trapping drives a global-scale nutrient redistribution, with net transfer to the deep ocean. Ensuing surface nutrient reductions north of 30°S drive steady declines in primary production and carbon export (decreases of 24 and 41%, respectively, by 2300). Potential fishery yields, constrained by lower–trophic-level productivity, decrease by more than 20% globally and by nearly 60% in the North Atlantic. Continued high levels of greenhouse gas emissions could suppress marine biological productivity for a millennium.
Local transformations of the hippocampal cognitive map Science (IF 37.205) Pub Date : 2018-03-09 Julija Krupic, Marius Bauza, Stephen Burton, John O’Keefe
Grid cells are neurons active in multiple fields arranged in a hexagonal lattice and are thought to represent the “universal metric for space.” However, they become nonhomogeneously distorted in polarized enclosures, which challenges this view. We found that local changes to the configuration of the enclosure induce individual grid fields to shift in a manner inversely related to their distance from the reconfigured boundary. The grid remained primarily anchored to the unchanged stable walls and showed a nonuniform rescaling. Shifts in simultaneously recorded colocalized grid fields were strongly correlated, which suggests that the readout of the animal’s position might still be intact. Similar field shifts were also observed in place and boundary cells—albeit of greater magnitude and more pronounced closer to the reconfigured boundary—which suggests that there is no simple one-to-one relationship between these three different cell types.
The spread of true and false news online Science (IF 37.205) Pub Date : 2018-03-09 Soroush Vosoughi, Deb Roy, Sinan Aral
We investigated the differential diffusion of all of the verified true and false news stories distributed on Twitter from 2006 to 2017. The data comprise ~126,000 stories tweeted by ~3 million people more than 4.5 million times. We classified news as true or false using information from six independent fact-checking organizations that exhibited 95 to 98% agreement on the classifications. Falsehood diffused significantly farther, faster, deeper, and more broadly than the truth in all categories of information, and the effects were more pronounced for false political news than for false news about terrorism, natural disasters, science, urban legends, or financial information. We found that false news was more novel than true news, which suggests that people were more likely to share novel information. Whereas false stories inspired fear, disgust, and surprise in replies, true stories inspired anticipation, sadness, joy, and trust. Contrary to conventional wisdom, robots accelerated the spread of true and false news at the same rate, implying that false news spreads more than the truth because humans, not robots, are more likely to spread it.
Gut bacteria selectively promoted by dietary fibers alleviate type 2 diabetes Science (IF 37.205) Pub Date : 2018-03-09 Liping Zhao, Feng Zhang, Xiaoying Ding, Guojun Wu, Yan Y. Lam, Xuejiao Wang, Huaqing Fu, Xinhe Xue, Chunhua Lu, Jilin Ma, Lihua Yu, Chengmei Xu, Zhongying Ren, Ying Xu, Songmei Xu, Hongli Shen, Xiuli Zhu, Yu Shi, Qingyun Shen, Weiping Dong, Rui Liu, Yunxia Ling, Yue Zeng, Xingpeng Wang, Qianpeng Zhang, Jing Wang, Linghua Wang, Yanqiu Wu, Benhua Zeng, Hong Wei, Menghui Zhang, Yongde Peng, Chenhong Zhang
The gut microbiota benefits humans via short-chain fatty acid (SCFA) production from carbohydrate fermentation, and deficiency in SCFA production is associated with type 2 diabetes mellitus (T2DM). We conducted a randomized clinical study of specifically designed isoenergetic diets, together with fecal shotgun metagenomics, to show that a select group of SCFA-producing strains was promoted by dietary fibers and that most other potential producers were either diminished or unchanged in patients with T2DM. When the fiber-promoted SCFA producers were present in greater diversity and abundance, participants had better improvement in hemoglobin A1c levels, partly via increased glucagon-like peptide-1 production. Promotion of these positive responders diminished producers of metabolically detrimental compounds such as indole and hydrogen sulfide. Targeted restoration of these SCFA producers may present a novel ecological approach for managing T2DM.
Translocation of a gut pathobiont drives autoimmunity in mice and humans Science (IF 37.205) Pub Date : 2018-03-09 S. Manfredo Vieira, M. Hiltensperger, V. Kumar, D. Zegarra-Ruiz, C. Dehner, N. Khan, F. R. C. Costa, E. Tiniakou, T. Greiling, W. Ruff, A. Barbieri, C. Kriegel, S. S. Mehta, J. R. Knight, D. Jain, A. L. Goodman, M. A. Kriegel
Despite multiple associations between the microbiota and immune diseases, their role in autoimmunity is poorly understood. We found that translocation of a gut pathobiont, Enterococcus gallinarum, to the liver and other systemic tissues triggers autoimmune responses in a genetic background predisposing to autoimmunity. Antibiotic treatment prevented mortality in this model, suppressed growth of E. gallinarum in tissues, and eliminated pathogenic autoantibodies and T cells. Hepatocyte–E. gallinarum cocultures induced autoimmune-promoting factors. Pathobiont translocation in monocolonized and autoimmune-prone mice induced autoantibodies and caused mortality, which could be prevented by an intramuscular vaccine targeting the pathobiont. E. gallinarum–specific DNA was recovered from liver biopsies of autoimmune patients, and cocultures with human hepatocytes replicated the murine findings; hence, similar processes apparently occur in susceptible humans. These discoveries show that a gut pathobiont can translocate and promote autoimmunity in genetically predisposed hosts.
C1orf106 is a colitis risk gene that regulates stability of epithelial adherens junctions Science (IF 37.205) Pub Date : 2018-03-09 Vishnu Mohanan, Toru Nakata, A. Nicole Desch, Chloé Lévesque, Angela Boroughs, Gaelen Guzman, Zhifang Cao, Elizabeth Creasey, Junmei Yao, Gabrielle Boucher, Guy Charron, Atul K. Bhan, Monica Schenone, Steven A. Carr, Hans–Christian Reinecker, Mark J. Daly, John D. Rioux, Kara G. Lassen, Ramnik J. Xavier
Polymorphisms in C1orf106 are associated with increased risk of inflammatory bowel disease (IBD). However, the function of C1orf106 and the consequences of disease-associated polymorphisms are unknown. Here we demonstrate that C1orf106 regulates adherens junction stability by regulating the degradation of cytohesin-1, a guanine nucleotide exchange factor that controls activation of ARF6. By limiting cytohesin-1–dependent ARF6 activation, C1orf106 stabilizes adherens junctions. Consistent with this model, C1orf106–/– mice exhibit defects in the intestinal epithelial cell barrier, a phenotype observed in IBD patients that confers increased susceptibility to intestinal pathogens. Furthermore, the IBD risk variant increases C1orf106 ubiquitination and turnover with consequent functional impairments. These findings delineate a mechanism by which a genetic polymorphism fine-tunes intestinal epithelial barrier integrity and elucidate a fundamental mechanism of cellular junctional control.
Nascent DNA methylome mapping reveals inheritance of hemimethylation at CTCF/cohesin sites Science (IF 37.205) Pub Date : 2018-03-09 Chenhuan Xu, Victor G. Corces
The faithful inheritance of the epigenome is critical for cells to maintain gene expression programs and cellular identity across cell divisions. We mapped strand-specific DNA methylation after replication forks and show maintenance of the vast majority of the DNA methylome within 20 minutes of replication and inheritance of some hemimethylated CpG dinucleotides (hemiCpGs). Mapping the nascent DNA methylome targeted by each of the three DNA methyltransferases (DNMTs) reveals interactions between DNMTs and substrate daughter cytosines en route to maintenance methylation or hemimethylation. Finally, we show the inheritance of hemiCpGs at short regions flanking CCCTC-binding factor (CTCF)/cohesin binding sites in pluripotent cells. Elimination of hemimethylation causes reduced frequency of chromatin interactions emanating from these sites, suggesting a role for hemimethylation as a stable epigenetic mark regulating CTCF-mediated chromatin interactions.
Thermal proximity coaggregation for system-wide profiling of protein complex dynamics in cells Science (IF 37.205) Pub Date : 2018-03-09 Chris Soon Heng Tan, Ka Diam Go, Xavier Bisteau, Lingyun Dai, Chern Han Yong, Nayana Prabhu, Mert Burak Ozturk, Yan Ting Lim, Lekshmy Sreekumar, Johan Lengqvist, Vinay Tergaonkar, Philipp Kaldis, Radoslaw M. Sobota, Pär Nordlund
Proteins differentially interact with each other across cellular states and conditions, but an efficient proteome-wide strategy to monitor them is lacking. We report the application of thermal proximity coaggregation (TPCA) for high-throughput intracellular monitoring of protein complex dynamics. Significant TPCA signatures observed among well-validated protein-protein interactions correlate positively with interaction stoichiometry and are statistically observable in more than 350 annotated human protein complexes. Using TPCA, we identified many complexes without detectable differential protein expression, including chromatin-associated complexes, modulated in S phase of the cell cycle. Comparison of six cell lines by TPCA revealed cell-specific interactions even in fundamental cellular processes. TPCA constitutes an approach for system-wide studies of protein complexes in nonengineered cells and tissues and might be used to identify protein complexes that are modulated in diseases.
Defining the earliest step of cardiovascular lineage segregation by single-cell RNA-seq Science (IF 37.205) Pub Date : 2018-03-09 Fabienne Lescroart, Xiaonan Wang, Xionghui Lin, Benjamin Swedlund, Souhir Gargouri, Adriana Sànchez-Dànes, Victoria Moignard, Christine Dubois, Catherine Paulissen, Sarah Kinston, Berthold Göttgens, Cédric Blanpain
Mouse heart development arises from Mesp1-expressing cardiovascular progenitors (CPs) that are specified during gastrulation. The molecular processes that control early regional and lineage segregation of CPs have been unclear. We performed single-cell RNA sequencing of wild-type and Mesp1-null CPs in mice. We showed that populations of Mesp1 CPs are molecularly distinct and span the continuum between epiblast and later mesodermal cells, including hematopoietic progenitors. Single-cell transcriptome analysis of Mesp1-deficient CPs showed that Mesp1 is required for the exit from the pluripotent state and the induction of the cardiovascular gene expression program. We identified distinct populations of Mesp1 CPs that correspond to progenitors committed to different cell lineages and regions of the heart, identifying the molecular features associated with early lineage restriction and regional segregation of the heart at the early stage of mouse gastrulation.
Chemically induced proximity in biology and medicine Science (IF 37.205) Pub Date : 2018-03-09 Benjamin Z. Stanton, Emma J. Chory, Gerald R. Crabtree
Proximity, or the physical closeness of molecules, is a pervasive regulatory mechanism in biology. For example, most posttranslational modifications such as phosphorylation, methylation, and acetylation promote proximity of molecules to play deterministic roles in cellular processes. To understand the role of proximity in biologic mechanisms, chemical inducers of proximity (CIPs) were developed to synthetically model biologically regulated recruitment. Chemically induced proximity allows for precise temporal control of transcription, signaling cascades, chromatin regulation, protein folding, localization, and degradation, as well as a host of other biologic processes. A systematic analysis of CIPs in basic research, coupled with recent technological advances utilizing CRISPR, distinguishes roles of causality from coincidence and allows for mathematical modeling in synthetic biology. Recently, induced proximity has provided new avenues of gene therapy and emerging advances in cancer treatment.
Structural basis for coupling protein transport and N-glycosylation at the mammalian endoplasmic reticulum Science (IF 37.205) Pub Date : 2018-03-08 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 (ER) by complex formation between the ribosome, the Sec61 protein-conducting channel and the 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 revealed how STT3A 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 co-translational machinery for N-glycosylation provides the basis for a mechanistic understanding of glycoprotein biogenesis at the ER.
Multidimensional quantum entanglement with large-scale integrated optics Science (IF 37.205) Pub Date : 2018-03-08 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 key for the investigation of fundamental science and for 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 dimension 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 key quantum applications experimentally unexplored before, such as quantum randomness expansion and self-testing on multidimensional states. Our work provides an experimental platform for the development of multidimensional quantum technologies.
Structure of the nuclear exosome captured on a maturing preribosome Science (IF 37.205) Pub Date : 2018-03-08 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. We used cryo-EM to visualize the yeast nuclear exosome holo-complex 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.
Hyperglycemia drives intestinal barrier dysfunction and risk for enteric infection Science (IF 37.205) Pub Date : 2018-03-08 Christoph A. Thaiss, Maayan Levy, Inna Grosheva, Danping Zheng, Eliran Soffer, Eran Blacher, Sofia Braverman, Anouk C. Tengeler, Oren Barak, Maya Elazar, Rotem Ben-Zeev, Dana Lehavi-Regev, Meirav N. Katz, Meirav Pevsner-Fischer, Arieh Gertler, Zamir Halpern, Alon Harmelin, Suhail Aamar, Patricia Serradas, Alexandra Grosfeld, Hagit Shapiro, Benjamin Geiger, Eran Elinav
Obesity, diabetes and related manifestations are associated with an enhanced, but poorly understood risk for mucosal infection and systemic inflammation. Here, we show in mouse models of obesity and diabetes that hyperglycemia drives intestinal barrier permeability, through GLUT2-dependent transcriptional reprogramming of intestinal epithelial cells and alteration of tight and adherence junction integrity. Consequently, hyperglycemia-mediated barrier disruption leads to systemic influx of microbial products and enhanced dissemination of enteric infection. Treatment of hyperglycemia, intestinal epithelial-specific GLUT2 deletion, or inhibition of glucose metabolism restores barrier function and bacterial containment. In humans, systemic influx of intestinal microbiome products correlates with individualized glycemic control, indicated by glycated hemoglobin levels. Together, our results mechanistically link hyperglycemia and intestinal barrier function with systemic infectious and inflammatory consequences of obesity and diabetes.
Photoperiodic control of seasonal growth is mediated by ABA acting on cell-cell communication Science (IF 37.205) Pub Date : 2018-03-08 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 inter-cellular communication through plasmodesmata is blocked by a process dependent upon the phytohormone abscisic acid (ABA). 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.
Observation of topological superconductivity on the surface of an iron-based superconductor Science (IF 37.205) Pub Date : 2018-03-08 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. Here 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 K) hosts Dirac-cone type spin-helical surface states at 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 2D topologically superconducting, providing a simple and possibly high temperature platform for realizing Majorana states.
Recurrences in an isolated quantum many-body system Science (IF 37.205) Pub Date : 2018-03-05 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 dynamics of large quantum systems even after they have reached a transient thermal-like state.
Science of science Science (IF 37.205) Pub Date : 2018-03-02 Santo Fortunato, Carl T. Bergstrom, Katy Börner, James A. Evans, Dirk Helbing, Staša Milojević, Alexander M. Petersen, Filippo Radicchi, Roberta Sinatra, Brian Uzzi, Alessandro Vespignani, Ludo Waltman, Dashun Wang, Albert-László Barabási
Identifying fundamental drivers of science and developing predictive models to capture its evolution are instrumental for the design of policies that can improve the scientific enterprise—for example, through enhanced career paths for scientists, better performance evaluation for organizations hosting research, discovery of novel effective funding vehicles, and even identification of promising regions along the scientific frontier. The science of science uses large-scale data on the production of science to search for universal and domain-specific patterns. Here, we review recent developments in this transdisciplinary field.
Observation of bulk Fermi arc and polarization half charge from paired exceptional points Science (IF 37.205) Pub Date : 2018-03-02 Hengyun Zhou, Chao Peng, Yoseob Yoon, Chia Wei Hsu, Keith A. Nelson, Liang Fu, John D. Joannopoulos, Marin Soljačić, Bo Zhen
The ideas of topology have found tremendous success in closed physical systems, but even richer properties exist in the more general open or dissipative framework. We theoretically propose and experimentally demonstrate a bulk Fermi arc that develops from non-Hermitian radiative losses in an open system of photonic crystal slabs. Moreover, we discover half-integer topological charges in the polarization of far-field radiation around the bulk Fermi arc. Both phenomena are shown to be direct consequences of the non-Hermitian topological properties of exceptional points, where resonances coincide in their frequencies and linewidths. Our work connects the fields of topological photonics, non-Hermitian physics, and singular optics, providing a framework to explore more complex non-Hermitian topological systems.
Ideal Weyl points and helicoid surface states in artificial photonic crystal structures Science (IF 37.205) Pub Date : 2018-03-02 Biao Yang, Qinghua Guo, Ben Tremain, Rongjuan Liu, Lauren E. Barr, Qinghui Yan, Wenlong Gao, Hongchao Liu, Yuanjiang Xiang, Jing Chen, Chen Fang, Alastair Hibbins, Ling Lu, Shuang Zhang
Weyl points are the crossings of linearly dispersing energy bands of three-dimensional crystals, providing the opportunity to explore a variety of intriguing phenomena such as topologically protected surface states and chiral anomalies. However, the lack of an ideal Weyl system in which the Weyl points all exist at the same energy and are separated from any other bands poses a serious limitation to the further development of Weyl physics and potential applications. By experimentally characterizing a microwave photonic crystal of saddle-shaped metallic coils, we observed ideal Weyl points that are related to each other through symmetry operations. Topological surface states exhibiting helicoidal structure have also been demonstrated. Our system provides a photonic platform for exploring ideal Weyl systems and developing possible topological devices.
Selective formation of γ-lactams via C–H amidation enabled by tailored iridium catalysts Science (IF 37.205) Pub Date : 2018-03-02 Seung Youn Hong, Yoonsu Park, Yeongyu Hwang, Yeong Bum Kim, Mu-Hyun Baik, Sukbok Chang
Intramolecular insertion of metal nitrenes into carbon-hydrogen bonds to form γ-lactam rings has traditionally been hindered by competing isocyanate formation. We report the application of theory and mechanism studies to optimize a class of pentamethylcyclopentadienyl iridium(III) catalysts for suppression of this competing pathway. Modulation of the stereoelectronic properties of the auxiliary bidentate ligands to be more electron-donating was suggested by density functional theory calculations to lower the C–H insertion barrier favoring the desired reaction. These catalysts transform a wide range of 1,4,2-dioxazol-5-ones, carbonylnitrene precursors easily accessible from carboxylic acids, into the corresponding γ-lactams via sp3 and sp2 C–H amidation with exceptional selectivity. The power of this method was further demonstrated by the successful late-stage functionalization of amino acid derivatives and other bioactive molecules.
Evolution of alluvial mudrock forced by early land plants Science (IF 37.205) Pub Date : 2018-03-02 William J. McMahon, Neil S. Davies
Mudrocks are a primary archive of Earth’s history from the Archean eon to recent times, and their source-to-sink production and deposition play a central role in long-term ocean chemistry and climate regulation. Using original and published stratigraphic data from all 704 of Earth’s known alluvial formations from the Archean eon (3.5 billion years ago) to the Carboniferous period (0.3 billion years ago), we prove contentions of an upsurge in the proportion of mud retained on land coeval with vegetation evolution. We constrain the onset of the upsurge to the Ordovician-Silurian and show that alluvium deposited after land plant evolution contains a proportion of mudrock that is, on average, 1.4 orders of magnitude greater than the proportion contained in alluvium from the preceding 90% of Earth’s history. We attribute this shift to the ways in which vegetation revolutionized mud production and sediment flux from continental interiors.
Evidence for a neural law of effect Science (IF 37.205) Pub Date : 2018-03-02 Vivek R. Athalye, Fernando J. Santos, Jose M. Carmena, Rui M. Costa
Thorndike’s law of effect states that actions that lead to reinforcements tend to be repeated more often. Accordingly, neural activity patterns leading to reinforcement are also reentered more frequently. Reinforcement relies on dopaminergic activity in the ventral tegmental area (VTA), and animals shape their behavior to receive dopaminergic stimulation. Seeking evidence for a neural law of effect, we found that mice learn to reenter more frequently motor cortical activity patterns that trigger optogenetic VTA self-stimulation. Learning was accompanied by gradual shaping of these patterns, with participating neurons progressively increasing and aligning their covariance to that of the target pattern. Motor cortex patterns that lead to phasic dopaminergic VTA activity are progressively reinforced and shaped, suggesting a mechanism by which animals select and shape actions to reliably achieve reinforcement.
Incomplete host immunity favors the evolution of virulence in an emergent pathogen Science (IF 37.205) Pub Date : 2018-03-02 Arietta E. Fleming-Davies, Paul D. Williams, André A. Dhondt, Andrew P. Dobson, Wesley M. Hochachka, Ariel E. Leon, David H. Ley, Erik E. Osnas, Dana M. Hawley
Immune memory evolved to protect hosts from reinfection, but incomplete responses that allow future reinfection may inadvertently select for more-harmful pathogens. We present empirical and modeling evidence that incomplete immunity promotes the evolution of higher virulence in a natural host-pathogen system. We performed sequential infections of house finches with Mycoplasma gallisepticum strains of various levels of virulence. Virulent bacterial strains generated stronger host protection against reinfection than less virulent strains and thus excluded less virulent strains from infecting previously exposed hosts. In a two-strain model, the resulting fitness advantage selected for an almost twofold increase in pathogen virulence. Thus, the same immune systems that protect hosts from infection can concomitantly drive the evolution of more-harmful pathogens in nature.
Winter color polymorphisms identify global hot spots for evolutionary rescue from climate change Science (IF 37.205) Pub Date : 2018-03-02 L. Scott Mills, Eugenia V. Bragina, Alexander V. Kumar, Marketa Zimova, Diana J. R. Lafferty, Jennifer Feltner, Brandon M. Davis, Klaus Hackländer, Paulo C. Alves, Jeffrey M. Good, José Melo-Ferreira, Andreas Dietz, Alexei V. Abramov, Natalia Lopatina, Kairsten Fay
Maintenance of biodiversity in a rapidly changing climate will depend on the efficacy of evolutionary rescue, whereby population declines due to abrupt environmental change are reversed by shifts in genetically driven adaptive traits. However, a lack of traits known to be under direct selection by anthropogenic climate change has limited the incorporation of evolutionary processes into global conservation efforts. In 21 vertebrate species, some individuals undergo a seasonal color molt from summer brown to winter white as camouflage against snow, whereas other individuals remain brown. Seasonal snow duration is decreasing globally, and fitness is lower for winter white animals on snowless backgrounds. Based on 2713 georeferenced samples of known winter coat color—from eight species across trophic levels—we identify environmentally driven clinal gradients in winter coat color, including polymorphic zones where winter brown and white morphs co-occur. These polymorphic zones, underrepresented by existing global protected area networks, indicate hot spots for evolutionary rescue in a changing climate.
Selective targeting of engineered T cells using orthogonal IL-2 cytokine-receptor complexes Science (IF 37.205) Pub Date : 2018-03-02 Jonathan T. Sockolosky, Eleonora Trotta, Giulia Parisi, Lora Picton, Leon L. Su, Alan C. Le, Akanksha Chhabra, Stephanie L. Silveria, Benson M. George, Indigo C. King, Matthew R. Tiffany, Kevin Jude, Leah V. Sibener, David Baker, Judith A. Shizuru, Antoni Ribas, Jeffrey A. Bluestone, K. Christopher Garcia
Interleukin-2 (IL-2) is a cytokine required for effector T cell expansion, survival, and function, especially for engineered T cells in adoptive cell immunotherapy, but its pleiotropy leads to simultaneous stimulation and suppression of immune responses as well as systemic toxicity, limiting its therapeutic use. We engineered IL-2 cytokine-receptor orthogonal (ortho) pairs that interact with one another, transmitting native IL-2 signals, but do not interact with their natural cytokine and receptor counterparts. Introduction of orthoIL-2Rβ into T cells enabled the selective cellular targeting of orthoIL-2 to engineered CD4+ and CD8+ T cells in vitro and in vivo, with limited off-target effects and negligible toxicity. OrthoIL-2 pairs were efficacious in a preclinical mouse cancer model of adoptive cell therapy and may therefore represent a synthetic approach to achieving selective potentiation of engineered cells.
Accurate computational design of multipass transmembrane proteins Science (IF 37.205) Pub Date : 2018-03-02 Peilong Lu, Duyoung Min, Frank DiMaio, Kathy Y. Wei, Michael D. Vahey, Scott E. Boyken, Zibo Chen, Jorge A. Fallas, George Ueda, William Sheffler, Vikram Khipple Mulligan, Wenqing Xu, James U. Bowie, David Baker
The computational design of transmembrane proteins with more than one membrane-spanning region remains a major challenge. We report the design of transmembrane monomers, homodimers, trimers, and tetramers with 76 to 215 residue subunits containing two to four membrane-spanning regions and up to 860 total residues that adopt the target oligomerization state in detergent solution. The designed proteins localize to the plasma membrane in bacteria and in mammalian cells, and magnetic tweezer unfolding experiments in the membrane indicate that they are very stable. Crystal structures of the designed dimer and tetramer—a rocket-shaped structure with a wide cytoplasmic base that funnels into eight transmembrane helices—are very close to the design models. Our results pave the way for the design of multispan membrane proteins with new functions.
An evolutionarily conserved gene family encodes proton-selective ion channels Science (IF 37.205) Pub Date : 2018-03-02 Yu-Hsiang Tu, Alexander J. Cooper, Bochuan Teng, Rui B. Chang, Daniel J. Artiga, Heather N. Turner, Eric M. Mulhall, Wenlei Ye, Andrew D. Smith, Emily R. Liman
Ion channels form the basis for cellular electrical signaling. Despite the scores of genetically identified ion channels selective for other monatomic ions, only one type of proton-selective ion channel has been found in eukaryotic cells. By comparative transcriptome analysis of mouse taste receptor cells, we identified Otopetrin1 (OTOP1), a protein required for development of gravity-sensing otoconia in the vestibular system, as forming a proton-selective ion channel. We found that murine OTOP1 is enriched in acid-detecting taste receptor cells and is required for their zinc-sensitive proton conductance. Two related murine genes, Otop2 and Otop3, and a Drosophila ortholog also encode proton channels. Evolutionary conservation of the gene family and its widespread tissue distribution suggest a broad role for proton channels in physiology and pathophysiology.
Transcription-coupled changes in nuclear mobility of mammalian cis-regulatory elements Science (IF 37.205) Pub Date : 2018-03-02 Bo Gu, Tomek Swigut, Andrew Spencley, Matthew R. Bauer, Mingyu Chung, Tobias Meyer, Joanna Wysocka
To achieve guide RNA (gRNA) multiplexing and an efficient delivery of tens of distinct gRNAs into single cells, we developed a molecular assembly strategy termed chimeric array of gRNA oligonucleotides (CARGO). We coupled CARGO with dCas9 (catalytically dead Cas9) imaging to quantitatively measure the movement of enhancers and promoters that undergo differentiation-associated activity changes in live embryonic stem cells. Whereas all examined functional elements exhibited subdiffusive behavior, their relative mobility increased concurrently with transcriptional activation. Furthermore, acute perturbation of RNA polymerase II activity can reverse these activity-linked increases in loci mobility. Through quantitative CARGO-dCas9 imaging, we provide direct measurements of cis-regulatory element dynamics in living cells and distinct cellular and activity states and uncover an intrinsic connection between cis-regulatory element mobility and transcription.
β2-adrenergic receptor–mediated negative regulation of group 2 innate lymphoid cell responses Science (IF 37.205) Pub Date : 2018-03-02 Saya Moriyama, Jonathan R. Brestoff, Anne-Laure Flamar, Jesper B. Moeller, Christoph S. N. Klose, Lucille C. Rankin, Naomi A. Yudanin, Laurel A. Monticelli, Gregory Garbès Putzel, Hans-Reimer Rodewald, David Artis
The type 2 inflammatory response is induced by various environmental and infectious stimuli. Although recent studies identified group 2 innate lymphoid cells (ILC2s) as potent sources of type 2 cytokines, the molecular pathways controlling ILC2 responses are incompletely defined. Here we demonstrate that murine ILC2s express the β2-adrenergic receptor (β2AR) and colocalize with adrenergic neurons in the intestine. β2AR deficiency resulted in exaggerated ILC2 responses and type 2 inflammation in intestinal and lung tissues. Conversely, β2AR agonist treatment was associated with impaired ILC2 responses and reduced inflammation in vivo. Mechanistically, we demonstrate that the β2AR pathway is a cell-intrinsic negative regulator of ILC2 responses through inhibition of cell proliferation and effector function. Collectively, these data provide the first evidence of a neuronal-derived regulatory circuit that limits ILC2-dependent type 2 inflammation.
Systematic discovery of antiphage defense systems in the microbial pangenome Science (IF 37.205) Pub Date : 2018-03-02 Shany Doron, Sarah Melamed, Gal Ofir, Azita Leavitt, Anna Lopatina, Mai Keren, Gil Amitai, Rotem Sorek
The arms race between bacteria and phages led to the development of sophisticated antiphage defense systems, including CRISPR-Cas and restriction-modification systems. Evidence suggests that known and unknown defense systems are located in “defense islands” in microbial genomes. Here, we comprehensively characterized the bacterial defensive arsenal by examining gene families that are clustered next to known defense genes in prokaryotic genomes. Candidate defense systems were systematically engineered and validated in model bacteria for their antiphage activities. We report nine previously unknown antiphage systems and one antiplasmid system that are widespread in microbes and strongly protect against foreign invaders. These include systems that adopted components of the bacterial flagella and condensin complexes. Our data also suggest a common, ancient ancestry of innate immunity components shared between animals, plants, and bacteria.
Observation of fractional Chern insulators in a van der Waals heterostructure Science (IF 37.205) Pub Date : 2018-03-01 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 non-trivial “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 observe phases at fractional filling of bands with Chern indices . Some of these, in and bands, are characterized by fractional Hall conductance—they are “fractional Chern insulators” and constitute an example of topological order beyond Landau levels.
Quantitative analysis of population-scale family trees with millions of relatives Science (IF 37.205) Pub Date : 2018-03-01 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 multiple fields from genetics to 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. Here, 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 longevity by inspecting millions of relative pairs and to provide insights into the geographical dispersion of families. We also report a simple digital procedure to overlay other datasets with our resource in order to empower studies with population-scale genealogical data.
Some contents have been Reproduced by permission of The Royal Society of Chemistry.
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