DOCSLIB.ORG

Influence of Vitamin D on Genome-Wide Expression in Natural Killer Cells

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Influence of Vitamin D on Genome-Wide Expression in Natural Killer Cells Aus dem Bereich Klinische Medizin der Medizinischen Fakultät der Universität des Saarlandes, Homburg/Saar Influence of Vitamin D on Genome-Wide Expression in Natural Killer Cells Dissertation zur Erlangung des Grades eines Doktors der Medizin der Medizinischen Fakultät der UNIVERSITÄT DES SAARLANDES 2021 vorgelegt von: Konstantinos Christofyllakis geb. am.: 06.05.1988 in Athen, Griechenland Tag der Promotion: 19. April 2021 Dekan: Univ.-Prof. Dr. med- Michael D. Menger Berichterstatter: PD Dr. Frank Neumann Prof. Dr. Markus Hoth The experiments for the present doctoral thesis were conducted at the Clinic for Internal Medicine I - Oncology, Hematology, Clinical Immunology and Rheumatology, as well as at the José Carreras Institute of Saarland University in Homburg (Saar). Konstantinos Christofyllakis Saarland University Medical Center – IMED (bldg. 41) Department of Internal Medicine I Oncology, Hematology, Rheumatology and clinical Immunology Director: Prof. Dr. Stephan Stilgenbauer Kirrberger Strasse 100 66421 Homburg/Saar, Germany Mail: [email protected] TABLE OF CONTENTS Table of Contents ................................................................................................................... i List of Figures ........................................................................................................................iv List of Tables ......................................................................................................................... v 1 Summary ........................................................................................................................ 1 2 Introduction ..................................................................................................................... 2 2.1 Natural Killer Cells ................................................................................................... 2 2.1.1 Subsets of NK Cells .......................................................................................... 2 2.1.2 NK-Cell-mediated Cytotoxicity .......................................................................... 3 2.1.3 Regulation of NK-Cell Activity – NK-Cell Receptors .......................................... 5 2.1.4 Toll-Like Receptors ........................................................................................... 7 2.1.5 Antibody-Dependent Cytotoxicity ...................................................................... 8 2.2 Vitamin D ................................................................................................................. 9 2.2.1 Synthesis and Metabolism of Vitamin D .......................................................... 10 2.2.2 Role of Vitamin D in Humans .......................................................................... 10 2.2.3 Vitamin D Deficiency ...................................................................................... 11 2.2.4 Skeletal Effects of Vitamin D Supplementation ............................................... 11 2.2.5 Non-Skeletal Effects of Vitamin D Supplementation ....................................... 11 2.2.6 Vitamin D and Cancer..................................................................................... 12 2.2.7 Vitamin D and the Immune System ................................................................. 12 2.2.8 Vitamin D and Natural Killer Cells ................................................................... 13 2.3 Aims of this Thesis ................................................................................................ 14 3 Materials and Methods ................................................................................................. 15 3.1 Study Design ......................................................................................................... 15 3.1.1 Inclusion and Exclusion Criteria ...................................................................... 15 3.1.2 Data Handling and Ethical Aspects ................................................................. 15 3.1.3 Vitamin D Supplementation ............................................................................ 15 3.1.4 Sample Labeling ............................................................................................. 16 3.1.5 Participant Characteristics and Vitamin D Levels ............................................ 16 i 3.2 Materials ................................................................................................................ 17 3.2.1 Chemicals, Reagents, Buffers, Mediums and Solutions .................................. 17 3.2.2 Antibodies, Enzymes, Primers ........................................................................ 19 3.2.3 Consumables ................................................................................................. 19 3.2.4 Equipment ...................................................................................................... 20 3.3 Methods................................................................................................................. 21 3.3.1 Cell Counting .................................................................................................. 21 3.3.2 Isolation of PBMC ........................................................................................... 22 3.3.3 NK-Cell Enrichment by Magnetic Cell Sorting ................................................. 22 3.3.4 Flow Cytometry............................................................................................... 23 3.3.5 RNA Extraction ............................................................................................... 24 3.3.6 Spectrophotometry ......................................................................................... 24 3.3.7 RNA Electrophoresis ...................................................................................... 25 3.3.8 Microarray Assay ............................................................................................ 25 3.3.9 Microarray Quality Control .............................................................................. 26 3.3.10 Quantitative Real Time Polymerase Chain Reaction Validation ...................... 33 3.4 Statistical Analysis ................................................................................................. 35 3.4.1 Data Analysis Strategy ................................................................................... 35 3.4.2 Comparisons .................................................................................................. 35 3.4.3 Differentially Expressed Genes ....................................................................... 36 3.4.4 Pathway Analysis ........................................................................................... 37 4 Results ......................................................................................................................... 39 4.1 Quantitative Real Time Polymerase Chain Reaction Validation ............................. 39 4.2 Comparison I: Deficiency – Substitution................................................................. 41 4.2.1 Overview of Differentially Expressed Genes ................................................... 41 4.2.2 Differentially Expressed Genes ....................................................................... 47 4.3 Comparisons Based on Vitamin D Status und Sex ................................................ 59 4.3.1 Comparison II: Male – Female ........................................................................ 59 4.3.2 Comparison III: Differentially Expressed Genes – Female Subjects................ 61 4.3.3 Comparison IV: Differentially Expressed Genes – Male Subjects ................... 64 ii 4.3.4 Comparison V: Female vs. Male in the Vitamin D Deficient State ................... 66 4.3.5 Comparison IV: Female vs. Male after Vitamin D Supplementation ................ 69 4.4 Pathway Analysis .................................................................................................. 70 4.4.1 NK-Cell Cytotoxicity Pathway ......................................................................... 72 4.4.2 Immune System-Related Pathways – Upregulated ......................................... 74 4.4.3 Immune System-Related Pathways – Downregulated .................................... 76 4.4.4 Unsupervised Pathway Analysis ..................................................................... 81 5 Discussion .................................................................................................................... 83 5.1 Role of Pathway Analysis in Genomic Research ................................................... 83 5.2 Altered Cytokine - mRNA Profile After Vitamin D Supplementation ........................ 84 5.3 Altered Pathways After Vitamin D Supplementation .............................................. 86 5.4 Indirect Influence of Vitamin D on NK Cells ........................................................... 89 5.5 Role of Sexual Dimorphism ................................................................................... 89 5.6 Vitamin D in the Context of Autoimmunity and Chronic Inflammation ..................... 91 5.7 Critical View and Outlook ....................................................................................... 92 5.8 Conclusion ............................................................................................................. 93 6 References ..................................................................................................................
Load more

Recommended publications
  • Downloaded from [266]
    Patterns of DNA methylation on the human X chromosome and use in analyzing X-chromosome inactivation by Allison Marie Cotton B.Sc., The University of Guelph, 2005 A THESIS SUBMITTED IN PARTIAL FULFILLMENT OF THE REQUIREMENTS FOR THE DEGREE OF DOCTOR OF PHILOSOPHY in The Faculty of Graduate Studies (Medical Genetics) THE UNIVERSITY OF BRITISH COLUMBIA (Vancouver) January 2012 © Allison Marie Cotton, 2012 Abstract The process of X-chromosome inactivation achieves dosage compensation between mammalian males and females. In females one X chromosome is transcriptionally silenced through a variety of epigenetic modifications including DNA methylation. Most X-linked genes are subject to X-chromosome inactivation and only expressed from the active X chromosome. On the inactive X chromosome, the CpG island promoters of genes subject to X-chromosome inactivation are methylated in their promoter regions, while genes which escape from X- chromosome inactivation have unmethylated CpG island promoters on both the active and inactive X chromosomes. The first objective of this thesis was to determine if the DNA methylation of CpG island promoters could be used to accurately predict X chromosome inactivation status. The second objective was to use DNA methylation to predict X-chromosome inactivation status in a variety of tissues. A comparison of blood, muscle, kidney and neural tissues revealed tissue-specific X-chromosome inactivation, in which 12% of genes escaped from X-chromosome inactivation in some, but not all, tissues. X-linked DNA methylation analysis of placental tissues predicted four times higher escape from X-chromosome inactivation than in any other tissue. Despite the hypomethylation of repetitive elements on both the X chromosome and the autosomes, no changes were detected in the frequency or intensity of placental Cot-1 holes.
    [Show full text]
  • Deregulated Mirnas in Bone Health Epigenetic Roles in Osteoporosis
    Bone 122 (2019) 52–75 Contents lists available at ScienceDirect Bone journal homepage: www.elsevier.com/locate/bone Review Article Deregulated miRNAs in bone health: Epigenetic roles in osteoporosis T ⁎ D. Bellaviaa, , A. De Lucaa, V. Carinaa, V. Costaa, L. Raimondia, F. Salamannab, R. Alessandroc,d, M. Finib, G. Giavaresib a IRCCS Istituto Ortopedico Rizzoli, Bologna, Italy b IRCCS Istituto Ortopedico Rizzoli, Laboratory of Preclinical and Surgical Studies, Bologna, Italy c Department of Biopathology and Medical Biotechnologies, Section of Biology and Genetics, University of Palermo, Palermo 90133, Italy d Institute of Biomedicine and Molecular Immunology (IBIM), National Research Council, Palermo, Italy. ARTICLE INFO ABSTRACT Keywords: MicroRNA (miRNA) has shown to enhance or inhibit cell proliferation, differentiation and activity of different miRNA cell types in bone tissue. The discovery of miRNA actions and their targets has helped to identify them as novel Osteoporosis regulations actors in bone. Various studies have shown that miRNA deregulation mediates the progression of Osteogenesis bone-related pathologies, such as osteoporosis. Osteoblast The present review intends to give an exhaustive overview of miRNAs with experimentally validated targets Osteoclast involved in bone homeostasis and highlight their possible role in osteoporosis development. Moreover, the review analyzes miRNAs identified in clinical trials and involved in osteoporosis. 1. Introduction degradation [7]. Mature miRNAs are generated by the sequential cleavage of precursor transcripts, indicated as pri-miRNAs, that is Bone is a mineralized connective tissue that has two essential bio- cleaved in the nucleus by Drosha and the Di George syndrome critical logical roles: 1) a mechanical role – supporting body locomotion and region gene 8 (DGCR8) complex, producing a hairpin of 70–100 nu- protecting brain and splanchnic organs; and 2) a metabolic role - reg- cleotides, named pre-miRNA.
    [Show full text]
  • Supplementary Materials
    Supplementary materials Supplementary Table S1: MGNC compound library Ingredien Molecule Caco- Mol ID MW AlogP OB (%) BBB DL FASA- HL t Name Name 2 shengdi MOL012254 campesterol 400.8 7.63 37.58 1.34 0.98 0.7 0.21 20.2 shengdi MOL000519 coniferin 314.4 3.16 31.11 0.42 -0.2 0.3 0.27 74.6 beta- shengdi MOL000359 414.8 8.08 36.91 1.32 0.99 0.8 0.23 20.2 sitosterol pachymic shengdi MOL000289 528.9 6.54 33.63 0.1 -0.6 0.8 0 9.27 acid Poricoic acid shengdi MOL000291 484.7 5.64 30.52 -0.08 -0.9 0.8 0 8.67 B Chrysanthem shengdi MOL004492 585 8.24 38.72 0.51 -1 0.6 0.3 17.5 axanthin 20- shengdi MOL011455 Hexadecano 418.6 1.91 32.7 -0.24 -0.4 0.7 0.29 104 ylingenol huanglian MOL001454 berberine 336.4 3.45 36.86 1.24 0.57 0.8 0.19 6.57 huanglian MOL013352 Obacunone 454.6 2.68 43.29 0.01 -0.4 0.8 0.31 -13 huanglian MOL002894 berberrubine 322.4 3.2 35.74 1.07 0.17 0.7 0.24 6.46 huanglian MOL002897 epiberberine 336.4 3.45 43.09 1.17 0.4 0.8 0.19 6.1 huanglian MOL002903 (R)-Canadine 339.4 3.4 55.37 1.04 0.57 0.8 0.2 6.41 huanglian MOL002904 Berlambine 351.4 2.49 36.68 0.97 0.17 0.8 0.28 7.33 Corchorosid huanglian MOL002907 404.6 1.34 105 -0.91 -1.3 0.8 0.29 6.68 e A_qt Magnogrand huanglian MOL000622 266.4 1.18 63.71 0.02 -0.2 0.2 0.3 3.17 iolide huanglian MOL000762 Palmidin A 510.5 4.52 35.36 -0.38 -1.5 0.7 0.39 33.2 huanglian MOL000785 palmatine 352.4 3.65 64.6 1.33 0.37 0.7 0.13 2.25 huanglian MOL000098 quercetin 302.3 1.5 46.43 0.05 -0.8 0.3 0.38 14.4 huanglian MOL001458 coptisine 320.3 3.25 30.67 1.21 0.32 0.9 0.26 9.33 huanglian MOL002668 Worenine
    [Show full text]
  • Functional Genomics Analysis of Vitamin D Effects on CD4+ T Cells In
    Functional genomics analysis of vitamin D effects PNAS PLUS on CD4+ T cells in vivo in experimental autoimmune encephalomyelitis Manuel Zeitelhofera,b, Milena Z. Adzemovica, David Gomez-Cabreroc,d,e, Petra Bergmana, Sonja Hochmeisterf, Marie N’diayea, Atul Paulsona, Sabrina Ruhrmanna, Malin Almgrena, Jesper N. Tegnérc,d,g, Tomas J. Ekströma, André Ortlieb Guerreiro-Cacaisa, and Maja Jagodica,1 aDepartment of Clinical Neuroscience, Center for Molecular Medicine, Karolinska Institutet, 171 76 Stockholm, Sweden; bVascular Biology Unit, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, 171 77 Stockholm, Sweden; cUnit of Computational Medicine, Department of Medicine, Solna, Center for Molecular Medicine, Karolinska Institutet, 171 76 Stockholm, Sweden; dScience for Life Laboratory, 171 21 Solna, Sweden; eMucosal and Salivary Biology Division, King’s College London Dental Institute, London SE1 9RT, United Kingdom; fDepartment of General Neurology, Medical University of Graz, 8036 Graz, Austria; and gBiological and Environmental Sciences and Engineering Division, Computer, Electrical and Mathematical Sciences and Engineering Division, King Abdullah University of Science and Technology, 23955 Thuwal, Kingdom of Saudi Arabia Edited by Tomas G. M. Hokfelt, Karolinska Institutet, Stockholm, Sweden, and approved January 19, 2017 (received for review September 24, 2016) Vitamin D exerts multiple immunomodulatory functions and has autoimmune destruction of myelin, axonal loss, and brain atro- been implicated in the etiology and treatment of several autoim- phy (6). Increased risk of developing MS has been described in mune diseases, including multiple sclerosis (MS). We have previously carriers of rare and common variants of the CYP27B gene (7, 8), reported that in juvenile/adolescent rats, vitamin D supplementation which encodes the enzyme that catalyzes the last step in con- protects from experimental autoimmune encephalomyelitis (EAE), a verting vitamin D to its active form, from 25(OH)D3 to 1,25 model of MS.
    [Show full text]
  • A Yeast Phenomic Model for the Influence of Warburg Metabolism on Genetic Buffering of Doxorubicin Sean M
    Santos and Hartman Cancer & Metabolism (2019) 7:9 https://doi.org/10.1186/s40170-019-0201-3 RESEARCH Open Access A yeast phenomic model for the influence of Warburg metabolism on genetic buffering of doxorubicin Sean M. Santos and John L. Hartman IV* Abstract Background: The influence of the Warburg phenomenon on chemotherapy response is unknown. Saccharomyces cerevisiae mimics the Warburg effect, repressing respiration in the presence of adequate glucose. Yeast phenomic experiments were conducted to assess potential influences of Warburg metabolism on gene-drug interaction underlying the cellular response to doxorubicin. Homologous genes from yeast phenomic and cancer pharmacogenomics data were analyzed to infer evolutionary conservation of gene-drug interaction and predict therapeutic relevance. Methods: Cell proliferation phenotypes (CPPs) of the yeast gene knockout/knockdown library were measured by quantitative high-throughput cell array phenotyping (Q-HTCP), treating with escalating doxorubicin concentrations under conditions of respiratory or glycolytic metabolism. Doxorubicin-gene interaction was quantified by departure of CPPs observed for the doxorubicin-treated mutant strain from that expected based on an interaction model. Recursive expectation-maximization clustering (REMc) and Gene Ontology (GO)-based analyses of interactions identified functional biological modules that differentially buffer or promote doxorubicin cytotoxicity with respect to Warburg metabolism. Yeast phenomic and cancer pharmacogenomics data were integrated to predict differential gene expression causally influencing doxorubicin anti-tumor efficacy. Results: Yeast compromised for genes functioning in chromatin organization, and several other cellular processes are more resistant to doxorubicin under glycolytic conditions. Thus, the Warburg transition appears to alleviate requirements for cellular functions that buffer doxorubicin cytotoxicity in a respiratory context.
    [Show full text]
  • Involvement of Human Micro-RNA in Growth and Response to Chemotherapy in Human Cholangiocarcinoma Cell Lines
    View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by Texas A&M Repository GASTROENTEROLOGY 2006;130:2113–2129 Involvement of Human Micro-RNA in Growth and Response to Chemotherapy in Human Cholangiocarcinoma Cell Lines FANYIN MENG,* ROGER HENSON,* MOLLY LANG,* HANIA WEHBE,* SHAIL MAHESHWARI,* JOSHUA T. MENDELL,‡ JINMAI JIANG,§ THOMAS D. SCHMITTGEN,§ and TUSHAR PATEL* *Department of Internal Medicine, Scott and White Clinic, Texas A&M University System Health Science Center College of Medicine, Temple, Texas; ‡The Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland; and §College of Pharmacy, The Ohio State University, Columbus, Ohio Background & Aims: Micro-RNA (miRNA) are endoge- age of target mRNA. Although several hundred miRNA nous regulatory RNA molecules that modulate gene have been cloned or predicted, a functional role for these expression. Alterations in miRNA expression can contrib- in many cellular processes has not been fully elucidated.1 ute to tumor growth by modulating the functional ex- The best characterized role of miRNA has been as a pression of critical genes involved in tumor cell prolifer- developmental regulator in Caenorhabditis elegans and ation or survival. Our aims were to identify specific Drosophilia. More recently, several other roles have been miRNA involved in the regulation of cholangiocarcinoma described including regulation of apoptosis and differen- growth and response to chemotherapy. Methods: miRNA tiation. miRNA are expressed as long precursor RNA expression in malignant and nonmalignant human that are processed by a single nuclease Drosha prior to cholangiocytes was assessed using a microarray. Ex- pression of selected miRNA and their precursors was transport into the cytoplasm by an exportin-5-dependent evaluated by Northern blots and real-time polymerase mechanism.
    [Show full text]
  • Genetic Determinants of Inter-Individual Variations in DNA Methylation
    Genetic determinants of inter-individual variations in DNA methylation Dissertation zur Erlangung des Doktorgrades der Naturwissenschaften (Dr. rer. nat.) der Fakultät für Biologie und Vorklinische Medizin der Universität Regensburg vorgelegt von Julia Wimmer (geb. Wegner) aus Neubrandenburg im Jahr 2014 The present work was carried out at the Clinic and Polyclininc of Internal Medicine III at the University Hospital Regensburg from March 2010 to August 2014. Die vorliegende Arbeit entstand im Zeitraum von März 2010 bis August 2014 an der Klinik und Poliklinik für Innere Medizin III des Universitätsklinikums Regensburg. Das Promotionsgesuch wurde eingereicht am: 01. September 2014 Die Arbeit wurde angeleitet von: Prof. Dr. Michael Rehli Prüfungsausschuss: Vorsitzender: Prof. Dr. Herbert Tschochner Erstgutachter: Prof. Dr. Michael Rehli Zweitgutachter: Prof. Dr. Axel Imhof Drittprüfer: Prof. Dr. Gernot Längst Ersatzprüfer: PD Dr. Joachim Griesenbeck Unterschrift: ____________________________ Who seeks shall find. (Sophocles) Table of Contents TABLE OF CONTENTS .......................................................................................................................... I LIST OF FIGURES ................................................................................................................................ IV LIST OF TABLES ................................................................................................................................... V 1 INTRODUCTION ..........................................................................................................................
    [Show full text]
  • Epigenetic of Colorectal Cancer: a Focus on Micrornas
    André Filipe Afonso de Sousa Fonseca Epigenetic of colorectal cancer: a focus on microRNAs UNIVERSIDADE DO ALGARVE Departamento de Ciências Biomédicas e Medicina 2018 André Filipe Afonso de Sousa Fonseca Epigenetic of colorectal cancer: a focus on microRNAs Master in Oncobiology - Molecular Mechanisms of Cancer This work was done under the supervision of: Pedro Castelo-Branco, Ph.D Vânia Palma Roberto, Ph.D UNIVERSIDADE DO ALGARVE Departamento de Ciências Biomédicas e Medicina 2018 i ii Epigenetic of colorectal cancer: a focus on microRNAs Declaração de autoria do trabalho Declaro ser a autora deste trabalho, que é original e inédito. Autores e trabalhos consultados estão devidamente citados no texto e constam da listagem de referências incluída. “I declare that I am the author of this work, that is original and unpublished. Authors and works consulted are properly cited in the text and included in the list of references.” ______________________________________ (André Fonseca) iii Copyright © 2018 André Filipe Afonso de Sousa Fonseca A Universidade do Algarve reserva para si o direito, em conformidade com o disposto no Código do Direito de Autor e dos Direitos Conexos, de arquivar, reproduzir e publicar a obra, independentemente do meio utilizado, bem como de a divulgar através de repositórios científicos e de admitir a sua cópia e distribuição para fins meramente educacionais ou de investigação e não comerciais, conquanto seja dado o devido crédito ao autor e editor respetivos. iv “If you want to succeed as bad as you want to breathe then you will be successful!” - Eric Thomas v vi Agradecimentos Em primeiro lugar gostaria de agradecer ao meu orientador, o professor doutor Pedro Castelo-Branco por me ter acolhido no seu laboratório, por depositar em mim a sua confiança e acreditar na minha capacidade para realizar o seguinte trabalho.
    [Show full text]
  • Epigenetic Alterations and Advancement of Treatment in Peripheral T-Cell Lymphoma
    Zhang and Zhang Clin Epigenet (2020) 12:169 https://doi.org/10.1186/s13148-020-00962-x REVIEW Open Access Epigenetic alterations and advancement of treatment in peripheral T-cell lymphoma Ping Zhang1,2 and Mingzhi Zhang1,2* Abstract Peripheral T-cell lymphoma (PTCL) is a rare and heterogeneous group of clinically aggressive diseases associated with poor prognosis. Except for ALK anaplastic large-cell lymphoma (ALCL), most peripheral T-cell lymphomas are highly malignant and have an aggressive+ disease course and poor clinical outcomes, with a poor remission rate and frequent relapse after frst-line treatment. Aberrant epigenetic alterations play an important role in the pathogenesis and development of specifc types of peripheral T-cell lymphoma, including the regulation of the expression of genes and signal transduction. The most common epigenetic alterations are DNA methylation and histone modifcation. Histone modifcation alters the level of gene expression by regulating the acetylation status of lysine residues on the promoter surrounding histones, often leading to the silencing of tumour suppressor genes or the overexpression of proto-oncogenes in lymphoma. DNA methylation refers to CpG islands, generally leading to tumour suppressor gene transcriptional silencing. Genetic studies have also shown that some recurrent mutations in genes involved in the epi- genetic machinery, including TET2, IDH2-R172, DNMT3A, RHOA, CD28, IDH2, TET2, MLL2, KMT2A, KDM6A, CREBBP, and EP300, have been observed in cases of PTCL. The aberrant expression of miRNAs has also gradually become a diag- nostic biomarker. These provide a reasonable molecular mechanism for epigenetic modifying drugs in the treatment of PTCL. As epigenetic drugs implicated in lymphoma have been continually reported in recent years, many new ideas for the diagnosis, treatment, and prognosis of PTCL originate from epigenetics in recent years.
    [Show full text]
  • Download Special Issue
    BioMed Research International Novel Bioinformatics Approaches for Analysis of High-Throughput Biological Data Guest Editors: Julia Tzu-Ya Weng, Li-Ching Wu, Wen-Chi Chang, Tzu-Hao Chang, Tatsuya Akutsu, and Tzong-Yi Lee Novel Bioinformatics Approaches for Analysis of High-Throughput Biological Data BioMed Research International Novel Bioinformatics Approaches for Analysis of High-Throughput Biological Data Guest Editors: Julia Tzu-Ya Weng, Li-Ching Wu, Wen-Chi Chang, Tzu-Hao Chang, Tatsuya Akutsu, and Tzong-Yi Lee Copyright © 2014 Hindawi Publishing Corporation. All rights reserved. This is a special issue published in “BioMed Research International.” All articles are open access articles distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Contents Novel Bioinformatics Approaches for Analysis of High-Throughput Biological Data,JuliaTzu-YaWeng, Li-Ching Wu, Wen-Chi Chang, Tzu-Hao Chang, Tatsuya Akutsu, and Tzong-Yi Lee Volume2014,ArticleID814092,3pages Evolution of Network Biomarkers from Early to Late Stage Bladder Cancer Samples,Yung-HaoWong, Cheng-Wei Li, and Bor-Sen Chen Volume 2014, Article ID 159078, 23 pages MicroRNA Expression Profiling Altered by Variant Dosage of Radiation Exposure,Kuei-FangLee, Yi-Cheng Chen, Paul Wei-Che Hsu, Ingrid Y. Liu, and Lawrence Shih-Hsin Wu Volume2014,ArticleID456323,10pages EXIA2: Web Server of Accurate and Rapid Protein Catalytic Residue Prediction, Chih-Hao Lu, Chin-Sheng
    [Show full text]
  • A Temporally Controlled Sequence of X-Chromosome Inactivation and Reactivation Defines Female Mouse in Vitro Germ Cells with Meiotic Potential
    bioRxiv preprint doi: https://doi.org/10.1101/2021.08.11.455976; this version posted August 11, 2021. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC 4.0 International license. A temporally controlled sequence of X-chromosome inactivation and reactivation defines female mouse in vitro germ cells with meiotic potential Jacqueline Severino1†, Moritz Bauer1,9†, Tom Mattimoe1, Niccolò Arecco1, Luca Cozzuto1, Patricia Lorden2, Norio Hamada3, Yoshiaki Nosaka4,5,6, So Nagaoka4,5,6, Holger Heyn2, Katsuhiko Hayashi7, Mitinori Saitou4,5,6 and Bernhard Payer1,8* Abstract The early mammalian germ cell lineage is characterized by extensive epigenetic reprogramming, which is required for the maturation into functional eggs and sperm. In particular, the epigenome needs to be reset before parental marks can be established and then transmitted to the next generation. In the female germ line, reactivation of the inactive X- chromosome is one of the most prominent epigenetic reprogramming events, and despite its scale involving an entire chromosome affecting hundreds of genes, very little is known about its kinetics and biological function. Here we investigate X-chromosome inactivation and reactivation dynamics by employing a tailor-made in vitro system to visualize the X-status during differentiation of primordial germ cell-like cells (PGCLCs) from female mouse embryonic stem cells (ESCs). We find that the degree of X-inactivation in PGCLCs is moderate when compared to somatic cells and characterized by a large number of genes escaping full inactivation.
    [Show full text]
  • Carlos Souza Do Nascimento
    CARLOS SOUZA DO NASCIMENTO EXPRESSÃO GÊNICA EM BIBLIOTECAS DE cDNA DE PELE DE BOVINOS F2 (HOLANDÊS × GIR) INFESTADOS COM O CARRAPATO RIPHICEPHALUS (BOOPHILUS) MICROPLUS Tese apresentada à Universidade Federal de Viçosa, como parte das exigências do Programa de Pós- Graduação em Zootecnia, para obtenção do título de Doctor Scientiae. VIÇOSA MINAS GERAIS - BRASIL 2009 CARLOS SOUZA DO NASCIMENTO EXPRESSÃO GÊNICAEM BIBLIOTECAS DE cDNA DE PELE DE BOVINOS F2 (HOLANDÊS x GIR) INFESTEDOS COM O CARRAPATO RIPHICEPHALUS (BOOPHILUS) MICROPLUS Tese apresentada à Universidade Federal de Viçosa, como parte das exigências do Programa de Pós- Graduação em Zootecnia, para obtenção do título de Doctor Scientiae. APROVADA: 19 de fevereiro de 2009. Dr. Marco Antonio Machado Dra. Marta Fonseca Martins (Co-Orientador) Guimarães Prof. Jose Bracini Neto Prof. Paulo Luiz Souza Carneiro Profª. Simone E. F. Guimarães (Orientadora) Para ser grande, sê inteiro: nada Teu exagera ou exclui. Sê todo em cada coisa. Põe quanto és No mínimo que fazes. Assim em cada coisa a Lua toda Brilha, porque alta vive. Ricardo Reis (heterônimo de Fernando Pessoa) ii AGRADECIMENTOS Agradeço a todos que, de forma direta ou indireta, estiveram presentes durante essa longa caminhada. À Universidade Federal de Viçosa (UFV) e ao Departamento de Zootecnia (DZO), pela oportunidade de realização do curso. Ao Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), pela concessão da bolsa de estudos. À Embrapa Gado de Leite (Juiz de fora, Minas Gerais), pela imprescindível contribuição na realização deste trabalho. Agradeço à minha orientadora, Profa. Simone E.F. Guimarães, pela oportunidade de aprendizado e pela confiança demonstrada na realização desta pesquisa.
    [Show full text]