DOCSLIB.ORG

UNSCEAR 2000 Report to the General Assembly, with Scientific Annexes

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
UNSCEAR 2000 Report to the General Assembly, with Scientific Annexes SOURCES AND EFFECTS OF IONIZING RADIATION United Nations Scientific Committee on the Effects of Atomic Radiation UNSCEAR 2000 Report to the General Assembly, with Scientific Annexes VOLUME II: EFFECTS UNITED NATIONS New York, 2000 NOTE The report of the Committee without its annexes appears as Official Records of the General Assembly, Fifty-fifth Session, Supplement No. 46 (A/55/46). The designation employed and the presentation of material in this publication do not imply the expression of any opinion whatsoever on the part of the Secretariat of the United Nations concerning the legal status of any country, territory, city or area, or of its authorities, or concerning the delimitation of its frontiers or boundaries. The country names used in this document are, in most cases, those that were in use at the time the data were collected or the text prepared. In other cases, however, the names have been updated, where this was possible and appropriate, to reflect political changes. UNITED NATIONS PUBLICATION Sales No. E.00.IX.4 ISBN 92-1-142239-6 ANNEX F DNA repair and mutagenesis CONTENTS Page INTRODUCTION..................................................... 2 I. DNADAMAGEANDREPAIR...................................... 2 A. THEROLEOFDNAREPAIRGENESINCELLFUNCTION .......... 2 B. TYPESOFDAMAGEANDPATHWAYSOFREPAIR ............... 3 C. SUMMARY................................................. 8 II. REPAIRPROCESSESANDRADIOSENSITIVITY ...................... 9 A. RADIOSENSITIVITYINMAMMALIANCELLSANDHUMANS...... 9 1. The identification of radiosensitive cell lines and disorders ......... 9 2. Mechanisms of enhanced sensitivity in human disorders .......... 11 3. Analysis of genes determining radiosensitivity .................. 12 4. Summary ............................................. 17 B. RELATIONSHIP BETWEEN REPAIR AND OTHERCELLREGULATORYPROCESSES...................... 18 1. Radiosensitivity and defective recombination in the immune system: non-homologousendjoiningofDNAdouble-strandbreaks........ 18 2. Radiosensitivity and the cell cycle ........................... 21 3. Apoptosis:analternativetorepair?.......................... 23 4. Summary.............................................. 25 III. HUMAN RADIATION RESPONSES ................................. 26 A. CONTRIBUTION OF MUTANT GENES TOHUMANRADIOSENSITIVITY ............................. 26 B. INFLUENCEOFREPAIRONRADIATIONRESPONSES............ 29 C. SUMMARY................................................ 32 IV. MECHANISMSOFRADIATIONMUTAGENESIS ..................... 33 A. MUTATIONASAREPAIR-RELATEDRESPONSE................ 33 B. THESPECTRUMOFRADIATION-INDUCEDMUTATIONS......... 35 C. MOLECULAR ANALYSIS OF RADIATION-INDUCED MUTATIONS . 36 D. EFFECTOFRADIATIONQUALITY............................ 39 E. NOVEL MECHANISMS OF GENETIC CHANGE .................. 41 F. MUTATIONFREQUENCIESANDCONSEQUENCES.............. 44 G. SUMMARY................................................ 47 CONCLUSIONS..................................................... 47 References .......................................................... 49 2 ANNEX F: DNA REPAIR AND MUTAGENESIS INTRODUCTION 1. Risk estimates for the induction of human disease are 3. DNA repair is itself controlled by a specific set of obtained primarilyfrom epidemiological studies.Thesestudies genes encoding the enzymes that catalysecellular response can clearly distinguish radiation effects only at relatively high to DNA damage. Loss of repair function, or alteration of doses and dose rates. Togain information at lowdoses and low the control of repair processes, can have very serious dose rates, which are more relevant to typical human radiation consequencesfor cellsand individuals. It isanticipated that exposures, it is necessary to extrapolate the results of these DNA repair plays a critical role in protecting normal studies. To be valid, this extrapolation requires a detailed individuals from radiation effects, including cancer. understanding of the mechanisms by which radiation induces Clinical experience has revealed individuals who are both cancer and genetic disorders. hypersensitivetoradiation and cancer-prone; someofthese individuals have recently been shown to have defects in 2. Several lines of evidence show that sites of radiation- genes involved in the response to DNA damage. induced cell lethality, mutation, and malignant change are situated within the nucleus and that DNA is the primary 4. In recent years there have been significant advances target. When DNA is damaged by radiation, enzymes within in the molecular analysis of repair processes and the the cell nucleus attempt to repair that damage. The efficiency understanding of the mechanisms that induce genetic of the enzymatic repair processes determines the outcome: changes. Additionally, new methods have been developed most commonly, the structure of DNA is repaired correctly to simplify the identification of the genes involved. As the and cellular functions return to normal. If the repair is details of damage-repair processes become clearer, it is unsuccessful, incomplete, or imprecise, the cell may die or seen that these processes have considerable overlap with may suffer alteration and loss of genetic information (seen as other cellular control functions, such as those regulating mutation and chromosomal aberration). These information the cell cycle and immune defences. In this Annex the changes determine heritable genetic defects and are thought Committee continues to review such developments in to be important in the development of radiation-induced molecular radiobiology, as it began to do in Annex E, cancer. The more complete the knowledge of the ways in “Mechanisms of radiation carcinogenesis” of the which human cells respond to damage and of the mechanisms UNSCEAR 1993 Report [U3], in order to improve the underlying the formation of mutations and chromosomal understanding of how radiation effects are manifested in aberrations, the more accurate will be the predictions of the cells and organisms. oncogenic and hereditary effects of ionizing radiation. I. DNA DAMAGE AND REPAIR A. THEROLEOFDNAREPAIRGENES 6. Loss or alteration of information in a specific gene may IN CELL FUNCTION mean that none of that gene product (protein) is formed, or that the protein is less active, or that it is formed in an 5. The information needed to control cellular functions uncontrolled fashion (e.g. at the wrong time or in the wrong such as growth, division, and differentiation is carried by amount). While some minor genetic alterations may not affect the genes. Genes, which are specific sequences of DNA, act protein activity or interactions, others may significantly mainlythrough theproduction ofcomplementarymessages disrupt cellular function. Since certain proteins work in a (mRNA) that are translated into proteins. Proteins can number of different processes or complexes, the loss or have a structural role but commonlywork asenzymes, each impairment of one type of protein can affect several different of which catalyses a particular metabolic reaction. Thus functions of the cell and organism (pleiotropic effect). specific genes contain the code for (encode) specific cellular functions. The production of proteins can be timed 7. A verylarge number of genes, 60,000-70,000 [F14], are so that they work at specific points in the development of required to control the normal functions of mammalian cells a cell or organism, but protein function can also be and organisms. However, the genes form only a small part of controlled by post-translational modifications. These the genome (the complete DNA sequence of an organism), the modifications are carried out by other proteins, so that a remainder of which largely consists of many copies of complex set of interactions is necessary to fine-tune repetetive DNA sequence. The genes are linked in linear cellular functions. Proteins involved in important aspects arrays interspersed by non-coding sequences, to form of cell metabolism (e.g. DNA replication) may also work chromosomes located in the cell nucleus. Most genes are in multi-protein complexes [A1]. There is some evidence present in only two copies, each on a separate homologous also that some of the complexes are assembled into larger chromosome, one inherited from the mother and one from the structures situated in defined regions of the nucleus (e.g. father. To monitor damage and to maintain the genes without the nuclear matrix) [H2]. significant alteration is a major concern for the cell. Repair ANNEX F: DNA REPAIR AND MUTAGENESIS 3 processes are common to all organisms from bacteria to are arranged in two linear arrays (or strands) held together by humans and have evolved to correct errors made in replicating hydrogen bonds centrally and linked externally by covalent the genes and to restore damaged DNA. This fact has in bonds to sugar-phosphate residues (the DNA "backbone"). recent years provided a useful tool for molecular geneticists in The adenine base pairs naturally with thymine (A:T base the analysis of repair processes; well characterized micro- pair), while guanine pairs with cytosine (G:C base pair), so organisms can serve as model systems to understand the that one DNA strand has the complementary sequence of the structureandfunction ofrepair genes. Theinformation gained other. The sequence of the bases defines the genetic code; each in this way can sometimes also be used directly to isolate gene has a unique sequence, although certain common human genes of related function [L1]. While
Load more

Recommended publications
  • A Mutant Drosophila Homolog of Mammalian Clock Disrupts
    Cell, Vol. 93, 791±804, May 29, 1998, Copyright 1998 by Cell Press AMutantDrosophila Homolog of Mammalian Clock Disrupts Circadian Rhythms and Transcription of period and timeless Ravi Allada,*²³§ Neal E. White,³ Aronson et al., 1994; Shearman et al., 1997; Sun et al., W. Venus So,²³ Jeffrey C. Hall,²³ 1997; Tei et al., 1997). ²³ and Michael Rosbash* k In Drosophila, there are two well-characterized clock *Howard Hughes Medical Institute genes: period (per) and timeless (tim). Protein levels, ² NSF, Center for Biological Timing RNA levels, and transcription rates of these two genes ³ Department of Biology undergo robust circadian oscillations (Zerr et al., 1990; Brandeis University Hardin et al., 1990, 1992; Hardin, 1994; Sehgal et al., Waltham, Massachusetts 02254 1995; So and Rosbash, 1997). In addition, mutations § Department of Pathology in the two proteins (PER and TIM) alter or abolish the Brigham and Women's Hospital periodicity and phase of these rhythms, demonstrating Boston, Massachusetts 02115 that both proteins regulate their own transcription (Har- din et al., 1990; Sehgal et al., 1995; Marrus et al., 1996). Although there is no evidence indicating that the effects Summary on transcription are direct, PER contains a PAS domain, which has been shown to mediate interactions between We report the identification, characterization, and transcription factors (Huang et al., 1993; Lindebro et cloning of a novel Drosophila circadian rhythm gene, al., 1995). Most of these PAS-containing transcription dClock. The mutant, initially called Jrk, manifests dom- factors also contain the well-characterized basic helix- inant effects: heterozygous flies have a period alter- loop-helix (bHLH) DNA-binding domains (Crews, 1998).
    [Show full text]
  • Case 3:17-Cr-00249-BJD-JRK Document 89 Filed 03/14/18 Page 1 of 32 Pageid 361
    Case 3:17-cr-00249-BJD-JRK Document 89 Filed 03/14/18 Page 1 of 32 PageID 361 UNITED STATES DISTRICT COURT MIDDLE DISTRICT OF FLORIDA JACKSONVILLE DIVISION UNITED STATES OF AMERICA v. CASE NO. 3:17-cr-249-BJD-JRK JOSHUA RYNE GOLDBERG DEFENDANT’S SENTENCING MEMORANDUM The Defendant, Joshua Ryne Goldberg, by and through counsel, Paul Shorstein, Shorstein, Lasnetski & Gihon, LLC, hereby submits the following Sentencing Memorandum setting forth all factors that the Court should consider in determining the type and length of sentence that is sufficient, but not greater than necessary, to comply with the statutory directives set forth in 18 U.S.C. §3553(a). BACKGROUND In 2015, law enforcement officials began investigating a certain online account that was posting threatening and other disturbing comments over the internet. Specifically, some of the internet discussion revolved around a potential attack of a 9/11 event in Kansas City, Missouri. That investigation ultimately led law enforcement officials to the Clay County home of Joshua Goldberg and his family. In the early morning hours of September 10, 2015, FBI agents and other law enforcement officials executed a search warrant inside 1 Case 3:17-cr-00249-BJD-JRK Document 89 Filed 03/14/18 Page 2 of 32 PageID 362 the Goldbergs’ home. They found Joshua Goldberg inside, as he always was. Joshua gave a statement that lasted a few hours despite not having slept for approximately 24 hours and not having taken his medication. Presumably, because the law enforcement officials found a severely mentally ill young man rather than what they expected as the source of the threatening internet activity, the government sought a criminal complaint (case number 3:15-mj-1170-J-JRK), which was filed on September 10, 2015, rather than more formal charges.
    [Show full text]
  • Epigenetic Modifications to Cytosine and Alzheimer's Disease
    University of Kentucky UKnowledge Theses and Dissertations--Chemistry Chemistry 2017 EPIGENETIC MODIFICATIONS TO CYTOSINE AND ALZHEIMER’S DISEASE: A QUANTITATIVE ANALYSIS OF POST-MORTEM TISSUE Elizabeth M. Ellison University of Kentucky, [email protected] Digital Object Identifier: https://doi.org/10.13023/ETD.2017.398 Right click to open a feedback form in a new tab to let us know how this document benefits ou.y Recommended Citation Ellison, Elizabeth M., "EPIGENETIC MODIFICATIONS TO CYTOSINE AND ALZHEIMER’S DISEASE: A QUANTITATIVE ANALYSIS OF POST-MORTEM TISSUE" (2017). Theses and Dissertations--Chemistry. 86. https://uknowledge.uky.edu/chemistry_etds/86 This Doctoral Dissertation is brought to you for free and open access by the Chemistry at UKnowledge. It has been accepted for inclusion in Theses and Dissertations--Chemistry by an authorized administrator of UKnowledge. For more information, please contact [email protected]. STUDENT AGREEMENT: I represent that my thesis or dissertation and abstract are my original work. Proper attribution has been given to all outside sources. I understand that I am solely responsible for obtaining any needed copyright permissions. I have obtained needed written permission statement(s) from the owner(s) of each third-party copyrighted matter to be included in my work, allowing electronic distribution (if such use is not permitted by the fair use doctrine) which will be submitted to UKnowledge as Additional File. I hereby grant to The University of Kentucky and its agents the irrevocable, non-exclusive, and royalty-free license to archive and make accessible my work in whole or in part in all forms of media, now or hereafter known.
    [Show full text]
  • In the United States District Court for the Northern District of Ohio Western Division
    Case: 3:16-cv-02724-JRK Doc #: 19 Filed: 01/29/18 1 of 19. PageID #: <pageID> IN THE UNITED STATES DISTRICT COURT FOR THE NORTHERN DISTRICT OF OHIO WESTERN DIVISION KAYLA D. SPENCER, Case No. 3:16 CV 2724 Plaintiff, v. Magistrate Judge James R. Knepp, II COMMISSIONER OF SOCIAL SECURITY, Defendant. MEMORANDUM OPINION AND ORDER INTRODUCTION Plaintiff Kayla D. Spencer (“Plaintiff”) filed a Complaint against the Commissioner of Social Security (“Commissioner”) seeking judicial review of the Commissioner’s decision to deny disability insurance benefits (“DIB”) and supplemental security income (“SSI”). (Doc. 1). The district court has jurisdiction under 42 U.S.C. §§ 1383(c) and 405(g). The parties consented to the undersigned’s exercise of jurisdiction in accordance with 28 U.S.C. § 636(c) and Civil Rule 73. (Non-document entry dated February 13, 2017). For the reasons stated below, the undersigned affirms the decision of the Commissioner. PROCEDURAL BACKGROUND Plaintiff filed for DIB and SSI in October 2011, alleging a disability onset date of September 30, 2010. (Tr. 326-35). Her claims were denied initially and upon reconsideration. (Tr. 198-203, 208-12). Plaintiff then requested a hearing before an administrative law judge (“ALJ”). (Tr. 213-14). Plaintiff (represented by counsel), and a vocational expert (“VE”) testified at a hearing before the ALJ on August 21, 2013. (Tr. 76-120). On October 18, 2013, the ALJ found Plaintiff not disabled in a written decision. (Tr. 169-92). On April 6, 2015, the Appeals Council Case: 3:16-cv-02724-JRK Doc #: 19 Filed: 01/29/18 2 of 19.
    [Show full text]
  • Oxidized Phospholipids Regulate Amino Acid Metabolism Through MTHFD2 to Facilitate Nucleotide Release in Endothelial Cells
    ARTICLE DOI: 10.1038/s41467-018-04602-0 OPEN Oxidized phospholipids regulate amino acid metabolism through MTHFD2 to facilitate nucleotide release in endothelial cells Juliane Hitzel1,2, Eunjee Lee3,4, Yi Zhang 3,5,Sofia Iris Bibli2,6, Xiaogang Li7, Sven Zukunft 2,6, Beatrice Pflüger1,2, Jiong Hu2,6, Christoph Schürmann1,2, Andrea Estefania Vasconez1,2, James A. Oo1,2, Adelheid Kratzer8,9, Sandeep Kumar 10, Flávia Rezende1,2, Ivana Josipovic1,2, Dominique Thomas11, Hector Giral8,9, Yannick Schreiber12, Gerd Geisslinger11,12, Christian Fork1,2, Xia Yang13, Fragiska Sigala14, Casey E. Romanoski15, Jens Kroll7, Hanjoong Jo 10, Ulf Landmesser8,9,16, Aldons J. Lusis17, 1234567890():,; Dmitry Namgaladze18, Ingrid Fleming2,6, Matthias S. Leisegang1,2, Jun Zhu 3,4 & Ralf P. Brandes1,2 Oxidized phospholipids (oxPAPC) induce endothelial dysfunction and atherosclerosis. Here we show that oxPAPC induce a gene network regulating serine-glycine metabolism with the mitochondrial methylenetetrahydrofolate dehydrogenase/cyclohydrolase (MTHFD2) as a cau- sal regulator using integrative network modeling and Bayesian network analysis in human aortic endothelial cells. The cluster is activated in human plaque material and by atherogenic lipo- proteins isolated from plasma of patients with coronary artery disease (CAD). Single nucleotide polymorphisms (SNPs) within the MTHFD2-controlled cluster associate with CAD. The MTHFD2-controlled cluster redirects metabolism to glycine synthesis to replenish purine nucleotides. Since endothelial cells secrete purines in response to oxPAPC, the MTHFD2- controlled response maintains endothelial ATP. Accordingly, MTHFD2-dependent glycine synthesis is a prerequisite for angiogenesis. Thus, we propose that endothelial cells undergo MTHFD2-mediated reprogramming toward serine-glycine and mitochondrial one-carbon metabolism to compensate for the loss of ATP in response to oxPAPC during atherosclerosis.
    [Show full text]
  • Clockwork Genes: Discoveries in Biological Time Lecture Three—Perfect Timing Michael Rosbash, Ph.D
    Clockwork Genes: Discoveries in Biological Time Lecture Three—PERfect TIMing Michael Rosbash, Ph.D. 1. Start of Lecture Three (00:15) From the Howard Hughes Medical Institute, the 2000 Holiday Lectures on Science…This year's lectures, "Clockwork Genes: Discoveries in Biological Time," will be given by Dr. Michael Rosbash, Howard Hughes Medical Institute investigator at Brandeis University and Dr. Joseph S. Takahashi, Howard Hughes Medical Institute investigator at Northwestern University. The third lecture is titled "PERfect TIMing." And now, to introduce our program, the president of the Howard Hughes Medical Institute, Dr. Thomas Cech. 2. Introduction by HHMI President Dr. Thomas Cech (01:05) Good morning, everyone, and welcome back to the Holiday Lectures on Science. Yesterday, we had a really terrific introduction to how scientists have explored the very molecular nature of what a biological clock is. Joe Takahashi talked about how the circadian clock in mammals is located in a specific part of the brain, and Michael Rosbash talked about how he and his colleagues had cloned and sequenced the period gene, "p-e-r," from the fruit fly Drosophila melanogaster. Today, our speakers will continue their story. Michael will tell you how the period gene and its protein interact in a biological feedback mechanism. Then after a break, Joe will shift the focus from the fruit fly to mammals, and he'll discuss how all of this research might also have an impact on human patients. I wish I knew more about biological clocks when I was your age. During my first year of college, I would stay up until 2:00 in the morning and then stagger out of bed for my 8:00 class.
    [Show full text]
  • Circadian Clock Genes in Drosophila: Recent Developments
    In dian Journ al of Experimental Biology Vo l. 41, August 2003, pp. 797-804 Review Article Circadian clock genes in Drosophila: Recent developments P Subramanian', E Balamurugan & G Suthakar Department of Bi ochemi stry. Faculty o f Science, Annamalai University, Annamalain agar 608002, India Circadian rh ythms provide a temporal framcwork to li vin g organi sms and are establi shed in a majority of euk aryotes and in a few prokaryotes. The mo lecul ar mechani sms of c ircadian clock is constantly being investi gated in Drosophila melanogaster. The core of th e clock mechan ism was described by a transcription-translati o n feedback loop mode l involving period (per), timeless (t im ), dc/ock and cycle gcnes. However, recent rescarch has idcntified multiple feedback loops cont rolli ng rh ythm generation and expressio n. Novcl mutations o f timeless throw more li ght on thc functions of per and tilll products. Analysis of pdf neuropcptide gene (expressed in c ircadian pacemaker cell s in Drosophila), indicate that PDF acts as the princ ipal c ircadian transmitter and is in vo lved in output path ways. The product of cryptoci!rollle is known to functi on as a circadian photoreceptor as well as component of the circadian clock. This review focuses on thc recent progress in th c fie ld of molecular rhythm research in the fruit n y. The genc(s) andthc gcne product(s) that are in volved in the transmi ssion of environment al information to the clock, as well as the timing signal s from the clock outward to ccllular functi ons are remai n to be determined.
    [Show full text]
  • Ncomms6697.Pdf
    ARTICLE Received 23 May 2014 | Accepted 29 Oct 2014 | Published 16 Dec 2014 DOI: 10.1038/ncomms6697 An ecdysone-responsive nuclear receptor regulates circadian rhythms in Drosophila Shailesh Kumar1, Dechun Chen1, Christopher Jang1, Alexandra Nall1, Xiangzhong Zheng1 & Amita Sehgal1,2 Little is known about molecular links between circadian clocks and steroid hormone signalling, although both are important for normal physiology. Here we report a circadian function for a nuclear receptor, ecdysone-induced protein 75 (Eip75/E75), which we iden- tified through a gain-of-function screen for circadian genes in Drosophila melanogaster. Overexpression or knockdown of E75 in clock neurons disrupts rest:activity rhythms and dampens molecular oscillations. E75 represses expression of the gene encoding the transcriptional activator, CLOCK (CLK), and may also affect circadian output. PER inhibits the activity of E75 on the Clk promoter, thereby providing a mechanism for a previously proposed de-repressor effect of PER on Clk transcription. The ecdysone receptor is also expressed in central clock cells and manipulations of its expression produce effects similar to those of E75 on circadian rhythms. We find that E75 protects rhythms under stressful conditions, suggesting a function for steroid signalling in the maintenance of circadian rhythms in Drosophila. 1 Department of Neuroscience, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA. 2 Howard Hughes Medical Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA. Correspondence and requests for materials should be addressed to A.S. (email: [email protected]). NATURE COMMUNICATIONS | 5:5697 | DOI: 10.1038/ncomms6697 | www.nature.com/naturecommunications 1 & 2014 Macmillan Publishers Limited. All rights reserved.
    [Show full text]
  • Circadian Rhythms New Functions for Old Clock Genes?
    Clock genes Perspective Circadian rhythms new functions for old clock genes? The mechanisms of circadian clocks, which time daily events, are being investigated by characterizing ‘clock genes’ that affect daily rhythms. The core of the clock mechanism in Drosophila, Neurospora, mammals and cyanobacteria is described by a transcription–translation feedback-loop model. However, problems with this model could indicate that it is time to look at the functions of these genes in a different light. Our a priori assumptions about the nature of circadian clocks might have restricted our search for new mutants in ways that prevent us from finding important clock genes. ow does a fungus, or a fruitfly, or a mouse, tell time? levels, which beget rhythmic protein levels, which beget HWhat are the molecular mechanisms of the circadian rhythmic DNA-binding activity, which begets rhythmic clocks (Boxes 1 and 2) that allow organisms to measure transcription, and so on; this sequence of events takes the passage of a day, and regulate their activities appropri- approximately 24 hours to complete one loop. The identity ately? There has recently been an explosion1 of interest in of the components might be different in different species, this topic, with the isolation of new ‘clock genes’ (Box 2), but the structure of this causal chain is assumed to be simi- the finding of homologous clock genes in Drosophila lar. Although this model has now been applied to melanogaster and mammals, and the identification of a Neurospora, mammals and cyanobacteria, it has never had common sequence motif, the PAS domain (Box 2), in the potential to be a universal mechanism.
    [Show full text]
  • Disturbed Prefrontal Cortex Activity in the Absence of Schizophrenia-Like Behavioral Dysfunction in Arc/Arg3.1 Deficient Mice
    The Journal of Neuroscience, October 9, 2019 • 39(41):8149–8163 • 8149 Behavioral/Cognitive Disturbed Prefrontal Cortex Activity in the Absence of Schizophrenia-Like Behavioral Dysfunction in Arc/Arg3.1 Deficient Mice X Xiaoyan Gao,1 Jasper Grendel,1 Mary Muhia,2 Sergio Castro-Gomez,1 Ute Su¨sens,1 XDirk Isbrandt,3,4,5 Matthias Kneussel,2 XDietmar Kuhl,1 and XOra Ohana1 1Institute for Molecular and Cellular Cognition, 2Institute for Molecular Neurogenetics, 3Experimental Neuropediatrics, Center for Molecular Neurobiology Hamburg, University Medical Center Hamburg–Eppendorf, 20251 Hamburg, Germany, 4Institute for Molecular and Behavioral Neuroscience, University of Cologne, 50937 Cologne, Germany, and 5Experimental Neurophysiology, German Center for Neurodegenerative Diseases, 53175 Bonn, Germany Arc/Arg3.1, an activity regulated immediate early gene, is essential for learning and memory, synaptic plasticity, and maturation of neural networks. It has also been implicated in several neurodevelopmental disorders, including schizophrenia. Here, we used male and female constitutive and conditional Arc/Arg3.1 knock-out (KO) mice to investigate the causal relationship between Arc/Arg3.1 deletion and schizophrenia-linked neurophysiological and behavioral phenotypes. Using in vivo local field potential recordings, we observed damp- ened oscillatory activity in the prefrontal cortex (PFC) of the KO and early conditional KO (early-cKO) mice, in which Arc/Arg3.1 was deleted perinatally. Whole-cell patch-clamp recordings from neurons in PFC slices revealed altered synaptic properties and reduced network gain in the KO mice as possible mechanisms underlying the oscillation deficits. In contrast, we measured normal oscillatory activity in the PFC of late conditional KO (late-cKO) mice, in which Arc/Arg3.1 was deleted during late postnatal development.
    [Show full text]
  • Biological Clocks
    Corrections BIOCHEMISTRY. For the article ‘‘BH4 domain of antiapoptotic FROM THE ACADEMY. For the article ‘‘Biological clocks’’ by Norio Bcl-2 family members closes voltage-dependent anion channel Ishida, Maki Kaneko, and Ravi Allada, which appeared in and inhibits apoptotic mitochondrial changes and cell death’’ by number 16, August 3, 1999, of Proc. Natl. Acad. Sci. USA (96, Shigeomi Shimizu, Akimitsu Konishi, Takashi Kodama, and 8819–8820), the authors note that (i) the first name of Dr. Honjo Yoshihide Tsujimoto, which appeared in number 7, March 28, that appeared in the acknowledgments is misspelled and should 2000, of Proc. Natl. Acad. Sci. USA (97, 3100–3105), it has been be Tasuku and (ii) the name of the last author in ref. 5 also is brought to the authors’ attention that Fig. 3A is identical to figure misspelled and should be Tanimura. 1c in our previous article published in Nature [Shimizu, S., Narita, M. & Tsujimoto, Y. (1999) Nature (London) 399, Correction published online before print: Proc. Natl. Acad. Sci. USA, 10.1073͞ 483–487]. Although the two figures report different experi- pnas.160264397. Text and publication date are at www.pnas.org͞cgi͞doi͞10.1073͞ ments, the PNAS paper is correct as it stands; the authors pnas.160264397 submitted the figure to Nature by mistake and regret the error. CORRECTIONS PNAS ͉ August 1, 2000 ͉ vol. 97 ͉ no. 16 ͉ 9347 Downloaded by guest on September 27, 2021 Proc. Natl. Acad. Sci. USA Vol. 96, pp. 8819–8820, August 1999 From the Academy This paper is a summary of a session presented at the first Japanese-American Frontiers of Science symposium, held August 21–23, 1998, at the Arnold and Mabel Beckman Center of the National Academies of Sciences and Engineering in Irvine, CA.
    [Show full text]
  • Mental Disorders Among Adults with Asthma: Results from the World Mental Health Survey Kate M
    General Hospital Psychiatry 29 (2007) 123–133 Mental disorders among adults with asthma: results from the World Mental Health Survey Kate M. Scott, Ph.D.a,4, Michael Von Korff, Sc.D. b, Johan Ormel, Ph.D.c, Ming-yuan Zhang, M.D.d, Ronny Bruffaerts, Ph.D.e, Jordi Alonso, M.D., Ph.D.f, Ronald C. Kessler, Ph.D.g, Hisateru Tachimori, Ph.D.h, Elie Karam, M.D.i, Daphna Levinson, Ph.D.j, Evelyn J. Bromet, Ph.D.k, Jose´ Posada-Villa, M.D.l, Isabelle Gasquet, M.D., Ph.D.m, Matthias C. Angermeyer, M.D.n, Guilherme Borges, Ph.D.o, Giovanni de Girolamo, M.D.p, Allen Herman, M.D., Ph.D.q, Josep Maria Haro, M.D., Ph.D.r aDepartment of Psychological Medicine, Wellington School of Medicine and Health Sciences, University of Otago, P.O. Box 7343, Wellington South, New Zealand bCenter for Health Studies, Group Health Cooperative, Seattle, WA 98101, USA cDepartment of Psychiatry, University Medical Center Groningen, Groningen 9700 RB, The Netherlands dShanghai Mental Health Center, Shanghai 200030, China eDepartment of Neurosciences and Psychiatry, University Hospital Gasthuisberg, Leuven B-300, Belgium fHealth Services Research Unit, Institut Municipal d’Investigacio Medica (IMIM), E-08003 Barcelona, Spain gDepartment of Health Care Policy, Harvard Medical School, Boston, MA 02115, USA hNational Institute of Mental Health, National Center of Neurology and Psychiatry, Kodaira-Shi, Tokyo 187-8502, Japan iInstitute for Development, Research, Advocacy and Applied Care (IDRAAC), 166227 Achrafieh, Beirut 1100 2110, Lebanon jMental Health Services, Ministry of
    [Show full text]