Acknowledgment of Reviewers, 2017
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Cell Circuitry || Science Teaches English || The Chicken Genome Is Hot || Magnets in Medicine SEPTEMBER 2002 www.hhmi.org/bulletin Leading Doublea Life It’s a stretch, but doctors who work bench to bedside say they wouldn’t do it any other way. FEATURES 14 On Human Terms 24 The Evolutionary War A small—some say too small—group of Efforts to undermine evolution education have physician-scientists believes the best science evolved into a 21st-century marketing cam- requires patient contact. paign that relies on legal acumen, manipulation By Marlene Cimons of scientific literature and grassroots tactics. 20 Engineering the Cell By Trisha Gura Adam Arkin sees the cell as a mechanical system. He hopes to transform molecular 28 Call of the Wild biology into a kind of cellular engineering Could quirky, new animal models help scien- and in the process, learn how to move cells tists learn how to regenerate human limbs or from sickness to health. avert the debilitating effects of a stroke? By M. Mitchell Waldrop By Kathryn Brown 24 In front of a crowd of 1,500, Ohio’s Board of Education heard testimony on whether students should learn about intelligent design in science class. DEPARTMENTS 2 NOTA BENE 33 PERSPECTIVE ulletin Intelligent Design Is a Cop-Out 4 LETTERS September 2002 || Volume 15 Number 3 NEWS AND NOTES HHMI TRUSTEES PRESIDENT’S LETTER 5 JAMES A. BAKER, III, ESQ. 34 Senior Partner, Baker & Botts A Creative Influence In from the Fields ALEXANDER G. BEARN, M.D. Executive Officer, American Philosophical Society 35 Lost on the Tip of the Tongue Adjunct Professor, The Rockefeller University UP FRONT Professor Emeritus of Medicine, Cornell University Medical College 36 Biology by Numbers FRANK WILLIAM GAY 6 Follow the Songbird Former President and Chief Executive Officer, SUMMA Corporation JAMES H. -
Establishment of Sister Chromatid Cohesion During Dna Replication in Saccharomyces Cerevisiae
ESTABLISHMENT OF SISTER CHROMATID COHESION DURING DNA REPLICATION IN SACCHAROMYCES CEREVISIAE Vanessa de Sousa Ferreira Borges Thesis submitted for the degree of Doctor of Philosophy to University College London Supervisor: Dr. Frank Uhlmann September 2012 Chromosome Segregation Laboratory Cancer Research UK, London Research Institute 44 Lincoln’s Inn Fields London WC2A 3LY United Kingdom Declaration I, Vanessa de Sousa Ferreira Borges, confirm that the work presented in this thesis is my own. Where information has been derived from other sources, I confirm that this has been indicated in the thesis. 2 Acknowledgements One day scientific research became part of me, a world of puzzles, challenges and open questions waiting to be answered. Four years ago this decision brought me to London to do my PhD and many people became part of this exciting adventure and helped me through it in so many different ways. For this I would like to thank… …My supervisor Frank Uhlmann, for his continuous support, guidance and excellent scientific advice throughout the last 4 years. For always having the door of his office opened and time to discuss important or trivial questions about my project. For his contagious enthusiasm about science and for everything he taught me during my PhD. For being a great supervisor. …Everyone in the Chromosome and Segregation Laboratory for a very stimulating working environment and for making it such a nice place to work. I would like to thank Maria for all her help around the lab, Sebastian who taught me a lot in the beginning of my PhD, Adrian, Thomas, Celine, Molly, Rahul, Sandra, Lesia, Yasuto and Yasu. -
Masthead 2019
Masthead AngewandteA Journal of the German Chemical Society International Edition Chemie Editorial Board Chair: Annette G. Beck-Sickinger, Universität Leipzig Michael Brands, Bayer (Berlin) Editor: Neville A. Compton Holger Braunschweig, Julius-Maximilians-Universität (Würzburg) Martin Brudermüller, BASF (Ludwigshafen) Deputy Editors: Frank Maaß, Nathalie Weickgenannt Thomas Carell, Ludwig-Maximilians-Universität München Klaus Griesar, Merck (Darmstadt) Editorial Office: Senior Associate Editors: Jens Ackermann, Stefan Grimme, Universität Bonn Jonathan Faiz, Tamaryin Godinho, Hansjörg Grützmacher, Eidgenöss. Techn. Hochschule Zürich Nicole Harrington-Frost, Stephen Horner, (Switzerland) Volker Jacob, Guy Richardson, Rainer Haag, Freie Universität Berlin Rachel Schmidt-Radde, Diane Smith, Christian W. Kohlpaintner, Clariant (Pratteln, Switzerland) Xin Su, Suzanne Tobey Walter Leitner, Rheinisch-Westfälische Technische Hochschule Aachen Senior Web Editor: Mario Müller Wolfgang Parak, Universität Marburg Erwin Reisner, University of Cambridge (UK) Associate Editors: Eric Castro, Wolfgang Schnick, Ludwig-Maximilians-Universität München Arno Knappschneider, Kim Meyer Ferdi Schüth, Max-Planck-Institut für Kohlenforschung (Mülheim) Senior Assistant Editors: Gary Battle, Wolfgang Schuhmann, Ruhr-Universität Bochum Christiane Walter Harald Schwalbe, Johann Wolfgang Goethe-Universität Frankfurt Assistant Editors: Lisa Pecher, Petra Schwille, Max-Planck-Institut für Biochemie (Martinsried) Polina Smirnov, Laura Woodward Armido Studer, Westfälische -
The Meaning of Probability
CHAPTER 2 THE MEANING OF PROBABILITY INTRODUCTION by Glenn Shafer The meaning of probability has been debated since the mathematical theory of probability was formulated in the late 1600s. The five articles in this section have been selected to provide perspective on the history and present state of this debate. Mathematical statistics provided the main arena for debating the meaning of probability during the nineteenth and early twentieth centuries. The debate was conducted mainly between two camps, the subjectivists and the frequentists. The subjectivists contended that the probability of an event is the degree to which someone believes it, as indicated by their willingness to bet or take other actions. The frequentists contended that probability of an event is the frequency with which it occurs. Leonard J. Savage (1917-1971), the author of our first article, was an influential subjectivist. Bradley Efron, the author of our second article, is a leading contemporary frequentist. A newer debate, dating only from the 1950s and conducted more by psychologists and economists than by statisticians, has been concerned with whether the rules of probability are descriptive of human behavior or instead normative for human and machine reasoning. This debate has inspired empirical studies of the ways people violate the rules. In our third article, Amos Tversky and Daniel Kahneman report on some of the results of these studies. In our fourth article, Amos Tversky and I propose that we resolve both debates by formalizing a constructive interpretation of probability. According to this interpretation, probabilities are degrees of belief deliberately constructed and adopted on the basis of evidence, and frequencies are only one among many types of evidence. -
From Channelrhodopsins to Optogenetics ACCESS
Perspective OPEN From channelrhodopsins to optogenetics ACCESS From channelrhodopsins to optogenetics We did not expect that research on the and identified the role of Ca2þ influx in forming a single protein complex (Braun molecular mechanism of algal phototaxis flagellar beat frequency changes (Halldal, & Hegemann, 1999). or archaeal light-driven ion transport 1957, Schmidt & Eckert, 1976). Then Oleg In parallel, biophysicists had character- might interest readers of a medical Sineshchekov from Moscow State Uni- ized the precise nature of light-regulated journal when we conceived and per- versity recorded electrical light responses ion transport across cellular membranes. formed our experiments a decade ago. On from Haematococcus pluvialis, an alga Some of these studies started with the other hand, it did not escape our known for the production of the anti- investigations on animal rhodopsin and attention that channelrhodopsin is helping oxidant Astaxanthine (Litvin et al, 1978). even suggested rhodopsin-mediated an ever-increasing number of researchers Oleg used a suction pipette technique light-induced calcium entry with rhodop- to address their specific questions. For applied at the time by Dennis Baylor for sin itself as the carrier for calcium (Cone, example, the channelrhodopsin approach recording photocurrents from bovine 1972). Several decades later, we know is used to study the molecular events photoreceptor rods and cones. But Oleg’s that animal-type rhodopsins are G pro- during the induction of synaptic plasticity publication gave no hints about the type tein-coupled receptors indirectly modu- or to map long-range connections from of photoreceptor involved. Kenneth W. lating ion channel activity via signalling one side of the brain to the other, and to Foster however, a physicist at Mount molecules. -
Monitoring Synaptic and Neuronal Activity in 3D with Synthetic And
Journal of Neuroscience Methods 222 (2014) 69–81 Contents lists available at ScienceDirect Journal of Neuroscience Methods jou rnal homepage: www.elsevier.com/locate/jneumeth Basic Neuroscience Monitoring synaptic and neuronal activity in 3D with synthetic and genetic indicators using a compact acousto-optic lens two-photon microscopeଝ Tomás Fernández-Alfonso, K.M. Naga Srinivas Nadella, M. Florencia Iacaruso, ∗ Bruno Pichler, Hana Ros,ˇ Paul A. Kirkby, R. Angus Silver Department of Neuroscience, Physiology and Pharmacology, University College London, London WC1E 6BT, UK h i g h l i g h t s g r a p h i c a l a b s t r a c t • We expand the utility of acousto- optic lens (AOL) 3D 2P microscopy. • We show rapid, simultaneous moni- toring of synaptic inputs distributed in 3D. • First use of genetically encoded indicators with AOL 3D functional imaging. • Measurement of sensory-evoked neuronal population activity in 3D in vivo. • Strategies for improving the mea- surement of the timing of neuronal signals. a r t i c l e i n f o a b s t r a c t Article history: Background: Two-photon microscopy is widely used to study brain function, but conventional micro- Received 26 June 2013 scopes are too slow to capture the timing of neuronal signalling and imaging is restricted to one plane. Received in revised form 22 October 2013 Recent development of acousto-optic-deflector-based random access functional imaging has improved Accepted 26 October 2013 the temporal resolution, but the utility of these technologies for mapping 3D synaptic activity patterns and their performance at the excitation wavelengths required to image genetically encoded indicators Keywords: have not been investigated. -
Volume Xlvii--Part 1 Cold Spring Harbor Symposia on Quantitative Biology
COLD SPRING HARBOR SYMPOSIA ON QUANTITATIVE BIOLOGY VOLUME XLVII--PART 1 COLD SPRING HARBOR SYMPOSIA ON QUANTITATIVE BIOLOGY VOLUME XLVII STRUCTURES OF DNA COLD SPRING HARBOR LABORATORY 1983 COLD SPRING HARBOR SYMPOSIA ON QUANTITATIVE BIOLOGY VOLUME XLVII 1983 by The Cold Spring Harbor Laboratory International Standard Book Number 0-87969-046-1 International Standard Serial Number 0091-7451 Library of Congress Catalog Card Number 34-8174 Printed in the United States of America All rights reserved COLD SPRING HARBOR SYMPOSIA ON QUANTITATIVE BIOLOGY Founded in 1933 by REGINALD G. HARRIS Director of the Biological Laboratory 1924 to 1936 Previous Symposia Volumes I (1933) Surface Phenomena XXIH (1958) Exchange of Genetic Material: Mechanism and II (1934) Aspects of Growth Consequences IU (1935) Photochemical Reactions XXIV (1959) Genetics and Twentieth Century Darwinism IV (1936) Excitation Phenomena XXV (! 960) Biological Clocks V (1937) Internal Secretions XXVI (1961) Cellular Regulatory Mechanisms VI (1938) Protein Chemistry XXVII (1962) Basic Mechanisms in Animal Virus Biology VII (1939) Biological Oxidations XXVIU (1963) Synthesis and Structure of Macromolecules VIII (1940) Permeability and the Nature of Cell Membranes XXIX (1964) Human Genetics IX (1941) Genes and Chromosomes: Structure and Organization XXX (1965) Sensory Receptors X (1942) The Relation of Hormones to Development XXXI (1966) The Genetic Code XI (1946) Heredity and Variation in Microorganisms XXXII (1967) Antibodies XII (1947) Nucleic Acids and Nucleoproteins XXXIU (1968) -
Strength in Numbers: the Rising of Academic Statistics Departments In
Agresti · Meng Agresti Eds. Alan Agresti · Xiao-Li Meng Editors Strength in Numbers: The Rising of Academic Statistics DepartmentsStatistics in the U.S. Rising of Academic The in Numbers: Strength Statistics Departments in the U.S. Strength in Numbers: The Rising of Academic Statistics Departments in the U.S. Alan Agresti • Xiao-Li Meng Editors Strength in Numbers: The Rising of Academic Statistics Departments in the U.S. 123 Editors Alan Agresti Xiao-Li Meng Department of Statistics Department of Statistics University of Florida Harvard University Gainesville, FL Cambridge, MA USA USA ISBN 978-1-4614-3648-5 ISBN 978-1-4614-3649-2 (eBook) DOI 10.1007/978-1-4614-3649-2 Springer New York Heidelberg Dordrecht London Library of Congress Control Number: 2012942702 Ó Springer Science+Business Media New York 2013 This work is subject to copyright. All rights are reserved by the Publisher, whether the whole or part of the material is concerned, specifically the rights of translation, reprinting, reuse of illustrations, recitation, broadcasting, reproduction on microfilms or in any other physical way, and transmission or information storage and retrieval, electronic adaptation, computer software, or by similar or dissimilar methodology now known or hereafter developed. Exempted from this legal reservation are brief excerpts in connection with reviews or scholarly analysis or material supplied specifically for the purpose of being entered and executed on a computer system, for exclusive use by the purchaser of the work. Duplication of this publication or parts thereof is permitted only under the provisions of the Copyright Law of the Publisher’s location, in its current version, and permission for use must always be obtained from Springer. -
SMC Complexes Orchestrate the Mitotic Chromatin Interaction Landscape
Curr Genet DOI 10.1007/s00294-017-0755-y REVIEW SMC complexes orchestrate the mitotic chromatin interaction landscape Yasutaka Kakui1 · Frank Uhlmann1 Received: 13 September 2017 / Revised: 14 September 2017 / Accepted: 16 September 2017 © The Author(s) 2017. This article is an open access publication Abstract Chromatin is a very long DNA–protein complex Keywords Chromosome condensation · SMC complex · that controls the expression and inheritance of the genetic Chromatin · Cell cycle · Hi-C information. Chromatin is stored within the nucleus in interphase and further compacted into chromosomes dur- ing mitosis. This process, known as chromosome condensa- Introduction tion, is essential for faithful segregation of genomic DNA into daughter cells. Condensin and cohesin, members of How chromatin is spatially organized within the cell nucleus the structural maintenance of chromosomes (SMC) fam- and within chromosomes is a fundamental question in cell ily, are fundamental for chromosome architecture, both biology. Centimeter-long DNA molecules change their spa- for establishment of chromatin structure in the interphase tial chromatin organization within micrometer-sized cells nucleus and for the formation of condensed chromosomes during cell cycle progression. In interphase, chromatin is in mitosis. These ring-shaped SMC complexes are thought distributed throughout the nucleus to express the genetic to regulate the interactions between DNA strands by topo- information. When cells enter mitosis, chromatin becomes logically entrapping DNA. How this activity shapes chro- compacted to form mitotic chromosomes. Chromosome mosomes is not yet understood. Recent high throughput condensation, the gross morphological change of spatial chromosome conformation capture studies revealed how chromatin organization in mitosis, is indispensable for chromatin is reorganized during the cell cycle and have the faithful inheritance of genetic information. -
Curriculum Vitae
Curriculum vitae BRUCE WILLIAM STILLMAN PLACE AND DATE OF BIRTH October 16, 1953, Melbourne, Australia ADDRESS Cold Spring Harbor Laboratory 1 Bungtown Road Cold Spring Harbor, New York 11724 Phone: (516) 367-8383 Email: [email protected] NATIONALITY Australian; Permanent Resident, U.S.A. EDUCATION Glen Waverley High School, Victoria, Australia (1966-69) Sydney Boys’ High School, N.S.W., Australia (1970-71) B.Sc., First Class Honours, University of Sydney (1972-75) Ph.D., Australian National University (1976-79) POSITIONS Postgraduate Student, Department of Microbiology John Curtin School of Medical Research Australian National University (1976-1979) Postdoctoral Fellow, Cold Spring Harbor Laboratory (1979-80) Staff Investigator, Cold Spring Harbor Laboratory (1981-82) Senior Staff Investigator, Cold Spring Harbor Laboratory (1983-1985) Professor, Cold Spring Harbor Laboratory (1985 - present) Assistant Director, Cold Spring Harbor Laboratory (1990-1993) Director, Cold Spring Harbor Laboratory Cancer Center (1992-present) Director, Cold Spring Harbor Laboratory (1994-2003) (Chief Executive Officer title added by CSHL Board, November 2000) President, Cold Spring Harbor Laboratory, (2003-present) Curriculum vitae: Bruce W. Stillman 2 HONORS and AWARDS Commonwealth Postgraduate Award (1976-1978); Damon Runyon-Walter Winchell Cancer Fund Fellow (1979-1980); Rita Allen Foundation Scholar (1982-1987); Merit Award - National Institutes of Health (1986); The Royal Society (London), Elected Fellow (1993); Julian Wells Medal and Lecture, Genome -
Physical Determinants of Vesicle Mobility and Supply at a Central
RESEARCH ARTICLE Physical determinants of vesicle mobility and supply at a central synapse Jason Seth Rothman1, Laszlo Kocsis2, Etienne Herzog3,4, Zoltan Nusser2*, Robin Angus Silver1* 1Department of Neuroscience, Physiology and Pharmacology, University College London, London, United Kingdom; 2Laboratory of Cellular Neurophysiology, Institute of Experimental Medicine, Hungarian Academy of Sciences, Budapest, Hungary; 3Department of Molecular Neurobiology, Max Planck Institute of Experimental Medicine, Go¨ ttingen, Germany; 4Team Synapse in Cognition, Interdisciplinary Institute for Neuroscience, Universite´ de Bordeaux, UMR 5297, F-33000, Bordeaux, France Abstract Encoding continuous sensory variables requires sustained synaptic signalling. At several sensory synapses, rapid vesicle supply is achieved via highly mobile vesicles and specialized ribbon structures, but how this is achieved at central synapses without ribbons is unclear. Here we examine vesicle mobility at excitatory cerebellar mossy fibre synapses which sustain transmission over a broad frequency bandwidth. Fluorescent recovery after photobleaching in slices from VGLUT1Venus knock-in mice reveal 75% of VGLUT1-containing vesicles have a high mobility, comparable to that at ribbon synapses. Experimentally constrained models establish hydrodynamic interactions and vesicle collisions are major determinants of vesicle mobility in crowded presynaptic terminals. Moreover, models incorporating 3D reconstructions of vesicle clouds near active zones (AZs) predict the measured releasable pool size and replenishment rate from the reserve pool. They also show that while vesicle reloading at AZs is not diffusion-limited at the onset of release, *For correspondence: nusser@ diffusion limits vesicle reloading during sustained high-frequency signalling. koki.hu (ZN); [email protected] DOI: 10.7554/eLife.15133.001 (RAS) Competing interests: The authors declare that no competing interests exist. -
On the Technology Prospects and Investment Opportunities for Scalable Neuroscience
On the Technology Prospects and Investment Opportunities for Scalable Neuroscience Thomas Dean1,2,3 Biafra Ahanonu3 Mainak Chowdhury3 Anjali Datta3 Andre Esteva3 Daniel Eth3 Nobie Redmon3 Oleg Rumyantsev3 Ysis Tarter3 1 Google Research, 2 Brown University, 3 Stanford University Contents 1 Executive Summary 1 2 Introduction 4 3 Evolving Imaging Technologies 6 4 Macroscale Reporting Devices 10 5 Automating Systems Neuroscience 14 6 Synthetic Neurobiology 16 7 Nanotechnology 20 8 Acknowledgements 28 A Leveraging Sequencing for Recording — Biafra Ahanonu 28 B Scalable Analytics and Data Mining — Mainak Chowdhury 32 C Macroscale Imaging Technologies — Anjali Datta 35 D Nanoscale Recording and Wireless Readout — Andre Esteva 38 E Hybrid Biological and Nanotechnology Solutions — Daniel Eth 41 F Advances in Contrast Agents and Tissue Preparation — Nobie Redmon 44 G Microendoscopy and Optically Coupled Implants — Oleg Rumyantsev 46 H Opportunities for Automating Laboratory Procedures — Ysis Tarter 49 i 1 Executive Summary Two major initiatives to accelerate research in the brain sciences have focused attention on devel- oping a new generation of scientific instruments for neuroscience. These instruments will be used to record static (structural) and dynamic (behavioral) information at unprecedented spatial and temporal resolution and report out that information in a form suitable for computational analysis. We distinguish between recording — taking measurements of individual cells and the extracellu- lar matrix — and reporting — transcoding, packaging and transmitting the resulting information for subsequent analysis — as these represent very different challenges as we scale the relevant technologies to support simultaneously tracking the many neurons that comprise neural circuits of interest. We investigate a diverse set of technologies with the purpose of anticipating their devel- opment over the span of the next 10 years and categorizing their impact in terms of short-term [1-2 years], medium-term [2-5 years] and longer-term [5-10 years] deliverables.