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Journal Cover Science
  [SJR: 13.217]   [H-I: 915]   [3064 followers]  Follow
   Full-text available via subscription Subscription journal  (Not entitled to full-text)
   ISSN (Print) 0036-8075 - ISSN (Online) 1095-9203
   Published by AAAS Homepage  [6 journals]
  • [Research Article] Cell-wide analysis of protein thermal unfolding reveals
           determinants of thermostability
    • Authors: Pascal Leuenberger
      Abstract: Temperature-induced cell death is thought to be due to protein denaturation, but the determinants of thermal sensitivity of proteomes remain largely uncharacterized. We developed a structural proteomic strategy to measure protein thermostability on a proteome-wide scale and with domain-level resolution. We applied it to Escherichia coli, Saccharomyces cerevisiae, Thermus thermophilus, and human cells, yielding thermostability data for more than 8000 proteins. Our results (i) indicate that temperature-induced cellular collapse is due to the loss of a subset of proteins with key functions, (ii) shed light on the evolutionary conservation of protein and domain stability, and (iii) suggest that natively disordered proteins in a cell are less prevalent than predicted and (iv) that highly expressed proteins are stable because they are designed to tolerate translational errors that would lead to the accumulation of toxic misfolded species.
      Authors : Pascal Leuenberger, Stefan Ganscha, Abdullah Kahraman, Valentina Cappelletti, Paul J. Boersema, Christian von Mering, Manfred Claassen, Paola Picotti
      PubDate: 2017-02-24
      DOI: 10.1126/science.aai7825
  • [Research Article] The [4Fe4S] cluster of human DNA primase functions as a
           redox switch using DNA charge transport
    • Authors: Elizabeth O’Brien
      Abstract: DNA charge transport chemistry offers a means of long-range, rapid redox signaling. We demonstrate that the [4Fe4S] cluster in human DNA primase can make use of this chemistry to coordinate the first steps of DNA synthesis. Using DNA electrochemistry, we found that a change in oxidation state of the [4Fe4S] cluster acts as a switch for DNA binding. Single-atom mutations that inhibit this charge transfer hinder primase initiation without affecting primase structure or polymerization. Generating a single base mismatch in the growing primer duplex, which attenuates DNA charge transport, inhibits primer truncation. Thus, redox signaling by [4Fe4S] clusters using DNA charge transport regulates primase binding to DNA and illustrates chemistry that may efficiently drive substrate handoff between polymerases during DNA replication.
      Authors : Elizabeth O’Brien, Marilyn E. Holt, Matthew K. Thompson, Lauren E. Salay, Aaron C. Ehlinger, Walter J. Chazin, Jacqueline K. Barton
      PubDate: 2017-02-24
      DOI: 10.1126/science.aag1789
  • [Review] Mechanisms for initiating cellular DNA replication
    • Authors: Franziska Bleichert
      Abstract: Cellular DNA replication factories depend on ring-shaped hexameric helicases to aid DNA synthesis by processively unzipping the parental DNA helix. Replicative helicases are loaded onto DNA by dedicated initiator, loader, and accessory proteins during the initiation of DNA replication in a tightly regulated, multistep process. We discuss here the molecular choreography of DNA replication initiation across the three domains of life, highlighting similarities and differences in the strategies used to deposit replicative helicases onto DNA and to melt the DNA helix in preparation for replisome assembly. Although initiators and loaders are phylogenetically related, the mechanisms they use for accomplishing similar tasks have diverged considerably and in an unpredictable manner.
      Authors : Franziska Bleichert, Michael R. Botchan, James M. Berger
      PubDate: 2017-02-24
      DOI: 10.1126/science.aah6317
  • [Editorial] Approving new drugs
    • Authors: John L. LaMattina
      Abstract: As the Trump administration takes shape, there is much speculation as to what major changes will be made. A dominant theme of the Trump campaign was to cut through bureaucracy in Washington, D.C., thereby enhancing innovation and bringing new technology to Americans more quickly. Nowhere could such a philosophical change have more impact than on Food and Drug Administration (FDA) approval of new drugs.Author: John L. LaMattina
      PubDate: 2017-02-24
      DOI: 10.1126/science.aam9914
  • [In Brief] News at a glance
    • Abstract: In science news around the world, China sees a spike in cases of H7N9 infection, India plans a follow-up Mars mission and considers a mission to Venus, the U.S. Department of Agriculture restores some of the tens of thousands of animal welfare documents scrubbed from its website earlier this month, NASA says its Juno spacecraft will remain in a long orbit around Jupiter to avoid possible engine misfire, and more. Also, the U.S. Senate confirms former Oklahoma Attorney General Scott Pruitt as Environmental Protection Agency administrator. And Science rounds up some of the research highlights from the AAAS annual meeting.
      Keywords: SCI COMMUN
      PubDate: 2017-02-24
      DOI: 10.1126/science.355.6327.778
  • [In Depth] California rains put spotlight on atmospheric rivers
    • Authors: Julia Rosen
      Abstract: In just a few months, California has moved from extreme drought to dangerous flooding, thanks to atmospheric rivers: long, narrow ribbons of water vapor in the sky. Just a few hundred kilometers wide, atmospheric rivers stretch thousands of kilometers from the tropical oceans toward the poles, carrying up to 20 times as much water as the Mississippi River. That moisture gets tugged along by the windy paddle wheels of spinning storms ahead of its path. When the atmospheric rivers make landfall and the vapor condenses, they can release a staggering amount of rain and snow. Scientists are now working to unravel their physics so that they can provide better forecasts, both now and in a future, hotter world. For dry, midlatitude regions like California, any changes could have a profound impact.Author: Julia Rosen
      Keywords: Atmospheric Science
      PubDate: 2017-02-24
      DOI: 10.1126/science.355.6327.787
  • [Perspective] A Mesozoic aviary
    • Authors: Stephen L. Brusatte
      Abstract: The evolution of birds from a group of small dinosaurs between 170 million and 150 million years ago has emerged as a textbook example of a major evolutionary transformation in the fossil record (1). The attainment of powered flight—that is, active flapping that generates thrust—has been widely regarded, sometimes explicitly but often implicitly, as a long evolutionary march in which natural selection progressively refined one subgroup of dinosaurs into ever-better aerialists. However, recent fossil discoveries reveal a much more interesting story that is beginning to be corroborated by biomechanical studies. According to this story, the development of flight was chaotic, with different dinosaurs experimenting with different airborne behaviors using different airfoil and feather arrangements (see the figure), until ultimately only modern birds survived.Author: Stephen L. Brusatte
      Keywords: Paleontology
      PubDate: 2017-02-24
      DOI: 10.1126/science.aal2397
  • [Perspective] Quantifying protein (dis)order
    • Authors: Christine Vogel
      Abstract: Twenty-five years ago, Chothia predicted that the structural domains of all proteins can be classified into about 1000 folds (1). Later studies refined this number; however, scientists also found that some proteins or parts of proteins never assume a specific fold. These regions are called intrinsically unstructured or disordered (2). Oncogenes such as p53 or breast cancer 1 (BRCA1) contain long disordered stretches, and aggregation of the disordered α-synuclein is thought to underlie Parkinson's and Alzheimer's diseases (3, 4). On page 812 of this issue, Leuenberger et al. (5) map the thermodynamic stabilities of more than 8000 proteins across four organisms, providing insights not only into the evolution of protein structure and expression in cells but also into possible molecular causes and consequences of human disease.Author: Christine Vogel
      Keywords: Proteome
      PubDate: 2017-02-24
      DOI: 10.1126/science.aam8036
  • [Perspective] Why tolerance invites resistance
    • Authors: Kim Lewis
      Abstract: Bacteria use two strategies to avoid being killed by antibiotics: resistance and tolerance. Resistance mechanisms such as destruction of a drug or modification of its target allow bacteria to grow in the presence of antibiotics. Tolerance is a property of dormant, nongrowing bacterial cells in which antibiotic targets are inactive, allowing bacteria to survive. The two phenomena are mechanistically distinct and assumed to be unrelated. On page 826 of this issue, Levin-Reisman et al. (1) show that tolerance nevertheless leads to resistance.
      Authors : Kim Lewis, Yue Shan
      Keywords: Infectious Disease
      PubDate: 2017-02-24
      DOI: 10.1126/science.aam7926
  • [Perspective] Molecular stitches for enhanced recycling of packaging
    • Authors: Costantino Creton
      Abstract: Polymers made of even slightly different repeat units are usually immiscible and form materials with two separate phases, like oil and water. Not only do different polymers not mix, but the interfaces between them are very sharp and mechanically weak. This lack of interfacial strength poses a very serious challenge to the recycling of blends of different polymers and, notably, polyethylene (PE) and isotactic polypropylene (iPP), the two polymers most commonly found in the industrial and domestic waste that come from packaging. If these two tough polymers are simply blended together, the resulting material is brittle and cannot be used. On page 814 of this issue, Eagan et al. (1) report that adding just 1% of a suitable block copolymer—a chain of PE connected to a chain of iPP—can create molecular stitches between the two phases and make the resulting blend as tough as iPP and PE themselves.Author: Costantino Creton
      Keywords: Polymers
      PubDate: 2017-02-24
      DOI: 10.1126/science.aam5803
  • [Perspective] Hematopoietic stem cells gone rogue
    • Authors: Yanfang Peipei Zhu
      Abstract: Cardiovascular disease is considered to be an aging-related disease and is the leading cause of death in the elderly in developed countries (1). As of 2013, 65% of deaths attributed to cardiovascular disease occurred among patients 75 years and older. A hallmark of aging is the accumulation of somatic DNA mutations in proliferative tissue. Although somatic mutations in the hematopoietic (blood cell) system are frequently observed in patients with hematological cancers, there is also a close correlation between hematopoietic somatic mutations and increased incidence of diabetes, atherosclerosis, and cardiovascular disease-related deaths (2). On page 842 of this issue, Fuster et al. (3) report that somatic mutation in a gene called ten-eleven translocation 2 (Tet2) in hematopoietic stem cells increases atherosclerosis development in a mouse model.
      Authors : Yanfang Peipei Zhu, Catherine C. Hedrick, Dalia E. Gaddis
      Keywords: Cardiovascular Disease
      PubDate: 2017-02-24
      DOI: 10.1126/science.aam7939
  • [Perspective] Thomas Crombie Schelling (1921–2016)
    • Authors: Richard Zeckhauser
      Abstract: Thomas Schelling, the distinguished economist, died on 13 December 2016 at his home in Bethesda, Maryland. He was 95 years old. Schelling applied his prolific work in game theory to arms control and deterrence, negotiation strategy, and most recently, global warming. His strategic insights made the world a much safer place.Author: Richard Zeckhauser
      Keywords: Retrospective
      PubDate: 2017-02-24
      DOI: 10.1126/science.aam9079
  • [Policy Forum] To slow or not? Challenges in subsecond networks
    • Authors: Neil F. Johnson
      Abstract: Fall 2016 brought a fundamental change to the United States. Its fastest and largest network—the decentralized network of electronic market exchanges—began to experience its first ever intentional delay. Specifically, a 38-mile coil of fiber-optic cable was embedded into a new exchange network node, which, given the finite speed of light, introduced a systematic 350-µs (microsecond) delay in signal transmission (1). The future impacts this might have at the systems level are unknown.Author: Neil F. Johnson
      Keywords: Science and Business
      PubDate: 2017-02-24
      DOI: 10.1126/science.aai8618
  • [Book Review] Podcast
    • Authors: Craig A. Tovey
      Abstract: Author: Craig A. Tovey
      Keywords: Podcast
      PubDate: 2017-02-24
      DOI: 10.1126/science.aam9287
  • [Letter] Dams threaten rare Mekong dolphins
    • Authors: Robert L. Brownell
      Authors : Robert L. Brownell, Randall R. Reeves, Peter O. Thomas, Brian D. Smith, Gerard E. Ryan
      PubDate: 2017-02-24
      DOI: 10.1126/science.aam6406
  • [Letter] Photos belong in the taxonomic Code
    • Authors: André Rinaldo Senna Garraffoni
      Authors : André Rinaldo Senna Garraffoni, André Victor Lucci Freitas
      PubDate: 2017-02-24
      DOI: 10.1126/science.aam7686
  • [Letter] Lee Rubin: Our mentor and role model
    • Authors: Chantal Bazenet
      Authors : Chantal Bazenet, Howard Desmond, Eric Frank, Patrick Doherty, Andreas Eilers, Christine Gatchalian, Marcie Glicksman, Piotr Graczyk, Fabian Gusovsky, Jonathan Ham, David Kaplan, Michael Klymkoswsky, Karen Kotkow, Richard Krolewski, Paul Lang, Alison Linsley O'Neil, Mary Jane McCarthy, Karina Meiri, Freda Miller, Monica Mota Neumage, Ceren Ozek, Karen Philpott, Silvia Piccinotti, Feodor Price, Martin Raff, Marianne Ratcliffe, Jane Relton, Ken Rhodes, James Schwob, Caroline Smales, Terrence Smith, Cesare Spadoni, Joanne Taylor, Kostas Vekrellis, Jonny Whitfield
      PubDate: 2017-02-24
      DOI: 10.1126/science.aam8703
  • [Technical Comment] Comment on “Ducklings imprint on the relational
           concept of ‘same or different'”
    • Authors: Jean-Michel Hupé
      Abstract: Martinho and Kacelnik’s (Reports, 15 July 2016, p. 286) finding that mallard ducklings can deal with abstract concepts is important for understanding the evolution of cognition. However, a statistically more robust analysis of the data calls their conclusions into question. This example brings to light the risk of drawing too strong an inference by relying solely on P values.Author: Jean-Michel Hupé
      PubDate: 2017-02-24
      DOI: 10.1126/science.aah6047
  • [Technical Comment] Comment on “Ducklings imprint on the relational
           concept of ‘same or different’”
    • Authors: Jan Langbein
      Abstract: Martinho and Kacelnik (Reports, 15 July 2016, p. 286) reported that newly hatched ducklings imprinted on relational concepts. We argue that reanalyzing the data at the individual level shows that this conclusion cannot be applied for all sets of stimuli presented and that the ability to grasp relational concepts is limited to the stimulus category that is most beneficial for survival.
      Authors : Jan Langbein, Birger Puppe
      PubDate: 2017-02-24
      DOI: 10.1126/science.aai7431
  • [Technical Response] Response to Comments on “Ducklings imprint on the
           relational concept of ‘same or different’”
    • Authors: Antone Martinho
      Abstract: Two Comments by Hupé and by Langbein and Puppe address our choice of statistical analysis in assigning preference between sets of stimuli to individual ducklings in our paper. We believe that our analysis remains the most appropriate approach for our data and experimental design.
      Authors : Antone Martinho, Alex Kacelnik
      PubDate: 2017-02-24
      DOI: 10.1126/science.aai8397
  • [Association Affairs] New AAAS president emphasizes making the case for
    • Authors: Michaela Jarvis
      Abstract: Susan Hockfield has built support for major research initiativesAuthor: Michaela Jarvis
      PubDate: 2017-02-24
      DOI: 10.1126/science.355.6327.807
  • [This Week in Science] How will this molecule smell?
    • Authors: Peter Stern
      Abstract: Author: Peter Stern
      Keywords: Neuroscience
      PubDate: 2017-02-24
      DOI: 10.1126/science.355.6327.808-a
  • [This Week in Science] Bacterial battles on your skin
    • Authors: Lindsey Pujanandez
      Abstract: Author: Lindsey Pujanandez
      Keywords: Microbiome
      PubDate: 2017-02-24
      DOI: 10.1126/science.355.6327.808-b
  • [This Week in Science] Very clever bees use tools
    • Authors: Sacha Vignieri
      Abstract: Author: Sacha Vignieri
      Keywords: Cognition
      PubDate: 2017-02-24
      DOI: 10.1126/science.355.6327.808-c
  • [This Week in Science] Faulty blood cells and heart disease
    • Authors: Paula A. Kiberstis
      Abstract: Author: Paula A. Kiberstis
      Keywords: Vascular Disease
      PubDate: 2017-02-24
      DOI: 10.1126/science.355.6327.808-d
  • [This Week in Science] Spinning up an extragalactic neutron star
    • Authors: Keith T. Smith
      Abstract: Author: Keith T. Smith
      Keywords: Extreme Astrophysics
      PubDate: 2017-02-24
      DOI: 10.1126/science.355.6327.808-e
  • [This Week in Science] Shining a light on cell signaling
    • Authors: Valda Vinson
      Abstract: Author: Valda Vinson
      Keywords: Protein Design
      PubDate: 2017-02-24
      DOI: 10.1126/science.355.6327.808-f
  • [This Week in Science] How to make opposites compatible
    • Authors: Marc S. Lavine
      Abstract: Author: Marc S. Lavine
      Keywords: Polymers
      PubDate: 2017-02-24
      DOI: 10.1126/science.355.6327.808-g
  • [This Week in Science] How red berries reduce inflammation
    • Authors: John F. Foley
      Abstract: Author: John F. Foley
      Keywords: Inflammation
      PubDate: 2017-02-24
      DOI: 10.1126/science.355.6327.808-h
  • [This Week in Science] Diverse molecular choreography of replication
    • Authors: Guy Riddihough
      Authors : Guy Riddihough, Caroline Ash
      Keywords: DNA Replication
      PubDate: 2017-02-24
      DOI: 10.1126/science.355.6327.808-i
  • [This Week in Science] How proteomes take the heat
    • Authors: Valda Vinson
      Abstract: Author: Valda Vinson
      Keywords: Proteomics
      PubDate: 2017-02-24
      DOI: 10.1126/science.355.6327.808-j
  • [This Week in Science] DNA charged with regulating replication
    • Authors: Guy Riddihough
      Authors : Guy Riddihough, Jake Yeston
      Keywords: DNA Charge Transport
      PubDate: 2017-02-24
      DOI: 10.1126/science.355.6327.808-k
  • [This Week in Science] Resistance on a background of tolerance
    • Authors: Caroline Ash
      Abstract: Author: Caroline Ash
      Keywords: Antibiotic Resistance
      PubDate: 2017-02-24
      DOI: 10.1126/science.355.6327.808-l
  • [This Week in Science] What's in a fold?
    • Authors: Stella M. Hurtley
      Abstract: Author: Stella M. Hurtley
      Keywords: Toxic Amyloids
      PubDate: 2017-02-24
      DOI: 10.1126/science.355.6327.808-m
  • [This Week in Science] How dinosaurs took to the air
    • Authors: Julia Fahrenkamp-Uppenbrink
      Abstract: Author: Julia Fahrenkamp-Uppenbrink
      Keywords: Paleontology
      PubDate: 2017-02-24
      DOI: 10.1126/science.355.6327.808-n
  • [This Week in Science] Defining the tree rings of T cells
    • Authors: Anand Balasubramani
      Abstract: Author: Anand Balasubramani
      Keywords: Immunogenomics
      PubDate: 2017-02-24
      DOI: 10.1126/science.355.6327.808-o
  • [Editors' Choice] DNA methylation curbs mast cell response
    • Authors: Priscilla Kelly
      Abstract: Author: Priscilla Kelly
      Keywords: Mast Cells
      PubDate: 2017-02-24
      DOI: 10.1126/science.355.6327.809-a
  • [Editors' Choice] An old motif with new specificity
    • Authors: Valda Vinson
      Abstract: Author: Valda Vinson
      Keywords: RNA Design
      PubDate: 2017-02-24
      DOI: 10.1126/science.355.6327.809-b
  • [Editors' Choice] How tissues can take the heat
    • Authors: Laura M. Zahn
      Abstract: Author: Laura M. Zahn
      Keywords: Stress Response
      PubDate: 2017-02-24
      DOI: 10.1126/science.355.6327.809-c
  • [Editors' Choice] A supermassive black hole awakes
    • Authors: Keith M. Smith
      Abstract: Author: Keith M. Smith
      Keywords: Active Galaxies
      PubDate: 2017-02-24
      DOI: 10.1126/science.355.6327.809-d
  • [Editors' Choice] Polarity reversal during tissue remodeling
    • Authors: Megan Eldred
      Abstract: Author: Megan Eldred
      Keywords: Development
      PubDate: 2017-02-24
      DOI: 10.1126/science.355.6327.809-e
  • [Editors' Choice] CO2 reduction off base
    • Authors: Phil Szuromi
      Abstract: Author: Phil Szuromi
      Keywords: Electrochemistry
      PubDate: 2017-02-24
      DOI: 10.1126/science.355.6327.809-f
  • [Editors' Choice] How animals sense CO2 in blood
    • Authors: Julia Fahrenkamp-Uppenbrink
      Abstract: Author: Julia Fahrenkamp-Uppenbrink
      Keywords: Evolution
      PubDate: 2017-02-24
      DOI: 10.1126/science.355.6327.809-g
  • [Report] Combining polyethylene and polypropylene: Enhanced performance
           with PE/iPP multiblock polymers
    • Authors: James M. Eagan
      Abstract: Polyethylene (PE) and isotactic polypropylene (iPP) constitute nearly two-thirds of the world’s plastic. Despite their similar hydrocarbon makeup, the polymers are immiscible with one another. Thus, common grades of PE and iPP do not adhere or blend, creating challenges for recycling these materials. We synthesized PE/iPP multiblock copolymers using an isoselective alkene polymerization initiator. These polymers can weld common grades of commercial PE and iPP together, depending on the molecular weights and architecture of the block copolymers. Interfacial compatibilization of phase-separated PE and iPP with tetrablock copolymers enables morphological control, transforming brittle materials into mechanically tough blends.
      Authors : James M. Eagan, Jun Xu, Rocco Di Girolamo, Christopher M. Thurber, Christopher W. Macosko, Anne M. LaPointe, Frank S. Bates, Geoffrey W. Coates
      PubDate: 2017-02-24
      DOI: 10.1126/science.aah5744
  • [Report] An accreting pulsar with extreme properties drives an
           ultraluminous x-ray source in NGC 5907
    • Authors: Gian Luca Israel
      Abstract: Ultraluminous x-ray sources (ULXs) in nearby galaxies shine brighter than any x-ray source in our Galaxy. ULXs are usually modeled as stellar-mass black holes (BHs) accreting at very high rates or intermediate-mass BHs. We present observations showing that NGC 5907 ULX is instead an x-ray accreting neutron star (NS) with a spin period evolving from 1.43 seconds in 2003 to 1.13 seconds in 2014. It has an isotropic peak luminosity of ~1000 times the Eddington limit for a NS at 17.1 megaparsec. Standard accretion models fail to explain its luminosity, even assuming beamed emission, but a strong multipolar magnetic field can describe its properties. These findings suggest that other extreme ULXs (x-ray luminosity ≥ 1041 erg second −1) might harbor NSs.
      Authors : Gian Luca Israel, Andrea Belfiore, Luigi Stella, Paolo Esposito, Piergiorgio Casella, Andrea De Luca, Martino Marelli, Alessandro Papitto, Matteo Perri, Simonetta Puccetti, Guillermo A. Rodríguez Castillo, David Salvetti, Andrea Tiengo, Luca Zampieri, Daniele D’Agostino, Jochen Greiner, Frank Haberl, Giovanni Novara, Ruben Salvaterra, Roberto Turolla, Mike Watson, Joern Wilms, Anna Wolter
      PubDate: 2017-02-24
      DOI: 10.1126/science.aai8635
  • [Report] Predicting human olfactory perception from chemical features of
           odor molecules
    • Authors: Andreas Keller
      Abstract: It is still not possible to predict whether a given molecule will have a perceived odor or what olfactory percept it will produce. We therefore organized the crowd-sourced DREAM Olfaction Prediction Challenge. Using a large olfactory psychophysical data set, teams developed machine-learning algorithms to predict sensory attributes of molecules based on their chemoinformatic features. The resulting models accurately predicted odor intensity and pleasantness and also successfully predicted 8 among 19 rated semantic descriptors (“garlic,” “fish,” “sweet,” “fruit,” “burnt,” “spices,” “flower,” and “sour”). Regularized linear models performed nearly as well as random forest–based ones, with a predictive accuracy that closely approaches a key theoretical limit. These models help to predict the perceptual qualities of virtually any molecule with high accuracy and also reverse-engineer the smell of a molecule.
      Authors : Andreas Keller, Richard C. Gerkin, Yuanfang Guan, Amit Dhurandhar, Gabor Turu, Bence Szalai, Joel D. Mainland, Yusuke Ihara, Chung Wen Yu, Russ Wolfinger, Celine Vens, Leander Schietgat, Kurt De Grave, Raquel Norel, , Gustavo Stolovitzky, Guillermo A. Cecchi, Leslie B. Vosshall, Pablo Meyer
      PubDate: 2017-02-24
      DOI: 10.1126/science.aal2014
  • [Report] Antibiotic tolerance facilitates the evolution of resistance
    • Authors: Irit Levin-Reisman
      Abstract: Controlled experimental evolution during antibiotic treatment can help to explain the processes leading to antibiotic resistance in bacteria. Recently, intermittent antibiotic exposures have been shown to lead rapidly to the evolution of tolerance—that is, the ability to survive under treatment without developing resistance. However, whether tolerance delays or promotes the eventual emergence of resistance is unclear. Here we used in vitro evolution experiments to explore this question. We found that in all cases, tolerance preceded resistance. A mathematical population-genetics model showed how tolerance boosts the chances for resistance mutations to spread in the population. Thus, tolerance mutations pave the way for the rapid subsequent evolution of resistance. Preventing the evolution of tolerance may offer a new strategy for delaying the emergence of resistance.
      Authors : Irit Levin-Reisman, Irine Ronin, Orit Gefen, Ilan Braniss, Noam Shoresh, Nathalie Q. Balaban
      PubDate: 2017-02-24
      DOI: 10.1126/science.aaj2191
  • [Report] The cytotoxic Staphylococcus aureus PSMα3 reveals a
           cross-α amyloid-like fibril
    • Authors: Einav Tayeb-Fligelman
      Abstract: Amyloids are ordered protein aggregates, found in all kingdoms of life, and are involved in aggregation diseases as well as in physiological activities. In microbes, functional amyloids are often key virulence determinants, yet the structural basis for their activity remains elusive. We determined the fibril structure and function of the highly toxic, 22-residue phenol-soluble modulin α3 (PSMα3) peptide secreted by Staphylococcus aureus. PSMα3 formed elongated fibrils that shared the morphological and tinctorial characteristics of canonical cross-β eukaryotic amyloids. However, the crystal structure of full-length PSMα3, solved de novo at 1.45 angstrom resolution, revealed a distinctive “cross-α” amyloid-like architecture, in which amphipathic α helices stacked perpendicular to the fibril axis into tight self-associating sheets. The cross-α fibrillation of PSMα3 facilitated cytotoxicity, suggesting that this assembly mode underlies function in S. aureus.
      Authors : Einav Tayeb-Fligelman, Orly Tabachnikov, Asher Moshe, Orit Goldshmidt-Tran, Michael R. Sawaya, Nicolas Coquelle, Jacques-Philippe Colletier, Meytal Landau
      PubDate: 2017-02-24
      DOI: 10.1126/science.aaf4901
  • [Report] Bumblebees show cognitive flexibility by improving on an observed
           complex behavior
    • Authors: Olli J. Loukola
      Abstract: We explored bees’ behavioral flexibility in a task that required transporting a small ball to a defined location to gain a reward. Bees were pretrained to know the correct location of the ball. Subsequently, to obtain a reward, bees had to move a displaced ball to the defined location. Bees that observed demonstration of the technique from a live or model demonstrator learned the task more efficiently than did bees observing a “ghost” demonstration (ball moved via magnet) or without demonstration. Instead of copying demonstrators moving balls over long distances, observers solved the task more efficiently, using the ball positioned closest to the target, even if it was of a different color than the one previously observed. Such unprecedented cognitive flexibility hints that entirely novel behaviors could emerge relatively swiftly in species whose lifestyle demands advanced learning abilities, should relevant ecological pressures arise.
      Authors : Olli J. Loukola, Clint J. Perry, Louie Coscos, Lars Chittka
      PubDate: 2017-02-24
      DOI: 10.1126/science.aag2360
  • [Report] Optical control of cell signaling by single-chain photoswitchable
    • Authors: Xin X. Zhou
      Abstract: Protein kinases transduce signals to regulate a wide array of cellular functions in eukaryotes. A generalizable method for optical control of kinases would enable fine spatiotemporal interrogation or manipulation of these various functions. We report the design and application of single-chain cofactor-free kinases with photoswitchable activity. We engineered a dimeric protein, pdDronpa, that dissociates in cyan light and reassociates in violet light. Attaching two pdDronpa domains at rationally selected locations in the kinase domain, we created the photoswitchable kinases psRaf1, psMEK1, psMEK2, and psCDK5. Using these photoswitchable kinases, we established an all-optical cell-based assay for screening inhibitors, uncovered a direct and rapid inhibitory feedback loop from ERK to MEK1, and mediated developmental changes and synaptic vesicle transport in vivo using light.
      Authors : Xin X. Zhou, Linlin Z. Fan, Pengpeng Li, Kang Shen, Michael Z. Lin
      PubDate: 2017-02-24
      DOI: 10.1126/science.aah3605
  • [Report] Clonal hematopoiesis associated with TET2 deficiency accelerates
           atherosclerosis development in mice
    • Authors: José J. Fuster
      Abstract: Human aging is associated with an increased frequency of somatic mutations in hematopoietic cells. Several of these recurrent mutations, including those in the gene encoding the epigenetic modifier enzyme TET2, promote expansion of the mutant blood cells. This clonal hematopoiesis correlates with an increased risk of atherosclerotic cardiovascular disease. We studied the effects of the expansion of Tet2-mutant cells in atherosclerosis-prone, low-density lipoprotein receptor–deficient (Ldlr–/–) mice. We found that partial bone marrow reconstitution with TET2-deficient cells was sufficient for their clonal expansion and led to a marked increase in atherosclerotic plaque size. TET2-deficient macrophages exhibited an increase in NLRP3 inflammasome–mediated interleukin-1β secretion. An NLRP3 inhibitor showed greater atheroprotective activity in chimeric mice reconstituted with TET2-deficient cells than in nonchimeric mice. These results support the hypothesis that somatic TET2 mutations in blood cells play a causal role in atherosclerosis.
      Authors : José J. Fuster, Susan MacLauchlan, María A. Zuriaga, Maya N. Polackal, Allison C. Ostriker, Raja Chakraborty, Chia-Ling Wu, Soichi Sano, Sujatha Muralidharan, Cristina Rius, Jacqueline Vuong, Sophia Jacob, Varsha Muralidhar, Avril A. B. Robertson, Matthew A. Cooper, Vicente Andrés, Karen K. Hirschi, Kathleen A. Martin, Kenneth Walsh
      PubDate: 2017-02-24
      DOI: 10.1126/science.aag1381
  • [Departments] Gordon Research Conferences
    • Abstract: The 2017 Gordon Research Conference schedule was published on pages 848 to 870 of this issue of the print version of Science. The current schedule can also be found online at
      PubDate: 2017-02-24
      DOI: 10.1126/science.355.6327.848
  • [New Products] New Products
    • Abstract: A weekly roundup of information on newly offered instrumentation, apparatus, and laboratory materials of potential interest to researchers.
      PubDate: 2017-02-24
      DOI: 10.1126/science.355.6327.871
  • [Working Life] How I'm standing up for science
    • Authors: Susan J. Cheng
      Abstract: Author: Susan J. Cheng
      PubDate: 2017-02-24
      DOI: 10.1126/science.355.6327.878
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