DOCSLIB.ORG

Bathypelagic Boundary in C. Rupestris

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Bathypelagic Boundary in C. Rupestris Durham E-Theses Adaptation in the Deep Sea: How Depth Aects Morphology and Protein Function in Coryphaenoides rupestris and its Congeners STEEDS, NATASHA,JANE How to cite: STEEDS, NATASHA,JANE (2020) Adaptation in the Deep Sea: How Depth Aects Morphology and Protein Function in Coryphaenoides rupestris and its Congeners, Durham theses, Durham University. Available at Durham E-Theses Online: http://etheses.dur.ac.uk/13841/ Use policy The full-text may be used and/or reproduced, and given to third parties in any format or medium, without prior permission or charge, for personal research or study, educational, or not-for-prot purposes provided that: • a full bibliographic reference is made to the original source • a link is made to the metadata record in Durham E-Theses • the full-text is not changed in any way The full-text must not be sold in any format or medium without the formal permission of the copyright holders. Please consult the full Durham E-Theses policy for further details. Academic Support Oce, Durham University, University Oce, Old Elvet, Durham DH1 3HP e-mail: [email protected] Tel: +44 0191 334 6107 http://etheses.dur.ac.uk 2 Adaptation in the Deep Sea: How Depth Affects Morphology and Protein Function in Coryphaenoides rupestris and its Congeners Natasha Steeds Submitted to the Department of Biosciences, Durham University in fulfilment of the requirements for the degree MSCR Biological Sciences C1A009 March 2020 Material Abstract Adaptation in the Deep Sea: How Depth Affects Morphology and Protein Function in Coryphaenoides rupestris and its Congeners Natasha Steeds Although the deep sea is the largest habitat on Earth, there is little understanding of how adaptation and speciation occur across depth gradients. The roundnose grenadier, Coryphaenoides rupestris, has demonstrated genetic segregation according to habitat depth across several functional loci. In this study, 139 C. rupestris individuals were sampled for morphological analysis, and the protein OBSL1 was modelled to explore the impact of non-synonymous single nucleotide polymorphisms (SNPs) across the species’ depth range. It was confirmed that the genetic segregation is mirrored by morphological differences in deeper-living individuals. C. rupestris sampled from deeper habitats were smaller and had more slender body forms, along with larger eyes and mouth gapes. Lipid stores in the liver and swimbladder both increased with habitat depth. OBSL1, the modelled muscle protein, was shown to have tighter intra-domain boning in fish from shallower habitats. These changes were linked to changes in foraging strategy and an increased demand for energy conservation in deeper habitats. Analyses were extended to explore adaptation to even deeper habitats. OBSL1 was modelled for 13 additional Coryphaenoides species from abyssal and non-abyssal habitats. These analyses suggested that hydrostatic pressure was the key selection pressure for this protein as habitat depths increase to reach the abyssal zone. This finding was contrasted with those from the single-species analysis of C. rupestris to illustrate how selection pressures for adaptation and speciation change across a depth gradient in the deep sea. i Table of contents Material Abstract ................................................................................................................................................... i Table of Contents .................................................................................................................................................. ii Statement of Copyright ..................................................................................................................................... iv Acknowledgements ............................................................................................................................................. v Chapter 1: Introduction and Background .............................................................................................. 1 Potential for adaptation in the deep sea ................................................................................. 1 Phenotypic responses to environmental factors ...................................................................... 2 The study species Coryphaenoides rupestris ........................................................................... 5 Fishery, conservation and management ................................................................................. 8 Project rationale and aims .................................................................................................... 10 Chapter 2: Morphometric Analysis of C. rupestris ......................................................................... 11 Introduction ........................................................................................................................... 11 The mesopelagic-bathypelagic boundary ............................................................................ 11 Expected morphological trends in C. rupestris .................................................................... 12 Methods .................................................................................................................................. 18 Measurement and dissection protocol ................................................................................. 19 Otolith preparation and sectioning ....................................................................................... 21 Statistical analysis ................................................................................................................. 23 Results .................................................................................................................................... 27 Demographic and general trends.......................................................................................... 27 Single trait tests .................................................................................................................... 30 Principal component analysis .............................................................................................. 36 Clustering analyses ............................................................................................................... 41 Discussion ............................................................................................................................... 43 Demographic and general trends.......................................................................................... 43 Body size ............................................................................................................................... 44 Body shape ........................................................................................................................... 46 Energy storage ..................................................................................................................... 49 Conclusion ............................................................................................................................ 51 Chapter 3: Changes to Protein Function Across the Meso-Bathypelagic Boundary in C. rupestris ............................................................................................................................................................ 53 Introduction ........................................................................................................................... 53 Known protein adaptations to life in the deep sea ................................................................ 53 Initial exploration of potential study proteins ....................................................................... 56 OBSL1 and its function ......................................................................................................... 59 ii Methods ................................................................................................................................. 62 Initial analysis ...................................................................................................................... 62 OBSL1 size analysis ............................................................................................................. 63 SNP modelling ...................................................................................................................... 64 Results .................................................................................................................................... 66 Initial analysis ...................................................................................................................... 66 OBSL1 size analysis ............................................................................................................. 68 SNP modelling ...................................................................................................................... 69 Discussion .............................................................................................................................. 74 Chapter 4: Beyond C. rupestris: Changes to Protein Structure and Function Across the Abyssal Boundary in Coryphaenoides .......................................................................................... 82 Introduction .......................................................................................................................... 82 The abyssal zone ..................................................................................................................
Load more

Recommended publications
  • Clinical Utility Gene Card For: 3-M Syndrome – Update 2013
    European Journal of Human Genetics (2014) 22, doi:10.1038/ejhg.2013.156 & 2014 Macmillan Publishers Limited All rights reserved 1018-4813/14 www.nature.com/ejhg CLINICAL UTILITY GENE CARD UPDATE Clinical utility gene card for: 3-M syndrome – Update 2013 Muriel Holder-Espinasse*,1, Melita Irving1 and Vale´rie Cormier-Daire2 European Journal of Human Genetics (2014) 22, doi:10.1038/ejhg.2013.156; published online 31 July 2013 Update to: European Journal of Human Genetics (2011) 19, doi:10.1038/ejhg.2011.32; published online 2 March 2011 1. DISEASE CHARACTERISTICS nonsense and missense mutations c.4333C4T (p.Arg1445*) and 1.1 Name of the disease (synonyms) c.4391A4C (p.His1464Pro), respectively, render CUL7 deficient 3-M syndrome (gloomy face syndrome, dolichospondylic dysplasia). in recruiting ROC1, leading to impaired ubiquitination. OBSL1: microsatellites analysis of the locus (2q35-36.1) in con- 1.2 OMIM# of the disease sanguineous families. OBSL1: microsatellites analysis of the locus 273750. (2q35-36.1) in consanguineous families. Mutations induce non- sense mediated decay. Knockdown of OBSL1 in HEK293 cells 1.3 Name of the analysed genes or DNA/chromosome segments shows the role of this gene in the maintenance of normal levels of CUL7, OBSL1 and CCDC8.1–5 CUL7. Abnormal IGFBP2 andIGFBP5 mRNA levels in two patients with OBSL1 mutations, suggesting that OBSL1 modulates the 1.4 OMIM# of the gene(s) expression of IGFBP proteins. CCDC8: microsatellites analysis 609577 (CUL7), 610991 (OBSL1) and 614145 (CCDC8). at the locus (19q13.2-q13.32). CCDC8, 1-BP DUP, 612G and CCDC8, 1-BP.
    [Show full text]
  • Why It Is Difficult to Distinguish the Silver-Russell
    Why it is dicult to distinguish the Silver-Russell syndrome (SRS) and 3M syndrome in clinical practice Beibei Zhang Department of Endocrinology, Genetics, Metabolism, Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health, Beijing 100045, China Chunxiu Gong ( [email protected] ) Department of Endocrinology, Genetics, Metabolism, Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health, Beijing 100045, China Research Keywords: Silver-Russell syndrome, 3M syndrome, NH-CSS, Phenotype Posted Date: April 15th, 2020 DOI: https://doi.org/10.21203/rs.3.rs-22088/v1 License: This work is licensed under a Creative Commons Attribution 4.0 International License. Read Full License Page 1/10 Abstract Background: To analyze why 3M syndrome can be regarded as a SRS-like syndrome by examining the patients with 3M syndrome and research the connection between 3M syndrome and SRS. Methods: The term “3M syndrome” was retrieved by Web of Science and the 3M patients were screened by NH-CSS to determine whether it was consist with the diagnosis of clinical SRS, and to analyze the relationship between the two diseases by exploring literature. Results: Among patients with 3M syndrome, 60/70 (83%) were in accordance with clinical SRS, and the coincidence rates of CUL7, OBSL1, CCDC8 gene mutations were: 30 (42%), 17 (24%) and 4 (6%) respectively; The phenotypes of 3M syndrome conrmed as clinical SRS were SGA (90%), short stature (100%), forehead protruding (100%), relative macrocephaly (100%), feeding diculties/low BMI (33%), body asymmetry (0); Skeletal abnormalities and pathogenesis were previously considered as the key points of differentiation also were overlaps between two diseases; Symptomatic treatment and GH- treatment were carried out.
    [Show full text]
  • Murine Obscurin and Obsl1 Have Functionally Redundant Roles in Sarcolemmal Integrity, Sarcoplasmic Reticulum Organization, and Muscle Metabolism
    UC San Diego UC San Diego Previously Published Works Title Murine obscurin and Obsl1 have functionally redundant roles in sarcolemmal integrity, sarcoplasmic reticulum organization, and muscle metabolism. Permalink https://escholarship.org/uc/item/46t7g5hw Journal Communications biology, 2(1) ISSN 2399-3642 Authors Blondelle, Jordan Marrocco, Valeria Clark, Madison et al. Publication Date 2019 DOI 10.1038/s42003-019-0405-7 Peer reviewed eScholarship.org Powered by the California Digital Library University of California ARTICLE https://doi.org/10.1038/s42003-019-0405-7 OPEN Murine obscurin and Obsl1 have functionally redundant roles in sarcolemmal integrity, sarcoplasmic reticulum organization, and muscle metabolism 1234567890():,; Jordan Blondelle1,7, Valeria Marrocco1,7, Madison Clark1, Patrick Desmond1, Stephanie Myers1, Jim Nguyen1, Matthew Wright1, Shannon Bremner2, Enrico Pierantozzi3, Samuel Ward2, Eric Estève1,4, Vincenzo Sorrentino 3, Majid Ghassemian5 & Stephan Lange 1,6 Biological roles of obscurin and its close homolog Obsl1 (obscurin-like 1) have been enig- matic. While obscurin is highly expressed in striated muscles, Obsl1 is found ubiquitously. Accordingly, obscurin mutations have been linked to myopathies, whereas mutations in Obsl1 result in 3M-growth syndrome. To further study unique and redundant functions of these closely related proteins, we generated and characterized Obsl1 knockouts. Global Obsl1 knockouts are embryonically lethal. In contrast, skeletal muscle-specific Obsl1 knockouts show a benign phenotype similar to obscurin knockouts. Only deletion of both proteins and removal of their functional redundancy revealed their roles for sarcolemmal stability and sarcoplasmic reticulum organization. To gain unbiased insights into changes to the muscle proteome, we analyzed tibialis anterior and soleus muscles by mass spectrometry, unco- vering additional changes to the muscle metabolism.
    [Show full text]
  • Interactions with Titin and Myomesin Target Obscurin and Obscurin-Like 1 to the M-Band – Implications for Hereditary Myopathies
    Research Article 1841 Interactions with titin and myomesin target obscurin and obscurin-like 1 to the M-band – implications for hereditary myopathies Atsushi Fukuzawa1,*, Stephan Lange1,*,‡, Mark Holt1, Anna Vihola2, Virginie Carmignac3,4,§, Ana Ferreiro3,4, Bjarne Udd2,5 and Mathias Gautel1,¶ 1Kingʼs College London, The Randall Division for Cell and Molecular Biophysics, and Cardiovascular Division, New Huntʼs House, London SE1 1UL, UK 2The Folkhälsan Institute of Genetics and Department of Medical Genetics, University of Helsinki, Biomedicum, Helsinki, Finland 3INSERM, U582, Institut de Myologie, Paris, France 4Université Pierre et Marie Curie, Paris, France 5Department of Neurology, Vasa Central Hospital, Vasa, Finland *These authors contributed equally to this work ‡Current address: Department of Medicine, University of California San Diego, USA §Current address: Department of Experimental Medical Science, Lund University, Sweden ¶Author for correspondence (e-mail: [email protected]) Accepted 11 March 2008 Journal of Cell Science 121, 1841-1851 Published by The Company of Biologists 2008 doi:10.1242/jcs.028019 Summary Obscurin, a giant modular muscle protein implicated in G- does overexpression of the binding sites on either myomesin, protein and protein-kinase signalling, can localize to both obscurin or Obsl1. Furthermore, all titin mutations that have sarcomeric Z-disks and M-bands. Interaction of obscurin with been linked to limb-girdle muscular dystrophy 2J (LGMD2J) the Z-disk is mediated by Z-disk titin. Here, we unravel the or Salih myopathy weaken or abrogate titin-obscurin and titin- molecular basis for the unusual localization of obscurin, a Z- Obsl1 binding, and lead to obscurin mislocalization, suggesting disk-associated protein, to the M-band, where its invertebrate that interference with the interaction of these proteins might analogue UNC-89 is also localized.
    [Show full text]
  • Impaired Plasma Membrane Localization of Ubiquitin Ligase Complex Underlies 3-M Syndrome Development
    The Journal of Clinical Investigation RESEARCH ARTICLE Impaired plasma membrane localization of ubiquitin ligase complex underlies 3-M syndrome development Pu Wang,1 Feng Yan,1 Zhijun Li,1 Yanbao Yu,2 Scott E. Parnell,3,4 and Yue Xiong1,5,6 1Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, North Carolina, USA. 2J. Craig Venter Institute, Rockville, Maryland, USA. 3Bowles Center for Alcohol Studies, 4Department of Cell Biology and Physiology, 5Department of Biochemistry and Biophysics, and 6Integrative Program for Biological and Genome Sciences, University of North Carolina at Chapel Hill, North Carolina, USA. 3-M primordial dwarfism is an inherited disease characterized by severe pre- and postnatal growth retardation and by mutually exclusive mutations in 3 genes, CUL7, OBSL1, and CCDC8. The mechanism underlying 3-M dwarfism is not clear. We showed here that CCDC8, derived from a retrotransposon Gag protein in placental mammals, exclusively localized on the plasma membrane and was phosphorylated by CK2 and GSK3. Phosphorylation of CCDC8 resulted in its binding first with OBSL1, and then CUL7, leading to the membrane assembly of the 3-M E3 ubiquitin ligase complex. We identified LL5β, a plasma membrane protein that regulates cell migration, as a substrate of 3-M ligase. Wnt inhibition of CCDC8 phosphorylation or patient-derived mutations in 3-M genes disrupted membrane localization of the 3-M complex and accumulated LL5β. Deletion of Ccdc8 in mice impaired trophoblast migration and placental development, resulting in intrauterine growth restriction and perinatal lethality. These results identified a mechanism regulating cell migration and placental development that underlies the development of 3-M dwarfism.
    [Show full text]
  • Obscurin-Like 1, OBSL1, Is a Novel Cytoskeletal Protein Related to Obscurin
    View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by Elsevier - Publisher Connector Genomics 89 (2007) 521–531 www.elsevier.com/locate/ygeno Obscurin-like 1, OBSL1, is a novel cytoskeletal protein related to obscurin Sarah B. Geisler a, Dustin Robinson b, Maria Hauringa a, Maide O. Raeker a, ⁎ Andrei B. Borisov b, Margaret V. Westfall b, Mark W. Russell a, a Department of Pediatrics and Communicable Diseases, University of Michigan, L1242 Women’s Hospital/Box 0204, 1500 E. Medical Center Drive, Ann Arbor, MI 48109-0204, USA b Department of Internal Medicine, University of Michigan, Ann Arbor, MI 48109-0723, USA Received 8 May 2006; accepted 9 December 2006 Available online 6 February 2007 Abstract Cytoskeletal adaptor proteins serve vital functions in linking the internal cytoskeleton of cells to the cell membrane, particularly at sites of cell– cell and cell–matrix interactions. The importance of these adaptors to the structural integrity of the cell is evident from the number of clinical disease states attributable to defects in these networks. In the heart, defects in the cytoskeletal support system that surrounds and supports the myofibril result in dilated cardiomyopathy and congestive heart failure. In this study, we report the cloning and characterization of a novel cytoskeletal adaptor, obscurin-like 1 (OBSL1), which is closely related to obscurin, a giant structural protein required for sarcomere assembly. Multiple isoforms arise from alternative splicing, ranging in predicted molecular mass from 130 to 230 kDa. OBSL1 is located on human chromosome 2q35 within 100 kb of SPEG, another gene related to obscurin.
    [Show full text]
  • Inhibition of HIV-1 Assembly by Coiled-Coil Domain Containing Protein 8 in Human Cells
    www.nature.com/scientificreports OPEN Inhibition of HIV-1 assembly by coiled-coil domain containing protein 8 in human cells Received: 02 February 2015 1,2,3 2 3 2 2 2 1,3,4 Accepted: 03 September 2015 Min Wei , Xia Zhao , Mi Liu , Zhi Huang , Yong Xiao , Meijuan Niu , Yiming Shao & 2 Published: 01 October 2015 Lawrence Kleiman Human Immunodeficiency Virus type 1 (HIV-1) major structure protein Gag is synthesized in the cytoplasm, assembles on the plasma membrane, subsequently buds and releases. HIV-1 viral particles incorporate a number of host proteins to facilitate or inhibit HIV-1 replication. Here we identify a new host protein, coiled-coil domain containing protein 8 (CCDC8), in HIV-1 particles. Incorporation of CCDC8 into virions is dependent on the interaction between CCDC8 and Gag matrix region. Exogenous overexpression of CCDC8 can strongly inhibit HIV-1 production, up to ~30 fold. CCDC8 is a membrane-associated protein. The interaction between exogenously expressed CCDC8 and Gag on the plasma membrane changes the assembly of Gag, and redirects it into intracellular sites, or causes Gag endocytosis. CCDC8, along with cytoskeleton protein obscuring-like1 (Obsl1) and E3 ligase Cul7, induces Gag polyubiquitination and degradation. Thus we identify a new host protein and a new pathway for HIV-1 Gag polyubiquitination and degradation. This pathway presents potential therapeutic strategies against HIV infection. Human immunodeficiency virus type 1 (HIV-1), the pathogen of AIDS, is a complex retrovirus and encodes structure proteins Gag, GagPol, Env, and regulatory proteins Vif, Vpu, Vpr, Tat, Nef, and Rev1. Expression of viral proteins is dependent on the viral mRNA export from the nucleus to the cytoplasm in host cells, which are facilitated by Rev and cis-acting element RRE (Rev-responsive element)1,2.
    [Show full text]
  • Table S1. 103 Ferroptosis-Related Genes Retrieved from the Genecards
    Table S1. 103 ferroptosis-related genes retrieved from the GeneCards. Gene Symbol Description Category GPX4 Glutathione Peroxidase 4 Protein Coding AIFM2 Apoptosis Inducing Factor Mitochondria Associated 2 Protein Coding TP53 Tumor Protein P53 Protein Coding ACSL4 Acyl-CoA Synthetase Long Chain Family Member 4 Protein Coding SLC7A11 Solute Carrier Family 7 Member 11 Protein Coding VDAC2 Voltage Dependent Anion Channel 2 Protein Coding VDAC3 Voltage Dependent Anion Channel 3 Protein Coding ATG5 Autophagy Related 5 Protein Coding ATG7 Autophagy Related 7 Protein Coding NCOA4 Nuclear Receptor Coactivator 4 Protein Coding HMOX1 Heme Oxygenase 1 Protein Coding SLC3A2 Solute Carrier Family 3 Member 2 Protein Coding ALOX15 Arachidonate 15-Lipoxygenase Protein Coding BECN1 Beclin 1 Protein Coding PRKAA1 Protein Kinase AMP-Activated Catalytic Subunit Alpha 1 Protein Coding SAT1 Spermidine/Spermine N1-Acetyltransferase 1 Protein Coding NF2 Neurofibromin 2 Protein Coding YAP1 Yes1 Associated Transcriptional Regulator Protein Coding FTH1 Ferritin Heavy Chain 1 Protein Coding TF Transferrin Protein Coding TFRC Transferrin Receptor Protein Coding FTL Ferritin Light Chain Protein Coding CYBB Cytochrome B-245 Beta Chain Protein Coding GSS Glutathione Synthetase Protein Coding CP Ceruloplasmin Protein Coding PRNP Prion Protein Protein Coding SLC11A2 Solute Carrier Family 11 Member 2 Protein Coding SLC40A1 Solute Carrier Family 40 Member 1 Protein Coding STEAP3 STEAP3 Metalloreductase Protein Coding ACSL1 Acyl-CoA Synthetase Long Chain Family Member 1 Protein
    [Show full text]
  • OBSL1 (E-16): Sc-241578
    SAN TA C RUZ BI OTEC HNOL OG Y, INC . OBSL1 (E-16): sc-241578 BACKGROUND PRODUCT OBSL1 (obscurin-like 1) is a novel 1,401 amino acid cytoskeletal adaptor pro - Each vial contains 200 µg IgG in 1.0 ml of PBS with < 0.1% sodium azide tein that is closely related to obscurin and links internal cytoskeletons to the and 0.1% gelatin. cell membrane. Existing as two alternatively spliced isoforms, OBSL1 belongs Blocking peptide available for competition studies, sc-241578 P, (100 µg to the Unc-89/obscurin family and is widely expressed, with highest levels peptide in 0.5 ml PBS containing < 0.1% sodium azide and 0.2% BSA). found in heart and ovary, followed by testis, brain and skeletal muscle. OBSL1 contains one fibronectin type-III domain, 11 Ig-like (immunoglobulin-like) APPLICATIONS domains, and is encoded by a gene that maps to human chromosome 2q35. Defects in the OBSL1 gene are the cause of an autosomal recessive disorder OBSL1 (E-16) is recommended for detection of OBSL1 of mouse, rat and known as 3M syndrome type 2 (3M2), in which patients exhibit short stature, human origin by Western Blotting (starting dilution 1:200, dilution range a short upturned nose with anteverted nares, full lips, triangular shaped face, 1:100-1:1000), immunoprecipitation [1-2 µg per 100-500 µg of total protein frontal bossing and distinguished heels. (1 ml of cell lysate)], immunofluorescence (starting dilution 1:50, dilution range 1:50-1:500) and solid phase ELISA (starting dilution 1:30, dilution REFERENCES range 1:30-1:3000); non cross-reactive with Obscurin.
    [Show full text]
  • Comprehensive Analysis of DNA Methylation and Prediction of Response to Neoadjuvanttherapy in Locally Advanced Rectal Cancer
    cancers Article Comprehensive Analysis of DNA Methylation and Prediction of Response to NeoadjuvantTherapy in Locally Advanced Rectal Cancer Luisa Matos do Canto 1,2 , Mateus Camargo Barros-Filho 2,3 , Cláudia Aparecida Rainho 4 , Diogo Marinho 5, Bruna Elisa Catin Kupper 6, Maria Dirlei Ferreira de Souza Begnami 7, Cristovam Scapulatempo-Neto 8, Birgitte Mayland Havelund 9,10, Jan Lindebjerg 10,11 , Fabio Albuquerque Marchi 2 , Jan Baumbach 12, Samuel Aguiar Jr. 6 and Silvia Regina Rogatto 1,10,13,* 1 Department of Clinical Genetics, University Hospital of Southern Denmark, 7100 Vejle, Denmark; [email protected] 2 International Research Center–CIPE, A.C. Camargo Cancer Center, Sao Paulo 04002-010, Brazil; mfi[email protected] (M.C.B.-F.); [email protected] (F.A.M.) 3 Department of Head and Neck Surgery, Hospital das Clinicas HCFMUSP, Sao Paulo 01246-903, Brazil 4 Department of Chemical and Biological Sciences, Institute of Biosciences, Sao Paulo State University (Unesp), Botucatu 18618-689, Brazil; [email protected] 5 Institute of Biological Psychiatry, Psykiatrisk Center Sct. Hans, 4000 Roskilde, Denmark; [email protected] 6 Colorectal Cancer Service, A.C. Camargo Cancer Center, Sao Paulo 04002-010, Brazil; [email protected] (B.E.C.K.); [email protected] (S.A.J.) 7 Department of Pathology, Sírio-Libanês Hospital, Sao Paulo 01308-050, Brazil; [email protected] 8 Molecular Oncology Research Center, Barretos – 14784-400, and Diagnósticos da América (DASA), Barueri
    [Show full text]
  • Orphananesthesia
    orphananesthesia Anesthesia recommendations for patients suffering from 3-M syndrome Disease name 3M syndrome ICD 10: Q87.1 Synonyms: Dolichospondylic dysplasia, 3Μ dwarfism, gloomy face syndrome, le Merrer syndrome 3M syndrome is a recessive autosomal genetic growth disorder, characterized by significant pre- and postnatal growth retardation. It is listed as a rare or an “orphan” disease having a prevalence in Europe of less than 1 person per 2000 in the general population or affecting less than 200000 people in the US population, with fewer than 100 patients having been reported in the medical literature since 1975. The name of the disease originates from the initials of the three authors, Miller, McKusick and Malvaux, who first reported the syndrome in the literature. The disease is caused by mutations in Cullin 7 (CUL7) gene on chromosome 6p21.1, in most cases, or in the Obscurin-like 1 (OBSL1) gene on chromosome 2q35-36.1 encoding a cytoskeletal adaptor protein. A third gene has recently been identified, encoding the Coiled coil domain containing protein 8 (CCDC8), on chromosome 19q13.32. Medicine in progress Perhaps new knowledge Every patient is unique Perhaps the diagnostic is wrong Find more information on the disease, its centres of reference and patient organisations on Orphanet: www.orpha.net 1 Disease summary 3M syndrome is characterised by proportional but severely delayed growth, a process that begins in uterus. It results in an adult height of 115-150cm. Pre- and postnatal retardation is accompanied by specific facial and skeletal features and normal intelligence. Craniofacial characteristics are: a triangular face, full eyebrows, a hypoplastic midface, a fleshy nose tip, upturned nares, long philtrum with a prominent mouth and lips and pointed chin.
    [Show full text]
  • Characterization of Ataxin-2 and Its Interaction Partners
    CHARACTERIZATION OF ATAXIN-2 AND ITS INTERACTION PARTNERS DISSERTATION ZUR ERLANGUNG DES DOKTORGRADES DER NATURWISSENSCHAFTEN VORGELEGT BEIM FACHBEREICH BIOWISSENSCHAFTEN DER JOHANN WOLFGANG GOETHE -UNIVERSITÄT IN FRANKFURT AM MAIN VON MELANIE VANESSA HALBACH (GEB. HECK) AUS KARLSRUHE FRANKFURT AM MAIN, 2015 (D30) Vom Fachbereich Biowissenschaften (15) der Johann Wolfgang Goethe - Universität als Dissertation angenommen. Dekanin: Prof. Dr. rer. nat. Meike Piepenbring Gutachter: Prof. Dr. rer. nat. Anna Starzinski-Powitz Prof. Dr. med. Georg Auburger Datum der Disputation: Table of contents 1 Introduction .................................................................................................... 1 1.1 Cerebellum: the movement coordination system .................................................. 1 1.2 Structure and connectivity of the cerebellum ........................................................ 1 1.3 Cerebellar ataxias and their classification ............................................................. 3 1.3.1 Autosomal dominant cerebellar ataxias ..................................................................... 5 1.3.2 Spinocerebellar ataxias .............................................................................................. 6 1.3.3 Trinucleotide repeat expansion disorders .................................................................. 8 1.3.4 Pathomechanism of polyglutamine disorders ............................................................ 9 1.3.4.1 The question of gain- or loss-of-function ......................................................................
    [Show full text]