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RANDY SCHEKMAN Department of Molecular and Cell Biology, Howard Hughes Medical Institute, University of California, Berkeley, USA
GENES AND PROTEINS THAT CONTROL THE SECRETORY PATHWAY Nobel Lecture, 7 December 2013 by RANDY SCHEKMAN Department of Molecular and Cell Biology, Howard Hughes Medical Institute, University of California, Berkeley, USA. Introduction George Palade shared the 1974 Nobel Prize with Albert Claude and Christian de Duve for their pioneering work in the characterization of organelles interrelated by the process of secretion in mammalian cells and tissues. These three scholars established the modern field of cell biology and the tools of cell fractionation and thin section transmission electron microscopy. It was Palade’s genius in particular that revealed the organization of the secretory pathway. He discovered the ribosome and showed that it was poised on the surface of the endoplasmic reticulum (ER) where it engaged in the vectorial translocation of newly synthesized secretory polypeptides (1). And in a most elegant and technically challenging investigation, his group employed radioactive amino acids in a pulse-chase regimen to show by autoradiograpic exposure of thin sections on a photographic emulsion that secretory proteins progress in sequence from the ER through the Golgi apparatus into secretory granules, which then discharge their cargo by membrane fusion at the cell surface (1). He documented the role of vesicles as carriers of cargo between compartments and he formulated the hypothesis that membranes template their own production rather than form by a process of de novo biogenesis (1). As a university student I was ignorant of the important developments in cell biology; however, I learned of Palade’s work during my first year of graduate school in the Stanford biochemistry department. -
Unrestricted Immigration and the Foreign Dominance Of
Unrestricted Immigration and the Foreign Dominance of United States Nobel Prize Winners in Science: Irrefutable Data and Exemplary Family Narratives—Backup Data and Information Andrew A. Beveridge, Queens and Graduate Center CUNY and Social Explorer, Inc. Lynn Caporale, Strategic Scientific Advisor and Author The following slides were presented at the recent meeting of the American Association for the Advancement of Science. This project and paper is an outgrowth of that session, and will combine qualitative data on Nobel Prize Winners family histories along with analyses of the pattern of Nobel Winners. The first set of slides show some of the patterns so far found, and will be augmented for the formal paper. The second set of slides shows some examples of the Nobel families. The authors a developing a systematic data base of Nobel Winners (mainly US), their careers and their family histories. This turned out to be much more challenging than expected, since many winners do not emphasize their family origins in their own biographies or autobiographies or other commentary. Dr. Caporale has reached out to some laureates or their families to elicit that information. We plan to systematically compare the laureates to the population in the US at large, including immigrants and non‐immigrants at various periods. Outline of Presentation • A preliminary examination of the 609 Nobel Prize Winners, 291 of whom were at an American Institution when they received the Nobel in physics, chemistry or physiology and medicine • Will look at patterns of -
The Creation of Neuroscience
The Creation of Neuroscience The Society for Neuroscience and the Quest for Disciplinary Unity 1969-1995 Introduction rom the molecular biology of a single neuron to the breathtakingly complex circuitry of the entire human nervous system, our understanding of the brain and how it works has undergone radical F changes over the past century. These advances have brought us tantalizingly closer to genu- inely mechanistic and scientifically rigorous explanations of how the brain’s roughly 100 billion neurons, interacting through trillions of synaptic connections, function both as single units and as larger ensem- bles. The professional field of neuroscience, in keeping pace with these important scientific develop- ments, has dramatically reshaped the organization of biological sciences across the globe over the last 50 years. Much like physics during its dominant era in the 1950s and 1960s, neuroscience has become the leading scientific discipline with regard to funding, numbers of scientists, and numbers of trainees. Furthermore, neuroscience as fact, explanation, and myth has just as dramatically redrawn our cultural landscape and redefined how Western popular culture understands who we are as individuals. In the 1950s, especially in the United States, Freud and his successors stood at the center of all cultural expla- nations for psychological suffering. In the new millennium, we perceive such suffering as erupting no longer from a repressed unconscious but, instead, from a pathophysiology rooted in and caused by brain abnormalities and dysfunctions. Indeed, the normal as well as the pathological have become thoroughly neurobiological in the last several decades. In the process, entirely new vistas have opened up in fields ranging from neuroeconomics and neurophilosophy to consumer products, as exemplified by an entire line of soft drinks advertised as offering “neuro” benefits. -
Dehaene Et Al (2008)
Log or Linear? Distinct Intuitions of the Number Scale in Western and Amazonian Indigene Cultures Stanislas Dehaene, et al. Science 320, 1217 (2008); DOI: 10.1126/science.1156540 The following resources related to this article are available online at www.sciencemag.org (this information is current as of June 6, 2008 ): Updated information and services, including high-resolution figures, can be found in the online version of this article at: http://www.sciencemag.org/cgi/content/full/320/5880/1217 Supporting Online Material can be found at: http://www.sciencemag.org/cgi/content/full/320/5880/1217/DC1 This article cites 24 articles, 4 of which can be accessed for free: http://www.sciencemag.org/cgi/content/full/320/5880/1217#otherarticles Information about obtaining reprints of this article or about obtaining permission to reproduce this article in whole or in part can be found at: on June 6, 2008 http://www.sciencemag.org/about/permissions.dtl www.sciencemag.org Downloaded from Science (print ISSN 0036-8075; online ISSN 1095-9203) is published weekly, except the last week in December, by the American Association for the Advancement of Science, 1200 New York Avenue NW, Washington, DC 20005. Copyright 2008 by the American Association for the Advancement of Science; all rights reserved. The title Science is a registered trademark of AAAS. REPORTS Before formal schooling, Western children may Log or Linear? Distinct Intuitions of the acquire the number-line concept from Arabic nu- merals seen on elevators, rulers, books, etc. Thus, Number Scale in Western and existing studies do not reveal which aspects of the number-space mapping constitute a basic in- tuition that would continue to exist in the absence Amazonian Indigene Cultures of a structured mathematical language and educa- 1,2,3,4 1,2,4,5 5 6 tion. -
Randy W. Schekman, Phd
Randy W. Schekman, PhD Current Position Professor of molecular and cell biology at the University of California, Berkeley Investigator at the Howard Hughes Medical Institute Editor-in-Chief, eLIFE Journal Education BA, molecular biology, University of California, Los Angeles PhD, biochemistry, Stanford University Awards Nobel Prize in Physiology or Medicine 2013 (shared with James E. Rothman and Thomas C. Südhof ) Albert Lasker Award for Basic Medical Research Eli Lilly Research Award in Microbiology and Immunology Lewis S. Rosenstiel Award in Basic Biomedical Science, Brandeis University Gairdner Foundation International Award Louisa Gross Horwitz Prize, Columbia University 2008 Dickson Prize in Medicine, University of Pittsburgh E.B. Wilson Medal, American Society for Cell Biology Memberships US National Academy of Sciences American Academy of Arts and Sciences American Society of Cell Biology American Association for the Advancement of Science American Philosophical Society Biography Traffic inside a cell is as complicated as rush hour near any metropolitan area. But drivers know how to follow the signs and roadways to reach their destinations. How do different cellular proteins "read" molecular signposts to find their way inside or outside of a cell? For the past three decades, Randy Schekman has been characterizing the traffic drivers that shuttle cellular proteins as they move in membrane-bound sacs, or vesicles, within a cell. His detailed elucidation of cellular travel patterns has provided fundamental knowledge about cells and has enhanced understanding of diseases that arise when bottlenecks impede some of the protein flow. His work earned him one of the most prestigious prizes in science, the 2002 Albert Lasker Award for Basic Medical Research, which he shared with James Rothman. -
Science & Policy Meeting Jennifer Lippincott-Schwartz Science in The
SUMMER 2014 ISSUE 27 encounters page 9 Science in the desert EMBO | EMBL Anniversary Science & Policy Meeting pageS 2 – 3 ANNIVERSARY TH page 8 Interview Jennifer E M B O 50 Lippincott-Schwartz H ©NI Membership expansion EMBO News New funding for senior postdoctoral In perspective Georgina Ferry’s enlarges its membership into evolution, researchers. EMBO Advanced Fellowships book tells the story of the growth and ecology and neurosciences on the offer an additional two years of financial expansion of EMBO since 1964. occasion of its 50th anniversary. support to former and current EMBO Fellows. PAGES 4 – 6 PAGE 11 PAGES 16 www.embo.org HIGHLIGHTS FROM THE EMBO|EMBL ANNIVERSARY SCIENCE AND POLICY MEETING transmissible cancer: the Tasmanian devil facial Science meets policy and politics tumour disease and the canine transmissible venereal tumour. After a ceremony to unveil the 2014 marks the 50th anniversary of EMBO, the 45th anniversary of the ScienceTree (see box), an oak tree planted in soil European Molecular Biology Conference (EMBC), the organization of obtained from countries throughout the European member states who fund EMBO, and the 40th anniversary of the European Union to symbolize the importance of European integration, representatives from the govern- Molecular Biology Laboratory (EMBL). EMBO, EMBC, and EMBL recently ments of France, Luxembourg, Malta, Spain combined their efforts to put together a joint event at the EMBL Advanced and Switzerland took part in a panel discussion Training Centre in Heidelberg, Germany, on 2 and 3 July 2014. The moderated by Marja Makarow, Vice President for Research of the Academy of Finland. -
Making Your Mind: Molecules, Motion, and Memory Lecture One – Mapping Memory in the Brain Eric R
Making Your Mind: Molecules, Motion, and Memory Lecture One – Mapping Memory in the Brain Eric R. Kandel, M.D. 1. Start of Lecture I (0:15) [ANNOUNCER:] From the Howard Hughes Medical Institute. The 2008 Holiday Lectures on Science. This year's lectures, "Making Your Mind: Molecules, Motion, and Memory," will be given by Dr. Eric Kandel, Howard Hughes Medical Institute investigator at Columbia University, and Dr. Thomas Jessell, Howard Hughes Medical Institute investigator also at Columbia University. The first lecture is titled "Mapping Memory in the Brain." And now to introduce our program, the President of the Howard Hughes Medical Institute, Dr. Thomas Cech. 2. Welcome by HHMI President Dr. Thomas Cech (1:08) [DR. CECH] Welcome to the Howard Hughes Medical Institute and the 2008 Holiday Lectures on Science. The Institute initiated this series in 1993. In 1995 I had the pleasure of coming here and delivering the lectures on catalytic RNA, and since I've been President of the Institute it's been a great pleasure to be involved in choosing 18 terrific scientists to talk to students here in the auditorium. The Holiday Lectures are one of more than 30 research and education programs of the Institute and please visit our website www.hhmi.org to learn more about all of our activities. This lecture series focuses on the most complex organ in our body and arguably the one that most is responsible for making us human. Clearly without this organ you wouldn't be able to find this auditorium, and even if you got here you wouldn't understand a word that was being said. -
Lettre Des Neurosciences / Lettreprintemps-ÉTÉ 2013 Numéro 44
la LA LETTRE DES NEUROSCIENCES / LettrePRINTEMPS-ÉTÉ 2013 NUMÉRO 44 Éditorial 3 Histoire des Neurosciences 4 Histoire récente des récepteurs aux neurotransmetteurs Dossier 8 Le sommeil dans tous ses états Nouveautés en neurosciences 24 La révolution de l’imagerie nanoscopique pour la neurobiologie cellulaire Tribune libre 28 Les neurosciences et le Droit Vie de la Société 31 Des métiers et des emplois pour les docteurs Comptes rendus colloques Changement de décor pour le secrétariat de la Société ! NUMÉRO 44 ISSN 2117-5535 La Lettre des Neurosciences est éditée par la Société des Neurosciences UUniversiténiversité BordeauxSegalen Bordeaux Segalen ·2 case · case 67 67 146, rue Léo-Léo-SaignatSaignat 33076 Bordeaux CCedexedex · France TTél.él. :: +(0)5+(0)557573740 57 57 37 40 | |Fax Fax : :+(0)5 +(0)5 57 57 57 57 3736 6950 [email protected] www.neurosciences.asso.fr Directeur de la publication-Rédacteur en Chef : YvesTillet | INRA - PRC - CNRS UMR 7 247 Univ. de Tours | IFCE Centre de Recherche de Tours 37380 Nouzilly | Fax : 02 47 42 77 43 [email protected] Fabrication : I. Conjat, J.-M. Israel, J.-F. Renaudon Concept maquette : Mazarine communication Comité de rédaction : J.-G. Barbara (Paris), D. Blum (Lille), C. Cleren (Rouen), A. Didier (Lyon), F. Eustache (Caen), S. Gaillard (Strasbourg), M. Garret (Bordeaux), J.-L. Gonzalez De Aguilar (Strasbourg), S. Pinto (Aix-en-Provence), A. Réaux-Le Goazigo (Paris). Ont participé à ce numéro : E. Audinat, B. Buisson, H. Chneiweiss, D. Choquet, J. Falcon, R. Garcia, I. Ghorayeb, C. Gronfier, A. Jean, M. Jouvet, P.-H. Luppi, A. -
Metastasis and Invasion 3 – Metastasis Science Cancer
CANCER SCIENCE 3 Cancer Science 3 – Metastasis and Invasion 3 – Metastasis Science Cancer www.ipsen.com 2FI 0069 Metastasis and Invasion Tuscany, May 20-23, 2007 24, rue Erlanger – 75016 Paris – Tel.: 33(0)1 44 96 10 10 – Fax: 33(0)1 44 96 11 99 COLLOQUES MÉDECINE ET RECHERCHE Fondation Ipsen SCIENTIFIC REPORT BY APOORVA MANDAVILLI 2 Fondation Ipsen is placed under the auspices of Fondation de France MOLECULAR MARKERS 3 4 Foreword by Inder M. Verma 7 Part I: Molecular markers 9 J. Michael Bishop Senescence and metastasis in mouse models of breast cancer 15 Joan Massagué Metastasis genes and functions 21 Zena Werb Transcriptional regulation of the metastatic program 25 Inder M. Verma BRCA1 maintains constitutive heterochromatin formation: a unifying hypothesis of its function 29 Tak Wah Mak The role of RhoC in development and metastasis 35 Part II: Motility and invasiveness 37 Robert Weinberg Mechanisms of malignant progression 43 Daniel Louvard Fascin, a novel target of b-catenin-Tcf signaling, is expressed at the invasive front of human colon cancer 49 Gerhard Christofori Distinct mechanisms of tumor cell invasion and metastasis 55 Douglas Hanahan Multiple parameters influence acquisition by solid tumors CONTENTS of a capability for invasive growth 59 Part III : Mechanisms of metastasis 61 Richard Hynes Cellular mechanisms contributing to metastasis 67 Ann Chambers Novel imaging approaches for studying tumor metastasis 73 Jeffrey Pollard Macrophages are a cellular toolbox that tumors sequester to promote their progression to malignancy 79 Wolf-Hervé Fridman T effector/memory cells, the ultimate control of metastasis in humans 85 Kari Alitalo Inhibition of lymphangiogenesis and metastasis 91 Shahin Rafii Contribution of CXCR4+VEGFR1+ pro-angiogenic hematopoietic cells to tumor oncogenesis 97 Part IV : Cancer stem cells 99 Paolo Comoglio Invasive growth : a MET-driven genetic program for cancer and stem cells 105 Hans Clevers Wnt and Notch cooperate to maintain proliferative compartments in crypts and intestinal neoplasia 111 Owen N. -
Peer Review College Newsletter
Peer Review College Newsletter Winter 2014 Launch of New EPSRC Strategic plan CONTENTS Over the last five years the national and international research landscape, and the 1. Launch of New EPSRC context in which EPSRC operates, have changed and continue to develop. To take Strategic plan – page 1 account of this new environment our Strategic Plan has been up-dated, with input from our partners and communities, recognising external influences including 2. EPSRC Policy on the Use the international research landscape, global economic situation and government of Animals in Research strategies. – page 1 We have developed our goals and strategies to reflect this changing landscape and 3. College Member On-line to ensure we maintain focus on our ambitious and unwavering vision: for the UK to Training – page 3 be the best place in the world to research, discover and innovate. Our Strategic Plan also recognises the importance of working in partnership if the UK is to maintain its 4. EPSRCs Peer Review position as a world-leading location for high quality research, and be equally renowned Extranet – page 4 for its innovation. 5. Return for Amendments EPSRC’s CEO, Professor Philip Nelson said: “Our Strategic Plan describes the – page 4 potential of UK science and engineering, its importance to addressing the global and 6. The importance of Pre- domestic challenges that range from energy security to healthcare, and the vital role scores – page 5 it plays in economic growth by fuelling technological progress. It sets out how EPSRC, in partnership with the academic community and industry partners, will unlock that 7. -
Jean-Pierre G. Changeux
EDITORIAL ADVISORY COMMITTEE Marina Bentivoglio Larry F. Cahill Stanley Finger Duane E. Haines Louise H. Marshall Thomas A. Woolsey Larry R. Squire (Chairperson) The History of Neuroscience in Autobiography VOLUME 4 Edited by Larry R. Squire ELSEVIER ACADEMIC PRESS Amsterdam Boston Heidelberg London New York Oxford Paris San Diego San Francisco Singapore Sydney Tokyo This book is printed on acid-free paper. (~ Copyright 9 byThe Society for Neuroscience All Rights Reserved. No part of this publication may be reproduced or transmitted in any form or by any means, electronic or mechanical, including photocopy, recording, or any information storage and retrieval system, without permission in writing from the publisher. Permissions may be sought directly from Elsevier's Science & Technology Rights Department in Oxford, UK: phone: (+44) 1865 843830, fax: (+44) 1865 853333, e-mail: [email protected]. You may also complete your request on-line via the Elsevier homepage (http://elsevier.com), by selecting "Customer Support" and then "Obtaining Permissions." Academic Press An imprint of Elsevier 525 B Street, Suite 1900, San Diego, California 92101-4495, USA http ://www.academicpress.com Academic Press 84 Theobald's Road, London WC 1X 8RR, UK http://www.academicpress.com Library of Congress Catalog Card Number: 2003 111249 International Standard Book Number: 0-12-660246-8 PRINTED IN THE UNITED STATES OF AMERICA 04 05 06 07 08 9 8 7 6 5 4 3 2 1 Contents Per Andersen 2 Mary Bartlett Bunge 40 Jan Bures 74 Jean Pierre G. Changeux 116 William Maxwell (Max) Cowan 144 John E. Dowling 210 Oleh Hornykiewicz 240 Andrew F. -
Correlating STED and Synchrotron XRF Nano-Imaging Unveils
TOOLS AND RESOURCES Correlating STED and synchrotron XRF nano-imaging unveils cosegregation of metals and cytoskeleton proteins in dendrites Florelle Domart1,2,3, Peter Cloetens4, Ste´ phane Roudeau1,2, Asuncion Carmona1,2, Emeline Verdier3, Daniel Choquet3,5†, Richard Ortega1,2†* 1Chemical Imaging and Speciation, CENBG, Univ. Bordeaux, Gradignan, France; 2CNRS, IN2P3, CENBG, UMR 5797, Gradignan, France; 3Univ. Bordeaux, CNRS, Interdisciplinary Institute for Neuroscience, IINS, UMR 5297, Bordeaux, France; 4ESRF, the European Synchrotron, Grenoble, France; 5Univ. Bordeaux, CNRS, INSERM, Bordeaux Imaging Center, BIC, UMS, Bordeaux, France Abstract Zinc and copper are involved in neuronal differentiation and synaptic plasticity but the molecular mechanisms behind these processes are still elusive due in part to the difficulty of imaging trace metals together with proteins at the synaptic level. We correlate stimulated- emission-depletion microscopy of proteins and synchrotron X-ray fluorescence imaging of trace metals, both performed with 40 nm spatial resolution, on primary rat hippocampal neurons. We reveal the co-localization at the nanoscale of zinc and tubulin in dendrites with a molecular ratio of about one zinc atom per tubulin-ab dimer. We observe the co-segregation of copper and F-actin within the nano-architecture of dendritic protrusions. In addition, zinc chelation causes a decrease in the expression of cytoskeleton proteins in dendrites and spines. Overall, these results indicate *For correspondence: new functions for zinc and copper in the modulation of the cytoskeleton morphology in dendrites, a [email protected] mechanism associated to neuronal plasticity and memory formation. †These authors contributed equally to this work Competing interests: The Introduction authors declare that no The neurobiology of copper and zinc is a matter of intense investigation since they have been competing interests exist.