Kuru, the First Human Prion Disease "2279

Total Page:16

File Type:pdf, Size:1020Kb

Kuru, the First Human Prion Disease viruses Review Kuru, the First Human Prion Disease † 1, 2 1 3 PawePawełł P. LiberskiLiberski 1,*,* Agata, Agata Gajos Gajos 2, Beata, Beata Sikorska Sikorska 1 and Shirleyand Shirley Lindenbaum Lindenbaum 3 1 1 LaboratoryLaboratory of of Electron Electron Microscopy Microscopy and and Neurop Neuropathology,athology, Department Department of of Molecular Molecular Pathology Pathology and and Neuropathology,Neuropathology, Medical Medical University University Lodz, Lodz, 90-419 90-419 Lodz, Lodz, Poland; Poland; [email protected] [email protected] 2 Department of Extrapyramidal Diseases, Medical University of Lodz, 90-419 Lodz, Poland; 2 Department of Extrapyramidal Diseases, Medical University of Lodz, 90-419 Lodz, Poland; [email protected] [email protected] 3 Department of Anthropology, Graduate Center, City University of New York, New York, NY 10016, USA; 3 Department of Anthropology, Graduate Center, City University of New York, New York, NY 10016, USA; [email protected] [email protected] * Correspondence: [email protected] * Correspondence: [email protected] † This paper is dedicated to late Daniel Carleton Gajdusek (1923–2008). † This paper is dedicated to late Daniel Carleton Gajdusek (1923–2008). Received: 1 February 2019; Accepted: 1 March 2019; Published: date 7 March 2019 Abstract: Kuru,Kuru, the the first first human prion disease was tran transmittedsmitted to chimpanzees by D. Carleton Gajdusek (1923–2008). In In this this review, review, we we summar summarizeize the the history history of of this this seminal discovery, its anthropological background,background, epidemiology, epidemiology, clinical clinical picture, picture, neuropathology, neuropathology, and molecular and molecular genetics. Wegenetics. provide We descriptions provide descriptions of electron of microscopyelectron micr andoscopy confocal and confocal microscopy microscopy of kuru amyloidof kuru amyloid plaques plaquesretrieved retrieved from a paraffin-embedded from a paraffin-embedded block of anbloc oldk of kuru an case,old kuru named case, Kupenota. named Kupenota. The discovery The discoveryof kuru opened of kuru new opened vistas ofnew human vistas medicine of huma andn medicine was pivotal and in was the subsequentpivotal in the transmission subsequent of transmissionCreutzfeldt–Jakob of Creutzfeldt–Jakob disease, as well as disease, the relevance as well that as bovine the relevance spongiform that encephalopathy bovine spongiform had for encephalopathytransmission to humans. had for transmission The transmission to humans. of kuru wasThe onetransmission of the greatest of kuru contributions was one of to the biomedical greatest contributionssciences of the to 20th biomedical century. sciences of the 20th century. Keywords: Kuru; prion diseases; neuropathology; Carleton Gajdusek 1. Introduction “Kuru”, the first first prion disease, was discovered by D. Carleton GajdusekGajdusek (Figure(Figure1 1))[ 1[1–11].–11]. Figure 1.Figure Dr. D. 1. CarletonDr. D. Carleton Gajdusek Gajdusek (lhr-57-ng-332) (lhr-57-ng-332).. Courtesy Courtesy of D. Carleton of D. Carleton Gajdusek. Gajdusek. Viruses 2019,, 11,, 232;x; doi: doi: FOR10.3390/v11030232 PEER REVIEW www.mdpi.com/journal/viruseswww.mdpi.com/journal/viruses Viruses 2019, 11, 232 2 of 25 Viruses 2019, 11, x FOR PEER REVIEW 2 of 24 It was also the firstfirst humanhuman prion diseasedisease transmitted to chimpanzees and was classified classified as “a transmissible spongiform encephalopathy” (TSE), or slow unconventional virus disease. It was first first reported in two publications by Gajdusek andand VincentVincent ZigasZigas inin 19571957 (Figure(Figure2 2))[ 12[12,13].,13]. Figure 2. Dr. Vin Zigas (dcg-57-ng-336). Cour Courtesytesy of D. Carleton Gajdusek. The definitiondefinition ofof kurukuru asas bothboth neurodegenerative neurodegenerative (not (not inflammatory) inflammatory) and and infectious infectious [14 [14,15],15] led led to tosubsequent subsequent transmission transmission of Creutzfeldt–Jakob of Creutzfeldt–Jako diseaseb disease (CJD) [ 16(CJD)] and suggested[16] and suggested that kuru represents that kuru a representsnovel class a of novel diseases class caused of diseases by a novel caused class by of a pathogensnovel class called of pathogens prions. Kurucalled won prions. a Nobel Kuru prize won for a NobelGajdusek prize in 1976for Gajdusek and, indirectly, in 1976 as and, he discoveredindirectly, “prions”,as he discovered for Stanley “prions”, B. Prusiner for Stanley in 1997. B. Kuru Prusiner was inlinked, 1997. also Kuru indirectly, was linked, to a also third indirectly, Nobel Prize to a for third Kurt Nobel Wüthrich, Prize for who Kurt determined Wüthrich, the who structure determined of the prionthe structure protein of [17 the]. Asprion Gajdusek protein emphasized[17]. As Gajdusek for the emphasized last time in for his the life la atst thetime Royal in his Society life at the meeting Royal Societyon kuru meeting in 2007 [on18 ],kuru the researchin 2007 [18], on kuru the research advanced on the kuru ideas advanced of molecular the ideas casting, of molecular dermatoglyphics, casting, dermatoglyphics,osmium shadowing osmium in electron shadowing microscopy, in electron and amyloid-enhancing microscopy, and amyloid-enhancing factors. Kuru research factors. impacted Kuru researchthe concepts impacted of nucleation–polymerization the concepts of nucleation–polymerization and led to an idea of and conformational led to an idea disorders of conformational [19–21] or prionoidsdisorders [19–21] [22]. or prionoids [22]. 2. Background and Ethnographic Setting “Kuru”, in the Fore language (Figures 33 andand4 ),4), means means to to tremble tremble from from fever fever or or cold cold [ [23–36]:23–36]: “The“The nativesnatives ofof almostalmost all all of of the the Fore Fore hamlets hamlets have have stated stated that that it hasit has been been present present for for a ‘long a ‘long time’, time’, but butthey they soon soon modify modify to mean to mean that that in recent in recent years year it hass it becomehas become an increasingly an increasingly severe severe problem problem and thatand thatin the in early the early youth youth of our of oldestour oldest informants informants there there was nowas kuru no kuru at all” at [all”15]. [15]. Viruses 2019, 11, 232 3 of 25 Viruses 2019,, 11,, xx FORFOR PEERPEER REVIEWREVIEW 3 of 24 Figure 3. AA general general view view of of a Fore hamlet. A A kuru kuru victim victim is is sitting sitting in in the the first first row between two supporters (dcg-ng-bw-12). Courtesy of D. Carleton Gajdusek. Figure 4. AA general general view of a Fore hamlet (dcg-57-ng (dcg-57-ng-186).-186).-186). CourtesyCourtesy ofof D.D. CarletonCarleton Gajdusek. Gajdusek. The disease was confined confined to natives of the Fore linguistic group in Papua New Guinea’s Eastern Highlands andand neighboring neighboring linguistic linguistic groups groups (Auiana, (Auiana, Awa, Awa, Usurufa, Usurufa, Kanite, Kanite, Keiagana, Keiagana, Iate, Kamano, Iate, Kamano,and Gimi). and The Gimi). Fore The reports Fore suggested reports suggested that kuru that first kuru appeared first appeared at Uwami, at a Uwami, Keiagana a villageKeiagana to villagethe northwest, to the northwest, around 1900, around and 1900, then and in then the North in the North Fore around Fore around 1920. 1920. It then It then traveled traveled down down the thesoutheastern southeastern border, border, arriving arriving at Wanitabe at Wanitabe in the in central the central South ForeSouth by Fore 1930. by From 1930. Wanikanto, From Wanikanto, where it whereappeared it appeared in 1927, it in turned 1927, towardit turned the toward northwest, the no torthwest, Miarasa to and Miarasa Paigata. and The Paigata. first cases Theat first Purosa, cases six at Purosa,miles south six ofmiles Wanitabe, south appearedof Wanitabe, in the appeared 1930s, and, in inthe some 1930s, southwestern and, in some and southeasternsouthwestern areas, and southeasternit arrived as lateareas, as it the arrived 1940s as (see late map as the [37 1940s]). Zigas (see map and Gajdusek[37]). Zigas [38 and] noticed Gajdusek that, [38] when noticed the that, Fore whenpeople the at KasaraiFore people moved at Kasarai temporarily moved to livetemporarily with the to Yar live people with andthe Yar settled people there and for settled about athere decade, for aboutkuru casesa decade, still kuru occurred. cases still As Lindenbaumoccurred. As Lindenba observedum [39 observed], the Fore [39], descriptions the Fore descriptionsdescriptions of their encounter ofof theirtheir encounterwith the new with disease the new were disease rich in were detail. rich It in is detail. now thought It isis nownow that thoughtthought kuru first thatthatarose kurukuru infirstfirst asingle arosearose individualinin aa singlesingle individualfromindividual a spontaneous fromfrom aa spontaneousspontaneous change that changechange created thatthat a pathogenic, createdcreated aa pathogenic,pathogenic, infectious agentinfectiousinfectious in the agentagent brain, inin inthethe the brain,brain, same inin way thethe samethat sporadic way that Creutzfeldt–Jakob sporadic Creutzfeldt–Jakob disease occurs. disease The occurs. recycling The of recycling the infectious of the agent infectious through agent the throughconsumption the consumption of deceased of relatives deceased amplified relatives the ampl agentifiedified and thethethe agentagent disease andand thethe in the diseasedisease community, inin
Recommended publications
  • A Spongiform Encephalopathy Outbreak: Anthropophagy Or Not?
    A SPONGIFORM ENCEPHALOPATHY OUTBREAK: ANTHROPOPHAGY OR NOT? Mani Vessal A thesis submitted to the Faculty of Graduate Studies and Research in partial fulfilmrnt of the requirements for the degree of Master of Arts Department of Anthropology Carleton University Ottawa, Ontario June 281 1 999 copyright 1999, Mani Vessal National Library Bibliothèque nationale ($1 of Canada du Canada Acquisitions and Acquisitions et Bibliographie Services seMces bibliographiques 395 Wellington Street 395, rue Wellington Ottawa ON KIA ON4 Otiawa ON KiA OF14 Canada Canada Your fi& Vorre refamœ Our IW Notre feWrI)Ree The author has granted a non- L'auteur a accordé une licence non exclusive Licence allowing the exclusive permettant à la National Library of Canada to Bibliothèque nationale du Canada de reproduce, loan, distribute or sel1 reproduire, prêter, distribuer ou copies of ths thesis in rnicroform, vendre des copies de cette thèse sous paper or electronic formats. la forme de rnicrofiche/fd.m, de reproduction sur papier ou sur format électronique. The author retains ownership of the L'auteur conserve la propriété du copyright in this thesis. Neither the droit d'auteur qui protège cette thèse. thesis nor substantial extracts fiom it Ni la thèse ni des extraits substantiels may be p~tedor otherwike de celle-ci ne doivent être imprimés reproduced without the author's ou autrement reproduits sans son permission. autorisation. Abstract Since the Kum endemic among the Fore Papua New Guinea, there have ken numerous theories proposed to explain the mode of transmission of the agent responsible for the spread of this fatal neurodegenerative disorder. The "cannibaiism" theory proposed by S.
    [Show full text]
  • A Review on Kuru: Fatal Neurodenegerative Disease”
    IOSR Journal Of Pharmacy And Biological Sciences (IOSR-JPBS) e-ISSN:2278-3008, p-ISSN:2319-7676. Volume 15, Issue 3 Ser. II (May –June 2020), PP 10-15 www.Iosrjournals.Org A Review on Kuru: Fatal Neurodegenerative Disease Dr.Velicharla Raviteja1, Ms SaiSreeja Meka2 Department Of Pharm. D, Holy Mary Institute Of Technology And Science(College Of Pharmacy), Keesara, Hyderabad, Telangana-501 301 Abstract: Kuru, a very rare fatal neurodegenerative disease. It mainly affects the cerebellar region of the brain. It is caused by infectious proteins called prions. These prions are a deviant form of harmless protein. Kuru is a transmissible spongiform encephalopathy, prion disease. It is a human prion disease. The symptoms include tremors, loss of coordination, depression, muscle spasms and behavioural changes and ultimately lead to death. The incubation period of this disease varies from person to person and it could be as short as 5years and could be as long as 50 years. It is most prevalently seen in Papua New Guinea where a ritual of cannibalism is practiced, where most of the elderly women and children are affected as they are the one to whom human brain is given to consume during cannibalism. The neuropathological changes are observed on brain tissue during biopsy or after death. There is no treatment for this disease only supportive therapy is given. Moreover, this disease is almost vanished as there are no cases reported in recent years. The practice of cannibalism ritual was also banned by Australian government in 1960s. Keywords:kuru, neurodegenerative disease, prions, transmissible spongiform encephalopathy, tremors, cannibalism, biopsy.
    [Show full text]
  • Transmissibility Versus Pathogenicity of Self-Propagating Protein Aggregates
    viruses Review Transmissibility versus Pathogenicity of Self-Propagating Protein Aggregates Byron Caughey 1,* and Allison Kraus 2,* 1 Laboratory of Persistent Viral Diseases, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT 59840, USA 2 Department of Pathology, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA * Correspondence: [email protected] (B.C.); [email protected] (A.K.); Tel.: +1-406-363-9264 (B.C.) Received: 26 September 2019; Accepted: 6 November 2019; Published: 9 November 2019 Abstract: The prion-like spreading and accumulation of specific protein aggregates appear to be central to the pathogenesis of many human diseases, including Alzheimer’s and Parkinson’s. Accumulating evidence indicates that inoculation of tissue extracts from diseased individuals into suitable experimental animals can in many cases induce the aggregation of the disease-associated protein, as well as related pathological lesions. These findings, together with the history of the prion field, have raised the questions about whether such disease-associated protein aggregates are transmissible between humans by casual or iatrogenic routes, and, if so, do they propagate enough in the new host to cause disease? These practical considerations are important because real, and perhaps even only imagined, risks of human-to-human transmission of diseases such as Alzheimer’s and Parkinson’s may force costly changes in clinical practice that, in turn, are likely to have unintended consequences. The prion field has taught us that a single protein, PrP, can aggregate into forms that can propagate exponentially in vitro, but range from being innocuous to deadly when injected into experimental animals in ways that depend strongly on factors such as conformational subtleties, routes of inoculation, and host responses.
    [Show full text]
  • Chapitre Quatre La Spécificité D'hôtes Des Virophages Sputnik
    AIX-MARSEILLE UNIVERSITE FACULTE DE MEDECINE DE MARSEILLE ECOLE DOCTORALE DES SCIENCES DE LA VIE ET DE LA SANTE THESE DE DOCTORAT Présentée par Morgan GAÏA Né le 24 Octobre 1987 à Aubagne, France Pour obtenir le grade de DOCTEUR de l’UNIVERSITE AIX -MARSEILLE SPECIALITE : Pathologie Humaine, Maladies Infectieuses Les virophages de Mimiviridae The Mimiviridae virophages Présentée et publiquement soutenue devant la FACULTE DE MEDECINE de MARSEILLE le 10 décembre 2013 Membres du jury de la thèse : Pr. Bernard La Scola Directeur de thèse Pr. Jean -Marc Rolain Président du jury Pr. Bruno Pozzetto Rapporteur Dr. Hervé Lecoq Rapporteur Faculté de Médecine, 13385 Marseille Cedex 05, France URMITE, UM63, CNRS 7278, IRD 198, Inserm 1095 Directeur : Pr. Didier RAOULT Avant-propos Le format de présentation de cette thèse correspond à une recommandation de la spécialité Maladies Infectieuses et Microbiologie, à l’intérieur du Master des Sciences de la Vie et de la Santé qui dépend de l’Ecole Doctorale des Sciences de la Vie de Marseille. Le candidat est amené à respecter des règles qui lui sont imposées et qui comportent un format de thèse utilisé dans le Nord de l’Europe permettant un meilleur rangement que les thèses traditionnelles. Par ailleurs, la partie introduction et bibliographie est remplacée par une revue envoyée dans un journal afin de permettre une évaluation extérieure de la qualité de la revue et de permettre à l’étudiant de commencer le plus tôt possible une bibliographie exhaustive sur le domaine de cette thèse. Par ailleurs, la thèse est présentée sur article publié, accepté ou soumis associé d’un bref commentaire donnant le sens général du travail.
    [Show full text]
  • Alpha-Satellite RNA Transcripts Are Repressed by Centromere
    RESEARCH ARTICLE Alpha-satellite RNA transcripts are repressed by centromere–nucleolus associations Leah Bury1†, Brittania Moodie1†, Jimmy Ly1,2, Liliana S McKay1, Karen HH Miga3, Iain M Cheeseman1,2* 1Whitehead Institute for Biomedical Research, Cambridge, United States; 2Department of Biology, Massachusetts Institute of Technology, Cambridge, United States; 3UC Santa Cruz Genomics Institute, University of California, Santa Cruz, Santa Cruz, United States Abstract Although originally thought to be silent chromosomal regions, centromeres are instead actively transcribed. However, the behavior and contributions of centromere-derived RNAs have remained unclear. Here, we used single-molecule fluorescence in-situ hybridization (smFISH) to detect alpha-satellite RNA transcripts in intact human cells. We find that alpha-satellite RNA- smFISH foci levels vary across cell lines and over the cell cycle, but do not remain associated with centromeres, displaying localization consistent with other long non-coding RNAs. Alpha-satellite expression occurs through RNA polymerase II-dependent transcription, but does not require established centromere or cell division components. Instead, our work implicates centromere– nucleolar interactions as repressing alpha-satellite expression. The fraction of nucleolar-localized centromeres inversely correlates with alpha-satellite transcripts levels across cell lines and transcript levels increase substantially when the nucleolus is disrupted. The control of alpha-satellite transcripts by centromere-nucleolar contacts provides a mechanism to modulate centromere transcription and chromatin dynamics across diverse cell states and conditions. *For correspondence: [email protected] †These authors contributed equally to this work Introduction Chromosome segregation requires the function of a macromolecular kinetochore structure to con- Competing interests: The nect chromosomal DNA and spindle microtubule polymers.
    [Show full text]
  • Anthropology of Religion Magic and Witchcraft 3Rd Edition Stein Test Bank
    Anthropology of Religion Magic and Witchcraft 3rd Edition Stein Test Bank Full Download: https://alibabadownload.com/product/anthropology-of-religion-magic-and-witchcraft-3rd-edition-stein-test-bank/ Chapter 1: The Anthropological Study of Religion Chapter One THE ANTHROPOLOGICAL STUDY OF RELIGION CHAPTER OUTLINE THE ANTHROPOLOGICAL PERSPECTIVE The Holistic Approach The Study of Human Societies The Fore of New Guinea: An Ethnographic Example Two Ways of Viewing Culture Cultural Relativism Postmodernism Universal Human Rights The Concept of Culture Viewing the World THE STUDY OF RELIGION Attempts at Defining Religion The Domain of Religion Theoretical Approaches to the Study of Religion The Evolutionary Approach The Marxist Approach The Functional Approach The Interpretive Approach The Psychosocial Approach The Biological Basis of Religious Behavior Belief in Spirit Beings The Evolution of Religion CONCLUSION SUMMARY BOX 1.1 KAREN MCCARTHY BROWN AND VODOU BOX 1.2 MALINOWSKI AND THE TROBRIAND ISLANDS BOX 1.3 EVANS-PRITCHARD AND THE AZANDE CHAPTER SUMMARY Anthropology is the study of humanity. Anthropologists study human societies as integrated wholes, an approach that is termed holism. This approach is seen in the broad scope of anthro- 1 This sample only, Download all chapters at: AlibabaDownload.com Instructor’s Manual for The Anthropology of Religion, Magic, and Witchcraft pology, which is often divided into the fields of physical anthropology, archaeology, linguistic anthropology, and cultural anthropology. This approach requires that societies be studied over long periods of time, during which the investigator lives within the community and participates in the lives of the people under study, a technique known as participant observation.
    [Show full text]
  • Scrapie and Tagging/Tattooing Your Goats and Sheep 2017 PRESENTATION for ASHTABULA COUNTY 4-H by STEPHANIE MAROUS What Is Scrapie?
    Scrapie and Tagging/Tattooing Your Goats and Sheep 2017 PRESENTATION FOR ASHTABULA COUNTY 4-H BY STEPHANIE MAROUS What is Scrapie? Scrapie is a fatal degenerative disease of the central nervous system of sheep and goats. (Basically it is the sheep and goat version of Mad Cow Disease) Scrapie is commonly spread from a female to her offspring. Other members of the herd can catch it through contact with the placenta or its fluids. Scrapie can only truly be tested after an animal is dead. This is done by testing the brain tissue and looking for the disease. SYMPTOMS Symptoms may take 2-5 years to appear Head and Neck Tremors Skin Itching (this is where the term scrapie comes from) Inability to control legs (remember this attacks the Nervous System) Good appetite accompanied by weight loss. Remember just because an animal exhibits these symptoms does not mean it has scrapie. Consult your Vet to rule out possible reasons for symptoms. Scrapie Eradication Program The National Scrapie Eradication Program, coordinated by the U.S. Department of Agriculture’s (USDA) Animal and Plant Health Inspection Service (APHIS), has reduced the prevalence of scrapie by over 85 percent. To find and eliminate the last few cases in the United States, the cooperation of sheep and goat producers throughout the country is needed. Producers are required to follow Federal and State regulations for officially identifying their sheep and goats. Producers must also keep herd records showing what new animals were added and what animals left the herd/flock Scrapie Eradication Program APHIS provides official plastic or metal eartags free of charge to producers.
    [Show full text]
  • Genetic Studies in Relation to Kuru: an Overview
    Current Molecular Medicine 2004, 4, 375-384 375 Genetic Studies in Relation to Kuru: An Overview L.G. Goldfarb*, L. Cervenakova and D.C. Gajdusek National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892, USA American Red Cross J .H . Holland Laboratory , Rockville, MD 20855, USA Centre National de la Recharche Scientifique, Institut Alfred Fessard, Gif-sur-Yvette, France Abstract: Kuru is a subacute neurodegenerative disease presenting with limb ataxia, dysarthria, and a shivering tremor. The disease progress to complete motor and mental incapacity and death within 6 to 24 months. Neuropathologically, a typical pattern of neuronal loss, astrocytic and microglial proliferation, characteristic “kuru-type” amyloid plaques, and PrP deposits in the cerebral cortex and cerebellum are observed. Kuru is the prototype of a group of human transmissible spongiform encephalopathies (TSEs), or “prion” diseases, that include hereditary, sporadic and infectious forms. The latest member of this group, the variant Creutzfeldt-Jakob disease (vCJD), linked to transmission of bovine spongiform encephalopathy (BSE) to humans, shows features similar to kuru. Kuru has emerged at the beginning of the 1900s in a small indigenous population of New-Guinean Eastern Highlands, reached epidemic proportions in the mid-1950s and disappeared progressively in the latter half of the century to complete absence at the end of the 1990s. Early studies made infection, the first etiologic assumption, seem unlikely and led to a hypothesis that kuru might be a genetically determined or genetically mediated illness. After transmissibility of kuru had been discovered and all major epidemiologic phenomena adequately explained by the spread of an infectious agent with long incubation period through the practice of cannibalism, the pattern of occurrence still continued to suggest a role for genetic predisposition.
    [Show full text]
  • The Expression of Human Endogenous Retroviruses Is Modulated by the Tat Protein of HIV‐1
    The Expression of Human Endogenous Retroviruses is modulated by the Tat protein of HIV‐1 by Marta Jeannette Gonzalez‐Hernandez A dissertation submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy (Immunology) in The University of Michigan 2012 Doctoral Committee Professor David M. Markovitz, Chair Professor Gary Huffnagle Professor Michael J. Imperiale Associate Professor David J. Miller Assistant Professor Akira Ono Assistant Professor Christiane E. Wobus © Marta Jeannette Gonzalez‐Hernandez 2012 For my family and friends, the most fantastic teachers I have ever had. ii Acknowledgements First, and foremost, I would like to thank David Markovitz for his patience and his scientific and mentoring endeavor. My time in the laboratory has been an honor and a pleasure. Special thanks are also due to all the members of the Markovitz laboratory, past and present. It has been a privilege, and a lot of fun, to work near such excellent scientists and friends. You all have a special place in my heart. I would like to thank all the members of my thesis committee for all the valuable advice, help and jokes whenever needed. Our collaborators from the Bioinformatics Core, particularly James Cavalcoli, Fan Meng, Manhong Dai, Maureen Sartor and Gil Omenn gave generous support, technical expertise and scientific insight to a very important part of this project. Thank you. Thanks also go to Mariana Kaplan’s and Akira Ono’s laboratory for help with experimental designs and for being especially generous with time and reagents. iii Table of Contents Dedication ............................................................................................................................ ii Acknowledgements ............................................................................................................. iii List of Figures ...................................................................................................................
    [Show full text]
  • Chronic Wasting Disease and Atypical Forms of Bovine Spongiform
    Journal of General Virology (2012), 93, 1624–1629 DOI 10.1099/vir.0.042507-0 Short Chronic wasting disease and atypical forms of Communication bovine spongiform encephalopathy and scrapie are not transmissible to mice expressing wild-type levels of human prion protein Rona Wilson,1 Chris Plinston,1 Nora Hunter,1 Cristina Casalone,2 Cristiano Corona,2 Fabrizio Tagliavini,3 Silvia Suardi,3 Margherita Ruggerone,3 Fabio Moda,3 Silvia Graziano,4 Marco Sbriccoli,4 Franco Cardone,4 Maurizio Pocchiari,4 Loredana Ingrosso,4 Thierry Baron,5 Juergen Richt,63 Olivier Andreoletti,7 Marion Simmons,8 Richard Lockey,8 Jean C. Manson1 and Rona M. Barron1 Correspondence 1Neuropathogenesis Division, The Roslin Institute and R(D)SVS, University of Edinburgh, Roslin, Rona M. Barron Midlothian, UK [email protected] 2Istituto Zooprofilattico Sperimentale del Piemonte, Liguria e Valle d’Aosta, Turin, Italy 3IRCCS Foundation, ‘Carlo Besta’ Neurological Institute, Milan, Italy 4Department of Cell Biology and Neurosciences, Istituto Superiore di Sanita`, Viale Regina Elena 299, 00161 Rome, Italy 5Agence Nationale de Se´curite´ Sanitaire, Lyon, France 6USDA, ARS, National Animal Disease Center, PO Box 70, Ames, IA 50010, USA 7UMR 1225 Interactions Hoˆtes-Agents Pathoge`nes, INRA, Ecole Nationale Ve´te´rinaire, 23 chemin des Capelles, B.P. 87614, 31076 Toulouse Cedex 3, France 8Neuropathology Section, Department of Pathology and Host Susceptibility, Animal Health and Veterinary Laboratories Agency, Addlestone, Surrey KT15 3NB, UK The association between bovine spongiform encephalopathy (BSE) and variant Creutzfeldt–Jakob disease (vCJD) has demonstrated that cattle transmissible spongiform encephalopathies (TSEs) can pose a risk to human health and raises the possibility that other ruminant TSEs may be transmissible to humans.
    [Show full text]
  • Brain Biopsy Is More Reliable Than the DNA Test for JC Virus in Cerebrospinal Fluid for the Diagnosis of Progressive Multifocal Leukoencephalopathy
    □ CASE REPORT □ Brain Biopsy Is More Reliable than the DNA test for JC Virus in Cerebrospinal Fluid for the Diagnosis of Progressive Multifocal Leukoencephalopathy Junji Ikeda 1, Akira Matsushima 1, Wataru Ishii 1, Tetuya Goto 2, Kenta Takahashi 3, Kazuo Nakamichi 4, Masayuki Saijo 4, Yoshiki Sekijima 1 and Shu-ichi Ikeda 1 Abstract The current standard diagnostic approach for progressive multifocal leukoencephalopathy (PML) is to per- form a DNA test to identify the presence of the JC virus in cerebrospinal fluid (CSF). A 32-year-old woman with a 5-year history of systemic lupus erythematosus developed right hemiplegia and motor aphasia. MRI revealed a large white matter lesion in the left frontal lobe. JC virus DNA was undetectable in the CSF, but a brain biopsy showed typical histopathology and a high DNA load of the JC virus. The patient was treated with mefloquine and mirtazapine, and is currently alive at 24 months after onset. An early brain biopsy may therefore be important for making a timely diagnosis of PML. Key words: progressive multifocal leukoencephalopathy, JC virus, DNA test, brain biopsy, demyelination, slow virus infection (Intern Med 56: 1231-1234, 2017) (DOI: 10.2169/internalmedicine.56.7689) Introduction Case Report Progressive multifocal leukoencephalopathy (PML) is a A 32-year-old, right-handed woman was referred to us be- demyelinating disease of the central nervous system (CNS) cause of right hemiplegia and motor aphasia. She had been caused by a lytic infection of oligodendrocytes due to the diagnosed with systemic lupus erythematosus (SLE) 5 years presence of the JC polyomavirus (1).
    [Show full text]
  • The Fore Language of Papua New Guinea
    PACIFIC LINGUISTICS Se�ie� B - No. 47 THE FORE LANGUAGE OF PAPUA NEW GUINEA by Graham Scott Department of Linguistics Research School of Pacific Studies THE AUSTRALIAN NATIONAL UNIVERSITY Scott, G. The Fore language of Papua New Guinea. B-47, xvi + 225 pages. Pacific Linguistics, The Australian National University, 1978. DOI:10.15144/PL-B47.cover ©1978 Pacific Linguistics and/or the author(s). Online edition licensed 2015 CC BY-SA 4.0, with permission of PL. A sealang.net/CRCL initiative. r PACIFIC LINGUISTICS is published through the Lingu��tic Ci�cle 06 Canb e��a and consists of four series: SERIES A - OCCASIONA L PAPERS SERIES B - MONOGRAPHS SERIES C - BOOKS SERIES V - SPECIAL PUB LICATIONS EDITOR: S.A. Wurm. ASSOCIATE EDITORS: D.C. Laycock, C.L. Voorhoeve, D.T. Tryon, T.E. Dutton. EDITORIAL ADVISERS: B. Bender, University of Hawaii N.D. Liem, University of Hawaii D. Bradley, Australian National J. Lynch, University of Papua University New Guinea A. Capell, University of Sydney K.A. McElhanon, University of S. Elbert, University of Hawaii Texas K. Franklin, Summer Institute of H. McKaughan, University of Hawaii Linguistics P. MUhlh�usler, Technische W.W. Glover, Summer Institute of Universit�t Berlin Linguis tics G.N. O'Grady, University of G. Grace, University of Hawaii Victoria, B.C. M.A.K. Halliday, University of K. Pike, University of Michigan; Sydney Summer Institute of Linguistics A. Healey, Summer Institute of E.C. Polome, University of Texas Linguistics E. Uhlenbeck, University of Leiden L. Hercus, Australian National J.W.M. Verhaar, University of University Indonesia, Jakarta ALL CORRESPONDENCE concerning PA CIFIC LINGUIS TICS, including orders and subscriptions, should be addressed to: The Secretary, PACIFIC LINGUIS TICS, Department of Linguistics , School of Pacific Studies , The Australian National University , Box 4, P.O., Canberra , A.C.T.
    [Show full text]