DOCSLIB.ORG

Katherine L. Crossland Abstract Abstract

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Katherine L. Crossland Abstract Abstract Characterisation of a Novel Transmembrane Protein in Primary Human CD4+ T-cells Katherine Louise Crossland Doctor of Philosophy Institute of Cellular Medicine December 2013 Katherine L. Crossland Abstract Abstract There are two main mechanisms of tolerance, one in the thymus and one in the periphery. Anergy, a peripheral mechanism, is a state of hypo-responsiveness where T-cells fail to respond to antigenic stimulus. A breakdown in immunological self-tolerance leads to autoimmunity and so provides an exciting research area for therapeutic intervention in autoimmune disease. Differential display studies comparing anergic and activated CD4+ T-cells identified claudin domain containing protein 1 (CLDND1) to be differentially expressed between these two states. In addition, preliminary experiments performed in our lab identified CLDND1 as a potential negative regulator of CD4+ T-cell activation. The aim of this study was to identify the role of CLDND1 in CD4+ T-cells. Antibodies against CLDND1 were raised and validated before use to determine CLDND1 expression in immune cell subsets and during T-cell activation. The function of CLDND1 in T-cells was investigated using gene silencing or over- expression techniques. CLDND1 expression was also sought in the autoimmune disease, rheumatoid arthritis (RA), to identify whether CLDND1 may be involved in disease pathogenesis. Antibodies were successfully raised against CLDND1 and CLDND1 was found to be transiently up-regulated during CD4+ T-cell activation. CLDND1 gene silencing attempts, while successful at the RNA level, did not translate to a reduction in CLDND1 protein, suggesting CLDND1 may be regulated independently of gene transcription. Over-expression studies were consistent with CLDND1 being a negative regulator of T-cell proliferation or an inducer of cell death, depending on the activating stimulus used. CLDND1 expression was found to correlate with rheumatoid factor (RF) status in early RA patients and may suggest a role for CLDND1 in the disease setting. Some findings identify similarities between CLDND1 and other proteins, providing links for functional pathways and a plethora of further avenues of research. ii Katherine L. Crossland Acknowledgements Acknowledgments I would like to acknowledge my supervisors, firstly John Isaacs for help in the planning and execution of the project, his ambitious ideas and his input during the writing of the thesis. In addition I would like to thank Amy Anderson who helped with day to day queries in the lab and for reading every chapter of this thesis. I would like to thank all my supervisors, including David Young and Catharien Hilkens for their valuable input to the project. A major part of this work was supported by employees at UCB Celltech and co- ordinated through Tim Bourne, Louise Healy and Gillian McCluskey and so I would like to thank them for their willingness to help and drive the project forward. I also appreciate the work that Helene Finney, Kerry Tyson and Terry Baker performed in generating peptides, performing the immunisations for antibody generation and advice on molecular cloning. Many members of the MRG, in particular Rachel Harry, Julie Diboll and Matt Barter, provided invaluable advice and some were also willing and regular blood donors. I would also like to say a massive thanks to my partner, Adam, who cheered me up and pulled me through the rough times and celebrated with me during the highs. I would also like to acknowledge my parents who continue to support me in my aspirations. Finally, thanks to the biotechnology and biological sciences research council (BBSRC) and UCB Celltech for providing funding for this CASE Studentship, for without this, the research would not have been possible. iii Katherine L. Crossland Declaration Declaration The candidate confirms that the work submitted is her own work and that appropriate credit has been given where reference has been made to the work of others. The work in this thesis was performed from September 2010 to September 2013. All work was performed in either the Musculoskeletal Research Group, Institute of Cellular Medicine, Newcastle University or at UCB Celltech, Slough. No part of this thesis has been submitted for the award of any other degree. iv Katherine L. Crossland Table of Contents Table of Contents Abstract .......................................................................................... ii Acknowledgments ........................................................................ iii Declaration .................................................................................... iv Table of Contents .......................................................................... v List of Figures and Tables ......................................................... xiii List of Abbreviations .................................................................xviii Chapter 1. Introduction ............................................................. 1 1.1 T-cell Selection in the Thymus ........................................................... 1 1.2 T-cell Activation ................................................................................... 2 1.2.1 Importance of IL-2 signalling ........................................................... 4 1.2.2 Calcium signalling ........................................................................... 4 1.3 Types of T-Effector Cells ..................................................................... 5 1.4 The Regulation of T-cell Activation .................................................... 7 1.4.1 Control of APC activation ................................................................ 7 1.4.2 Treg ................................................................................................. 8 1.4.3 Anergy ............................................................................................. 8 1.4.4 Negative regulators of the immune response ................................ 11 1.5 Immune Cells in Disease ................................................................... 12 1.6 RA........................................................................................................ 12 1.7 Synovial Joints .................................................................................. 13 1.8 Proposed Models of RA Pathogenesis ............................................ 15 1.8.1 B-cells ........................................................................................... 15 1.8.2 T-cells ............................................................................................ 15 1.8.3 Other players in RA disease pathogenesis ................................... 16 1.9 Therapeutic Tolerance in RA ............................................................ 17 1.10 Identification of Tolerance Markers in T-cells ................................. 18 1.11 CLDND1 .............................................................................................. 22 1.11.1 Discovery of the CLDND1 gene .................................................... 22 1.11.2 Predicted CLDND1 protein characteristics .................................... 22 v Katherine L. Crossland Table of Contents 1.11.3 The PMP-22/EMP/MP20/claudin superfamily ............................... 24 1.11.4 The clarin family ............................................................................ 24 1.11.5 The PMP-22/EMP/MP20 family ..................................................... 24 1.11.6 The claudin family ......................................................................... 26 1.11.7 The voltage-dependent calcium channel, gamma subunit family .. 27 1.11.8 Potential CLDND1 function based on the PMP- 22/EMP/MP20/claudin family ...................................................................... 28 1.11.9 CLDND1 gene function ................................................................. 28 1.11.10 Pilot data indicating a function for CLDND1 in CD4+ T-cells ......... 29 1.12 Hypothesis and Aims of the Thesis ................................................. 31 Chapter 2. Methods ................................................................. 32 2.1 List of Materials ................................................................................. 32 2.1.1 Stocks ........................................................................................... 32 2.1.2 Antibodies ..................................................................................... 34 2.1.3 Buffers ........................................................................................... 38 2.2 Vector Generation .............................................................................. 40 2.2.1 PCR amplification of DNA inserts .................................................. 40 2.2.2 Restriction digests ......................................................................... 41 2.2.3 Ligations and transformations ....................................................... 41 2.2.4 In-house minipreps ........................................................................ 42 2.2.5 DNA sequencing ........................................................................... 42 2.2.6 Qiagen maxi and giga preps ......................................................... 42 2.3 Antibody Generation ......................................................................... 46 2.3.1 Peptide generation ........................................................................ 46 2.3.2 Immunisation strategy ..................................................................
Load more

Recommended publications
  • GATA2 Regulates Mast Cell Identity and Responsiveness to Antigenic Stimulation by Promoting Chromatin Remodeling at Super- Enhancers
    ARTICLE https://doi.org/10.1038/s41467-020-20766-0 OPEN GATA2 regulates mast cell identity and responsiveness to antigenic stimulation by promoting chromatin remodeling at super- enhancers Yapeng Li1, Junfeng Gao 1, Mohammad Kamran1, Laura Harmacek2, Thomas Danhorn 2, Sonia M. Leach1,2, ✉ Brian P. O’Connor2, James R. Hagman 1,3 & Hua Huang 1,3 1234567890():,; Mast cells are critical effectors of allergic inflammation and protection against parasitic infections. We previously demonstrated that transcription factors GATA2 and MITF are the mast cell lineage-determining factors. However, it is unclear whether these lineage- determining factors regulate chromatin accessibility at mast cell enhancer regions. In this study, we demonstrate that GATA2 promotes chromatin accessibility at the super-enhancers of mast cell identity genes and primes both typical and super-enhancers at genes that respond to antigenic stimulation. We find that the number and densities of GATA2- but not MITF-bound sites at the super-enhancers are several folds higher than that at the typical enhancers. Our studies reveal that GATA2 promotes robust gene transcription to maintain mast cell identity and respond to antigenic stimulation by binding to super-enhancer regions with dense GATA2 binding sites available at key mast cell genes. 1 Department of Immunology and Genomic Medicine, National Jewish Health, Denver, CO 80206, USA. 2 Center for Genes, Environment and Health, National Jewish Health, Denver, CO 80206, USA. 3 Department of Immunology and Microbiology, University of Colorado Anschutz Medical Campus, Aurora, ✉ CO 80045, USA. email: [email protected] NATURE COMMUNICATIONS | (2021) 12:494 | https://doi.org/10.1038/s41467-020-20766-0 | www.nature.com/naturecommunications 1 ARTICLE NATURE COMMUNICATIONS | https://doi.org/10.1038/s41467-020-20766-0 ast cells (MCs) are critical effectors in immunity that at key MC genes.
    [Show full text]
  • CLDND1 (NM 001040183) Human Tagged ORF Clone – RC211544
    OriGene Technologies, Inc. 9620 Medical Center Drive, Ste 200 Rockville, MD 20850, US Phone: +1-888-267-4436 [email protected] EU: [email protected] CN: [email protected] Product datasheet for RC211544 CLDND1 (NM_001040183) Human Tagged ORF Clone Product data: Product Type: Expression Plasmids Product Name: CLDND1 (NM_001040183) Human Tagged ORF Clone Tag: Myc-DDK Symbol: CLDND1 Synonyms: C3orf4; GENX-3745; Z38 Vector: pCMV6-Entry (PS100001) E. coli Selection: Kanamycin (25 ug/mL) Cell Selection: Neomycin ORF Nucleotide >RC211544 ORF sequence Sequence: Red=Cloning site Blue=ORF Green=Tags(s) TTTTGTAATACGACTCACTATAGGGCGGCCGGGAATTCGTCGACTGGATCCGGTACCGAGGAGATCTGCC GCCGCGATCGCC ATGGATAACCGTTTTGCTACAGCATTTGTAATTGCTTGTGTGCTGAGCCTCATTTCCACCATCTACATGG CAGCCTCCATTGGCACAGACTTCTGGTATGAATATCGAAGTCCAGTTCAAGAAAATTCCAGTGATTTGAA TAAAAGCATCTGGGATGAATTCATTAGTGATGAGGCAGATGAAAAGACTTATAATGATGCACTTTTTCGA TACAATGGCACAGTGGGATTGTGGAGACGGTGTATCACCATACCCAAAAACATGCATTGGTATAGCCCAC CAGAAAGGACAGAGTCATTTGATGTGGTCACAAAATGTGTGAGTTTCACACTAACTGAGCAGTTCATGGA GAAATTTGTTGATCCCGGAAACCACAATAGCGGGATTGATCTCCTTAGGACCTATCTTTGGCGTTGCCAG TTCCTTTTACCTTTTGTGAGTTTAGGTTTGATGTGCTTTGGGGCTTTGATCGGACTTTGTGCTTGCATTT GCCGAAGCTTATATCCCACCATTGCCACGGGCATTCTCCATCTCCTTGCAGGTCTGTGTACACTGGGCTC AGTAAGTTGTTATGTTGCTGGAATTGAACTACTCCACCAGAAACTAGAGCTCCCTGACAATGTATCCGGT GAATTTGGATGGTCCTTCTGCCTGGCTTGTGTCTCTGCTCCCTTACAGTTCATGGCTTCTGCTCTCTTCA TCTGGGCTGCTCACACCAACCGGAAAGAGTACACCTTAATGAAGGCATATCGTGTGGCA ACGCGTACGCGGCCGCTCGAGCAGAAACTCATCTCAGAAGAGGATCTGGCAGCAAATGATATCCTGGATT ACAAGGATGACGACGATAAGGTTTAA
    [Show full text]
  • Transcriptional Regulation of Cancer Genes in the Xiphophorus
    Transcriptional regulation of cancer genes in the Xiphophorus melanoma system Dissertation zur Erlangung des naturwissenschaftlichen Doktorgrades der Julius-Maximilians-Universität Würzburg vorgelegt von Janine Regneri aus Herdecke Würzburg 2013 Eingereicht am: ....................................................................................................................... Mitglieder der Promotionskommission: Vorsitzender: .......................................................................................................................... Gutachter : .............................................................................................................................. Gutachter: ............................................................................................................................... Tag des Promotionskolloquiums: ............................................................................................. Doktorurkunde ausgehändigt am: ............................................................................................ Eidesstattliche Erklärung Gemäß §4, Abs. 3, Ziff. 3, 5 und 8 der Promotionsordnung der Fakultät für Biologie der Bayerischen Julius-Maximilians-Universität Würzburg Hiermit erkläre ich ehrenwörtlich, dass ich die vorliegende Dissertation selbständig angefertigt und keine anderen als die angegebenen Quellen und Hilfsmittel verwendet habe. Ich erkläre weiterhin, dass die vorliegende Dissertation weder in gleicher, noch in ähnlicher Form bereits in einem anderen Prüfungsverfahren
    [Show full text]
  • Gene Expression in Blood Reflects Smoking Exposure Among Cancer
    www.nature.com/scientificreports OPEN Gene expression in blood refects smoking exposure among cancer‑free women in the Norwegian Women and Cancer (NOWAC) postgenome cohort Nikita Baiju1*, Torkjel M. Sandanger1, Pål Sætrom2,3,4,5 & Therese H. Nøst1,5 Active smoking has been linked to modulated gene expression in blood. However, there is a need for a more thorough understanding of how quantitative measures of smoking exposure relate to diferentially expressed genes (DEGs) in whole‑blood among ever smokers. This study analysed microarray‑based gene expression profles from whole‑blood samples according to smoking status and quantitative measures of smoking exposure among cancer‑free women (n = 1708) in the Norwegian Women and Cancer postgenome cohort. When compared with never smokers and former smokers, current smokers had 911 and 1082 DEGs, respectively and their biological functions could indicate systemic impacts of smoking. LRRN3 was associated with smoking status with the lowest FDR‑adjusted p‑value. When never smokers and all former smokers were compared, no DEGs were observed, but LRRN3 was diferentially expressed when never smokers were compared with former smokers who quit smoking ≤ 10 years ago. Further, LRRN3 was positively associated with smoking intensity, pack‑years, and comprehensive smoking index score among current smokers; and negatively associated with time since cessation among former smokers. Consequently, LRRN3 expression in whole‑blood is a molecular signal of smoking exposure that could supplant self‑reported smoking data in further research targeting blood‑based markers related to the health efects of smoking. Tobacco smoking is one of the major threats to public health, and it is currently responsible for more than 8 million deaths worldwide each year 1.
    [Show full text]
  • Cldnd1 (NM 171826) Mouse Tagged ORF Clone – MR203231 | Origene
    OriGene Technologies, Inc. 9620 Medical Center Drive, Ste 200 Rockville, MD 20850, US Phone: +1-888-267-4436 [email protected] EU: [email protected] CN: [email protected] Product datasheet for MR203231 Cldnd1 (NM_171826) Mouse Tagged ORF Clone Product data: Product Type: Expression Plasmids Product Name: Cldnd1 (NM_171826) Mouse Tagged ORF Clone Tag: Myc-DDK Symbol: Cldnd1 Synonyms: 1110019C08Rik; AA407103; AI849195; AW489850; Cldn25 Vector: pCMV6-Entry (PS100001) E. coli Selection: Kanamycin (25 ug/mL) Cell Selection: Neomycin ORF Nucleotide >MR203231 ORF sequence Sequence: Red=Cloning site Blue=ORF Green=Tags(s) TTTTGTAATACGACTCACTATAGGGCGGCCGGGAATTCGTCGACTGGATCCGGTACCGAGGAGATCTGCC GCCGCGATCGCC ATGGATAACCGTTTTGCTACTGCGTTTGTGATTGCTTGTGTGCTTAGTCTGATTTCCACCATCTACATGG CGGCCTCCATAGGCACGGACTTCTGGTATGAGTATCGAAGTCCCATTCAAGAGAATTCAAGTGACTCGAA TAAAATCGCCTGGGAAGATTTCCTCGGTGACGAGGCGGATGAGAAGACTTACAACGATGTTCTGTTCCGA TACAACGGCAGCTTGGGGCTGTGGAGACGGTGCATCACCATACCCAAAAACACTCACTGGTATGCGCCAC CGGAAAGGACAGAGTCATTTGATGTGGTTACCAAATGCATGAGTTTCACACTAAACGAGCAGTTCATGGA GAAGTATGTGGACCCCGGCAACCACAATAGCGGCATCGACCTGCTTCGCACCTACCTGTGGCGCTGCCAG TTCCTTTTACCCTTCGTCAGCTTGGGCTTGATGTGCTTTGGGGCGTTGATTGGCCTCTGTGCCTGTATCT GCCGCAGCCTGTATCCCACCCTCGCCACTGGCATTCTCCATCTCCTTGCAGGTCTGTGCACACTGGGCTC CGTGAGTTGCTATGTTGCCGGCATTGAACTCTTACATCAGAAAGTAGAGCTGCCCAAGGATGTATCTGGA GAATTTGGATGGTCCTTCTGCCTGGCCTGCGTCTCGGCTCCCTTACAGTTCATGGCGGCCGCTCTCTTCA TCTGGGCTGCCCACACCAACCGGAAAGAGTACACCTTAATGAAGGCTTATCGTGTGGCA ACGCGTACGCGGCCGCTCGAGCAGAAACTCATCTCAGAAGAGGATCTGGCAGCAAATGATATCCTGGATT
    [Show full text]
  • Molecular Targeting and Enhancing Anticancer Efficacy of Oncolytic HSV-1 to Midkine Expressing Tumors
    University of Cincinnati Date: 12/20/2010 I, Arturo R Maldonado , hereby submit this original work as part of the requirements for the degree of Doctor of Philosophy in Developmental Biology. It is entitled: Molecular Targeting and Enhancing Anticancer Efficacy of Oncolytic HSV-1 to Midkine Expressing Tumors Student's name: Arturo R Maldonado This work and its defense approved by: Committee chair: Jeffrey Whitsett Committee member: Timothy Crombleholme, MD Committee member: Dan Wiginton, PhD Committee member: Rhonda Cardin, PhD Committee member: Tim Cripe 1297 Last Printed:1/11/2011 Document Of Defense Form Molecular Targeting and Enhancing Anticancer Efficacy of Oncolytic HSV-1 to Midkine Expressing Tumors A dissertation submitted to the Graduate School of the University of Cincinnati College of Medicine in partial fulfillment of the requirements for the degree of DOCTORATE OF PHILOSOPHY (PH.D.) in the Division of Molecular & Developmental Biology 2010 By Arturo Rafael Maldonado B.A., University of Miami, Coral Gables, Florida June 1993 M.D., New Jersey Medical School, Newark, New Jersey June 1999 Committee Chair: Jeffrey A. Whitsett, M.D. Advisor: Timothy M. Crombleholme, M.D. Timothy P. Cripe, M.D. Ph.D. Dan Wiginton, Ph.D. Rhonda D. Cardin, Ph.D. ABSTRACT Since 1999, cancer has surpassed heart disease as the number one cause of death in the US for people under the age of 85. Malignant Peripheral Nerve Sheath Tumor (MPNST), a common malignancy in patients with Neurofibromatosis, and colorectal cancer are midkine- producing tumors with high mortality rates. In vitro and preclinical xenograft models of MPNST were utilized in this dissertation to study the role of midkine (MDK), a tumor-specific gene over- expressed in these tumors and to test the efficacy of a MDK-transcriptionally targeted oncolytic HSV-1 (oHSV).
    [Show full text]
  • An RNA-Sequencing Transcriptome and Splicing Database of Glia, Neurons, and Vascular Cells of the Cerebral Cortex
    The Journal of Neuroscience, September 3, 2014 • 34(36):11929–11947 • 11929 Cellular/Molecular An RNA-Sequencing Transcriptome and Splicing Database of Glia, Neurons, and Vascular Cells of the Cerebral Cortex Ye Zhang,1* Kenian Chen,2,3* Steven A. Sloan,1* Mariko L. Bennett,1 Anja R. Scholze,1 Sean O’Keeffe,4 Hemali P. Phatnani,4 XPaolo Guarnieri,7,9 Christine Caneda,1 Nadine Ruderisch,5 Shuyun Deng,2,3 Shane A. Liddelow,1,6 Chaolin Zhang,4,7,8 Richard Daneman,5 Tom Maniatis,4 XBen A. Barres,1† and XJia Qian Wu2,3† 1Department of Neurobiology, Stanford University School of Medicine, Stanford, California 94305-5125, 2The Vivian L. Smith Department of Neurosurgery, University of Texas Medical School at Houston, Houston, Texas 77057, 3Center for Stem Cell and Regenerative Medicine, University of Texas Brown Institute of Molecular Medicine, Houston, Texas 77057, 4Department of Biochemistry and Molecular Biophysics, Columbia University Medical Center, New York, New York 10032, 5Department of Anatomy, University of California, San Francisco, San Francisco, California 94143-0452, 6Department of Pharmacology and Therapeutics, University of Melbourne, Parkville, Victoria, Australia 3010, and 7Department of Systems Biology, 8Center for Motor Neuron Biology and Disease, and 9Herbert Irving Comprehensive Cancer Center, Columbia University, New York, New York 10032 The major cell classes of the brain differ in their developmental processes, metabolism, signaling, and function. To better understand the functions and interactions of the cell types that comprise these classes, we acutely purified representative populations of neurons, astrocytes, oligodendrocyte precursor cells, newly formed oligodendrocytes, myelinating oligodendrocytes, microglia, endothelial cells, and pericytes from mouse cerebral cortex.
    [Show full text]
  • Chromosomal Instability Is Associated with Higher Expression of Genes
    Volume 10 Number 11 November 2008 pp. 1222–1230 1222 www.neoplasia.com Anna V. Roschke*, Oleg K. Glebov*, Chromosomal Instability Is † Samir Lababidi , Kristen S. Gehlhaus*, † Associated with Higher John N. Weinstein and Ilan R. Kirsch* Expression of Genes Implicated *Genetics Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20889-5105, USA; in Epithelial-Mesenchymal † Laboratory of Molecular Pharmacology, Center for Transition, Cancer Invasiveness, Cancer Research, National Cancer Institute, Bethesda, and Metastasis and with MD 20889-5105, USA Lower Expression of Genes Involved in Cell Cycle Checkpoints, DNA Repair, and Chromatin Maintenance1 Abstract Chromosomal instability—a hallmark of epithelial cancers—is an ongoing process that results in aneuploidy and karyotypic heterogeneity of a cancer cell population. Previously, we stratified cancer cell lines in the NCI-60 drug discovery panel based on their karyotypic complexity and heterogeneity. Using this stratification in conjunction with drug response data for the cell lines allowed us to identify classes of chemical compounds whose growth- inhibitory activity correlates with karyotypic complexity and chromosomal instability. In this article, we asked the question: What are the biological processes, pathways, or genes associated with chromosomal instability of can- cer cells? We found that increased instability of the chromosomal content in a cancer cell population, particularly, persistent gains and losses of chromosomes, is associated with elevated expression of genes involved with aggressive cellular behavior, including invasion- and metastasis-associated changes in cell communication, ad- hesion, motility, and migration. These same karyotypic features are negatively correlated with the expression of genes involved in cell cycle checkpoints, DNA repair, and chromatin maintenance.
    [Show full text]
  • Coexpression Networks Based on Natural Variation in Human Gene Expression at Baseline and Under Stress
    University of Pennsylvania ScholarlyCommons Publicly Accessible Penn Dissertations Fall 2010 Coexpression Networks Based on Natural Variation in Human Gene Expression at Baseline and Under Stress Renuka Nayak University of Pennsylvania, [email protected] Follow this and additional works at: https://repository.upenn.edu/edissertations Part of the Computational Biology Commons, and the Genomics Commons Recommended Citation Nayak, Renuka, "Coexpression Networks Based on Natural Variation in Human Gene Expression at Baseline and Under Stress" (2010). Publicly Accessible Penn Dissertations. 1559. https://repository.upenn.edu/edissertations/1559 This paper is posted at ScholarlyCommons. https://repository.upenn.edu/edissertations/1559 For more information, please contact [email protected]. Coexpression Networks Based on Natural Variation in Human Gene Expression at Baseline and Under Stress Abstract Genes interact in networks to orchestrate cellular processes. Here, we used coexpression networks based on natural variation in gene expression to study the functions and interactions of human genes. We asked how these networks change in response to stress. First, we studied human coexpression networks at baseline. We constructed networks by identifying correlations in expression levels of 8.9 million gene pairs in immortalized B cells from 295 individuals comprising three independent samples. The resulting networks allowed us to infer interactions between biological processes. We used the network to predict the functions of poorly-characterized human genes, and provided some experimental support. Examining genes implicated in disease, we found that IFIH1, a diabetes susceptibility gene, interacts with YES1, which affects glucose transport. Genes predisposing to the same diseases are clustered non-randomly in the network, suggesting that the network may be used to identify candidate genes that influence disease susceptibility.
    [Show full text]
  • Inbred Mouse Strains Expression in Primary Immunocytes Across
    Downloaded from http://www.jimmunol.org/ by guest on September 28, 2021 Daphne is online at: average * The Journal of Immunology published online 29 September 2014 from submission to initial decision 4 weeks from acceptance to publication Sara Mostafavi, Adriana Ortiz-Lopez, Molly A. Bogue, Kimie Hattori, Cristina Pop, Daphne Koller, Diane Mathis, Christophe Benoist, The Immunological Genome Consortium, David A. Blair, Michael L. Dustin, Susan A. Shinton, Richard R. Hardy, Tal Shay, Aviv Regev, Nadia Cohen, Patrick Brennan, Michael Brenner, Francis Kim, Tata Nageswara Rao, Amy Wagers, Tracy Heng, Jeffrey Ericson, Katherine Rothamel, Adriana Ortiz-Lopez, Diane Mathis, Christophe Benoist, Taras Kreslavsky, Anne Fletcher, Kutlu Elpek, Angelique Bellemare-Pelletier, Deepali Malhotra, Shannon Turley, Jennifer Miller, Brian Brown, Miriam Merad, Emmanuel L. Gautier, Claudia Jakubzick, Gwendalyn J. Randolph, Paul Monach, Adam J. Best, Jamie Knell, Ananda Goldrath, Vladimir Jojic, J Immunol http://www.jimmunol.org/content/early/2014/09/28/jimmun ol.1401280 Koller, David Laidlaw, Jim Collins, Roi Gazit, Derrick J. Rossi, Nidhi Malhotra, Katelyn Sylvia, Joonsoo Kang, Natalie A. Bezman, Joseph C. Sun, Gundula Min-Oo, Charlie C. Kim and Lewis L. Lanier Variation and Genetic Control of Gene Expression in Primary Immunocytes across Inbred Mouse Strains Submit online. Every submission reviewed by practicing scientists ? is published twice each month by http://jimmunol.org/subscription http://www.jimmunol.org/content/suppl/2014/09/28/jimmunol.140128 0.DCSupplemental Information about subscribing to The JI No Triage! Fast Publication! Rapid Reviews! 30 days* Why • • • Material Subscription Supplementary The Journal of Immunology The American Association of Immunologists, Inc., 1451 Rockville Pike, Suite 650, Rockville, MD 20852 Copyright © 2014 by The American Association of Immunologists, Inc.
    [Show full text]
  • Milger Et Al. Pulmonary CCR2+CD4+ T Cells Are Immune Regulatory And
    Milger et al. Pulmonary CCR2+CD4+ T cells are immune regulatory and attenuate lung fibrosis development Supplemental Table S1 List of significantly regulated mRNAs between CCR2+ and CCR2- CD4+ Tcells on Affymetrix Mouse Gene ST 1.0 array. Genewise testing for differential expression by limma t-test and Benjamini-Hochberg multiple testing correction (FDR < 10%). Ratio, significant FDR<10% Probeset Gene symbol or ID Gene Title Entrez rawp BH (1680) 10590631 Ccr2 chemokine (C-C motif) receptor 2 12772 3.27E-09 1.33E-05 9.72 10547590 Klrg1 killer cell lectin-like receptor subfamily G, member 1 50928 1.17E-07 1.23E-04 6.57 10450154 H2-Aa histocompatibility 2, class II antigen A, alpha 14960 2.83E-07 1.71E-04 6.31 10590628 Ccr3 chemokine (C-C motif) receptor 3 12771 1.46E-07 1.30E-04 5.93 10519983 Fgl2 fibrinogen-like protein 2 14190 9.18E-08 1.09E-04 5.49 10349603 Il10 interleukin 10 16153 7.67E-06 1.29E-03 5.28 10590635 Ccr5 chemokine (C-C motif) receptor 5 /// chemokine (C-C motif) receptor 2 12774 5.64E-08 7.64E-05 5.02 10598013 Ccr5 chemokine (C-C motif) receptor 5 /// chemokine (C-C motif) receptor 2 12774 5.64E-08 7.64E-05 5.02 10475517 AA467197 expressed sequence AA467197 /// microRNA 147 433470 7.32E-04 2.68E-02 4.96 10503098 Lyn Yamaguchi sarcoma viral (v-yes-1) oncogene homolog 17096 3.98E-08 6.65E-05 4.89 10345791 Il1rl1 interleukin 1 receptor-like 1 17082 6.25E-08 8.08E-05 4.78 10580077 Rln3 relaxin 3 212108 7.77E-04 2.81E-02 4.77 10523156 Cxcl2 chemokine (C-X-C motif) ligand 2 20310 6.00E-04 2.35E-02 4.55 10456005 Cd74 CD74 antigen
    [Show full text]
  • Supplementary Material Peptide-Conjugated Oligonucleotides Evoke Long-Lasting Myotonic Dystrophy Correction in Patient-Derived C
    Supplementary material Peptide-conjugated oligonucleotides evoke long-lasting myotonic dystrophy correction in patient-derived cells and mice Arnaud F. Klein1†, Miguel A. Varela2,3,4†, Ludovic Arandel1, Ashling Holland2,3,4, Naira Naouar1, Andrey Arzumanov2,5, David Seoane2,3,4, Lucile Revillod1, Guillaume Bassez1, Arnaud Ferry1,6, Dominic Jauvin7, Genevieve Gourdon1, Jack Puymirat7, Michael J. Gait5, Denis Furling1#* & Matthew J. A. Wood2,3,4#* 1Sorbonne Université, Inserm, Association Institut de Myologie, Centre de Recherche en Myologie, CRM, F-75013 Paris, France 2Department of Physiology, Anatomy and Genetics, University of Oxford, South Parks Road, Oxford, UK 3Department of Paediatrics, John Radcliffe Hospital, University of Oxford, Oxford, UK 4MDUK Oxford Neuromuscular Centre, University of Oxford, Oxford, UK 5Medical Research Council, Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge, UK 6Sorbonne Paris Cité, Université Paris Descartes, F-75005 Paris, France 7Unit of Human Genetics, Hôpital de l'Enfant-Jésus, CHU Research Center, QC, Canada † These authors contributed equally to the work # These authors shared co-last authorship Methods Synthesis of Peptide-PMO Conjugates. Pip6a Ac-(RXRRBRRXRYQFLIRXRBRXRB)-CO OH was synthesized and conjugated to PMO as described previously (1). The PMO sequence targeting CUG expanded repeats (5′-CAGCAGCAGCAGCAGCAGCAG-3′) and PMO control reverse (5′-GACGACGACGACGACGACGAC-3′) were purchased from Gene Tools LLC. Animal model and ASO injections. Experiments were carried out in the “Centre d’études fonctionnelles” (Faculté de Médecine Sorbonne University) according to French legislation and Ethics committee approval (#1760-2015091512001083v6). HSA-LR mice are gift from Pr. Thornton. The intravenous injections were performed by single or multiple administrations via the tail vein in mice of 5 to 8 weeks of age.
    [Show full text]