Weighted Gene Co-Expression Network Analysis and Machine Learning Identify Critical Genes in the Development of Osteomyelitis After Staphylococcus Aureus Infections
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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 -
Computational Analyses of Small Molecules Activity from Phenotypic Screens
Computational analyses of small molecules activity from phenotypic screens Azedine Zoufir Hughes Hall This dissertation is submitted for the degree of Doctor of Philosophy July 2018 Declaration This thesis is submitted as the result of my own work and includes nothing which is the outcome of work done in collaboration except where specifically indicated in the text. It is not substantially the same as any that I have submitted, or, is being concurrently submitted for a degree or diploma or other qualification at the University of Cambridge or any other University or similar institution except as declared in the preface and specified in the text. I further state that no substantial part of my dissertation has already been submitted, or, is being concurrently submitted for any such degree, diploma or other qualification at the University of Cambridge or any other University or similar institution except as declared in the Preface and specified in the text. This dissertation does not exceed the word limit of 60,000 words. Azedine Zoufir July 2018 Summary Title: Computational analyses of small molecules activity from phenotypic screens Author: Azedine Zoufir Drug discovery is no longer relying on the one gene-one disease paradigm nor on target-based screening alone to discover new drugs. Phenotypic-based screening is regaining momentum to discover new compounds since those assays provide an environment closer to the physiological state of the disease and allow to better anticipate off-target effects and other factors that can limit the efficacy of the drugs. However, uncovering the mechanism of action of the compounds active in those assays relies on in vitro techniques that are expensive and time- consuming. -
Identification of Transcriptional Mechanisms Downstream of Nf1 Gene Defeciency in Malignant Peripheral Nerve Sheath Tumors Daochun Sun Wayne State University
Wayne State University DigitalCommons@WayneState Wayne State University Dissertations 1-1-2012 Identification of transcriptional mechanisms downstream of nf1 gene defeciency in malignant peripheral nerve sheath tumors Daochun Sun Wayne State University, Follow this and additional works at: http://digitalcommons.wayne.edu/oa_dissertations Recommended Citation Sun, Daochun, "Identification of transcriptional mechanisms downstream of nf1 gene defeciency in malignant peripheral nerve sheath tumors" (2012). Wayne State University Dissertations. Paper 558. This Open Access Dissertation is brought to you for free and open access by DigitalCommons@WayneState. It has been accepted for inclusion in Wayne State University Dissertations by an authorized administrator of DigitalCommons@WayneState. IDENTIFICATION OF TRANSCRIPTIONAL MECHANISMS DOWNSTREAM OF NF1 GENE DEFECIENCY IN MALIGNANT PERIPHERAL NERVE SHEATH TUMORS by DAOCHUN SUN DISSERTATION Submitted to the Graduate School of Wayne State University, Detroit, Michigan in partial fulfillment of the requirements for the degree of DOCTOR OF PHILOSOPHY 2012 MAJOR: MOLECULAR BIOLOGY AND GENETICS Approved by: _______________________________________ Advisor Date _______________________________________ _______________________________________ _______________________________________ © COPYRIGHT BY DAOCHUN SUN 2012 All Rights Reserved DEDICATION This work is dedicated to my parents and my wife Ze Zheng for their continuous support and understanding during the years of my education. I could not achieve my goal without them. ii ACKNOWLEDGMENTS I would like to express tremendous appreciation to my mentor, Dr. Michael Tainsky. His guidance and encouragement throughout this project made this dissertation come true. I would also like to thank my committee members, Dr. Raymond Mattingly and Dr. John Reiners Jr. for their sustained attention to this project during the monthly NF1 group meetings and committee meetings, Dr. -
Maternal Plasma Autoantibodies Screening in Fetal Down Syndrome
Hindawi Publishing Corporation Journal of Immunology Research Volume 2016, Article ID 9362169, 11 pages http://dx.doi.org/10.1155/2016/9362169 Research Article Brief Communication: Maternal Plasma Autoantibodies Screening in Fetal Down Syndrome Karol Charkiewicz,1 Monika Zbucka-Kretowska,2 Joanna Goscik,3 Slawomir Wolczynski,2 Adam Lemancewicz,1 and Piotr Laudanski1 1 Department of Perinatology and Obstetrics, Medical University of Bialystok, Marii Sklodowskiej-Curie 24a, 15-276 Bialystok, Poland 2Department of Reproduction and Gynecological Endocrinology, Medical University of Bialystok, Marii Sklodowskiej-Curie 24a, 15-276 Bialystok, Poland 3Faculty of Computer Science, Bialystok University of Technology, Wiejska 45A, 15-351 Bialystok, Poland Correspondence should be addressed to Piotr Laudanski; [email protected] Received 21 July 2015; Revised 14 January 2016; Accepted 27 January 2016 Academic Editor: Mario Clerici Copyright © 2016 Karol Charkiewicz et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Imbalance in the metabolites levels which can potentially be related to certain fetal chromosomal abnormalities can stimulate mother’s immune response to produce autoantibodies directed against proteins. The aim of the study was to determine the concentration of 9000 autoantibodies in maternal plasma to detect fetal Down syndrome. Method. Weperformed 190 amniocenteses and found 10 patients with confirmed fetal Down syndrome (15th–18th weeks of gestation). For the purpose of our control we chose 11 women without confirmed chromosomal aberration. To assess the expression of autoantibodies in the blood plasma, we used a protein microarray, which allows for simultaneous determination of 9000 proteins per sample. -
KLEIN-DISSERTATION-2014.Pdf (5.178Mb)
IDENTIFICATION AND CHARACTERIZATION OF THE MULTIFUNCTIONAL EPIGENETIC REGULATOR CFP1 AS AN ERK1/2 SUBSTRATE APPROVED BY SUPERVISORY COMMITTEE Melanie H. Cobb, Ph.D. Paul Sternweis, Ph.D. Joel Goodman, Ph.D. Nicholas Conrad, Ph.D. ii DEDICATION Thank you to all of the nerds, geeks and dorks who inspired and supported me through this endeavor, especially TJ, my parents, and Melanie. IDENTIFICATION AND CHARACTERIZATION OF THE MULTIFUNCTIONAL EPIGENETIC REGULATOR CFP1 AS AN ERK1/2 SUBSTRATE by AILEEN MELANIE KLEIN DISSERTATION Presented to the Faculty of the Graduate School of Biomedical Sciences The University of Texas Southwestern Medical Center at Dallas In Partial Fulfillment of the Requirements For the Degree of DOCTOR OF PHILOSOPHY The University of Texas Southwestern Medical Center at Dallas Dallas, Texas December, 2014 Copyright by Aileen Melanie Klein, 2014 All Rights Reserved IDENTIFICATION AND CHARACTERIZATION OF THE MULTIFUNCTIONAL EPIGENETIC REGULATOR CFP1 AS AN ERK1/2 SUBSTRATE Aileen Melanie Klein The University of Texas Southwestern Medical Center at Dallas, 2014 Supervising Professor: Melanie H. Cobb, Ph.D. Epigenetic regulation of gene transcription occurs as an integration of multiple layers of signals at a genetic locus. These signals can include local chromatin structure, covalent modifications to both histone proteins and DNA, the presence of transcription factors, and modification directly to the transcriptional machinery. Our lab is interested in the control of cellular processes by the mitogen activated protein kinases ERK1/2. In a yeast two-hybrid screen with activated ERK2 (extracellular signal-regulated kinase 2) to find novel interacting partners, our lab identified CFP1 (CxxC finger protein 1), a DNA-binding protein that is a vital component of the H3K4 trimethylating Set1A/B complexes to promote gene transcription. -
The Genetic Program of Pancreatic Beta-Cell Replication in Vivo
Page 1 of 65 Diabetes The genetic program of pancreatic beta-cell replication in vivo Agnes Klochendler1, Inbal Caspi2, Noa Corem1, Maya Moran3, Oriel Friedlich1, Sharona Elgavish4, Yuval Nevo4, Aharon Helman1, Benjamin Glaser5, Amir Eden3, Shalev Itzkovitz2, Yuval Dor1,* 1Department of Developmental Biology and Cancer Research, The Institute for Medical Research Israel-Canada, The Hebrew University-Hadassah Medical School, Jerusalem 91120, Israel 2Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel. 3Department of Cell and Developmental Biology, The Silberman Institute of Life Sciences, The Hebrew University of Jerusalem, Jerusalem 91904, Israel 4Info-CORE, Bioinformatics Unit of the I-CORE Computation Center, The Hebrew University and Hadassah, The Institute for Medical Research Israel- Canada, The Hebrew University-Hadassah Medical School, Jerusalem 91120, Israel 5Endocrinology and Metabolism Service, Department of Internal Medicine, Hadassah-Hebrew University Medical Center, Jerusalem 91120, Israel *Correspondence: [email protected] Running title: The genetic program of pancreatic β-cell replication 1 Diabetes Publish Ahead of Print, published online March 18, 2016 Diabetes Page 2 of 65 Abstract The molecular program underlying infrequent replication of pancreatic beta- cells remains largely inaccessible. Using transgenic mice expressing GFP in cycling cells we sorted live, replicating beta-cells and determined their transcriptome. Replicating beta-cells upregulate hundreds of proliferation- related genes, along with many novel putative cell cycle components. Strikingly, genes involved in beta-cell functions, namely glucose sensing and insulin secretion were repressed. Further studies using single molecule RNA in situ hybridization revealed that in fact, replicating beta-cells double the amount of RNA for most genes, but this upregulation excludes genes involved in beta-cell function. -
WO 2013/064702 A2 10 May 2013 (10.05.2013) P O P C T
(12) INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT) (19) World Intellectual Property Organization I International Bureau (10) International Publication Number (43) International Publication Date WO 2013/064702 A2 10 May 2013 (10.05.2013) P O P C T (51) International Patent Classification: AO, AT, AU, AZ, BA, BB, BG, BH, BN, BR, BW, BY, C12Q 1/68 (2006.01) BZ, CA, CH, CL, CN, CO, CR, CU, CZ, DE, DK, DM, DO, DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, (21) International Application Number: HN, HR, HU, ID, IL, IN, IS, JP, KE, KG, KM, KN, KP, PCT/EP2012/071868 KR, KZ, LA, LC, LK, LR, LS, LT, LU, LY, MA, MD, (22) International Filing Date: ME, MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, 5 November 20 12 (05 .11.20 12) NO, NZ, OM, PA, PE, PG, PH, PL, PT, QA, RO, RS, RU, RW, SC, SD, SE, SG, SK, SL, SM, ST, SV, SY, TH, TJ, (25) Filing Language: English TM, TN, TR, TT, TZ, UA, UG, US, UZ, VC, VN, ZA, (26) Publication Language: English ZM, ZW. (30) Priority Data: (84) Designated States (unless otherwise indicated, for every 1118985.9 3 November 201 1 (03. 11.201 1) GB kind of regional protection available): ARIPO (BW, GH, 13/339,63 1 29 December 201 1 (29. 12.201 1) US GM, KE, LR, LS, MW, MZ, NA, RW, SD, SL, SZ, TZ, UG, ZM, ZW), Eurasian (AM, AZ, BY, KG, KZ, RU, TJ, (71) Applicant: DIAGENIC ASA [NO/NO]; Grenseveien 92, TM), European (AL, AT, BE, BG, CH, CY, CZ, DE, DK, N-0663 Oslo (NO). -
Involvement of TGF-ß Receptor– and Integrin-Mediated Signaling Pathways in the Pathogenesis of Granular Corneal Dystrophy II
Biochemistry and Molecular Biology Involvement of TGF- Receptor– and Integrin-Mediated Signaling Pathways in the Pathogenesis of Granular Corneal Dystrophy II Seung-il Choi,1 Yeong-Min Yoo,2 Bong-Yoon Kim,1 Tae-im Kim,1 Hyun-ju Cho,1 So-yoen Ahn,1 Hyung Keun Lee,1 Hyun-Soo Cho,3 and Eung Kweon Kim1 PURPOSE. The purpose of this study was to elucidate the (Invest Ophthalmol Vis Sci. 2010;51:1832–1847) DOI: pathophysiological process in primary cultured corneal fibro- 10.1167/iovs.09-4149 blasts (PCFs) from normal subjects and granular corneal dys- trophy (GCD) II patients, by using cDNA microarrays. ranular corneal dystrophy II (GCD II) is a disorder char- METHODS. PCFs were isolated from the corneas of normal Gacterized by age-dependent progressive accumulation of subjects and GCD II patients who were heterozygous and protein deposits in the corneal epithelia and stroma, followed homozygous for the TGFBI R124H mutation. RNA was isolated by disruption of corneal transparency. GCD II is an autosomal from each sample, and gene expression profiles were analyzed dominant disorder caused by a point mutation (R124H) in the with a cDNA microarray consisting of approximately 29,000 transforming growth factor--induced gene (TGFBI) on chro- genes. Cell adhesion assays were performed to confirm the mosome 5, region q31.1,2 TGFBI encodes a highly conserved functionality of the detected gene expression profiles. 683 amino acid protein (TGFBIp) that contains a secretary signal sequence and an Arg-Gly-Asp (RGD) motif that serves as RESULTS. Twofold differences were detected in the expression a ligand recognition site for integrins.1 TGFBIp is a component of 555 genes between wild-type and homozygous GCD II PCFs. -
Goyette Guillaume 2009 These.Pdf (8.250Mb)
Université de Montréal Caractérisation moléculaire de la modulation spatio- temporelle des fonctions du phagosome Par Guillaume Goyette Département de pathologie et biologie cellulaire Faculté de médecine Thèse présentée à la faculté des études supérieures En vue de l’obtention du grade Philosophiae Doctor (Ph.D.) en pathologie et biologie cellulaire 24 avril 2009 © Guillaume Goyette 2009 ii Université de Montréal Faculté des études supérieures Cette thèse intitulée : Caractérisation moléculaire de la modulation spatio-temporelle des fonctions du phagosome présentée par : Guillaume Goyette a été évaluée par un jury composé des personnes suivantes : Jacques Paiement, président-rapporteur Michel Desjardins, directeur de recherche Dorin-Lucian Ghitescu, membre du jury John J.M. Bergeron, examinateur externe Nicole Leclerc, représentante du doyen de la FES iii Résumé La phagocytose est un processus par lequel des cellules spécialisées du système immunitaire comme les macrophages ingèrent des microorganismes envahisseurs afin de les détruire. Les microbes phagocytés se retrouvent dans un compartiment intracellulaire nommé le phagosome, qui acquiert graduellement de nombreuses molécules lui permettant de se transformer en phagolysosome possédant la capacité de tuer et dégrader son contenu. L’utilisation de la protéomique a permis de mettre en évidence la présence de microdomaines (aussi nommés radeaux lipidiques ou radeaux membranaires) sur les phagosomes des macrophages. Notre équipe a démontré que ces radeaux exercent des fonctions cruciales au niveau de la membrane du phagosome. D’abord nous avons observé que la survie du parasite intracellulaire L. donovani est possible dans un phagosome dépourvu de radeaux lipidiques. Parallèlement nous avons constaté qu’un mutant de L. donovani n’exprimant pas de LPG à sa surface (LPG-) est rapidement tué dans un phagosome arborant des radeaux membranaires. -
University of São Paulo
UNIVERSITY OF SÃO PAULO PHARMACEUTICAL SCIENCES FACULTY Department of Clinical and Toxicological Analysis Graduate Program in Pharmacy (Physiopathology and Toxicology) A non-targeted proteomics investigation of cylindrospermopsin-induced hepatotoxicity Carlos Andrey González Blanco Manuscript presented for the degree of P.h.D. Professor Advisor: Assoc. Prof. Ernani Pinto São Paulo 2017 UNIVERSIDADE DE SÃO PAULO FACULDADE DE CIÊNCIAS FARMACÊUTICAS Departamento de Analises Clinicas e Toxicológicas Programa de Pós-graduação em Farmacia (Fisiopatologia e Toxicologia) Uso de uma estratégia proteômica não-direcionada para investigar a hepatotoxicidade producida pela cilindrospermopsina Carlos Andrey González Blanco Versão corrigida da Tese conforme resolução CoPGr 6018 Tese para obtenção do Título de Doutor Orientador: Prof. Assoc. Ernani Pinto São Paulo 2017 CARLOS ANDREY GONZÁLEZ BLANCO A non-targeted proteomics investigation of cylindrospermopsin-induced hepatotoxicity Comissão Julgadora da Tese para obtenção do Título de Doutor Prof. Assoc. Ernani Pinto orientador/presidente _________________________________________________ 1o. examinador _________________________________________________ 2o. examinador __________________________________________________ 3o. examinador __________________________________________________ 4o. examinador São Paulo, ______ de _______________ de 2017 i “The map is not the territory”. A. Korzybski ii Acknowledgement I would like to thank my thesis advisor Prof. Ernani for his unconditional support and friendship. Throughout the years, I saw you taking risks in projects and making daring decisions in your academic career, which always turned up right. The audacity I saw in your work inspired me to strive harder and try out new ideas. I would also like to thank all the students I met throught the years at prof. Ernani`s lab, all of which are and will always be great friends; I learned something from each and every one of you. -
Cell Chronic Lymphocytic Leukemia Patients with 13Q14 Deletion
Author Manuscript Published OnlineFirst on October 14, 2010; DOI: 10.1158/1078-0432.CCR-10-0151 AuthorPublished manuscripts OnlineFirst have been onpeer October reviewed and14, accepted2010 as for 10.1158/1078-0432.CCR-10-0151 publication but have not yet been edited. Integrative genomics analyses reveal molecularly distinct subgroups of B- cell chronic lymphocytic leukemia patients with 13q14 deletion Laura Mosca,1,* Sonia Fabris,1,* Marta Lionetti1, Katia Todoerti1, Luca Agnelli,1 Fortunato Morabito,2 Giovanna Cutrona,3 Adrian Andronache,1 Serena Matis,3 Francesco Ferrari,4 Massimo Gentile,2 Mauro Spriano,5 Vincenzo Callea,6 Gianluca Festini,7 Stefano Molica,8 Giorgio Lambertenghi Deliliers,1 Silvio Bicciato,4 Manlio Ferrarini,3,9 Antonino Neri1 1Centro per lo Studio delle Leucemie, Dipartimento di Scienze Mediche, Università di Milano, U.O. Ematologia 1, Fondazione IRCCS Policlinico, Milan, Italy; 2U.O.C. di Ematologia, Azienda Ospedaliera di Cosenza, Italy; 3Divisione di Oncologia Medica C, Istituto Nazionale per la Ricerca sul Cancro, IST, Genoa, Italy; 4Dipartimento di Scienze Biomediche, Università di Modena e Reggio Emilia, Modena, Italy; 5Dipartimento di Ematologia, Azienda Ospedaliera S. Martino, Genoa, Italy; 6Divisione di Ematologia, Azienda Ospedaliera, Reggio Calabria, Italy: 7Centro di Riferimento Ematologico-Seconda Medicina Azienda Ospedaliero-Universitaria, Ospedali Riuniti, Trieste, Italy; 8U.O.C. di Oncologia, Azienda Ospedaliera “Pugliese-Ciaccio”, Catanzaro, Italy and 9Dipartimento di Oncologia, Biologia e Genetica, Università degli Studi di Genova, Genoa, Italy *These authors contributed equally to this work. Correspondence: Prof. Antonino Neri, Department of Medical Sciences, University of Milan, Via F. Sforza 35, 20122 Milano, Italy. Tel. +39.02.55033328; Fax: +39.02.50320403 E-mail: [email protected] Running title: Integrative genomics analysis of 13q14 deleted CLL Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. -
Global Gene Expression in Muscle from Fasted/Refed Trout Reveals Up
Rescan et al. BMC Genomics (2017) 18:447 DOI 10.1186/s12864-017-3837-9 RESEARCHARTICLE Open Access Global gene expression in muscle from fasted/refed trout reveals up-regulation of genes promoting myofibre hypertrophy but not myofibre production Pierre-Yves Rescan*, Aurelie Le Cam, Cécile Rallière and Jérôme Montfort Abstract Background: Compensatory growth is a phase of rapid growth, greater than the growth rate of control animals, that occurs after a period of growth-stunting conditions. Fish show a capacity for compensatory growth after alleviation of dietary restriction, but the underlying cellular mechanisms are unknown. To learn more about the contribution of genes regulating hypertrophy (an increase in muscle fibre size) and hyperplasia (the generation of new muscle fibres) in the compensatory muscle growth response in fish, we used high-density microarray analysis to investigate the global gene expression in muscle of trout during a fasting-refeeding schedule and in muscle of control-fed trout displaying normal growth. Results: The compensatory muscle growth signature, as defined by genes up-regulated in muscles of refed trout compared with control-fed trout, showed enrichment in functional categories related to protein biosynthesis and maturation, such as RNA processing, ribonucleoprotein complex biogenesis, ribosome biogenesis, translation and protein folding. This signature was also enriched in chromatin-remodelling factors of the protein arginine N-methyl transferase family. Unexpectedly, functional categories related to cell division and DNA replication were not inferred from the molecular signature of compensatory muscle growth, and this signature contained virtually none of the genes previously reported to be up-regulated in hyperplastic growth zones of the late trout embryo myotome and to potentially be involved in production of new myofibres, notably genes encoding myogenic regulatory factors, transmembrane receptors essential for myoblast fusion or myofibrillar proteins predominant in nascent myofibres.