DOCSLIB.ORG

Dna Methylome in Her2-Positive Resistant Breast Cancer

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Dna Methylome in Her2-Positive Resistant Breast Cancer DNA METHYLOME IN HER2-POSITIVE RESISTANT BREAST CANCER Sònia Palomeras Pairet Per citar o enllaçar aquest document: Para citar o enlazar este documento: Use this url to cite or link to this publication: http://hdl.handle.net/10803/667582 ADVERTIMENT. L'accés als continguts d'aquesta tesi doctoral i la seva utilització ha de respectar els drets de la persona autora. Pot ser utilitzada per a consulta o estudi personal, així com en activitats o materials d'investigació i docència en els termes establerts a l'art. 32 del Text Refós de la Llei de Propietat Intel·lectual (RDL 1/1996). Per altres utilitzacions es requereix l'autorització prèvia i expressa de la persona autora. En qualsevol cas, en la utilització dels seus continguts caldrà indicar de forma clara el nom i cognoms de la persona autora i el títol de la tesi doctoral. No s'autoritza la seva reproducció o altres formes d'explotació efectuades amb finalitats de lucre ni la seva comunicació pública des d'un lloc aliè al servei TDX. Tampoc s'autoritza la presentació del seu contingut en una finestra o marc aliè a TDX (framing). Aquesta reserva de drets afecta tant als continguts de la tesi com als seus resums i índexs. ADVERTENCIA. El acceso a los contenidos de esta tesis doctoral y su utilización debe respetar los derechos de la persona autora. Puede ser utilizada para consulta o estudio personal, así como en actividades o materiales de investigación y docencia en los términos establecidos en el art. 32 del Texto Refundido de la Ley de Propiedad Intelectual (RDL 1/1996). Para otros usos se requiere la autorización previa y expresa de la persona autora. En cualquier caso, en la utilización de sus contenidos se deberá indicar de forma clara el nombre y apellidos de la persona autora y el título de la tesis doctoral. No se autoriza su reproducción u otras formas de explotación efectuadas con fines lucrativos ni su comunicación pública desde un sitio ajeno al servicio TDR. Tampoco se autoriza la presentación de su contenido en una ventana o marco ajeno a TDR (framing). Esta reserva de derechos afecta tanto al contenido de la tesis como a sus resúmenes e índices. WARNING. Access to the contents of this doctoral thesis and its use must respect the rights of the author. It can be used for reference or private study, as well as research and learning activities or materials in the terms established by the 32nd article of the Spanish Consolidated Copyright Act (RDL 1/1996). Express and previous authorization of the author is required for any other uses. In any case, when using its content, full name of the author and title of the thesis must be clearly indicated. Reproduction or other forms of for profit use or public communication from outside TDX service is not allowed. Presentation of its content in a window or frame external to TDX (framing) is not authorized either. These rights affect both the content of the thesis and its abstracts and indexes. Doctoral thesis DNA methylome in HER2-positive resistant breast cancer Sònia Palomeras i Pairet 2018 Doctoral thesis DNA methylome in HER2-positive resistant breast cancer Sònia Palomeras i Pairet 2018 Doctoral Programme in Molecular Biology, Biomedicine and Health This doctoral thesis contains Annexes (Annex I and II) Directed and tutorized by: Dra. Teresa Puig Miquel Presented in partial fulfillment of the requirements for a doctoral degree from the University of Girona Dr. Teresa Puig Miquel, associate professor at the University of Girona and Director of the Targets Lab group, Certifies: That the thesis titled “DNA methylome in HER2-positive resistant breast cancer”, presented by Sònia Palomeras Pairet to obtain a doctoral degree, has been completed under my supervision and meets the requirements to opt for a Doctorate. For all intents and purposes, I hereby sign this document. Signature Girona, december 2nd of 2018 Per tu àvia, seguirem lluitant incansablement com vas fer-ho tu, perquè algun dia des d’on siguis, celebrem que l’hem vençut. Acknowledgments Un dia vaig llegir una frase que deia “la gratitud en silenci no serveix a ningú” i sempre he pensat que és totalment certa. Per això, m’agradaria intentar transmetre en poques paraules l’agraïment a totes les persones que en menor o major mesura m’han permès arribar fins aquí. Gràcies a la Teresa, per ser la primera a donar-me l’oportunitat de començar aquesta marató que suposa la tesi doctoral. Gràcies per confiar en mi, per donar- me l’oportunitat d’aprendre i formar-me com a investigadora. Moltes vegades m’havien dit que en el món de la ciència mai saps cap on acabarà la teva recerca ni quantes voltes donarà. Vaig començar la tesi pensant que se centraria tot en RANK i HER2, i de cop, tot va fer un gir de 180º i vaig descobrir un món nou, l’epigenètica. Aquí, entren a formar part de la meva vida noves tècniques, nous conceptes i naturalment, nova gent. Ángel, no sé muy bien como expresarte mi agradecimiento por toda tu ayuda y tu paciencia. Gracias por apoyarme y ayudarme. Me siento muy afortunada de que hayas sido tú el que me haya adentrado en este mundo de la epigenética. Has sido y eres para mí un gran referente. També vull agrair l’ajuda indispensable, la paciència, predisposició, amabilitat i confiança que m’han donat sempre la Gemma i l’Alejandro. Gràcies a vosaltres he après l’altra cara de la recerca, i he seguit creient que el que fem té una finalitat. Gràcies per la confiança dipositada en mi des del primer minut que ens vam conèixer i per totes les hores que heu destinat en aquest projecte. Sense sortir de l’hospital, també vull agrair l’ajuda i la predisposició que sempre m’ha ofert la Glòria (gràcies per totes les nostres petites xerrades), per tots els fàrmacs que ens has recollit, les mostres de teixit i per la paciència ensenyant-me a fer arrays. Si penso en tot el camí, en els bons i en els mals moments, si d’alguna cosa em sento plenament orgullosa d’aquesta tesi, són totes les persones amb qui m’he anat trobant i que formen part de la meva “història d’una tesi” personal. A l’Adriana, la primera persona amb qui vaig començar i a qui li he d’agrair moltes coses, sobretot, deixar-me poder gaudir d’en Ron! A l’Ariadna Serrats o AS, per ajudar-me, però sobretot, pels consells que em vas donar durant el temps compartit! A l’Ari, alies AG, no sé com explicar-te ni dir-te: gràcies. Em sento molt afortunada d’haver-me creuat amb tu en aquest camí. És genial poder recordar totes les hores al laboratori, al cotxe anant al curs d’animal a Barcelona, les hores dinant, les hores xerrant i treballant, escoltant música per fer més amenes les hores al laboratori, el dia a l’estany i mil moments més... Gràcies per tot el que m’has ensenyat de feina i no feina, fèiem un bon equip!! T’admiro, i t’enyoro molt! En Marc, amb qui he compartit molts moments de feina però també (i molt importants) de distracció. Gràcies per ser la meva parella de “laboratori” (guinyo- guinyo) i per totes les abraçades que m’has regalat. Segueix ballant a ritme de reggeaton, comprant a Asos, mirant vídeos de la Veneno (sobretot, segueix ensenyant a les noves generacions el famós vídeo). I no deixis si us plau, la tradició dels divendres! En Santi, siguem sincers, només l’anomeno perquè li fa il·lusió sortir a agraïments... ;) És broma, gràcies per ajudar-me sempre que ho he necessitat, per posar-me la música que més m’agrada les hores de cultius i per escoltar-me quan ho necessitava. Espero que no es faci molt dur la meva absència al laboratori i busquis ràpidament algú a qui SEMPRE portar la contraria (encara que en el fons saps que sempre tinc raó). Continuaré practicant flamenco i espero que tu, comencis a cuinar! A la Núria, la lladre oficial d’escombres del parc, gràcies per compartir aquest camí amb mi, ha estat un plaer. A en Beltrán (i la seva col·lecció de calçotets) per totes les nostres estones de xerrades psicològiques, els AVES compartits, els vídeos i els vermuts. Gràcies per tota l’ajuda que m’has ofert sempre. També a la Txell per totes les “reunions” importants que hem fet. A l’Emma l’encarregada de les comandes a CulteX i LorZa i la que sempre vol dinar a les 12am però que mai ho aconsegueix. També en Xifró i la segona caixa de bombons que estem esperant (ejem)... A en Joan, la Jessica, les PauleS, la Irene i la Marina i, a tota la gent que em deixo de nomenar però que d’una manera o altra han format part d’aquest petit gran grup que constantment ens hem recolzat, animat i celebrat a la nostra manera (a cops de vermut) qualsevol petita alegria!! Si us plau, no deixeu de parlar idiomes (Colombià, Mexicà, Gallec o de la frontera entre alguns països) i tampoc deixeu de comunicar-vos per GIFs. Us trobaré molt a faltar, gràcies per TOT! També agrair a la gent del PEBC, tant al grup de l’Eva González Suárez com el grup del Dr. Manel Esteller. Especialment a en Fer, l’home enciclopèdia i que més ajuda desinteressada m’ha ofert. Gracias por tu constante amabilidad y ayuda tanto durante mis estancias en el PEBC como fuera.
Load more

Recommended publications
  • Epigenetic Silencing of TGFBI Confers Resistance to Trastuzumab in Human Breast Cancer
    Palomeras et al. Breast Cancer Research (2019) 21:79 https://doi.org/10.1186/s13058-019-1160-x RESEARCH ARTICLE Open Access Epigenetic silencing of TGFBI confers resistance to trastuzumab in human breast cancer Sònia Palomeras1†, Ángel Diaz-Lagares2,3†, Gemma Viñas1,4,5, Fernando Setien2, Humberto J. Ferreira2, Glòria Oliveras1,6, Ana B. Crujeiras7,8, Alejandro Hernández4, David H. Lum9, Alana L. Welm9, Manel Esteller2,10,11,12,13* and Teresa Puig1* Abstract Background: Acquired resistance to trastuzumab is a major clinical problem in the treatment of HER2-positive (HER2+) breast cancer patients. The selection of trastuzumab-resistant patients is a great challenge of precision oncology. The aim of this study was to identify novel epigenetic biomarkers associated to trastuzumab resistance in HER2+ BC patients. Methods: We performed a genome-wide DNA methylation (450K array) and a transcriptomic analysis (RNA-Seq) comparing trastuzumab-sensitive (SK) and trastuzumab-resistant (SKTR) HER2+ human breast cancer cell models. The methylation and expression levels of candidate genes were validated by bisulfite pyrosequencing and qRT-PCR, respectively. Functional assays were conducted in the SK and SKTR models by gene silencing and overexpression. Methylation analysis in 24 HER2+ human BC samples with complete response or non-response to trastuzumab- based treatment was conducted by bisulfite pyrosequencing. Results: Epigenomic and transcriptomic analysis revealed the consistent hypermethylation and downregulation of TGFBI, CXCL2, and SLC38A1 genes in association with trastuzumab resistance. The DNA methylation and expression levels of these genes were validated in both sensitive and resistant models analyzed. Of the genes, TGFBI presented the highest hypermethylation-associated silencing both at the transcriptional and protein level.
    [Show full text]
  • A Computational Approach for Defining a Signature of Β-Cell Golgi Stress in Diabetes Mellitus
    Page 1 of 781 Diabetes A Computational Approach for Defining a Signature of β-Cell Golgi Stress in Diabetes Mellitus Robert N. Bone1,6,7, Olufunmilola Oyebamiji2, Sayali Talware2, Sharmila Selvaraj2, Preethi Krishnan3,6, Farooq Syed1,6,7, Huanmei Wu2, Carmella Evans-Molina 1,3,4,5,6,7,8* Departments of 1Pediatrics, 3Medicine, 4Anatomy, Cell Biology & Physiology, 5Biochemistry & Molecular Biology, the 6Center for Diabetes & Metabolic Diseases, and the 7Herman B. Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN 46202; 2Department of BioHealth Informatics, Indiana University-Purdue University Indianapolis, Indianapolis, IN, 46202; 8Roudebush VA Medical Center, Indianapolis, IN 46202. *Corresponding Author(s): Carmella Evans-Molina, MD, PhD ([email protected]) Indiana University School of Medicine, 635 Barnhill Drive, MS 2031A, Indianapolis, IN 46202, Telephone: (317) 274-4145, Fax (317) 274-4107 Running Title: Golgi Stress Response in Diabetes Word Count: 4358 Number of Figures: 6 Keywords: Golgi apparatus stress, Islets, β cell, Type 1 diabetes, Type 2 diabetes 1 Diabetes Publish Ahead of Print, published online August 20, 2020 Diabetes Page 2 of 781 ABSTRACT The Golgi apparatus (GA) is an important site of insulin processing and granule maturation, but whether GA organelle dysfunction and GA stress are present in the diabetic β-cell has not been tested. We utilized an informatics-based approach to develop a transcriptional signature of β-cell GA stress using existing RNA sequencing and microarray datasets generated using human islets from donors with diabetes and islets where type 1(T1D) and type 2 diabetes (T2D) had been modeled ex vivo. To narrow our results to GA-specific genes, we applied a filter set of 1,030 genes accepted as GA associated.
    [Show full text]
  • 4-6 Weeks Old Female C57BL/6 Mice Obtained from Jackson Labs Were Used for Cell Isolation
    Methods Mice: 4-6 weeks old female C57BL/6 mice obtained from Jackson labs were used for cell isolation. Female Foxp3-IRES-GFP reporter mice (1), backcrossed to B6/C57 background for 10 generations, were used for the isolation of naïve CD4 and naïve CD8 cells for the RNAseq experiments. The mice were housed in pathogen-free animal facility in the La Jolla Institute for Allergy and Immunology and were used according to protocols approved by the Institutional Animal Care and use Committee. Preparation of cells: Subsets of thymocytes were isolated by cell sorting as previously described (2), after cell surface staining using CD4 (GK1.5), CD8 (53-6.7), CD3ε (145- 2C11), CD24 (M1/69) (all from Biolegend). DP cells: CD4+CD8 int/hi; CD4 SP cells: CD4CD3 hi, CD24 int/lo; CD8 SP cells: CD8 int/hi CD4 CD3 hi, CD24 int/lo (Fig S2). Peripheral subsets were isolated after pooling spleen and lymph nodes. T cells were enriched by negative isolation using Dynabeads (Dynabeads untouched mouse T cells, 11413D, Invitrogen). After surface staining for CD4 (GK1.5), CD8 (53-6.7), CD62L (MEL-14), CD25 (PC61) and CD44 (IM7), naïve CD4+CD62L hiCD25-CD44lo and naïve CD8+CD62L hiCD25-CD44lo were obtained by sorting (BD FACS Aria). Additionally, for the RNAseq experiments, CD4 and CD8 naïve cells were isolated by sorting T cells from the Foxp3- IRES-GFP mice: CD4+CD62LhiCD25–CD44lo GFP(FOXP3)– and CD8+CD62LhiCD25– CD44lo GFP(FOXP3)– (antibodies were from Biolegend). In some cases, naïve CD4 cells were cultured in vitro under Th1 or Th2 polarizing conditions (3, 4).
    [Show full text]
  • Investigation of Candidate Genes and Mechanisms Underlying Obesity
    Prashanth et al. BMC Endocrine Disorders (2021) 21:80 https://doi.org/10.1186/s12902-021-00718-5 RESEARCH ARTICLE Open Access Investigation of candidate genes and mechanisms underlying obesity associated type 2 diabetes mellitus using bioinformatics analysis and screening of small drug molecules G. Prashanth1 , Basavaraj Vastrad2 , Anandkumar Tengli3 , Chanabasayya Vastrad4* and Iranna Kotturshetti5 Abstract Background: Obesity associated type 2 diabetes mellitus is a metabolic disorder ; however, the etiology of obesity associated type 2 diabetes mellitus remains largely unknown. There is an urgent need to further broaden the understanding of the molecular mechanism associated in obesity associated type 2 diabetes mellitus. Methods: To screen the differentially expressed genes (DEGs) that might play essential roles in obesity associated type 2 diabetes mellitus, the publicly available expression profiling by high throughput sequencing data (GSE143319) was downloaded and screened for DEGs. Then, Gene Ontology (GO) and REACTOME pathway enrichment analysis were performed. The protein - protein interaction network, miRNA - target genes regulatory network and TF-target gene regulatory network were constructed and analyzed for identification of hub and target genes. The hub genes were validated by receiver operating characteristic (ROC) curve analysis and RT- PCR analysis. Finally, a molecular docking study was performed on over expressed proteins to predict the target small drug molecules. Results: A total of 820 DEGs were identified between
    [Show full text]
  • Supplementary Table S4. FGA Co-Expressed Gene List in LUAD
    Supplementary Table S4. FGA co-expressed gene list in LUAD tumors Symbol R Locus Description FGG 0.919 4q28 fibrinogen gamma chain FGL1 0.635 8p22 fibrinogen-like 1 SLC7A2 0.536 8p22 solute carrier family 7 (cationic amino acid transporter, y+ system), member 2 DUSP4 0.521 8p12-p11 dual specificity phosphatase 4 HAL 0.51 12q22-q24.1histidine ammonia-lyase PDE4D 0.499 5q12 phosphodiesterase 4D, cAMP-specific FURIN 0.497 15q26.1 furin (paired basic amino acid cleaving enzyme) CPS1 0.49 2q35 carbamoyl-phosphate synthase 1, mitochondrial TESC 0.478 12q24.22 tescalcin INHA 0.465 2q35 inhibin, alpha S100P 0.461 4p16 S100 calcium binding protein P VPS37A 0.447 8p22 vacuolar protein sorting 37 homolog A (S. cerevisiae) SLC16A14 0.447 2q36.3 solute carrier family 16, member 14 PPARGC1A 0.443 4p15.1 peroxisome proliferator-activated receptor gamma, coactivator 1 alpha SIK1 0.435 21q22.3 salt-inducible kinase 1 IRS2 0.434 13q34 insulin receptor substrate 2 RND1 0.433 12q12 Rho family GTPase 1 HGD 0.433 3q13.33 homogentisate 1,2-dioxygenase PTP4A1 0.432 6q12 protein tyrosine phosphatase type IVA, member 1 C8orf4 0.428 8p11.2 chromosome 8 open reading frame 4 DDC 0.427 7p12.2 dopa decarboxylase (aromatic L-amino acid decarboxylase) TACC2 0.427 10q26 transforming, acidic coiled-coil containing protein 2 MUC13 0.422 3q21.2 mucin 13, cell surface associated C5 0.412 9q33-q34 complement component 5 NR4A2 0.412 2q22-q23 nuclear receptor subfamily 4, group A, member 2 EYS 0.411 6q12 eyes shut homolog (Drosophila) GPX2 0.406 14q24.1 glutathione peroxidase
    [Show full text]
  • Familial Cortical Myoclonus Caused by Mutation in NOL3 by Jonathan Foster Rnsseil DISSERTATION Submitted in Partial Satisfaction
    Familial Cortical Myoclonus Caused by Mutation in NOL3 by Jonathan Foster Rnsseil DISSERTATION Submitted in partial satisfaction of the requirements for the degree of DOCTOR OF PHILOSOPHY in Biomedical Sciences in the Copyright 2013 by Jonathan Foster Russell ii I dedicate this dissertation to Mom and Dad, for their adamantine love and support iii No man has earned the right to intellectual ambition until he has learned to lay his course by a star which he has never seen—to dig by the divining rod for springs which he may never reach. In saying this, I point to that which will make your study heroic. For I say to you in all sadness of conviction, that to think great thoughts you must be heroes as well as idealists. Only when you have worked alone – when you have felt around you a black gulf of solitude more isolating than that which surrounds the dying man, and in hope and in despair have trusted to your own unshaken will – then only will you have achieved. Thus only can you gain the secret isolated joy of the thinker, who knows that, a hundred years after he is dead and forgotten, men who never heard of him will be moving to the measure of his thought—the subtile rapture of a postponed power, which the world knows not because it has no external trappings, but which to his prophetic vision is more real than that which commands an army. -Oliver Wendell Holmes, Jr. iv ACKNOWLEDGMENTS I am humbled by the efforts of many, many others who were essential for this work.
    [Show full text]
  • PRODUCT SPECIFICATION Prest Antigen KIAA0895L Product
    PrEST Antigen KIAA0895L Product Datasheet PrEST Antigen PRODUCT SPECIFICATION Product Name PrEST Antigen KIAA0895L Product Number APrEST88165 Gene Description KIAA0895-like Alternative Gene LOC653319 Names Corresponding Anti-KIAA0895L (HPA065996) Antibodies Description Recombinant protein fragment of Human KIAA0895L Amino Acid Sequence Recombinant Protein Epitope Signature Tag (PrEST) antigen sequence: EDVDHLRPHGVLDNTRVPHFMQDLARYRQQLEHIMATNRLDEAELGRLLP D Fusion Tag N-terminal His6ABP (ABP = Albumin Binding Protein derived from Streptococcal Protein G) Expression Host E. coli Purification IMAC purification Predicted MW 24 kDa including tags Usage Suitable as control in WB and preadsorption assays using indicated corresponding antibodies. Purity >80% by SDS-PAGE and Coomassie blue staining Buffer PBS and 1M Urea, pH 7.4. Unit Size 100 µl Concentration Lot dependent Storage Upon delivery store at -20°C. Avoid repeated freeze/thaw cycles. Notes Gently mix before use. Optimal concentrations and conditions for each application should be determined by the user. Product of Sweden. For research use only. Not intended for pharmaceutical development, diagnostic, therapeutic or any in vivo use. No products from Atlas Antibodies may be resold, modified for resale or used to manufacture commercial products without prior written approval from Atlas Antibodies AB. Warranty: The products supplied by Atlas Antibodies are warranted to meet stated product specifications and to conform to label descriptions when used and stored properly. Unless otherwise stated, this warranty is limited to one year from date of sales for products used, handled and stored according to Atlas Antibodies AB's instructions. Atlas Antibodies AB's sole liability is limited to replacement of the product or refund of the purchase price. All products are supplied for research use only.
    [Show full text]
  • Matije Lucic Thesis
    Research Collection Doctoral Thesis The Good, the Bad and the Ugly: a three-way duel in microRNA targeting Author(s): Lucic, Matije Publication Date: 2019 Permanent Link: https://doi.org/10.3929/ethz-b-000335030 Rights / License: In Copyright - Non-Commercial Use Permitted This page was generated automatically upon download from the ETH Zurich Research Collection. For more information please consult the Terms of use. ETH Library DISS. ETH NO. 25693 The Good, the Bad and the Ugly: a three-way duel in microRNA targeting A thesis submitted to attain the degree of DOCTOR OF SCIENCES of ETH Zurich (Dr. sc. ETH Zurich) presented by MATIJE LUCIC M.Sc. Pharm. Sciences, ETH Zurich born on 09.01.1986 citizen of Muralto, Switzerland accepted on the recommendation of Prof. Dr. Jonathan Hall, examiner Prof. Dr. Constance Ciaudo, co-examiner 2019 To my loved ones. For ‘Science & Cigars’, may this be the start. ETH Zurich Matije Lucic 2 Table of contents Acknowledgements ............................................................................................................... 6 Abstract ................................................................................................................................ 7 Riassunto .............................................................................................................................. 8 1 Introduction ................................................................................................................... 9 1.1 Introduction to microRNAs (miRNAs) ....................................................................
    [Show full text]
  • Demography-Adjusted Tests of Neutrality Based on Genome-Wide SNP Data
    Demography-adjusted tests of neutrality based on genome-wide SNP data M. Rafajlovic´a,d, A. Klassmannb,d, A. Erikssonc, T. Wieheb, and B. Mehliga aDepartment of Physics, University of Gothenburg, SE-41296 Gothenburg, Sweden bInstitut f¨ur Genetik, Universitat¨ zu Koln,¨ 50674 Koln,¨ Germany cDepartment of Zoology, University of Cambridge, CB2 3EJ Cambridge, UK dThese authors have equally contributed to this work Tests of the neutral evolution hypothesis are usually built on the standard null model which assumes that mutations are neutral and population size remains constant over time. However, it is unclear how such tests are affected if the last assumption is dropped. Here, we extend the unifying framework for tests based on the site frequency spectrum, introduced by Achaz and Ferretti, to populations of varying size. A key ingredient is to specify the first two moments of the frequency spectrum. We show that these moments can be determined analytically if a population has experienced two instantaneous size changes in the past. We apply our method to data from ten human populations gathered in the 1000 genomes project, estimate their demographies and define demography-adjusted versions of Tajima’s D, Fay & Wu’s H, and Zeng’s E. The adjusted test statistics facilitate the direct comparison between populations and they show that most of the differences among populations seen in the original tests can be explained by demography. We carried out whole genome screens for deviation from neutrality and identified candidate regions of recent positive selec- tion. We provide track files with values of the adjusted and original tests for upload to the UCSC genome browser.
    [Show full text]
  • Genome-Wide DNA Methylation Analysis of Human Pancreatic Islets from Type 2 Diabetic and Non-Diabetic Donors Identifies Candidat
    Genome-wide DNA methylation analysis of human pancreatic islets from type 2 diabetic and non-diabetic donors identifies candidate genes that influence insulin secretion. Dayeh, Tasnim; Volkov, Petr; Salö, Sofia; Hall, Elin; Nilsson, Emma A; Olsson, Anders H; Kirkpatrick, Clare L; Wollheim, Claes; Eliasson, Lena; Rönn, Tina; Bacos, Karl; Ling, Charlotte Published in: PLoS Genetics DOI: 10.1371/journal.pgen.1004160 2014 Link to publication Citation for published version (APA): Dayeh, T., Volkov, P., Salö, S., Hall, E., Nilsson, E. A., Olsson, A. H., Kirkpatrick, C. L., Wollheim, C., Eliasson, L., Rönn, T., Bacos, K., & Ling, C. (2014). Genome-wide DNA methylation analysis of human pancreatic islets from type 2 diabetic and non-diabetic donors identifies candidate genes that influence insulin secretion. PLoS Genetics, 10(3), [e1004160]. https://doi.org/10.1371/journal.pgen.1004160 Total number of authors: 12 General rights Unless other specific re-use rights are stated the following general rights apply: Copyright and moral rights for the publications made accessible in the public portal are retained by the authors and/or other copyright owners and it is a condition of accessing publications that users recognise and abide by the legal requirements associated with these rights. • Users may download and print one copy of any publication from the public portal for the purpose of private study or research. • You may not further distribute the material or use it for any profit-making activity or commercial gain • You may freely distribute the URL identifying the publication in the public portal Read more about Creative commons licenses: https://creativecommons.org/licenses/ Take down policy If you believe that this document breaches copyright please contact us providing details, and we will remove access to the work immediately and investigate your claim.
    [Show full text]
  • Supplementary Material Study Sample the Vervets Used in This
    Supplementary Material Study sample The vervets used in this study are part of a pedigreed research colony that has included more than 2,000 monkeys since its founding. Briefly, the Vervet Research Colony (VRC) was established at UCLA during the 1970’s and 1980’s from 57 founder animals captured from wild populations on the adjacent Caribbean islands of St. Kitts and Nevis; Europeans brought the founders of these populations to the Caribbean from West Africa in the 17th Century 1. The breeding strategy of the VRC has emphasized the promotion of diversity, the preservation of the founding matrilines, and providing all females and most of the males an opportunity to breed. The colony design modeled natural vervet social groups to facilitate behavioral investigations in semi-natural conditions. Social groups were housed in large outdoor enclosures with adjacent indoor shelters. Each enclosure had chain link siding that provided visual access to the outside, with one or two large sitting platforms and numerous shelves, climbing structures and enrichments devices. The monkeys studied were members of 16 different social matrilineal groups, containing from 15 to 46 members per group. In 2008 the VRC was moved to Wake Forest School of Medicine’s Center for Comparative Medicine Research, however the samples for gene expression measurements in Dataset 1 (see below) and the MRI assessments used in this study occurred when the colony was at UCLA. Gene expression phenotypes Two sets of gene expression measurements were collected. Dataset 1 used RNA obtained from whole blood in 347 vervets, assayed by microarray (Illumina HumanRef-8 v2); Dataset 2 assayed gene expression by RNA-Seq, in RNA obtained from 58 animals, with seven tissues (adrenal, blood, Brodmann area 46 [BA46], caudate, fibroblast, hippocampus and pituitary) measured in each animal.
    [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]