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Molecular Mechanisms Involved Involved in the Interaction Effects of HCV and Ethanol on Liver Cirrhosis
Virginia Commonwealth University VCU Scholars Compass Theses and Dissertations Graduate School 2010 Molecular Mechanisms Involved Involved in the Interaction Effects of HCV and Ethanol on Liver Cirrhosis Ryan Fassnacht Virginia Commonwealth University Follow this and additional works at: https://scholarscompass.vcu.edu/etd Part of the Physiology Commons © The Author Downloaded from https://scholarscompass.vcu.edu/etd/2246 This Thesis is brought to you for free and open access by the Graduate School at VCU Scholars Compass. It has been accepted for inclusion in Theses and Dissertations by an authorized administrator of VCU Scholars Compass. For more information, please contact [email protected]. Ryan C. Fassnacht 2010 All Rights Reserved Molecular Mechanisms Involved in the Interaction Effects of HCV and Ethanol on Liver Cirrhosis A thesis submitted in partial fulfillment of the requirements for the degree of Master of Science at Virginia Commonwealth University. by Ryan Christopher Fassnacht, B.S. Hampden Sydney University, 2005 M.S. Virginia Commonwealth University, 2010 Director: Valeria Mas, Ph.D., Associate Professor of Surgery and Pathology Division of Transplant Department of Surgery Virginia Commonwealth University Richmond, Virginia July 9, 2010 Acknowledgement The Author wishes to thank his family and close friends for their support. He would also like to thank the members of the molecular transplant team for their help and advice. This project would not have been possible with out the help of Dr. Valeria Mas and her endearing -
New Approaches to Functional Process Discovery in HPV 16-Associated Cervical Cancer Cells by Gene Ontology
Cancer Research and Treatment 2003;35(4):304-313 New Approaches to Functional Process Discovery in HPV 16-Associated Cervical Cancer Cells by Gene Ontology Yong-Wan Kim, Ph.D.1, Min-Je Suh, M.S.1, Jin-Sik Bae, M.S.1, Su Mi Bae, M.S.1, Joo Hee Yoon, M.D.2, Soo Young Hur, M.D.2, Jae Hoon Kim, M.D.2, Duck Young Ro, M.D.2, Joon Mo Lee, M.D.2, Sung Eun Namkoong, M.D.2, Chong Kook Kim, Ph.D.3 and Woong Shick Ahn, M.D.2 1Catholic Research Institutes of Medical Science, 2Department of Obstetrics and Gynecology, College of Medicine, The Catholic University of Korea, Seoul; 3College of Pharmacy, Seoul National University, Seoul, Korea Purpose: This study utilized both mRNA differential significant genes of unknown function affected by the display and the Gene Ontology (GO) analysis to char- HPV-16-derived pathway. The GO analysis suggested that acterize the multiple interactions of a number of genes the cervical cancer cells underwent repression of the with gene expression profiles involved in the HPV-16- cancer-specific cell adhesive properties. Also, genes induced cervical carcinogenesis. belonging to DNA metabolism, such as DNA repair and Materials and Methods: mRNA differential displays, replication, were strongly down-regulated, whereas sig- with HPV-16 positive cervical cancer cell line (SiHa), and nificant increases were shown in the protein degradation normal human keratinocyte cell line (HaCaT) as a con- and synthesis. trol, were used. Each human gene has several biological Conclusion: The GO analysis can overcome the com- functions in the Gene Ontology; therefore, several func- plexity of the gene expression profile of the HPV-16- tions of each gene were chosen to establish a powerful associated pathway, identify several cancer-specific cel- cervical carcinogenesis pathway. -
SF3B2-Mediated RNA Splicing Drives Human Prostate Cancer Progression
Published OnlineFirst August 20, 2019; DOI: 10.1158/0008-5472.CAN-18-3965 Cancer Molecular Cell Biology Research SF3B2-Mediated RNA Splicing Drives Human Prostate Cancer Progression Norihiko Kawamura1,2, Keisuke Nimura1, Kotaro Saga1, Airi Ishibashi1, Koji Kitamura1,3, Hiromichi Nagano1, Yusuke Yoshikawa4, Kyoso Ishida1,5, Norio Nonomura2, Mitsuhiro Arisawa4, Jun Luo6, and Yasufumi Kaneda1 Abstract Androgen receptor splice variant-7 (AR-V7) is a General RNA splicing SF3B2 complex-mediated alternative RNA splicing constitutively active AR variant implicated in U2 castration-resistant prostate cancers. Here, we show U2 snRNA that the RNA splicing factor SF3B2, identified by 3’ 3’ in silico and CRISPR/Cas9 analyses, is a critical 5’ 3’ splice site 5’ SF3B7 AR-V7 5’ A U2AF2 AGA Exon ? determinant of expression and is correlated SF3B6(p14) SF3B4 SF3B1 SF3B4 SF3B1 with aggressive cancer phenotypes. Transcriptome SF3B5 SF3B2 SF3B3 SF3B2 SF3B3 and PAR-CLIP analyses revealed that SF3B2 con- SF3A3 SF3B2 complex SF3A3 SF3A1 SF3A1 SF3b complex trols the splicing of target genes, including AR, to AR pre-mRNA drive aggressive phenotypes. SF3B2-mediated CE3 aggressive phenotypes in vivo were reversed by AR-V7 mRNA AR mRNA AR-V7 knockout. Pladienolide B, an inhibitor of CE3 a splicing modulator of the SF3b complex, sup- Drive malignancy pressed the growth of tumors addicted to high While the SF3b complex is critical for general RNA splicing, SF3B2 promotes inclusion of the target exon through recognizing a specific RNA motif. SF3B2 expression. These findings support the idea © 2019 American Association for Cancer Research that alteration of the splicing pattern by high SF3B2 expression is one mechanism underlying prostate cancer progression and therapeutic resistance. -
(12) Patent Application Publication (10) Pub. No.: US 2005/0010974A1 Milligan Et Al
US 20050010974A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2005/0010974A1 Milligan et al. (43) Pub. Date: Jan. 13, 2005 (54) PROMOTERS FOR REGULATION OF GENE Publication Classification EXPRESSION IN PLANT ROOTS (51) Int. Cl." ............................ C12N 15/82; C12O 1/68; (76) Inventors: Stephen B Milligan, Kirkland, WA C12N 15/87; C12N 15/63; (US); Dale Skalla, Research Triangle C12N 15/85; C12N 5/10; Park, NC (US); Kay Lawton, Research C12N 15/09; CO7H 21/04 Triangle Park, NC (US) (52) U.S. Cl. ..................... 800/287; 536/23.6; 435/320.1; 435/455; 435/419; 435/468; Correspondence Address: 800/278; 435/6; 536/24.33 Randee S Schwatz Syngenta Biotechnology 3054 Cornwallis Road (57) ABSTRACT Research Triangle Park, NC 27709 (US) The present invention is directed to promoters isolated from (21) Appl. No.: 10/490,147 maize and functional equivalents thereto. The promoters of the present invention have particular utility in driving root (22) PCT Filed: Nov. 4, 2002 Specific expression of heterologous genes that impart (86) PCT No.: PCT/US02/35374 increased agronomic, horticultural and/or pesticidal charac teristics to a given promoters of the invention and trans (30) Foreign Application Priority Data formed plant tissues containing DNA molecules comprising a promoter of the invention operably linked to a heterolo Nov. 7, 2001 (US)........................................... 60337026 gous gene or genes, and Seeds thereof. US 2005/0010974 A1 Jan. 13, 2005 PROMOTERS FOR REGULATION OF GENE latory Sequences may be short regions of DNA sequence EXPRESSION IN PLANT ROOTS 6-100 base pairs that define the binding sites for trans-acting factors, Such as transcription factors. -
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. -
Downloaded and Searched Against the Dbest Database to Identify Ests
BMC Genomics BioMed Central Research article Open Access A transcription map of the 6p22.3 reading disability locus identifying candidate genes Eric R Londin1, Haiying Meng2 and Jeffrey R Gruen*2 Address: 1Graduate Program in Genetics, State University of New York at Stony Brook, NY, USA and 2Yale Child Health Research Center, Department of Pediatrics, Yale University School of Medicine, New Haven, CT, USA Email: Eric R Londin - [email protected]; Haiying Meng - [email protected]; Jeffrey R Gruen* - [email protected] * Corresponding author Published: 30 June 2003 Received: 22 April 2003 Accepted: 30 June 2003 BMC Genomics 2003, 4:25 This article is available from: http://www.biomedcentral.com/1471-2164/4/25 © 2003 Londin et al; licensee BioMed Central Ltd. This is an Open Access article: verbatim copying and redistribution of this article are permitted in all media for any purpose, provided this notice is preserved along with the article's original URL. reading disabilitydyslexia6p22.3In silicoESTs Abstract Background: Reading disability (RD) is a common syndrome with a large genetic component. Chromosome 6 has been identified in several linkage studies as playing a significant role. A more recent study identified a peak of transmission disequilibrium to marker JA04 (G72384) on chromosome 6p22.3, suggesting that a gene is located near this marker. Results: In silico cloning was used to identify possible candidate genes located near the JA04 marker. The 2 million base pairs of sequence surrounding JA04 was downloaded and searched against the dbEST database to identify ESTs. In total, 623 ESTs from 80 different tissues were identified and assembled into 153 putative coding regions from 19 genes and 2 pseudogenes encoded near JA04. -
Supplementary Files for Understanding the Functional Impact of Copy Number Alterations in Breast Cancers Using a Network Modeling Approach
Electronic Supplementary Material (ESI) for Molecular BioSystems. This journal is © The Royal Society of Chemistry 2016 Supplementary files for Understanding the functional impact of copy number alterations in breast cancers using a network modeling approach Sriganesh Srihari1#, Murugan Kalimutho2#, Samir Lal3, Jitin Singla4, Dhaval Patel4, Peter T. Simpson3,5, Kum Kum Khanna2 and Mark A. Ragan1* 1Institute for Molecular Bioscience, The University of Queensland, St. Lucia, QLD 4072, Australia 2 QIMR-Berghofer Medical Research Institute, Brisbane, QLD 4006, Australia 3 The University of Queensland, UQ Centre for Clinical Research, Brisbane, QLD 4029, Australia 4 Indian Institute of Technology Roorkee, Roorkee, Uttarakhand 247667, India 5 The University of Queensland, School of Medicine, Brisbane, QLD 4006, Australia Supplementary website: http://bioinformatics.org.au/tools-data/ under NetStrat Section 4.1 of main text (Materials and Methods) Choosing cut-off A pair of genes (proteins) could be co-expressed due to a number of reasons – for example, by being co- regulated by the same transcription factor or due to co-functioning in a complex via direct interactions. To identify trans-associated genes we are only interested in gene pairs (i.e. interactions in the network) whose co- expression associates with the CNA of one or both genes. In Equation 2 (main manuscript), since we compute the weighted sum of CNAs, those gene pairs which do not exhibit any CNAs (zero or low CNAs) would be assigned zero or low weights and hence will not be accounted for. In addition, we would also like to discount gene pairs from the network that show low co-expression values, by using an cut-off on the co-expression. -
Peripheral Neuropathy in Complex Inherited Diseases: an Approach To
PERIPHERAL NEUROPATHY IN COMPLEX INHERITED DISEASES: AN APPROACH TO DIAGNOSIS Rossor AM1*, Carr AS1*, Devine H1, Chandrashekar H2, Pelayo-Negro AL1, Pareyson D3, Shy ME4, Scherer SS5, Reilly MM1. 1. MRC Centre for Neuromuscular Diseases, UCL Institute of Neurology and National Hospital for Neurology and Neurosurgery, London, WC1N 3BG, UK. 2. Lysholm Department of Neuroradiology, National Hospital for Neurology and Neurosurgery, London, WC1N 3BG, UK. 3. Unit of Neurological Rare Diseases of Adulthood, Carlo Besta Neurological Institute IRCCS Foundation, Milan, Italy. 4. Department of Neurology, University of Iowa, 200 Hawkins Drive, Iowa City, IA 52242, USA 5. Department of Neurology, University of Pennsylvania, Philadelphia, PA 19014, USA. * These authors contributed equally to this work Corresponding author: Mary M Reilly Address: MRC Centre for Neuromuscular Diseases, 8-11 Queen Square, London, WC1N 3BG, UK. Email: [email protected] Telephone: 0044 (0) 203 456 7890 Word count: 4825 ABSTRACT Peripheral neuropathy is a common finding in patients with complex inherited neurological diseases and may be subclinical or a major component of the phenotype. This review aims to provide a clinical approach to the diagnosis of this complex group of patients by addressing key questions including the predominant neurological syndrome associated with the neuropathy e.g. spasticity, the type of neuropathy, and the other neurological and non- neurological features of the syndrome. Priority is given to the diagnosis of treatable conditions. Using this approach, we associated neuropathy with one of three major syndromic categories - 1) ataxia, 2) spasticity, and 3) global neurodevelopmental impairment. Syndromes that do not fall easily into one of these three categories can be grouped according to the predominant system involved in addition to the neuropathy e.g. -
Proteomics Provides Insights Into the Inhibition of Chinese Hamster V79
www.nature.com/scientificreports OPEN Proteomics provides insights into the inhibition of Chinese hamster V79 cell proliferation in the deep underground environment Jifeng Liu1,2, Tengfei Ma1,2, Mingzhong Gao3, Yilin Liu4, Jun Liu1, Shichao Wang2, Yike Xie2, Ling Wang2, Juan Cheng2, Shixi Liu1*, Jian Zou1,2*, Jiang Wu2, Weimin Li2 & Heping Xie2,3,5 As resources in the shallow depths of the earth exhausted, people will spend extended periods of time in the deep underground space. However, little is known about the deep underground environment afecting the health of organisms. Hence, we established both deep underground laboratory (DUGL) and above ground laboratory (AGL) to investigate the efect of environmental factors on organisms. Six environmental parameters were monitored in the DUGL and AGL. Growth curves were recorded and tandem mass tag (TMT) proteomics analysis were performed to explore the proliferative ability and diferentially abundant proteins (DAPs) in V79 cells (a cell line widely used in biological study in DUGLs) cultured in the DUGL and AGL. Parallel Reaction Monitoring was conducted to verify the TMT results. γ ray dose rate showed the most detectable diference between the two laboratories, whereby γ ray dose rate was signifcantly lower in the DUGL compared to the AGL. V79 cell proliferation was slower in the DUGL. Quantitative proteomics detected 980 DAPs (absolute fold change ≥ 1.2, p < 0.05) between V79 cells cultured in the DUGL and AGL. Of these, 576 proteins were up-regulated and 404 proteins were down-regulated in V79 cells cultured in the DUGL. KEGG pathway analysis revealed that seven pathways (e.g. -
Association of Gene Ontology Categories with Decay Rate for Hepg2 Experiments These Tables Show Details for All Gene Ontology Categories
Supplementary Table 1: Association of Gene Ontology Categories with Decay Rate for HepG2 Experiments These tables show details for all Gene Ontology categories. Inferences for manual classification scheme shown at the bottom. Those categories used in Figure 1A are highlighted in bold. Standard Deviations are shown in parentheses. P-values less than 1E-20 are indicated with a "0". Rate r (hour^-1) Half-life < 2hr. Decay % GO Number Category Name Probe Sets Group Non-Group Distribution p-value In-Group Non-Group Representation p-value GO:0006350 transcription 1523 0.221 (0.009) 0.127 (0.002) FASTER 0 13.1 (0.4) 4.5 (0.1) OVER 0 GO:0006351 transcription, DNA-dependent 1498 0.220 (0.009) 0.127 (0.002) FASTER 0 13.0 (0.4) 4.5 (0.1) OVER 0 GO:0006355 regulation of transcription, DNA-dependent 1163 0.230 (0.011) 0.128 (0.002) FASTER 5.00E-21 14.2 (0.5) 4.6 (0.1) OVER 0 GO:0006366 transcription from Pol II promoter 845 0.225 (0.012) 0.130 (0.002) FASTER 1.88E-14 13.0 (0.5) 4.8 (0.1) OVER 0 GO:0006139 nucleobase, nucleoside, nucleotide and nucleic acid metabolism3004 0.173 (0.006) 0.127 (0.002) FASTER 1.28E-12 8.4 (0.2) 4.5 (0.1) OVER 0 GO:0006357 regulation of transcription from Pol II promoter 487 0.231 (0.016) 0.132 (0.002) FASTER 6.05E-10 13.5 (0.6) 4.9 (0.1) OVER 0 GO:0008283 cell proliferation 625 0.189 (0.014) 0.132 (0.002) FASTER 1.95E-05 10.1 (0.6) 5.0 (0.1) OVER 1.50E-20 GO:0006513 monoubiquitination 36 0.305 (0.049) 0.134 (0.002) FASTER 2.69E-04 25.4 (4.4) 5.1 (0.1) OVER 2.04E-06 GO:0007050 cell cycle arrest 57 0.311 (0.054) 0.133 (0.002) -
Noelia Díaz Blanco
Effects of environmental factors on the gonadal transcriptome of European sea bass (Dicentrarchus labrax), juvenile growth and sex ratios Noelia Díaz Blanco Ph.D. thesis 2014 Submitted in partial fulfillment of the requirements for the Ph.D. degree from the Universitat Pompeu Fabra (UPF). This work has been carried out at the Group of Biology of Reproduction (GBR), at the Department of Renewable Marine Resources of the Institute of Marine Sciences (ICM-CSIC). Thesis supervisor: Dr. Francesc Piferrer Professor d’Investigació Institut de Ciències del Mar (ICM-CSIC) i ii A mis padres A Xavi iii iv Acknowledgements This thesis has been made possible by the support of many people who in one way or another, many times unknowingly, gave me the strength to overcome this "long and winding road". First of all, I would like to thank my supervisor, Dr. Francesc Piferrer, for his patience, guidance and wise advice throughout all this Ph.D. experience. But above all, for the trust he placed on me almost seven years ago when he offered me the opportunity to be part of his team. Thanks also for teaching me how to question always everything, for sharing with me your enthusiasm for science and for giving me the opportunity of learning from you by participating in many projects, collaborations and scientific meetings. I am also thankful to my colleagues (former and present Group of Biology of Reproduction members) for your support and encouragement throughout this journey. To the “exGBRs”, thanks for helping me with my first steps into this world. Working as an undergrad with you Dr. -
Trypanosoma Brucei Ribonuclease H2A Is an Essential Enzyme That Resolves R-Loops Associated with Transcription Initiation and Antigenic Variation
bioRxiv preprint doi: https://doi.org/10.1101/541300; this version posted February 5, 2019. 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 4.0 International license. Trypanosoma brucei ribonuclease H2A is an essential enzyme that resolves R-loops associated with transcription initiation and antigenic variation Emma Briggs1, Kathryn Crouch1, Leandro Lemgruber1, Graham Hamilton2, Craig Lapsley1 and Richard McCulloch1 1. The Wellcome Centre for Molecular Parasitology, University of Glasgow, College of Medical, Veterinary and Life Sciences, Institute of Infection, Immunity and Inflammation, Sir Graeme Davies Building, 120 University Place, Glasgow, G12 8TA, U.K. 2. Glasgow Polyomics, University of Glasgow, Wolfson Wohl Cancer Res Centre, Garscube Estate, Switchback Rd, Bearsden, G61 1QH, U.K. *Correspondence: [email protected] 1 bioRxiv preprint doi: https://doi.org/10.1101/541300; this version posted February 5, 2019. 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 4.0 International license. In every cell ribonucleotides represent a threat to the stability and transmission of the DNA genome. Two types of Ribonuclease H (RNase H) tackle such ribonucleotides, either by excision when they form part of the DNA strand, or by hydrolysing RNA when it base-pairs with DNA, in structures termed R-loops. Loss of either RNase H is lethal in mammals, whereas yeast can prosper in the absence of both enzymes.