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Journal Cover Science
  [SJR: 12.465]   [H-I: 801]   [2285 followers]  Follow
   Full-text available via subscription Subscription journal
   ISSN (Print) 0036-8075 - ISSN (Online) 1095-9203
   Published by American Association for the Advancement of Science (AAAS) Homepage  [5 journals]
  • [Research Article] Population-level analysis of gut microbiome variation
    • Authors: Gwen Falony
      Abstract: Fecal microbiome variation in the average, healthy population has remained under-investigated. Here, we analyzed two independent, extensively phenotyped cohorts: the Belgian Flemish Gut Flora Project (FGFP; discovery cohort; N = 1106) and the Dutch LifeLines-DEEP study (LLDeep; replication; N = 1135). Integration with global data sets (N combined = 3948) revealed a 14-genera core microbiota, but the 664 identified genera still underexplore total gut diversity. Sixty-nine clinical and questionnaire-based covariates were found associated to microbiota compositional variation with a 92% replication rate. Stool consistency showed the largest effect size, whereas medication explained largest total variance and interacted with other covariate-microbiota associations. Early-life events such as birth mode were not reflected in adult microbiota composition. Finally, we found that proposed disease marker genera associated to host covariates, urging inclusion of the latter in study design.
      Authors : Gwen Falony, Marie Joossens, Sara Vieira-Silva, Jun Wang, Youssef Darzi, Karoline Faust, Alexander Kurilshikov, Marc Jan Bonder, Mireia Valles-Colomer, Doris Vandeputte, Raul Y. Tito, Samuel Chaffron, Leen Rymenans, Chloë Verspecht, Lise De Sutter, Gipsi Lima-Mendez, Kevin D’hoe, Karl Jonckheere, Daniel Homola, Roberto Garcia, Ettje F. Tigchelaar, Linda Eeckhaudt, Jingyuan Fu, Liesbet Henckaerts, Alexandra Zhernakova, Cisca Wijmenga, Jeroen Raes
      PubDate: 2016-04-29
      DOI: 10.1126/science.aad3503
  • [Research Article] Changes in the composition of brain interstitial ions
           control the sleep-wake cycle
    • Authors: Fengfei Ding
      Abstract: Wakefulness is driven by the widespread release of neuromodulators by the ascending arousal system. Yet, it is unclear how these substances orchestrate state-dependent, global changes in neuronal activity. Here, we show that neuromodulators induce increases in the extracellular K+ concentration ([K+]e) in cortical slices electrically silenced by tetrodotoxin. In vivo, arousal was linked to AMPA receptor–independent elevations of [K+]e concomitant with decreases in [Ca2+]e, [Mg2+]e, [H+]e, and the extracellular volume. Opposite, natural sleep and anesthesia reduced [K+]e while increasing [Ca2+]e, [Mg2+]e, and [H+]e as well as the extracellular volume. Local cortical activity of sleeping mice could be readily converted to the stereotypical electroencephalography pattern of wakefulness by simply imposing a change in the extracellular ion composition. Thus, extracellular ions control the state-dependent patterns of neural activity.
      Authors : Fengfei Ding, John O’Donnell, Qiwu Xu, Ning Kang, Nanna Goldman, Maiken Nedergaard
      PubDate: 2016-04-29
      DOI: 10.1126/science.aad4821
  • [Research Article] Unconventional endocannabinoid signaling governs sperm
           activation via the sex hormone progesterone
    • Authors: Melissa R. Miller
      Abstract: Steroids regulate cell proliferation, tissue development, and cell signaling via two pathways: a nuclear receptor mechanism and genome-independent signaling. Sperm activation, egg maturation, and steroid-induced anesthesia are executed via the latter pathway, the key components of which remain unknown. Here, we present characterization of the human sperm progesterone receptor that is conveyed by the orphan enzyme α/β hydrolase domain–containing protein 2 (ABHD2). We show that ABHD2 is highly expressed in spermatozoa, binds progesterone, and acts as a progesterone-dependent lipid hydrolase by depleting the endocannabinoid 2-arachidonoylglycerol (2AG) from plasma membrane. The 2AG inhibits the sperm calcium channel (CatSper), and its removal leads to calcium influx via CatSper and ensures sperm activation. This study reveals that progesterone-activated endocannabinoid depletion by ABHD2 is a general mechanism by which progesterone exerts its genome-independent action and primes sperm for fertilization.
      Authors : Melissa R. Miller, Nadja Mannowetz, Anthony T. Iavarone, Rojin Safavi, Elena O. Gracheva, James F. Smith, Rose Z. Hill, Diana M. Bautista, Yuriy Kirichok, Polina V. Lishko
      PubDate: 2016-04-29
      DOI: 10.1126/science.aad6887
  • [Research Article] Structure and organization of heteromeric AMPA-type
           glutamate receptors
    • Authors: Beatriz Herguedas
      Abstract: AMPA-type glutamate receptors (AMPARs), which are central mediators of rapid neurotransmission and synaptic plasticity, predominantly exist as heteromers of the subunits GluA1 to GluA4. Here we report the first AMPAR heteromer structures, which deviate substantially from existing GluA2 homomer structures. Crystal structures of the GluA2/3 and GluA2/4 N-terminal domains reveal a novel compact conformation with an alternating arrangement of the four subunits around a central axis. This organization is confirmed by cysteine cross-linking in full-length receptors, and it permitted us to determine the structure of an intact GluA2/3 receptor by cryogenic electron microscopy. Two models in the ligand-free state, at resolutions of 8.25 and 10.3 angstroms, exhibit substantial vertical compression and close associations between domain layers, reminiscent of N-methyl-d-aspartate receptors. Model 1 resembles a resting state and model 2 a desensitized state, thus providing snapshots of gating transitions in the nominal absence of ligand. Our data reveal organizational features of heteromeric AMPARs and provide a framework to decipher AMPAR architecture and signaling.
      Authors : Beatriz Herguedas, Javier García-Nafría, Ondrej Cais, Rafael Fernández-Leiro, James Krieger, Hinze Ho, Ingo H. Greger
      PubDate: 2016-04-29
      DOI: 10.1126/science.aad3873
  • [Editors' Choice] Under pressure in the Magellanic Clouds
    • Authors: Keith T. Smith
      Abstract: Author: Keith T. Smith
      Keywords: Interstellar Medium
      PubDate: 2016-04-29
      DOI: 10.1126/science.352.6285.547-a
  • [Editors' Choice] Breaking down a barrier to tumor therapy
    • Authors: Paula A. Kiberstis
      Abstract: Author: Paula A. Kiberstis
      Keywords: Cancer Treatment
      PubDate: 2016-04-29
      DOI: 10.1126/science.352.6285.547-b
  • [Editors' Choice] Cyanobacteria put to work as chemists
    • Authors: Jake Yeston
      Abstract: Author: Jake Yeston
      Keywords: Biotechnology
      PubDate: 2016-04-29
      DOI: 10.1126/science.352.6285.547-c
  • [Editors' Choice] A chromatin modifier for the developing heart
    • Authors: Beverly A. Purnell
      Abstract: Author: Beverly A. Purnell
      Keywords: Heart Development
      PubDate: 2016-04-29
      DOI: 10.1126/science.352.6285.547-d
  • [Editors' Choice] Metagenomes yield archaeal metabolisms
    • Authors: Nicholas S. Wigginton
      Abstract: Author: Nicholas S. Wigginton
      Keywords: Microbiology
      PubDate: 2016-04-29
      DOI: 10.1126/science.352.6285.547-e
  • [Editors' Choice] How accurate are emission estimates?
    • Authors: Julia Fahrenkamp-Uppenbrink
      Abstract: Author: Julia Fahrenkamp-Uppenbrink
      Keywords: Climate Change
      PubDate: 2016-04-29
      DOI: 10.1126/science.352.6285.547-f
  • [Editors' Choice] Dabbling ducks disperse seeds
    • Authors: Andrew M. Sugden
      Abstract: Author: Andrew M. Sugden
      Keywords: Plant Ecology
      PubDate: 2016-04-29
      DOI: 10.1126/science.352.6285.547-g
  • [Perspective] Light flips a membrane-embedded helix
    • Authors: Christina M. Thiele
      Abstract: Signaling proteins embedded in cell membranes can transmit information from one side to another, usually by a conformational change within a bundle of transmembrane helices. The challenge of mimicking these proteins with smaller molecules has been picked up by synthetic chemists. On page 575 of this issue, De Poli et al. (1) show that a conformational change in a helical foldamer not only can be elicited by irradiation with light, it can also be allosterically transmitted within a membrane over a distance of up to 2 nm.
      Authors : Christina M. Thiele, Anne S. Ulrich
      Keywords: Synthetic Foldamers
      PubDate: 2016-04-29
      DOI: 10.1126/science.aaf6191
  • [Policy Forum] The growing problem of patent trolling
    • Authors: Lauren Cohen
      Abstract: The last decade has seen a sharp rise in patent litigation in the United States; 2015 has one of the highest patent lawsuit counts on record (1). In theory, this could reflect growth in commercialization of technology and innovation—lawsuits increase as more firms turn to intellectual property (IP) protection to safeguard their competitive advantages. However, the majority of recent patent litigation is driven by nonpracticing entities (NPEs), firms that generate no products but amass patent portfolios for the sake of “enforcing” IP rights (2). We discuss new, large-sample evidence adding to a growing literature (3–7) that suggests that NPEs—in particular, large patent aggregators—on average, act as “patent trolls,” suing cash-rich firms seemingly irrespective of actual patent infringement. This has a negative impact on innovation activity at targeted firms. These results suggest a need to change U.S. IP policy, particularly to screen out trolling early in the litigation process.
      Authors : Lauren Cohen, Umit G. Gurun, Scott Duke Kominers
      Keywords: Intellectual Property and Innovation
      PubDate: 2016-04-29
      DOI: 10.1126/science.aad2686
  • [This Week in Science] Persistence of fecal transplants
    • Authors: Caroline Ash
      Abstract: Author: Caroline Ash
      Keywords: Microbiome
      PubDate: 2016-04-29
      DOI: 10.1126/science.352.6285.546-i
  • [This Week in Science] EZ catalyst control in olefin metathesis
    • Authors: Jake Yeston
      Abstract: Author: Jake Yeston
      Keywords: Organic Chemistry
      PubDate: 2016-04-29
      DOI: 10.1126/science.352.6285.546-j
  • [This Week in Science] Phase separation organizes signaling
    • Authors: L. Bryan Ray
      Abstract: Author: L. Bryan Ray
      Keywords: Signal Transduction
      PubDate: 2016-04-29
      DOI: 10.1126/science.352.6285.546-k
  • [This Week in Science] RNA splicing links genetics to disease
    • Authors: Laura M. Zahn
      Abstract: Author: Laura M. Zahn
      Keywords: Human Genetics
      PubDate: 2016-04-29
      DOI: 10.1126/science.352.6285.546-l
  • [This Week in Science] Identifying nonequilibrium dynamics
    • Authors: Valda Vinson
      Abstract: Author: Valda Vinson
      Keywords: Biophysics
      PubDate: 2016-04-29
      DOI: 10.1126/science.352.6285.546-m
  • [This Week in Science] Sleep induction through ion changes
    • Authors: Peter Stern
      Abstract: Author: Peter Stern
      Keywords: Sleep Research
      PubDate: 2016-04-29
      DOI: 10.1126/science.352.6285.546-n
  • [This Week in Science] Progesterone signaling in sperm
    • Authors: Beverly A. Purnell
      Abstract: Author: Beverly A. Purnell
      Keywords: Reproductive Biology
      PubDate: 2016-04-29
      DOI: 10.1126/science.352.6285.546-o
  • [This Week in Science] How sleep deprivation impairs memory
    • Authors: Leslie K. Ferrarelli
      Abstract: Author: Leslie K. Ferrarelli
      Keywords: Neuroscience
      PubDate: 2016-04-29
      DOI: 10.1126/science.352.6285.546-p
  • [This Week in Science] Peering into a membrance oxidase
    • Authors: Nicholas S. Wigginton
      Abstract: Author: Nicholas S. Wigginton
      Keywords: Structural Biology
      PubDate: 2016-04-29
      DOI: 10.1126/science.352.6285.546-q
  • [Perspective] Ionic control of sleep and wakefulness
    • Authors: Hans-Peter Landolt
      Abstract: Brain electrical activity differs markedly between wakefulness and sleep. Concomitant shifts in the ion composition of brain extracellular fluids were thought to be a consequence rather than a cause of the sleep-wake–dependent changes in neuronal activity. On page 550 of this issue, Ding et al. (1) report the surprising observation that ionic changes in the extracellular fluid are a potent control of sleep-wake–dependent neuronal activity.
      Authors : Hans-Peter Landolt, Sebastian C. Holst
      Keywords: Neuroscience
      PubDate: 2016-04-29
      DOI: 10.1126/science.aaf8178
  • [Perspective] A bacterial oxidase like no other?
    • Authors: Gregory M. Cook
      Abstract: Most biological oxygen consumption is carried out by membrane-integrated oxidases, which fall into three main classes. The heme-copper oxidases (HCOs) of mitochondria and many bacteria (1) have a binuclear active site that contains a heme and a copper atom. They achieve rapid, virtually complete reduction of oxygen to water. The alternative oxidases (AOXs) found in certain plants, fungi, and bacteria have a heme-free iron-iron reactive site (2) that confers nitric oxide–resistant respiration (3). The last class, the bacterial cytochrome bd–type oxidases (4), are found in many pathogenic bacteria and have a distinctive heme composition consisting of two hemes b and one heme d. On page 583 of this issue, Safarian et al. report the atomic-resolution structure of a cytochrome bd–type oxidase from Geobacillus thermodenitrificans (5). The structure will facilitate targeted and rational drug development against cytochrome bd–type oxidases.
      Authors : Gregory M. Cook, Robert K. Poole
      Keywords: Biochemistry
      PubDate: 2016-04-29
      DOI: 10.1126/science.aaf5514
  • [Report] Helminth infection promotes colonization resistance via type 2
    • Authors: Deepshika Ramanan
      Abstract: Increasing incidence of inflammatory bowel diseases, such as Crohn’s disease, in developed nations is associated with changes to the microbial environment, such as decreased prevalence of helminth colonization and alterations to the gut microbiota. We find that helminth infection protects mice deficient in the Crohn’s disease susceptibility gene Nod2 from intestinal abnormalities by inhibiting colonization by an inflammatory Bacteroides species. Resistance to Bacteroides colonization was dependent on type 2 immunity, which promoted the establishment of a protective microbiota enriched in Clostridiales. Additionally, we show that individuals from helminth-endemic regions harbor a similar protective microbiota and that deworming treatment reduced levels of Clostridiales and increased Bacteroidales. These results support a model of the hygiene hypothesis in which certain individuals are genetically susceptible to the consequences of a changing microbial environment.
      Authors : Deepshika Ramanan, Rowann Bowcutt, Soo Ching Lee, Mei San Tang, Zachary D. Kurtz, Yi Ding, Kenya Honda, William C. Gause, Martin J. Blaser, Richard A. Bonneau, Yvonne A.L. Lim, P’ng Loke, Ken Cadwell
      PubDate: 2016-04-29
      DOI: 10.1126/science.aaf3229
  • [Report] Phase separation of signaling molecules promotes T cell receptor
           signal transduction
    • Authors: Xiaolei Su
      Abstract: Activation of various cell surface receptors triggers the reorganization of downstream signaling molecules into micrometer- or submicrometer-sized clusters. However, the functional consequences of such clustering have been unclear. We biochemically reconstituted a 12-component signaling pathway on model membranes, beginning with T cell receptor (TCR) activation and ending with actin assembly. When TCR phosphorylation was triggered, downstream signaling proteins spontaneously separated into liquid-like clusters that promoted signaling outputs both in vitro and in human Jurkat T cells. Reconstituted clusters were enriched in kinases but excluded phosphatases and enhanced actin filament assembly by recruiting and organizing actin regulators. These results demonstrate that protein phase separation can create a distinct physical and biochemical compartment that facilitates signaling.
      Authors : Xiaolei Su, Jonathon A. Ditlev, Enfu Hui, Wenmin Xing, Sudeep Banjade, Julia Okrut, David S. King, Jack Taunton, Michael K. Rosen, Ronald D. Vale
      PubDate: 2016-04-29
      DOI: 10.1126/science.aad9964
  • [Report] RNA splicing is a primary link between genetic variation and
    • Authors: Yang I. Li
      Abstract: Noncoding variants play a central role in the genetics of complex traits, but we still lack a full understanding of the molecular pathways through which they act. We quantified the contribution of cis-acting genetic effects at all major stages of gene regulation from chromatin to proteins, in Yoruba lymphoblastoid cell lines (LCLs). About ~65% of expression quantitative trait loci (eQTLs) have primary effects on chromatin, whereas the remaining eQTLs are enriched in transcribed regions. Using a novel method, we also detected 2893 splicing QTLs, most of which have little or no effect on gene-level expression. These splicing QTLs are major contributors to complex traits, roughly on a par with variants that affect gene expression levels. Our study provides a comprehensive view of the mechanisms linking genetic variation to variation in human gene regulation.
      Authors : Yang I. Li, Bryce van de Geijn, Anil Raj, David A. Knowles, Allegra A. Petti, David Golan, Yoav Gilad, Jonathan K. Pritchard
      PubDate: 2016-04-29
      DOI: 10.1126/science.aad9417
  • [Report] Broken detailed balance at mesoscopic scales in active biological
    • Authors: Christopher Battle
      Abstract: Systems in thermodynamic equilibrium are not only characterized by time-independent macroscopic properties, but also satisfy the principle of detailed balance in the transitions between microscopic configurations. Living systems function out of equilibrium and are characterized by directed fluxes through chemical states, which violate detailed balance at the molecular scale. Here we introduce a method to probe for broken detailed balance and demonstrate how such nonequilibrium dynamics are manifest at the mesosopic scale. The periodic beating of an isolated flagellum from Chlamydomonas reinhardtii exhibits probability flux in the phase space of shapes. With a model, we show how the breaking of detailed balance can also be quantified in stationary, nonequilibrium stochastic systems in the absence of periodic motion. We further demonstrate such broken detailed balance in the nonperiodic fluctuations of primary cilia of epithelial cells. Our analysis provides a general tool to identify nonequilibrium dynamics in cells and tissues.
      Authors : Christopher Battle, Chase P. Broedersz, Nikta Fakhri, Veikko F. Geyer, Jonathon Howard, Christoph F. Schmidt, Fred C. MacKintosh
      PubDate: 2016-04-29
      DOI: 10.1126/science.aac8167
  • [Report] Durable coexistence of donor and recipient strains after fecal
           microbiota transplantation
    • Authors: Simone S. Li
      Abstract: Fecal microbiota transplantation (FMT) has shown efficacy in treating recurrent Clostridium difficile infection and is increasingly being applied to other gastrointestinal disorders, yet the fate of native and introduced microbial strains remains largely unknown. To quantify the extent of donor microbiota colonization, we monitored strain populations in fecal samples from a recent FMT study on metabolic syndrome patients using single-nucleotide variants in metagenomes. We found extensive coexistence of donor and recipient strains, persisting 3 months after treatment. Colonization success was greater for conspecific strains than for new species, the latter falling within fluctuation levels observed in healthy individuals over a similar time frame. Furthermore, same-donor recipients displayed varying degrees of microbiota transfer, indicating individual patterns of microbiome resistance and donor-recipient compatibilities.
      Authors : Simone S. Li, Ana Zhu, Vladimir Benes, Paul I. Costea, Rajna Hercog, Falk Hildebrand, Jaime Huerta-Cepas, Max Nieuwdorp, Jarkko Salojärvi, Anita Y. Voigt, Georg Zeller, Shinichi Sunagawa, Willem M. de Vos, Peer Bork
      PubDate: 2016-04-29
      DOI: 10.1126/science.aad8852
  • [Report] Slow waves, sharp waves, ripples, and REM in sleeping dragons
    • Authors: Mark Shein-Idelson
      Abstract: Sleep has been described in animals ranging from worms to humans. Yet the electrophysiological characteristics of brain sleep, such as slow-wave (SW) and rapid eye movement (REM) activities, are thought to be restricted to mammals and birds. Recording from the brain of a lizard, the Australian dragon Pogona vitticeps, we identified SW and REM sleep patterns, thus pushing back the probable evolution of these dynamics at least to the emergence of amniotes. The SW and REM sleep patterns that we observed in lizards oscillated continuously for 6 to 10 hours with a period of ~80 seconds. The networks controlling SW-REM antagonism in amniotes may thus originate from a common, ancient oscillator circuit. Lizard SW dynamics closely resemble those observed in rodent hippocampal CA1, yet they originate from a brain area, the dorsal ventricular ridge, that has no obvious hodological similarity with the mammalian hippocampus.
      Authors : Mark Shein-Idelson, Janie M. Ondracek, Hua-Peng Liaw, Sam Reiter, Gilles Laurent
      PubDate: 2016-04-29
      DOI: 10.1126/science.aaf3621
  • [This Week in Science] The dragon sleeps tonight
    • Authors: Peter Stern
      Abstract: Author: Peter Stern
      Keywords: Reptile Sleep
      PubDate: 2016-04-29
      DOI: 10.1126/science.352.6285.546-a
  • [This Week in Science] “Normal” for the gut microbiota
    • Authors: Caroline Ash
      Abstract: Author: Caroline Ash
      Keywords: Microbiome
      PubDate: 2016-04-29
      DOI: 10.1126/science.352.6285.546-b
  • [This Week in Science] Strengths that are now weaknesses
    • Authors: JBCJ
      Abstract: Author: JBCJ
      Keywords: Coral Reefs
      PubDate: 2016-04-29
      DOI: 10.1126/science.352.6285.546-c
  • [This Week in Science] Parasitic worms affect gut microbes
    • Authors: Kristen L. Mueller
      Abstract: Author: Kristen L. Mueller
      Keywords: Microbiota
      PubDate: 2016-04-29
      DOI: 10.1126/science.352.6285.546-d
  • [This Week in Science] Iron isotopes constrain core chemistry
    • Authors: Brent Grocholski
      Abstract: Author: Brent Grocholski
      Keywords: Geochemistry
      PubDate: 2016-04-29
      DOI: 10.1126/science.352.6285.546-e
  • [This Week in Science] Synthetic twists among lipids
    • Authors: Jake Yeston
      Abstract: Author: Jake Yeston
      Keywords: Chemistry
      PubDate: 2016-04-29
      DOI: 10.1126/science.352.6285.546-f
  • [This Week in Science] Beyond antibiotics
    • Authors: Angela Colmone
      Abstract: Author: Angela Colmone
      Keywords: Infectious Disease
      PubDate: 2016-04-29
      DOI: 10.1126/science.352.6285.546-g
  • [This Week in Science] Signaling at the synapse
    • Authors: Valda Vinson
      Abstract: Author: Valda Vinson
      Keywords: Structural Biology
      PubDate: 2016-04-29
      DOI: 10.1126/science.352.6285.546-h
  • [Report] Pressure-dependent isotopic composition of iron alloys
    • Authors: A. Shahar
      Abstract: Our current understanding of Earth’s core formation is limited by the fact that this profound event is far removed from us physically and temporally. The composition of the iron metal in the core was a result of the conditions of its formation, which has important implications for our planet’s geochemical evolution and physical history. We present experimental and theoretical evidence for the effect of pressure on iron isotopic composition, which we found to vary according to the alloy tested (FeO, FeHx, or Fe3C versus pure Fe). These results suggest that hydrogen or carbon is not the major light-element component in the core. The pressure dependence of iron isotopic composition provides an independent constraint on Earth’s core composition.
      Authors : A. Shahar, E. A. Schauble, R. Caracas, A. E. Gleason, M. M. Reagan, Y. Xiao, J. Shu, W. Mao
      PubDate: 2016-04-29
      DOI: 10.1126/science.aad9945
  • [Report] Structure of a bd oxidase indicates similar mechanisms for
           membrane-integrated oxygen reductases
    • Authors: Schara Safarian
      Abstract: The cytochrome bd oxidases are terminal oxidases that are present in bacteria and archaea. They reduce molecular oxygen (dioxygen) to water, avoiding the production of reactive oxygen species. In addition to their contribution to the proton motive force, they mediate viability under oxygen-related stress conditions and confer tolerance to nitric oxide, thus contributing to the virulence of pathogenic bacteria. Here we present the atomic structure of the bd oxidase from Geobacillus thermodenitrificans, revealing a pseudosymmetrical subunit fold. The arrangement and order of the heme cofactors support the conclusions from spectroscopic measurements that the cleavage of the dioxygen bond may be mechanistically similar to that in the heme-copper–containing oxidases, even though the structures are completely different.
      Authors : Schara Safarian, Chitra Rajendran, Hannelore Müller, Julia Preu, Julian D. Langer, Sergey Ovchinnikov, Taichiro Hirose, Tomoichirou Kusumoto, Junshi Sakamoto, Hartmut Michel
      PubDate: 2016-04-29
      DOI: 10.1126/science.aaf2477
  • [Report] Conformational photoswitching of a synthetic peptide foldamer
           bound within a phospholipid bilayer
    • Authors: Matteo De Poli
      Abstract: The dynamic properties of foldamers, synthetic molecules that mimic folded biomolecules, have mainly been explored in free solution. We report on the design, synthesis, and conformational behavior of photoresponsive foldamers bound in a phospholipid bilayer akin to a biological membrane phase. These molecules contain a chromophore, which can be switched between two configurations by different wavelengths of light, attached to a helical synthetic peptide that both promotes membrane insertion and communicates conformational change along its length. Light-induced structural changes in the chromophore are translated into global conformational changes, which are detected by monitoring the solid-state 19F nuclear magnetic resonance signals of a remote fluorine-containing residue located 1 to 2 nanometers away. The behavior of the foldamers in the membrane phase is similar to that of analogous compounds in organic solvents.
      Authors : Matteo De Poli, Wojciech Zawodny, Ophélie Quinonero, Mark Lorch, Simon J. Webb, Jonathan Clayden
      PubDate: 2016-04-29
      DOI: 10.1126/science.aad8352
  • [Report] Kinetically controlled E-selective catalytic olefin metathesis
    • Authors: Thach T. Nguyen
      Abstract: A major shortcoming in olefin metathesis, a chemical process that is central to research in several branches of chemistry, is the lack of efficient methods that kinetically favor E isomers in the product distribution. Here we show that kinetically E-selective cross-metathesis reactions may be designed to generate thermodynamically disfavored alkenyl chlorides and fluorides in high yield and with exceptional stereoselectivity. With 1.0 to 5.0 mole % of a molybdenum-based catalyst, which may be delivered in the form of air- and moisture-stable paraffin pellets, reactions typically proceed to completion within 4 hours at ambient temperature. Many isomerically pure E-alkenyl chlorides, applicable to catalytic cross-coupling transformations and found in biologically active entities, thus become easily and directly accessible. Similarly, E-alkenyl fluorides can be synthesized from simpler compounds or more complex molecules.
      Authors : Thach T. Nguyen, Ming Joo Koh, Xiao Shen, Filippo Romiti, Richard R. Schrock, Amir H. Hoveyda
      PubDate: 2016-04-29
      DOI: 10.1126/science.aaf4622
  • [Report] Population-based metagenomics analysis reveals markers for gut
           microbiome composition and diversity
    • Authors: Alexandra Zhernakova
      Abstract: Deep sequencing of the gut microbiomes of 1135 participants from a Dutch population-based cohort shows relations between the microbiome and 126 exogenous and intrinsic host factors, including 31 intrinsic factors, 12 diseases, 19 drug groups, 4 smoking categories, and 60 dietary factors. These factors collectively explain 18.7% of the variation seen in the interindividual distance of microbial composition. We could associate 110 factors to 125 species and observed that fecal chromogranin A (CgA), a protein secreted by enteroendocrine cells, was exclusively associated with 61 microbial species whose abundance collectively accounted for 53% of microbial composition. Low CgA concentrations were seen in individuals with a more diverse microbiome. These results are an important step toward a better understanding of environment-diet-microbe-host interactions.
      Authors : Alexandra Zhernakova, Alexander Kurilshikov, Marc Jan Bonder, Ettje F. Tigchelaar, Melanie Schirmer, Tommi Vatanen, Zlatan Mujagic, Arnau Vich Vila, Gwen Falony, Sara Vieira-Silva, Jun Wang, Floris Imhann, Eelke Brandsma, Soesma A. Jankipersadsing, Marie Joossens, Maria Carmen Cenit, Patrick Deelen, Morris A. Swertz, , Rinse K. Weersma, Edith J. M. Feskens, Mihai G. Netea, Dirk Gevers, Daisy Jonkers, Lude Franke, Yurii S. Aulchenko, Curtis Huttenhower, Jeroen Raes, Marten H. Hofker, Ramnik J. Xavier, Cisca Wijmenga, Jingyuan Fu
      PubDate: 2016-04-29
      DOI: 10.1126/science.aad3369
  • [Perspective] Liquidity in immune cell signaling
    • Authors: Michael L. Dustin
      Abstract: Tlymphocytes of the immune system need to integrate myriad signals to decide on life and death matters in defending the host from pathogens and in distinguishing normal from transformed cells, all while minimizing immunopathology. On page 595 in this issue, Su et al. (1) provide insight into how phase separation of signaling proteins in the two-dimensional (2D) liquid of the plasma membrane enables these critical decisions.
      Authors : Michael L. Dustin, James Muller
      Keywords: Cell Signaling
      PubDate: 2016-04-29
      DOI: 10.1126/science.aaf8179
  • [Special Issue Review] How colonization by microbiota in early life shapes
           the immune system
    • Authors: Thomas Gensollen
      Abstract: Microbial colonization of mucosal tissues during infancy plays an instrumental role in the development and education of the host mammalian immune system. These early-life events can have long-standing consequences: facilitating tolerance to environmental exposures or contributing to the development of disease in later life, including inflammatory bowel disease, allergy, and asthma. Recent studies have begun to define a critical period during early development in which disruption of optimal host-commensal interactions can lead to persistent and in some cases irreversible defects in the development and training of specific immune subsets. Here, we discuss the role of early-life education of the immune system during this “window of opportunity,” when microbial colonization has a potentially critical impact on human health and disease.
      Authors : Thomas Gensollen, Shankar S. Iyer, Dennis L. Kasper, Richard S. Blumberg
      PubDate: 2016-04-29
      DOI: 10.1126/science.aad9378
  • [Special Issue Perspective] Antibiotic use and its consequences for the
           normal microbiome
    • Authors: Martin J. Blaser
      Abstract: Anti-infectives, including antibiotics, are essentially different from all other drugs; they not only affect the individual to whom they are given but also the entire community, through selection for resistance to their own action. Thus, their use resides at the intersection of personal and public health. Antibiotics can be likened to a four-edged sword against bacteria. The first two edges of the antibiotic sword were identified immediately after their discovery and deployment in that they not only benefit an individual in treating their infection but also benefit the community in preventing the spread of that infectious agent. The third edge was already recognized by Alexander Fleming in 1945 in his Nobel acceptance speech, which warned about the cost to the community of antibiotic resistance that would inevitably evolve and be selected for during clinical practice. We have seen this cost mount up, as resistance curtails or precludes the activities of some of our most effective drugs for clinically important infections. But the fourth edge of the antibiotic sword remained unappreciated until recently, i.e., the cost that an antibiotic exerts on an individual’s own health via the collateral damage of the drug on bacteria that normally live on or in healthy humans: our microbiota. These organisms, their genes, metabolites, and interactions with one another, as well as with their host collectively, represent our microbiome. Our relationship with these symbiotic bacteria is especially important during the early years of life, when the adult microbiome has not yet formed. Author: Martin J. Blaser
      PubDate: 2016-04-29
      DOI: 10.1126/science.aad9358
  • [Perspective] A fresh eye on nonequilibrium systems
    • Authors: Jean-Francois Rupprecht
      Abstract: According to the physicist Richard Feynman, a system is in equilibrium when “all the fast things have happened but the slow things have not” (1). This definition really applies to a system at steady state, which can either be in thermodynamic equilibrium or in a nonequilibrium steady state. Most systems in nature are not in equilibrium; they exchange fluxes of matter or energy with their surroundings or undergo chemical reactions. When the fast “things” have happened but the slow ones have not, such systems are in a nonequilibrium steady state. The properties of nonequilibrium steady states are currently under intense theoretical investigation, and their similarities and differences with thermodynamic equilibrium states are starting to emerge (2). On page 604 of this issue, Battle et al. (3) propose a new way of probing the nonequilibrium nature of an apparent steady state and demonstrate how such nonequilibrium dynamics can be identified.
      Authors : Jean-Francois Rupprecht, Jacques Prost
      Keywords: Physical Biology
      PubDate: 2016-04-29
      DOI: 10.1126/science.aaf4611
  • [Association Affairs] Marijuana policy patchwork not based on science
    • Authors: Michaela Jarvis
      Abstract: Meanwhile, federal laws hobble research into the dangers, and the potential benefits, of the drug Author: Michaela Jarvis
      PubDate: 2016-04-29
      DOI: 10.1126/science.352.6285.529
  • [Introduction to Special Issue] Manipulating the Microbiota
    • Authors: Caroline Ash
      Authors : Caroline Ash, Kristen Mueller
      PubDate: 2016-04-29
      DOI: 10.1126/science.352.6285.530
  • [Special Issue Review] Cross-species comparisons of host genetic
           associations with the microbiome
    • Authors: Julia K. Goodrich
      Abstract: Recent studies in human populations and mouse models reveal notable congruences in gut microbial taxa whose abundances are partly regulated by host genotype. Host genes associating with these taxa are related to diet sensing, metabolism, and immunity. These broad patterns are further validated in similar studies of nonmammalian microbiomes. The next generation of genome-wide association studies will expand the size of the data sets and refine the microbial phenotypes to fully capture these intriguing signatures of host-microbiome coevolution.
      Authors : Julia K. Goodrich, Emily R. Davenport, Jillian L. Waters, Andrew G. Clark, Ruth E. Ley
      PubDate: 2016-04-29
      DOI: 10.1126/science.aad9379
  • [Special Issue Review] Resurrecting the intestinal microbiota to combat
           antibiotic-resistant pathogens
    • Authors: Eric G. Pamer
      Abstract: The intestinal microbiota, which is composed of diverse populations of commensal bacterial species, provides resistance against colonization and invasion by pathogens. Antibiotic treatment can damage the intestinal microbiota and, paradoxically, increase susceptibility to infections. Reestablishing microbiota-mediated colonization resistance after antibiotic treatment could markedly reduce infections, particularly those caused by antibiotic-resistant bacteria. Ongoing studies are identifying commensal bacterial species that can be developed into next-generation probiotics to reestablish or enhance colonization resistance. These live medicines are at various stages of discovery, testing, and production and are being subjected to existing regulatory gauntlets for eventual introduction into clinical practice. The development of next-generation probiotics to reestablish colonization resistance and eliminate potential pathogens from the gut is warranted and will reduce health care–associated infections caused by highly antibiotic-resistant bacteria. Author: Eric G. Pamer
      PubDate: 2016-04-29
      DOI: 10.1126/science.aad9382
  • [Letter] Wolbachia mosquito control: Tested
    • Authors: Scott L. O'Neill
      Abstract: Author: Scott L. O'Neill
      PubDate: 2016-04-29
      DOI: 10.1126/science.352.6285.526-a
  • [Letter] Wolbachia mosquito control: Regulated
    • Authors: Stephen L. Dobson
      Authors : Stephen L. Dobson, Seth R. Bordenstein, Robert I. Rose
      PubDate: 2016-04-29
      DOI: 10.1126/science.352.6285.526-b
  • [Technical Comment] Comment on “Extended-resolution structured
           illumination imaging of endocytic and cytoskeletal dynamics”
    • Authors: Steffen J. Sahl
      Abstract: Li et al. (Research Articles, 28 August 2015, aab3500) purport to present solutions to long-standing challenges in live-cell microscopy, reporting relatively fast acquisition times in conjunction with improved image resolution. We question the methods’ reliability to visualize specimen features at sub–100-nanometer scales, because the mandatory mathematical processing of the recorded data leads to artifacts that are either difficult or impossible to disentangle from real features. We are also concerned about the chosen approach of subjectively comparing images from different super-resolution methods, as opposed to using quantitative measures.
      Authors : Steffen J. Sahl, Francisco Balzarotti, Jan Keller-Findeisen, Marcel Leutenegger, Volker Westphal, Alexander Egner, Flavie Lavoie-Cardinal, Andriy Chmyrov, Tim Grotjohann, Stefan Jakobs
      PubDate: 2016-04-29
      DOI: 10.1126/science.aad7983
  • [Technical Response] Response to Comment on “Extended-resolution
           structured illumination imaging of endocytic and cytoskeletal
    • Authors: Dong Li
      Abstract: Sahl et al. in their Comment raise criticisms of our work that fall into three classes: image artifacts, resolution criteria, and comparative performance on live cells. We explore each of these in turn.
      Authors : Dong Li, Eric Betzig
      PubDate: 2016-04-29
      DOI: 10.1126/science.aad8396
  • [Letter] Online buzz: Bureaucracy or accountability?
    • Keywords: Online Buzz
      PubDate: 2016-04-29
      DOI: 10.1126/science.352.6285.527-c
  • [Book Review] After Ebola
    • Authors: Christopher Kemp
      Abstract: Since the beginning of the Industrial Age, humans have been perturbing the natural world in ways that bring us closer to the pathogens that kill us. Often, we are not their intended host. But we'll do. In Pandemic, journalist Sonia Shah explores the biological, sociological and political factors that can ignite a global disease outbreak. "The next great contagion is out there: waiting, hiding, weaponizing," writes reviewer Christopher Kemp. Will we be ready? Author: Christopher Kemp
      Keywords: Epidemiology
      PubDate: 2016-04-29
      DOI: 10.1126/science.aaf6279
  • [Book Review] Animal acumen
    • Authors: Nicola Clayton
      Abstract: Ever since the seminal writings of Charles Darwin, it has been well established that minds, like bodies, have evolved through the processes of natural and sexual selection. As a consequence, Darwin himself once argued that any difference between human and nonhuman animals "is one of degree, not kind." In Are We Smart Enough to Know How Smart Animals Are?, primatologist Frans de Waal explores whether our mode of investigating animal cognition is inherently biased against manifestations of intelligence that are decidedly non-humanlike. Reviewer Nicola Clayton praises the book as "inspiring," while acknowledging that its provocative premise will likely inflame skeptics. Author: Nicola Clayton
      Keywords: Ethology
      PubDate: 2016-04-29
      DOI: 10.1126/science.aaf2217
  • [Book Review] Wellcome Book Prize winner
    • Abstract: On 25 April, the Wellcome Book Prize 2016 was awarded to Suzanne O'Sullivan for her probing portrait of psychosomatic illness, It's All in Your Head. Inspired by O'Sullivan's work as a neurology consultant, the book explores the dramatic symptoms— from blindness to paralysis to chronic fatigue—that can arise in the absence of any discernible physical cause. Billed as "books for the incurably curious," the Wellcome Book Prize recognizes outstanding new titles in health and medicine.
      Keywords: Wellcome Book Prize Winner
      PubDate: 2016-04-29
      DOI: 10.1126/science.aaf6856
  • [Feature] Who's downloading pirated papers? Everyone
    • Authors: John Bohannon
      Abstract: In increasing numbers, researchers around the world are turning to Sci-Hub, the controversial website that hosts 50 million pirated papers and counting. Now, with server log data from Alexandra Elbakyan, the neuroscientist who created Sci-Hub in 2011 as a 22-year-old graduate student in Kazakhstan, Science addresses some basic questions: Who are Sci-Hub's users, where are they, and what are they reading? The Sci-Hub data provide the first detailed view of what is becoming the world's de facto open-access research library. Among the revelations that may surprise both fans and foes alike: Sci-Hub users are not limited to the developing world. Some critics of Sci-Hub have complained that many users can access the same papers through their libraries but turn to Sci-Hub instead—for convenience rather than necessity. The data provide some support for that claim. Over the 6 months leading up to March, Sci-Hub served up 28 million documents, with Iran, China, India, Russia, and the United States the leading requestors. Author: John Bohannon
      PubDate: 2016-04-29
      DOI: 10.1126/science.352.6285.508
  • [Feature] The frustrated science student behind Sci-Hub
    • Authors: John Bohannon
      Abstract: Beyond being the founder of Sci-Hub, the world's largest pirate site for academic papers, and risking arrest as a result, Alexandra Elbakyan is a typical science graduate student: idealistic, hard-working, and relatively poor. After becoming hooked on science at an early age, she discovered a knack for computer hacking when she went to university in Kazakhstan, where she was born. After a stint in Germany working on brain-computer interfaces, she returned home, where frustrations with journal paywalls led her to create Sci-Hub. She is now enrolled in a history of science master's program. Author: John Bohannon
      PubDate: 2016-04-29
      DOI: 10.1126/science.352.6285.511
  • [In Depth] Scandal clouds China's global vaccine ambitions
    • Authors: Kathleen McLaughlin
      Abstract: Health experts hail two new Chinese-made vaccines against hand, foot, and mouth disease as a milestone against a malady that has run rampant in China. But that triumph was overshadowed by a safety crisis involving other homegrown vaccines. In recent weeks, police have arrested more than 200 people in connection with the nationwide distribution of 2 million doses of expired Chinese-made vaccines against scourges such as hepatitis B and rabies. No adverse reactions have been confirmed. China's vaccine developers hope the debacle won't derail efforts to make inroads into the global $33 billion vaccine market. But without a major overhaul, China's vaccine system might not recover quickly. Author: Kathleen McLaughlin
      Keywords: Infectious Disease
      PubDate: 2016-04-29
      DOI: 10.1126/science.352.6285.506
  • [In Depth] Mexico struggles to woo expat genome jocks
    • Authors: Lizzie Wade
      Abstract: Over the last 10 years, Mexico has invested heavily in training young scientists in genomics and sent many promising students abroad for Ph.D.s and postdocs. The new International Laboratory for Human Genome Research (LIIGH) in Juriquilla, Mexico, which celebrated its first anniversary this month, was built to bring home some of these rising stars. But returnees have been stymied by limited funding and a stifling bureaucracy, and many end up longing for the comparative ease of doing research in the United States and Europe. LIIGH is a testimony to Mexico's eagerness to build homegrown expertise in genomics—and to the challenges it faces to fully realize its potential. Author: Lizzie Wade
      Keywords: Brain Drain
      PubDate: 2016-04-29
      DOI: 10.1126/science.352.6285.507
  • [In Depth] Kepler enlists relativity to find planets
    • Authors: Daniel Clery
      Abstract: Back in business after a heart-stopping near-shutdown in April, NASA's Kepler space telescope is about to begin an 80-day campaign to search for exoplanets using a novel technique. Called gravitational microlensing, it's based on Einstein's discovery that gravity bends light. That means massive objects in space can act as lenses, focusing the light from objects even farther from Earth. Astronomers have found many cases in which galaxies distort the images of quasars. Microlensing works on a much smaller scale: Individual stars or planets focus the light of more distant stars, making the background star appear to grow brighter and then dim again. By measuring those rising and falling "light curves," Kepler will give astronomers valuable information about planets orbiting other stars—including exoplanets in far-out orbits that other techniques can't detect—and even free-floating planets that don't orbit stars at all. Author: Daniel Clery
      Keywords: Astronomy
      PubDate: 2016-04-29
      DOI: 10.1126/science.352.6285.504
  • [Business Office Feature] Adding efficiency to general lab equipment
    • Authors: Mike May
      Abstract: Sometimes the latest equipment in a laboratory, say a next-generation sequencer, grabs lots of attention, but it's the workhorses—centrifuges, hoods, freezers, incubators, and more—that keep experiments and workflows moving. These general lab tools often determine how smoothly andcost effectively a lab runs. In large part, the results can be measured in one word—efficiency. In this case, efficiency means saving energy and time.Read the Feature (Full-Text HTML)Read the Feature (PDF)Read New Products (PDF) Author: Mike May
      Keywords: Business Office Feature
      PubDate: 2016-04-29
      DOI: 10.1126/science.352.6285.614
  • [New Products] New Products
    • Abstract: A weekly roundup of information on newly offered instrumentation, apparatus, and laboratory materials of potential interest to researchers.
      PubDate: 2016-04-29
      DOI: 10.1126/science.352.6285.617
  • [Working Life] The hidden perks of grad school
    • Authors: Nathan Johnson
      Abstract: Author: Nathan Johnson
      PubDate: 2016-04-29
      DOI: 10.1126/science.352.6285.622
  • [In Depth] Critics complain as U.S. shops in Iran's nuclear bazaar
    • Authors: Richard Stone
      Abstract: Mere months ago, Iran's nuclear program was an international pariah. Now, it's supplying the U.S. Department of Energy (DOE) with a strategic substance that the United States can't produce. Defying criticism, DOE last week consummated a deal to purchase 32 tons of heavy water—water containing the hydrogen isotope deuterium—from Iran. The $8.6 million sale helps Iran meet a commitment under last July's nuclear deal to shed heavy water, and it will have a swords-to-ploughshares payoff. DOE will resell a portion to industry for uses such as nuclear magnetic resonance imaging and protecting optical fibers against deterioration, and it will send 6 tons to Oak Ridge National Laboratory in Tennessee for an upgrade of the Spallation Neutron Source, an accelerator that generates powerful accelerator beams of neutrons for research. Author: Richard Stone
      Keywords: Arms Control
      PubDate: 2016-04-29
      DOI: 10.1126/science.352.6285.502
  • [In Depth] Saying no to harassment
    • Authors: Ann Gibbons
      Abstract: The field of physical anthropology recently has been convulsed by several high profile cases of alleged sexual harassment, and by a survey of field scientists showing that harassment during fieldwork is common. So when physical anthropologists gathered last week at their annual meeting, reducing such problems was high on the agenda. But how to change the culture of a discipline? Meeting organizers and advocates offered a menu of actions to battle harassment, from symbolic to concrete. All meeting registrants were required to agree to the American Association of Physical Anthropologists's code of ethics, and panels and workshops offered specific suggestions to women describing incidents of harassment and discrimination.
      Authors : Ann Gibbons, Elizabeth Culotta
      Keywords: Scientific Community
      PubDate: 2016-04-29
      DOI: 10.1126/science.352.6285.503
  • [In Depth] How Europe exported the Black Death
    • Authors: Andrew Lawler
      Abstract: Black Death—the bubonic plague—probably reached Europe from Asia in 1346, and later outbreaks were thought to have arrived from the east via a similar route. Now, scientists have evidence that a virulent strain of the Black Death bacterium lurked for centuries in Europe while also working its way back to Asia. At the recent Society for American Archaeology meeting, researchers reported analyzing the remains of medieval victims in London; Barcelona, Spain; and near the Volga River in Russia. They determined that the victims all died of a highly similar strain of Yersinia pestis, the plague bacterium, which had mutated in Europe and then traveled eastward. A descendant of the 14th century plague may also have caused more recent outbreaks, in East Asia in the 19th and 20th centuries and in Madagascar today. Author: Andrew Lawler
      Keywords: Ancient DNA
      PubDate: 2016-04-29
      DOI: 10.1126/science.352.6285.501
  • [In Brief] News at a glance
    • Abstract: In science news around the world, the European Commission pledges €1 billion for its third Flagship project, quantum technologies, the German government extends funding for its Excellence Initiative to create a German "Ivy League" indefinitely, an independent report finds that the Mexican government obstructed an investigation into the disappearance of 43 students from a rural teaching college in 2014, the Spanish National Research Council pushes back against lawsuits levied by postdoc and other employees seeking permanent employment, and more. Also, Science talks with Nobel laureate Richard Roberts about an upcoming science diplomacy mission to North Korea. And a sophisticated new wind tunnel constructed at Stanford University in Palo Alto, California, aims to capture the details of bird flight—and could help drone engineers design more maneuverable machines.
      Keywords: SCI COMMUN
      PubDate: 2016-04-29
      DOI: 10.1126/science.352.6285.498
  • [Editorial] My love-hate of Sci-Hub
    • Authors: Marcia McNutt
      Abstract: Like many scientist-editors of journals published by nonprofit scientific societies, I have a love-hate relationship with Sci-Hub, the website operated out of Russia that provides access to 50 million pirated scientific articles to researchers worldwide (see the News story on p. 508). I recognize the underlying motivation of bringing global research content to the developing world. However, I also recognize that much traffic to Sci-Hub is from researchers who already have access to the articles they seek through mechanisms such as site licenses, open access, or other means.
      Authors who publish in Science journals, for example, can make their papers available immediately upon publication through free referrer links at the authors' websites. Research published after 1996 in a Science journal is made free with registration 1 year after its publication date. So what does the scientific community risk by gathering papers illegally? Author: Marcia McNutt
      PubDate: 2016-04-29
      DOI: 10.1126/science.aaf9419
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