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Human Prion-Like Proteins and Their Relevance in Disease
ADVERTIMENT. Lʼaccés als continguts dʼaquesta tesi queda condicionat a lʼacceptació de les condicions dʼús establertes per la següent llicència Creative Commons: http://cat.creativecommons.org/?page_id=184 ADVERTENCIA. El acceso a los contenidos de esta tesis queda condicionado a la aceptación de las condiciones de uso establecidas por la siguiente licencia Creative Commons: http://es.creativecommons.org/blog/licencias/ WARNING. The access to the contents of this doctoral thesis it is limited to the acceptance of the use conditions set by the following Creative Commons license: https://creativecommons.org/licenses/?lang=en Universitat Autònoma de Barcelona Departament de Bioquímica i Biologia Molecular Institut de Biotecnologia i Biomedicina HUMAN PRION-LIKE PROTEINS AND THEIR RELEVANCE IN DISEASE Doctoral thesis presented by Cristina Batlle Carreras for the degree of PhD in Biochemistry, Molecular Biology and Biomedicine from the Universitat Autònoma de Barcelona. The work described herein has been performed in the Department of Biochemistry and Molecular Biology and in the Institute of Biotechnology and Biomedicine, supervised by Prof. Salvador Ventura i Zamora. Cristina Batlle Carreras Prof. Salvador Ventura i Zamora Bellaterra, 2020 Protein Folding and Conformational Diseases Lab. This work was financed with the fellowship “Formación de Profesorado Universitario” by “Ministerio de Ciencia, Innovación y Universidades”. This work is licensed under a Creative Commons Attributions-NonCommercial-ShareAlike 4.0 (CC BY-NC- SA 4.0) International License. The extent of this license does not apply to the copyrighted publications and images reproduced with permission. (CC BY-NC-SA 4.0) Batlle, Cristina: Human prion-like proteins and their relevance in disease. Doctoral Thesis, Universitat Autònoma de Barcelona (2020) English summary ENGLISH SUMMARY Prion-like proteins have attracted significant attention in the last years. -
Viewed Under 23 (B) Or 203 (C) fi M M Male Cko Mice, and Largely Unaffected Magni Cation; Scale Bars, 500 M (B) and 50 M (C)
BRIEF COMMUNICATION www.jasn.org Renal Fanconi Syndrome and Hypophosphatemic Rickets in the Absence of Xenotropic and Polytropic Retroviral Receptor in the Nephron Camille Ansermet,* Matthias B. Moor,* Gabriel Centeno,* Muriel Auberson,* † † ‡ Dorothy Zhang Hu, Roland Baron, Svetlana Nikolaeva,* Barbara Haenzi,* | Natalya Katanaeva,* Ivan Gautschi,* Vladimir Katanaev,*§ Samuel Rotman, Robert Koesters,¶ †† Laurent Schild,* Sylvain Pradervand,** Olivier Bonny,* and Dmitri Firsov* BRIEF COMMUNICATION *Department of Pharmacology and Toxicology and **Genomic Technologies Facility, University of Lausanne, Lausanne, Switzerland; †Department of Oral Medicine, Infection, and Immunity, Harvard School of Dental Medicine, Boston, Massachusetts; ‡Institute of Evolutionary Physiology and Biochemistry, St. Petersburg, Russia; §School of Biomedicine, Far Eastern Federal University, Vladivostok, Russia; |Services of Pathology and ††Nephrology, Department of Medicine, University Hospital of Lausanne, Lausanne, Switzerland; and ¶Université Pierre et Marie Curie, Paris, France ABSTRACT Tight control of extracellular and intracellular inorganic phosphate (Pi) levels is crit- leaves.4 Most recently, Legati et al. have ical to most biochemical and physiologic processes. Urinary Pi is freely filtered at the shown an association between genetic kidney glomerulus and is reabsorbed in the renal tubule by the action of the apical polymorphisms in Xpr1 and primary fa- sodium-dependent phosphate transporters, NaPi-IIa/NaPi-IIc/Pit2. However, the milial brain calcification disorder.5 How- molecular identity of the protein(s) participating in the basolateral Pi efflux remains ever, the role of XPR1 in the maintenance unknown. Evidence has suggested that xenotropic and polytropic retroviral recep- of Pi homeostasis remains unknown. Here, tor 1 (XPR1) might be involved in this process. Here, we show that conditional in- we addressed this issue in mice deficient for activation of Xpr1 in the renal tubule in mice resulted in impaired renal Pi Xpr1 in the nephron. -
Tfr2, Hfe, and Hjv in the Regulation of Body Iron Homeostasis
TFR2, HFE, AND HJV IN THE REGULATION OF BODY IRON HOMEOSTASIS By Christal Anna Worthen A DISSERTATION Presented to the Department of Cell & Developmental Biology and the Oregon Health and Science University School of Medicine in partial fulfillment of the requirements for the degree of Doctor of Philosophy June 2014 School of Medicine Oregon Health & Science University CERTIFICATE OF APPROVAL ___________________________________ This is to certify that the PhD dissertation of Christal A Worthen has been approved ______________________________________ Caroline Enns, Ph.D., mentor ______________________________________ Peter Mayinger, Ph.D., Chairman ______________________________________ Philip Stork, M.D. ______________________________________ David Koeller, M.D. ______________________________________ Alex Nechiporuk, Ph.D. TABLE OF CONTENTS i List of Figures ii Acknowledgements iv Abbreviations v Abstract: 1 Chapter 1: Introduction 5 Abstract and Introduction 6 Binding partners, regulation, and trafficking of TFR2 9 Disease-causing mutations in TFR2 12 Hepcidin regulation 12 Physiological function of TFR2 15 Current TFR2 models 18 Summary 19 Figure 21 Chapter 2: The cytoplasmic domain of TFR2 is necessary for 22 HFE, HJV, and TFR2 regulation of hepcidin Abstract 23 Capsule & Introduction 24 Materials and Methods 26 Results 32 Figures 41 Discussion 49 Chapter 3: Lack of functional TFR2 results in stress erythropoiesis 53 Introduction 54 Materials and Methods 55 Results 57 Figures 60 Discussion 65 Chapter 4: Conclusions and future directions 67 Appendices Appendix A: Coculture of HepG2 cells reduces hepcidin expression 71 Appendix B: Hfe-/- macrophages handle iron differently 80 Appendix C: Both ZIP14A and ZIP14B are regulated by HFE and iron 91 Appendix D: The cytoplasmic domain of HFE does not interact with 99 ZIP14 loop 2 by yeast-2-hybris References 105 i LIST OF FIGURES Figure Abstract 1: Body iron homeostasis. -
Ige – the Main Player of Food Allergy
DDMOD-431; No of Pages 8 Vol. xxx, No. xx 2016 Drug Discovery Today: Disease Models Editors-in-Chief Jan Tornell – AstraZeneca, Sweden DRUG DISCOVERY Andrew McCulloch – University of California, SanDiego, USA TODAY DISEASE MODELS IgE – the main player of food allergy 1 2,3 2 Henrike C.H. Broekman , Thomas Eiwegger , Julia Upton , 4, Katrine L. Bøgh * 1 Department of Dermatology/Allergology, University Medical Centre Utrecht (UMCU), Utrecht, The Netherlands 2 Division of Immunology and Allergy, Food Allergy and Anaphylaxis Program, The Department of Paediatrics, Hospital for Sick Children, Toronto, Canada 3 Research Institute, Physiology and Experimental Medicine, The University of Toronto, Toronto, Canada 4 National Food Institute, Technical University of Denmark, Søborg, Denmark Food allergy is a growing problem worldwide, presently Section editor: affecting 2–4% of adults and 5–8% of young children. IgE Michelle Epstein – Medical University of Vienna, is a key player in food allergy. Consequently huge Department of Dermatology, DIAID, Experimental Allergy, Waehringer Guertel 18-20, Room 4P9.02, A1090, efforts have been made to develop tests to detect Vienna, Austria. either the presence of IgE molecules, their allergen binding sites or their functionality, in order to provide allergen ingestion [1], and involve one or more of the follow- information regarding the patient’s food allergy. The ing systems; the skin (pruritus, urticaria, or angioedema), the ultimate goal is to develop tools that are capable of gastro-intestinal tract (diarrhea, vomiting, contractions, in- creased bowel movement), the respiratory tract (asthma at- discriminating between asymptomatic sensitization tack, hoarseness, stridor/laryngeal angioedema) or the and a clinically relevant food allergy, and between cardiovascular system (dizziness, drop in blood pressure, loss different allergic phenotypes in an accurate and trust- of consciousness) [2,3]. -
2013 New Molecular CPT Co
Cleveland Clinic Laboratories 2013 New Molecular CPT Codes 2013 Test Name Order Code Billing Code CPT Codes 2012 CPT Codes ACADM PCR, Complete, Tier 2 ACADM 88175 81404 83891, 83894x10, 83898x10, 83904x20 ACTA2 Gene Sequencing ACTA2 88528 81403 83898x9, 83904x9, 83891 ADmark ApoE Genotype (Symptomatic) APOALZ 82397 81401 83892, 83894, 83898, 81401, 83891 ADmark PS-1 Analysis, Symptomatic PS1SY 83019 81405 83904x10, 83909x10, 83898x10, 83891 Alpha Globin (HBA1 and HBA2) Sequencing HBA12 88847 81257 New test in 2013 Alpha Thalassemia Gene Deletion ATHAL 84123 81257 83891, 83900, 83901x8, 83894 Alpha-1-Antitrypsin Quantitation and Phenotyping PHA1A 84187 81332 82103, 82104 Angelman UBE3A Sequencing UBE3A 88200 81331 83898x8, 83904x10, 83909x10 APO E Genotype APOEG 79374 81401 83891, 81401, 83898, 83896x2 ARX Sequence Analysis ARXSEQ 87860 81404 83890, 83898x5, 83894, 83904x6 Autoimmune Polyglandular Syndrome Evaluation AIRE 83293 81479 83909x14, 83891, 83898x14, 83904x14 Autosomal Dom Ataxia Evaluation AUTOAT 82179 81401, 83909x88, 83898x88, 83904x77, 81479x13 83891 Barth Syndrome, Carrier BARCAR 82536 81406 83891, 83898, 83904x2 Barth Syndrome, Initial Patient BARINI 82535 81406 83891, 83898, 83904x9 Bartonella PCR, Tissue TBART 87924 87471 83898x4, 83890, 83894 B-Cell Clonality Using BIOMED-2 PCR Primers BCBMD 87904 81261, 83891, 83900, 83909x5, 83898x3, 83901x2, 81264 83912, 81261, 81264 BCL 2 mbr (PCR) BCL2 81099 81401 81401, 83890, 83898, 83894, 83912 BCR/ABL Kinase Domain Mutation Analysis KINASE 84529 81403 83891, 83898, 83902, 83904x4, -
Role of Serologic Testing in Rheumatic Diseases
Role of Serologic Testing in Rheumatic Diseases Debendra Pattanaik MD FACP Associate professor of Medicine UTHSC, Memphis TN Disclosure None Objectives Discuss commonly available serologic testing useful in daily clinical practice Recognize the serologic associations of rheumatic diseases Recognize their diagnostic utilities and limitations Diagnostic Accuracy for Lupus and other autoimmune diseases in the community setting 476 patients were evaluated at Autoimmunity Center of University of Florida, Gainesville for 13 months which were by from primary care physicians SLE was over diagnosed on many patients on the basis of + ANA 39 patients are taking prednisone 60 mg/day who have no autoimmune disease but only have + ANA Inappropriate diagnosis leads to inappropriate therapy, emotional and financial consequences The authors suggested continuing education in screening for autoimmune disease and identify patients who may benefit from early referral. Arch Intern Med. 2004;164:2435-2441 Antinuclear Antibody (ANA) Testing for Connective Tissue Disease British Columbia Population: 4.631 million. More than 94,000 ANA tests were performed in B.C. in fiscal year 2011/12 at a cost of $2.24 million annually. Incidence and Estimated New Cases in B.C. for Selected CTDs Connective Tissue Disease Disease incidence per million population Estimated new BC cases/year * Systemic lupus erythematosus 56 259 Scleroderma 19 88 Dermatomyositis & polymyositis < 10 < 46 Eighteen percent of first-time tested outpatients underwent unnecessary repeat testing in 2010/2011. In 57.2% of the repeat testing, both the initial and the repeat ANA tests were ordered by a GP. In 24.8% the initial test was ordered by a GP and the repeat test was ordered by a specialist, and in 10.2% both the initial and the repeat test were ordered by the same specialist. -
Proteogenomic Analysis of Inhibitor of Differentiation 4 (ID4) in Basal-Like Breast Cancer Laura A
Baker et al. Breast Cancer Research (2020) 22:63 https://doi.org/10.1186/s13058-020-01306-6 RESEARCH ARTICLE Open Access Proteogenomic analysis of Inhibitor of Differentiation 4 (ID4) in basal-like breast cancer Laura A. Baker1,2, Holly Holliday1,2†, Daniel Roden1,2†, Christoph Krisp3,4†, Sunny Z. Wu1,2, Simon Junankar1,2, Aurelien A. Serandour5, Hisham Mohammed5, Radhika Nair6, Geetha Sankaranarayanan5, Andrew M. K. Law1,2, Andrea McFarland1, Peter T. Simpson7, Sunil Lakhani7,8, Eoin Dodson1,2, Christina Selinger9, Lyndal Anderson9,10, Goli Samimi11, Neville F. Hacker12, Elgene Lim1,2, Christopher J. Ormandy1,2, Matthew J. Naylor13, Kaylene Simpson14,15, Iva Nikolic14, Sandra O’Toole1,2,9,10, Warren Kaplan1, Mark J. Cowley1,2, Jason S. Carroll5, Mark Molloy3 and Alexander Swarbrick1,2* Abstract Background: Basal-like breast cancer (BLBC) is a poorly characterised, heterogeneous disease. Patients are diagnosed with aggressive, high-grade tumours and often relapse with chemotherapy resistance. Detailed understanding of the molecular underpinnings of this disease is essential to the development of personalised therapeutic strategies. Inhibitor of differentiation 4 (ID4) is a helix-loop-helix transcriptional regulator required for mammary gland development. ID4 is overexpressed in a subset of BLBC patients, associating with a stem-like poor prognosis phenotype, and is necessary for the growth of cell line models of BLBC through unknown mechanisms. Methods: Here, we have defined unique molecular insights into the function of ID4 in BLBC and the related disease high-grade serous ovarian cancer (HGSOC), by combining RIME proteomic analysis, ChIP-seq mapping of genomic binding sites and RNA-seq. -
Pathological Relationships Involving Iron and Myelin May Constitute a Shared Mechanism Linking Various Rare and Common Brain Diseases
Rare Diseases ISSN: (Print) 2167-5511 (Online) Journal homepage: http://www.tandfonline.com/loi/krad20 Pathological relationships involving iron and myelin may constitute a shared mechanism linking various rare and common brain diseases Moones Heidari, Sam H. Gerami, Brianna Bassett, Ross M. Graham, Anita C.G. Chua, Ritambhara Aryal, Michael J. House, Joanna F. Collingwood, Conceição Bettencourt, Henry Houlden, Mina Ryten , John K. Olynyk, Debbie Trinder, Daniel M. Johnstone & Elizabeth A. Milward To cite this article: Moones Heidari, Sam H. Gerami, Brianna Bassett, Ross M. Graham, Anita C.G. Chua, Ritambhara Aryal, Michael J. House, Joanna F. Collingwood, Conceição Bettencourt, Henry Houlden, Mina Ryten , John K. Olynyk, Debbie Trinder, Daniel M. Johnstone & Elizabeth A. Milward (2016) Pathological relationships involving iron and myelin may constitute a shared mechanism linking various rare and common brain diseases, Rare Diseases, 4:1, e1198458, DOI: 10.1080/21675511.2016.1198458 To link to this article: http://dx.doi.org/10.1080/21675511.2016.1198458 © 2016 The Author(s). Published with View supplementary material license by Taylor & Francis Group, LLC© Moones Heidari, Sam H. Gerami, Brianna Bassett, Ross M. Graham, Anita C.G. Chua, Ritambhara Aryal, Michael J. House, Joanna Accepted author version posted online: 22 Submit your article to this journal JunF. Collingwood, 2016. Conceição Bettencourt, PublishedHenry Houlden, online: Mina 22 Jun Ryten, 2016. for the UK Brain Expression Consortium (UKBEC), John K. Olynyk, Debbie Trinder, Daniel M. Johnstone,Article views: and 541 Elizabeth A. Milward. View related articles View Crossmark data Citing articles: 2 View citing articles Full Terms & Conditions of access and use can be found at http://www.tandfonline.com/action/journalInformation?journalCode=krad20 Download by: [University of Newcastle, Australia] Date: 17 May 2017, At: 19:57 RARE DISEASES 2016, VOL. -
Importance of Ag-Ab Reactions
Ag-Ab reactions Tests for Ag-Ab reactions EISA SALEHI PhD. Immunology Dept. TUMS Importance of Ag-Ab Reactions • Understand the mechanisms of defense • Abs as tools in: – Treatment – Diagnosis • As biomarkers • As tools to measure analytes Nature of Ag/Ab Reactions http://www.med.sc.edu:85/chime2/lyso-abfr.htm • Lock and Key Concept • Non-covalent Bonds – Hydrogen bonds – Electrostatic bonds – Van der Waal forces – Hydrophobic bonds • Multiple Bonds • Reversible Source: Li, Y., Li, H., Smith-Gill, S. J., Mariuzza, R. A., Biochemistry 39, 6296, 2000 Affinity • Strength of the reaction between a single antigenic determinant and a single Ab combining site High Affinity Low Affinity Ab Ab Ag Ag Affinity = ( attractive and repulsive forces Calculation of Affinity Ag + Ab ↔ Ag-Ab Applying the Law of Mass Action: [[gAg-Ab] Keq = [Ag] x [Ab] Avidity • The overall strength of binding between an Ag with many determinants and multivalent Abs 4 6 10 Keq = 10 10 10 Affinity Avidity Avidity SifiitSpecificity • The ability of an individual antibody combining site to react with only one antigenic determinant. • The ability of a population of antibody molecules to react with only one antigen. Cross Reactivity • The ability of an individual Ab combining site to react with more than one antigenic determinant. • The ability of a population of Ab molecules to react with more than one Ag Cross reactions Anti-A Anti-A Anti-A Ab Ab Ab Ag A Ag B Ag C Shared epitope Similar epitope Factors Affecting Measurement of A/AbRAg/Ab Reac tions • Affinity • Avidity Ab excess Ag excess • AAbiAg:Ab ratio •Phyygsical form of Ag Equivalence – Lattice formation Do you need to know what happens in Lab. -
Tyr1 Phosphorylation Promotes Phosphorylation of Ser2 on the C-Terminal Domain
1 Tyr1 phosphorylation promotes phosphorylation of Ser2 on the C-terminal domain 2 of eukaryotic RNA polymerase II by P-TEFb 3 Joshua E. Mayfield1† *, Seema Irani2*, Edwin E. Escobar3, Zhao Zhang4, Nathanial T. 4 Burkholder1, Michelle R. Robinson3, M. Rachel Mehaffey3, Sarah N. Sipe3,Wanjie Yang1, 5 Nicholas A. Prescott1, Karan R. Kathuria1, Zhijie Liu4, Jennifer S. Brodbelt3, Yan Zhang1,5 6 1 Department of Molecular Biosciences, 2Department of Chemical Engineering, 7 3 Department of Chemistry and 5 Institute for Cellular and Molecular Biology, University of 8 Texas, Austin 9 4 Department of Molecular Medicine, Institute of Biotechnology, University of Texas 10 Health Science Center at San Antonio 11 †Current Address: Department of Pharmacology, University of California, San Diego, La 12 Jolla 13 * These authors contributed equally to this paper. 14 Correspondence: Yan Zhang ([email protected]) 15 16 1 17 Summary 18 The Positive Transcription Elongation Factor b (P-TEFb) phosphorylates 19 Ser2 residues of C-terminal domain (CTD) of the largest subunit (RPB1) of RNA 20 polymerase II and is essential for the transition from transcription initiation to 21 elongation in vivo. Surprisingly, P-TEFb exhibits Ser5 phosphorylation activity in 22 vitro. The mechanism garnering Ser2 specificity to P-TEFb remains elusive and 23 hinders understanding of the transition from transcription initiation to elongation. 24 Through in vitro reconstruction of CTD phosphorylation, mass spectrometry 25 analysis, and chromatin immunoprecipitation sequencing (ChIP-seq) analysis, we 26 uncover a mechanism by which Tyr1 phosphorylation directs the kinase activity of 27 P-TEFb and alters its specificity from Ser5 to Ser2. -
Principles of Immunochemical Techniques Used in Clinical Laboratories
Review Received 2.11.06 | Revisions Received 3.1.06 | Accepted 3.2.06 Principles of Immunochemical Techniques Used in Clinical Laboratories Marja E. Koivunen, Richard L. Krogsrud (Antibodies Incorporated, Davis, CA) DOI: 10.1309/MV9RM1FDLWAUWQ3F Abstract binding site. The type of antibody and its diseases. Immunoassays can measure low Immunochemistry offers simple, rapid, robust affinity and avidity for the antigen determines levels of disease biomarkers and therapeutic or yet sensitive, and easily automated methods assay sensitivity and specificity. Depending on illicit drugs in patient’s blood, serum, plasma, for routine analyses in clinical laboratories. the assay format, immunoassays can be urine, or saliva. Immunostaining is an example Immunoassays are based on highly specific qualitative or quantitative. They can be used for of an immunochemical technique, which binding between an antigen and an antibody. the detection of antibodies or antigens specific combined with fluorescent labels allows direct An epitope (immunodeterminant region) on the for bacterial, viral, and parasitic diseases as visualization of target cells and cell structures. antigen surface is recognized by the antibody’s well as for the diagnosis of autoimmune Immunochemistry offers simple, rapid, robust yet sensitive, bind to an antigen. The third domain (complement-binding Fc and in most cases, easily automated methods applicable to routine fragment) forms the base of the Y, and is important in immune analyses in clinical laboratories. Immunochemical methods do not system function and regulation. usually require extensive and destructive sample preparation or The region of an antigen that interacts with an antibody is expensive instrumentation. In fact, most methods are based on called an epitope or an immunodeterminant region. -
Genetic Testing Guidelines
GUIDELINE Genetic Testing Guidelines Categories This Guideline Applies To: Clinical Care Management CM, TCHP Texas Children's Health Plan Guidelines, Utilization Management UM Guideline # 6181 Document Owner Bhavana Babber GUIDELINE STATEMENT: Texas Children's Health Plan (TCHP) performs authorization of genetic testing requests. PRIOR AUTHORIZATION GUIDELINES 1. Genetic testing conducted by out-of-network providers will be treated as out-of-network requests and will comply with the out-of-network authorization Guidelines. 2. Requests for Noninvasive Prenatal Testing will comply with TCHP Noninvasive Prenatal Testing Guidelines. 3. All requests for prior authorization for genetic testing are received via fax, phone or mail by the Utilization Management Department and processed during normal business hours. 4. The Utilization Management professional receiving the request evaluates the submitted information to determine if the documentation supports the genetic testing as an eligible service. 5. To request prior authorization for genetic testing, documentation supporting the medical necessity of the test requested must be provided. 6. TCHP will apply clinical criteria in the current Texas Medicaid Provider Manual (TMPPM) at the time of the request when applicable for the following: 6.1.BRCA gene mutation analysis 6.2.Genetic Testing for colorectal cancer 6.3.Cytogenetic testing 6.4.Pharmacogenetic Testing Version #: 5 Genetic Testing Guidelines Page 1 of 10 Printed copies are for reference only. Please refer to the electronic copy for the latest version. GUIDELINE 6.5. A request for retroactive authorization must be submitted no later than seven calendar days beginning the day after the lab draw is performed per TMPPM 7. Whole genome sequencing (code 81415) requires preauthorization on a case-by-case basis.