DOCSLIB.ORG

Vaitoskirja Louhelainen

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Vaitoskirja Louhelainen CARDIOVASCULAR EFFECTS OF ORAL CALCIUM SENSITIZERS ON EXPERIMENTAL HEART FAILURE Marjut Louhelainen Institute of Biomedicine Pharmacology University of Helsinki Finland Academic Dissertation Helsinki 2010 To be presented, with the permission of the Medical Faculty of the University of Helsinki for public examination in Lecture Hall 2, Biomedicum Helsinki, Haartmaninkatu 8, on the 29 of January 2010 at 12 noon. Supervisor Professor Eero Mervaala, MD, PhD Institute of Biomedicine Pharmacology University of Helsinki Finland Reviewers Docent Jaana Rysä, PhD Institute of Biomedicine Department of pharmacology and toxicology University of Oulu Finland Docent Jyri Lommi, MD, PhD Division of Cardiology Department of Medicine Helsinki University Central Hospital Finland Opponent Professor Raimo Tuominen, MD, Ph.D Faculty of Pharmacy University of Helsinki Finland ISBN 978-952-92-6765-1 (paperback) ISBN 978-952-10-6016-8 (PDF) http://ethesis.helsinki.fi Helsinki University Print Helsinki 2009 2 To Jani and Martta 3 Table of contents List of original publications ...................................................................................................................... 6 Main abbreviations ...................................................................................................................................... 7 Abstract............................................................................................................................................................ 8 1 Introduction ............................................................................................................................................ 9 2 Review of the literature ....................................................................................................................11 2.1 Heart failure..................................................................................................................................11 2.1.1 Epidemiology and prevalence..........................................................................................................11 2.1.2 Clinical symptoms and diagnosis....................................................................................................11 2.1.3 Treatment..................................................................................................................................................12 2.1.4 Mechanisms of heart failure..............................................................................................................15 2.1.4.1 Single gene mutations and genetic polymorphisms ....................................................................... 15 2.1.4.2 Renin‐angiotensin‐aldosterone‐system............................................................................................... 16 2.1.4.3 Increased sympathetic signalling............................................................................................................ 16 2.1.4.4 Ca2+ handling and regulation of excitation‐contraction coupling............................................. 17 2.1.4.5 Cardiac hypertrophy..................................................................................................................................... 18 2.1.4.5.1 Mechanisms involved in heart failure‐related cardiac hypertrophy ............................. 19 2.1.4.6 Oxidative stress............................................................................................................................................... 21 2.1.4.7 Apoptosis........................................................................................................................................................... 23 2.1.4.8 Dysfunctional energy utilization ............................................................................................................. 24 2.1.4.9 Cardiomyocyte senescence........................................................................................................................ 25 2.2 Experimental models of heart failure ..................................................................................26 2.3 Levosimendan ..............................................................................................................................28 2.3.1 Mechanism of action.............................................................................................................................28 2.3.2 Pharmacokinetics of levosimendan...............................................................................................29 2.3.3 Pharmacodynamics of levosimendan ...........................................................................................29 2.3.3.1 Clinical use of levosimendan..................................................................................................................... 29 2.3.3.2 Adverse effects................................................................................................................................................ 30 2.3.3.3 Clinical studies on levosimendan............................................................................................................ 31 2.3.3.4 Clinical studies on oral levosimendan .................................................................................................. 35 2.3.3.5 Experimental studies on levosimendan............................................................................................... 35 2.3.4 The active metabolite OR‐1896.......................................................................................................36 2.3.4.1 Mechanism of action of OR‐1896............................................................................................................ 36 3 Aims of the study .................................................................................................................................37 4 Materials and methods......................................................................................................................38 4.1 Experimental models and animal welfare..........................................................................38 4.1.1 Dahl/Rapp salt sensitive (SS) rat....................................................................................................38 4.1.2 Diabetic Goto Kakizaki (GK) rat.......................................................................................................38 4.1.3 Animal welfare........................................................................................................................................39 4.2 Study design ..................................................................................................................................39 4.3 Experimental myocardial infarction ....................................................................................40 4.4 Levosimendan and OR­1896 dosage.....................................................................................40 4.5 Blood pressure measurement and sample preparation................................................41 4.6 Echocardiography .......................................................................................................................41 4.7 Infarct size, collagen volume fraction and cardiomyocyte cross­sectional area...41 4.8 Myocardial morphology............................................................................................................42 4.9 Immunohistochemistry.............................................................................................................42 4.10 TUNEL apoptosis assay ...........................................................................................................42 4.11 Apoptosis microarray .............................................................................................................43 4.12 Western blotting .......................................................................................................................43 4.13 Electrophoretic mobility shift assay of nuclear FOXO3a transcription factor.....43 4.14 Quantitative real­time RT­PCR.............................................................................................44 4 4.15 Biochemical analyses ..............................................................................................................46 4.16 Statistical analyses ...................................................................................................................46 5 Results.....................................................................................................................................................47 5.1 Survival (All studies)..................................................................................................................47 5.2 Cardiac functions and blood pressure (All studies) ........................................................47 5.3 Hypertrophy (All studies), cardiomyocyte cross­sectional area (Study III and IV)... ...........................................................................................................................................................48 5.4 Cardiomyocyte morphology (Studies I and II), infarct size, fibrosis (Studies III and IV).......................................................................................................................................................49 5.5 Calcium handling proteins (Studies I and III)....................................................................50
Load more

Recommended publications
  • Table 2. Significant
    Table 2. Significant (Q < 0.05 and |d | > 0.5) transcripts from the meta-analysis Gene Chr Mb Gene Name Affy ProbeSet cDNA_IDs d HAP/LAP d HAP/LAP d d IS Average d Ztest P values Q-value Symbol ID (study #5) 1 2 STS B2m 2 122 beta-2 microglobulin 1452428_a_at AI848245 1.75334941 4 3.2 4 3.2316485 1.07398E-09 5.69E-08 Man2b1 8 84.4 mannosidase 2, alpha B1 1416340_a_at H4049B01 3.75722111 3.87309653 2.1 1.6 2.84852656 5.32443E-07 1.58E-05 1110032A03Rik 9 50.9 RIKEN cDNA 1110032A03 gene 1417211_a_at H4035E05 4 1.66015788 4 1.7 2.82772795 2.94266E-05 0.000527 NA 9 48.5 --- 1456111_at 3.43701477 1.85785922 4 2 2.8237185 9.97969E-08 3.48E-06 Scn4b 9 45.3 Sodium channel, type IV, beta 1434008_at AI844796 3.79536664 1.63774235 3.3 2.3 2.75319499 1.48057E-08 6.21E-07 polypeptide Gadd45gip1 8 84.1 RIKEN cDNA 2310040G17 gene 1417619_at 4 3.38875643 1.4 2 2.69163229 8.84279E-06 0.0001904 BC056474 15 12.1 Mus musculus cDNA clone 1424117_at H3030A06 3.95752801 2.42838452 1.9 2.2 2.62132809 1.3344E-08 5.66E-07 MGC:67360 IMAGE:6823629, complete cds NA 4 153 guanine nucleotide binding protein, 1454696_at -3.46081884 -4 -1.3 -1.6 -2.6026947 8.58458E-05 0.0012617 beta 1 Gnb1 4 153 guanine nucleotide binding protein, 1417432_a_at H3094D02 -3.13334396 -4 -1.6 -1.7 -2.5946297 1.04542E-05 0.0002202 beta 1 Gadd45gip1 8 84.1 RAD23a homolog (S.
    [Show full text]
  • Imbim Annual Report 2015
    Department of Medical Biochemistry and Microbiology IMBIM ANNUAL REPORT 2015 DEPARTMENT OF MEDICAL BIOCHEMISTRY AND MICROBIOLOGY ANNUAL REPORT 2015 Pictures taken by Helena Öhrvik The role of copper in mast cell granule homeostasis Ctr2 is a protein involved in cellular transport of copper. Upper panels: staining for tryptase, a mast cell granule protease, in tryptase (Mcpt6)-deficient (negative control), Ctr2-/- and wild type (WT) mast cells. Note that the absence of Ctr2 causes upregulated expression of tryptase. Lower panels: staining of Ctr2-/- and WT mast cells with toluidine blue, a proteoglycan- binding dye. Note increased toluidine blue staining of Ctr2-/- mast cells, indicating increased proteoglycan content of granules. Öhrvik, H., Logeman, B., Noguchi, G., Eriksson, I., Kjellén, L., Thiele, D.J., Pejler, G. (2015) Ctr2 regulates mast cell maturation by affecting the storage and expression of tryptase and proteoglycans. J. Immunol. 195, 3654-364. Edited by Veronica Hammar ISBN no 978-91-979531-8-4 PREFACE Another year has passed with both small and large successes for the laboratory. The Department has a stable staff consisting of some 150 people. Including project workers, post doc etc we are around 250 persons that spend our daily work hours at the Department. Fortunately the granting situation for the IMBIM researchers improved considerably during 2015. Many of the small and medium sized research groups received grants that will help them continue to excel during the coming years. In addition Dan Andersson, Leif Andersson, Per Jemth, and a couple of scientists at ICM, received a hefty 47 milj kr grant from “Knut och Alice Wallenbergs Stiftelse” to support their research on the evolution of new genes and proteins.
    [Show full text]
  • Supplemental Materials
    The infection-tolerant mammalian reservoir of Lyme disease and other zoonoses broadly counters the inflammatory effects of endotoxin Supplemental Materials Figures S1-S5 Tables S1-S20 Figure S1. Digital photograph of two adult Peromyscus leucopus with exudative conjunctivitis and huddled together. The animals had received 10 mg/gm body of Escherichia coli lipopolysaccharide intraperitoneally the day before. Figure S2. Species- and tissue-specific responses to LPS. Independent differential gene expression analysis of RNA-seq data were performed for blood, spleen, and liver tissues of P. leucopus and M. musculus collected 4 h after injection with LPS or buffer alsone as control. These are represented as volcano plots with range- adjusted scales for the log2-transformed fold-changes on x-axes and log10-transformed FDR p values on y- axes. Colors of symbols denote the following: red, up-regulated gene with absolute fold-change > 4.0 and p value < 0.05; purple, down-regulated gene with absolute fold-change > 4.0 and p value < 0.05; and gray, all others. Numbers at the top left and right corners in each plot respresent numbers of down- and up-regulated genes, respectively. Figure 3 is same data with constant scales for x- and y-axes across the plots. Numerical values for each gene in the 6 datasets are provided in Tables S4-S9. Figure S3. Correlation of IL-10 and IL-10 P. leucopus and M. musculus from RNA-seq of spleen and of Figure 6B and TaBle S14. The scatter plot is log10 values of normalized unique reads of one coding sequence against another for each of the four groups, as defined in the legend for Figure 6 and indicated By different symBols.
    [Show full text]
  • Rabbit Anti-EWSR1 Polyclonal Antibody Reactivity: Hu, Rt, Ms, Dg Synonym: Ewing Sarcoma Breakpoint Region 1, EWS, EWSR1, EWSR-1
    Order Information Description: Rabbit anti-EWSR1 Catalogue#: 600-820 Lot#: See the label Size: 100 ug/200 ul Host: Rabbit Clone: N/A Application: ELISA, WB, IHC, Rabbit anti-EWSR1 Polyclonal Antibody Reactivity: Hu, Rt, Ms, Dg Synonym: Ewing sarcoma breakpoint region 1, EWS, EWSR1, EWSR-1. ANTIGEN PREPARATION A synthetic peptide corresponding to the internal segment of EWSR1 protein. This sequence is identical among human, rat, mouse and dog species. BACKGROUND The EWSR1 gene encodes a putative RNA binding protein. Mutation in this gene causes Ewing sarcoma and neuroectodermal and various other tumors. This gene is involved in a number of different sarcomas as a result of chromosomal translocations. EWSR1 is fused to an ETS transcription factor (FLI-1, ERG, ETV-1, E1AF or FEV) in Ewing sarcoma; to activating transcription factor-1 (ATF-1) in soft tissue clear cell sarcoma; to Wilms Tumor -1 (WT1) in desmoplastic small round cell; to nuclear receptor 4A3 (NR4A3) in extraskeletal myxoid chondrosarcoma, and to C/EBP- homologous protein (CHOP) in myxoid liposarcoma. EWSR1 genes are required for mitotic integrity and survival of neural cells in the early embryonic development, and that the involvement of EWSR1 in mitotic stability is conserved from zebrafish to human. PURIFICATION FORMULATION This affinity purified antibody is supplied in sterile phosphate- The Rabbit IgG is purified by Epitope Affinity Purification. buffered saline (pH7.2) containing antibody stabilizer SPECIFICITY STORAGE This antibody recognizes ~70 kDa of EWSR1 protein. It The antibodies are stable for 12 months from date of receipt when also cross reacts with human, mouse and rat tissues.
    [Show full text]
  • Mct6) Knockout Mice: Evidence of a Potential Role in Glucose and Lipid Metabolism
    Molecular Pharmacology Fast Forward. Published on July 10, 2019 as DOI: 10.1124/mol.119.116731 This article has not been copyedited and formatted. The final version may differ from this version. MOL # 116731 Characterization and proteomic-transcriptomic investigation of monocarboxylate transporter 6 (Mct6) knockout mice: evidence of a potential role in glucose and lipid metabolism Authors: Robert S. Jones 1, Chengjian Tu 1,2, Ming Zhang 2, Jun Qu 1,2, and Marilyn E. Morris 1, * 1 Department of Pharmaceutical Sciences, School of Pharmacy and Pharmaceutical Sciences, University at Buffalo, State University of New York, Buffalo, New York 14214, USA 2 New York State Center of Excellence in Bioinformatics and Life Sciences, 701 Ellicott Street, Downloaded from Buffalo, NY, USA molpharm.aspetjournals.org at ASPET Journals on October 1, 2021 1 Molecular Pharmacology Fast Forward. Published on July 10, 2019 as DOI: 10.1124/mol.119.116731 This article has not been copyedited and formatted. The final version may differ from this version. MOL # 116731 Running title: Mct6 knockout mice and role in glucose and lipid metabolism * Correspondence should be addressed to: Marilyn E. Morris, PhD Department of Pharmaceutical Sciences University at Buffalo State University of New York Downloaded from 352 Kapoor Hall Buffalo, NY 14214 molpharm.aspetjournals.org Ph: (716) 645-4839 [email protected] This manuscript contains: at ASPET Journals on October 1, 2021 23 text pages 5 tables 7 figures 54 references 226 words in Abstract 444 words in Introduction 1536 words in Discussion Nonstandard abbreviations: ALP: alkaline phosphatase, ALT: alanine aminotransferase, BUN: blood urea nitrogen, CRISPR/Cas9: clustered regularly interspaced short palindromic 2 Molecular Pharmacology Fast Forward.
    [Show full text]
  • Behavioral and Genomic Characterization of Scheduled Ethanol Deprivation
    Virginia Commonwealth University VCU Scholars Compass Theses and Dissertations Graduate School 2013 Behavioral and genomic characterization of scheduled ethanol deprivation Jonathan Warner Virginia Commonwealth University Follow this and additional works at: https://scholarscompass.vcu.edu/etd Part of the Medical Pharmacology Commons © The Author Downloaded from https://scholarscompass.vcu.edu/etd/3264 This Dissertation is brought to you for free and open access by the Graduate School at VCU Scholars Compass. It has been accepted for inclusion in Theses and Dissertations by an authorized administrator of VCU Scholars Compass. For more information, please contact [email protected]. Behavioral and genomic characterization of scheduled ethanol deprivation A dissertation submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy at Virginia Commonwealth University by Jonathan Andrew Warner Bachelor of Science, Virginia Commonwealth University, 2007 Director: Michael F. Miles, M.D., Ph.D. Professor, Department of Pharmacology and Toxicology Virginia Commonwealth University Richmond, Virginia November 8th, 2013 II Acknowledgments I would like to sincerely thank my advisor, Michael Miles, for his heroic patience and invaluable guidance throughout my graduate career. I learned an incredible amount during my time under his tutelage, and I say without reservation that I could not have had a better mentor. I feel very lucky to have found my way to Dr. Miles’ laboratory. I would also like to thank my graduate committee for their suggestions and input along the way, and for sitting through my presentations. I would like to thank my mother, father, and sister for all of their support and assistance. Without them this time would have been far more difficult, and I might not have made it this far.
    [Show full text]
  • Rôle Des Facteurs De Transcription NOR1 Et TLE1 Dans Les Macrophages Alternatifs Humains Federica De Paoli
    Rôle des facteurs de transcription NOR1 et TLE1 dans les macrophages alternatifs humains Federica de Paoli To cite this version: Federica de Paoli. Rôle des facteurs de transcription NOR1 et TLE1 dans les macrophages alternatifs humains. Médecine humaine et pathologie. Université du Droit et de la Santé - Lille II, 2015. Français. NNT : 2015LIL2S006. tel-01257811 HAL Id: tel-01257811 https://tel.archives-ouvertes.fr/tel-01257811 Submitted on 18 Jan 2016 HAL is a multi-disciplinary open access L’archive ouverte pluridisciplinaire HAL, est archive for the deposit and dissemination of sci- destinée au dépôt et à la diffusion de documents entific research documents, whether they are pub- scientifiques de niveau recherche, publiés ou non, lished or not. The documents may come from émanant des établissements d’enseignement et de teaching and research institutions in France or recherche français ou étrangers, des laboratoires abroad, or from public or private research centers. publics ou privés. UNIVERSITE LILLE NORD DE FRANCE FACULTE DE SCIENCES PHARMACEUTIQUES ET BIOLOGIQUES Thèse Pour obtenir le grade de : DOCTEUR DE L’UNIVERSITE LILLE 2 Spécialité : Biochimie et Biologie Moléculaire Rôle des facteurs de transcription NOR1 et TLE1 dans les macrophages alternatifs humains Presentée et soutenue publiquement par : Federica DE PAOLI Le 25 Février 2015 Directrice de thèse: Dr Giulia CHINETTI-GBAGUIDI Jury: Pr. Bart STAELS, Président Dr. Laurent YVAN-CHARVET, Rapporteur Pr. David MASSON, Rapporteur Dr. Philippe LEFEBVRE, Examinateur Tout est une question d’équilibre REMERCIEMENTS Je tiens tout d’abord à remercier Monsieur le Professeur Bart Staels, qui m’a accueillie au sein de son laboratoire et me fait l’honneur de présider le jury de cette soutenance de thèse.
    [Show full text]
  • SUPPLEMENTARY APPENDIX Exome Sequencing Reveals Heterogeneous Clonal Dynamics in Donor Cell Myeloid Neoplasms After Stem Cell Transplantation
    SUPPLEMENTARY APPENDIX Exome sequencing reveals heterogeneous clonal dynamics in donor cell myeloid neoplasms after stem cell transplantation Julia Suárez-González, 1,2 Juan Carlos Triviño, 3 Guiomar Bautista, 4 José Antonio García-Marco, 4 Ángela Figuera, 5 Antonio Balas, 6 José Luis Vicario, 6 Francisco José Ortuño, 7 Raúl Teruel, 7 José María Álamo, 8 Diego Carbonell, 2,9 Cristina Andrés-Zayas, 1,2 Nieves Dorado, 2,9 Gabriela Rodríguez-Macías, 9 Mi Kwon, 2,9 José Luis Díez-Martín, 2,9,10 Carolina Martínez-Laperche 2,9* and Ismael Buño 1,2,9,11* on behalf of the Spanish Group for Hematopoietic Transplantation (GETH) 1Genomics Unit, Gregorio Marañón General University Hospital, Gregorio Marañón Health Research Institute (IiSGM), Madrid; 2Gregorio Marañón Health Research Institute (IiSGM), Madrid; 3Sistemas Genómicos, Valencia; 4Department of Hematology, Puerta de Hierro General University Hospital, Madrid; 5Department of Hematology, La Princesa University Hospital, Madrid; 6Department of Histocompatibility, Madrid Blood Centre, Madrid; 7Department of Hematology and Medical Oncology Unit, IMIB-Arrixaca, Morales Meseguer General University Hospital, Murcia; 8Centro Inmunológico de Alicante - CIALAB, Alicante; 9Department of Hematology, Gregorio Marañón General University Hospital, Madrid; 10 Department of Medicine, School of Medicine, Com - plutense University of Madrid, Madrid and 11 Department of Cell Biology, School of Medicine, Complutense University of Madrid, Madrid, Spain *CM-L and IB contributed equally as co-senior authors. Correspondence:
    [Show full text]
  • Autocrine IFN Signaling Inducing Profibrotic Fibroblast Responses By
    Downloaded from http://www.jimmunol.org/ by guest on September 23, 2021 Inducing is online at: average * The Journal of Immunology , 11 of which you can access for free at: 2013; 191:2956-2966; Prepublished online 16 from submission to initial decision 4 weeks from acceptance to publication August 2013; doi: 10.4049/jimmunol.1300376 http://www.jimmunol.org/content/191/6/2956 A Synthetic TLR3 Ligand Mitigates Profibrotic Fibroblast Responses by Autocrine IFN Signaling Feng Fang, Kohtaro Ooka, Xiaoyong Sun, Ruchi Shah, Swati Bhattacharyya, Jun Wei and John Varga J Immunol cites 49 articles Submit online. Every submission reviewed by practicing scientists ? is published twice each month by Receive free email-alerts when new articles cite this article. Sign up at: http://jimmunol.org/alerts http://jimmunol.org/subscription Submit copyright permission requests at: http://www.aai.org/About/Publications/JI/copyright.html http://www.jimmunol.org/content/suppl/2013/08/20/jimmunol.130037 6.DC1 This article http://www.jimmunol.org/content/191/6/2956.full#ref-list-1 Information about subscribing to The JI No Triage! Fast Publication! Rapid Reviews! 30 days* Why • • • Material References Permissions Email Alerts Subscription Supplementary The Journal of Immunology The American Association of Immunologists, Inc., 1451 Rockville Pike, Suite 650, Rockville, MD 20852 Copyright © 2013 by The American Association of Immunologists, Inc. All rights reserved. Print ISSN: 0022-1767 Online ISSN: 1550-6606. This information is current as of September 23, 2021. The Journal of Immunology A Synthetic TLR3 Ligand Mitigates Profibrotic Fibroblast Responses by Inducing Autocrine IFN Signaling Feng Fang,* Kohtaro Ooka,* Xiaoyong Sun,† Ruchi Shah,* Swati Bhattacharyya,* Jun Wei,* and John Varga* Activation of TLR3 by exogenous microbial ligands or endogenous injury-associated ligands leads to production of type I IFN.
    [Show full text]
  • The Cellular Mirna, Mir-190, Is Upregulated in Type I Ebv Latency by Ebers and Modulates Cellular Mrnas Involved in Cell Survival and Viral Reactivation
    University of Pennsylvania ScholarlyCommons Publicly Accessible Penn Dissertations 2015 The Cellular Mirna, Mir-190, is Upregulated in Type I Ebv Latency by Ebers and Modulates Cellular Mrnas involved in Cell Survival and Viral Reactivation Elizabeth Mary Cramer University of Pennsylvania, [email protected] Follow this and additional works at: https://repository.upenn.edu/edissertations Part of the Cell Biology Commons, Molecular Biology Commons, and the Virology Commons Recommended Citation Cramer, Elizabeth Mary, "The Cellular Mirna, Mir-190, is Upregulated in Type I Ebv Latency by Ebers and Modulates Cellular Mrnas involved in Cell Survival and Viral Reactivation" (2015). Publicly Accessible Penn Dissertations. 1670. https://repository.upenn.edu/edissertations/1670 This paper is posted at ScholarlyCommons. https://repository.upenn.edu/edissertations/1670 For more information, please contact [email protected]. The Cellular Mirna, Mir-190, is Upregulated in Type I Ebv Latency by Ebers and Modulates Cellular Mrnas involved in Cell Survival and Viral Reactivation Abstract Epstein-Barr Virus (EBV) is a highly prevalent human pathogen infecting over 90% of the population. Much of the success of the virus is attributed to its ability to maintain latency through different programs in host cells. MicroRNAs (miRNA) are small, non-coding RNAs capable of post-transcriptionally regulating mRNA expression. A microarray comparison of EBV type I latency and type III latency infected cells yielded evidence of differential cellular microRNA expression. I hypothesized that one of these differentially upregulated type I latency miRNAs, miR-190, is important in maintenance of latency I, and miR-190 upregulation is due to viral gene expression.
    [Show full text]
  • Distinct Transcriptomes Define Rostral and Caudal 5Ht Neurons
    DISTINCT TRANSCRIPTOMES DEFINE ROSTRAL AND CAUDAL 5HT NEURONS by CHRISTI JANE WYLIE Submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy Dissertation Advisor: Dr. Evan S. Deneris Department of Neurosciences CASE WESTERN RESERVE UNIVERSITY May, 2010 CASE WESTERN RESERVE UNIVERSITY SCHOOL OF GRADUATE STUDIES We hereby approve the thesis/dissertation of ______________________________________________________ candidate for the ________________________________degree *. (signed)_______________________________________________ (chair of the committee) ________________________________________________ ________________________________________________ ________________________________________________ ________________________________________________ ________________________________________________ (date) _______________________ *We also certify that written approval has been obtained for any proprietary material contained therein. TABLE OF CONTENTS TABLE OF CONTENTS ....................................................................................... iii LIST OF TABLES AND FIGURES ........................................................................ v ABSTRACT ..........................................................................................................vii CHAPTER 1 INTRODUCTION ............................................................................................... 1 I. Serotonin (5-hydroxytryptamine, 5HT) ....................................................... 1 A. Discovery..............................................................................................
    [Show full text]
  • Imbim Annual Report 2016
    Department of Medical Biochemistry and Microbiology IMBIM ANNUAL REPORT 2016 DEPARTMENT OF MEDICAL BIOCHEMISTRY AND MICROBIOLOGY ANNUAL REPORT 2016 Pictures taken by Eva Garmendia IMBIM Day, February and September, 2016 Edited by Veronica Hammar ISBN no 978-91-983979-0-1 PREFACE I would like to take the opportunity to welcome two new research groups to IMBIM, Both Örjan Carlborg and Mikael Sellin, with their coworkers joined our Department during 2016. Örjans group joined us during summer whereas Mikaels group will move physically to their new laboratory, hopefully before summer 2017. During 2016 a position as a University Lecturer in Computational Genomics was filled. Örjan, who comes from SLU, was ranked as number one by the expert reviewers and was offered the position. With all the positive comments from the expert reviewers we took the opportunity to also offer Matthew Webster, who came in at second place, a position as a University Lecturer in Computational Genomics. Thus, in one stroke the number of permanent staff at the Genomic section at IMBIM doubled. Mikael Sellin was recruited as an Associate Senior Lecturer “biträdande universitetslektor (BUL)” in Medical Infection Biology sponsored by the SciLifeLab Uppsala. Mikael was ranked as number one among fifteen national and international applicants. We were pleased that Mikael decided to place his laboratory at IMBIM. BUL positions are a new type of career development positions. In fact, Mikael is the first BUL appointed at the Medical Faculty. Mikael started to work with us in December 2016 but his group will physically move to the B9:3 corridor during spring 2017.
    [Show full text]