Mutations in Genes Encoding Sorting Nexins Alter Production of Intracellular And
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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. -
Nuclear PTEN Safeguards Pre-Mrna Splicing to Link Golgi Apparatus for Its Tumor Suppressive Role
ARTICLE DOI: 10.1038/s41467-018-04760-1 OPEN Nuclear PTEN safeguards pre-mRNA splicing to link Golgi apparatus for its tumor suppressive role Shao-Ming Shen1, Yan Ji2, Cheng Zhang1, Shuang-Shu Dong2, Shuo Yang1, Zhong Xiong1, Meng-Kai Ge1, Yun Yu1, Li Xia1, Meng Guo1, Jin-Ke Cheng3, Jun-Ling Liu1,3, Jian-Xiu Yu1,3 & Guo-Qiang Chen1 Dysregulation of pre-mRNA alternative splicing (AS) is closely associated with cancers. However, the relationships between the AS and classic oncogenes/tumor suppressors are 1234567890():,; largely unknown. Here we show that the deletion of tumor suppressor PTEN alters pre-mRNA splicing in a phosphatase-independent manner, and identify 262 PTEN-regulated AS events in 293T cells by RNA sequencing, which are associated with significant worse outcome of cancer patients. Based on these findings, we report that nuclear PTEN interacts with the splicing machinery, spliceosome, to regulate its assembly and pre-mRNA splicing. We also identify a new exon 2b in GOLGA2 transcript and the exon exclusion contributes to PTEN knockdown-induced tumorigenesis by promoting dramatic Golgi extension and secretion, and PTEN depletion significantly sensitizes cancer cells to secretion inhibitors brefeldin A and golgicide A. Our results suggest that Golgi secretion inhibitors alone or in combination with PI3K/Akt kinase inhibitors may be therapeutically useful for PTEN-deficient cancers. 1 Department of Pathophysiology, Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Shanghai Jiao Tong University School of Medicine (SJTU-SM), Shanghai 200025, China. 2 Institute of Health Sciences, Shanghai Institutes for Biological Sciences of Chinese Academy of Sciences and SJTU-SM, Shanghai 200025, China. -
Appendix 2. Significantly Differentially Regulated Genes in Term Compared with Second Trimester Amniotic Fluid Supernatant
Appendix 2. Significantly Differentially Regulated Genes in Term Compared With Second Trimester Amniotic Fluid Supernatant Fold Change in term vs second trimester Amniotic Affymetrix Duplicate Fluid Probe ID probes Symbol Entrez Gene Name 1019.9 217059_at D MUC7 mucin 7, secreted 424.5 211735_x_at D SFTPC surfactant protein C 416.2 206835_at STATH statherin 363.4 214387_x_at D SFTPC surfactant protein C 295.5 205982_x_at D SFTPC surfactant protein C 288.7 1553454_at RPTN repetin solute carrier family 34 (sodium 251.3 204124_at SLC34A2 phosphate), member 2 238.9 206786_at HTN3 histatin 3 161.5 220191_at GKN1 gastrokine 1 152.7 223678_s_at D SFTPA2 surfactant protein A2 130.9 207430_s_at D MSMB microseminoprotein, beta- 99.0 214199_at SFTPD surfactant protein D major histocompatibility complex, class II, 96.5 210982_s_at D HLA-DRA DR alpha 96.5 221133_s_at D CLDN18 claudin 18 94.4 238222_at GKN2 gastrokine 2 93.7 1557961_s_at D LOC100127983 uncharacterized LOC100127983 93.1 229584_at LRRK2 leucine-rich repeat kinase 2 HOXD cluster antisense RNA 1 (non- 88.6 242042_s_at D HOXD-AS1 protein coding) 86.0 205569_at LAMP3 lysosomal-associated membrane protein 3 85.4 232698_at BPIFB2 BPI fold containing family B, member 2 84.4 205979_at SCGB2A1 secretoglobin, family 2A, member 1 84.3 230469_at RTKN2 rhotekin 2 82.2 204130_at HSD11B2 hydroxysteroid (11-beta) dehydrogenase 2 81.9 222242_s_at KLK5 kallikrein-related peptidase 5 77.0 237281_at AKAP14 A kinase (PRKA) anchor protein 14 76.7 1553602_at MUCL1 mucin-like 1 76.3 216359_at D MUC7 mucin 7, -
Unique Protein Expression Signatures of Survival Time in Kidney Renal Clear
The Author(s) BMC Genomics 2017, 18(Suppl 6):678 DOI 10.1186/s12864-017-4026-6 RESEARCH Open Access Unique protein expression signatures of survival time in kidney renal clear cell carcinoma through a pan-cancer screening Guangchun Han1, Wei Zhao2, Xiaofeng Song3, Patrick Kwok-Shing Ng4, Jose A. Karam5, Eric Jonasch6, Gordon B. Mills2, Zhongming Zhao1,7*, Zhiyong Ding2* and Peilin Jia1* From The International Conference on Intelligent Biology and Medicine (ICIBM) 2016 Houston, TX, USA. 08-10 December 2016 Abstract Background: In 2016, it is estimated that there will be 62,700 new cases of kidney cancer in the United States, and 14,240 patients will die from the disease. Because the incidence of kidney renal clear cell carcinoma (KIRC), the most common type of kidney cancer, is expected to continue to increase in the US, there is an urgent need to find effective diagnostic biomarkers for KIRC that could help earlier detection of and customized treatment strategies for the disease. Accordingly, in this study we systematically investigated KIRC’s prognostic biomarkers for survival using the reverse phase protein array (RPPA) data and the high throughput sequencing data from The Cancer Genome Atlas (TCGA). Results: With comprehensive data available in TCGA, we systematically screened protein expression based survival biomarkers in 10 major cancer types, among which KIRC presented many protein prognostic biomarkers of survival time. This is in agreement with a previous report that expression level changes (mRNAs, microRNA and protein) may have a better performance for prognosis of KIRC. In this study, we also identified 52 prognostic genes for KIRC, many of which are involved in cell-cycle and cancer signaling, as well as 15 tumor-stage-specific prognostic biomarkers. -
The Landscape of Human Mutually Exclusive Splicing
bioRxiv preprint doi: https://doi.org/10.1101/133215; this version posted May 2, 2017. 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-ND 4.0 International license. The landscape of human mutually exclusive splicing Klas Hatje1,2,#,*, Ramon O. Vidal2,*, Raza-Ur Rahman2, Dominic Simm1,3, Björn Hammesfahr1,$, Orr Shomroni2, Stefan Bonn2§ & Martin Kollmar1§ 1 Group of Systems Biology of Motor Proteins, Department of NMR-based Structural Biology, Max-Planck-Institute for Biophysical Chemistry, Göttingen, Germany 2 Group of Computational Systems Biology, German Center for Neurodegenerative Diseases, Göttingen, Germany 3 Theoretical Computer Science and Algorithmic Methods, Institute of Computer Science, Georg-August-University Göttingen, Germany § Corresponding authors # Current address: Roche Pharmaceutical Research and Early Development, Pharmaceutical Sciences, Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd., Basel, Switzerland $ Current address: Research and Development - Data Management (RD-DM), KWS SAAT SE, Einbeck, Germany * These authors contributed equally E-mail addresses: KH: [email protected], RV: [email protected], RR: [email protected], DS: [email protected], BH: [email protected], OS: [email protected], SB: [email protected], MK: [email protected] - 1 - bioRxiv preprint doi: https://doi.org/10.1101/133215; this version posted May 2, 2017. 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. -
Genome-Scale Single-Cell Mechanical Phenotyping Reveals Disease-Related Genes Involved in Mitotic Rounding
ARTICLE DOI: 10.1038/s41467-017-01147-6 OPEN Genome-scale single-cell mechanical phenotyping reveals disease-related genes involved in mitotic rounding Yusuke Toyoda 1,2, Cedric J. Cattin3, Martin P. Stewart 3,4,5, Ina Poser1, Mirko Theis6, Teymuras V. Kurzchalia1, Frank Buchholz1,6, Anthony A. Hyman1 & Daniel J. Müller 3 To divide, most animal cells drastically change shape and round up against extracellular confinement. Mitotic cells facilitate this process by generating intracellular pressure, which the contractile actomyosin cortex directs into shape. Here, we introduce a genome-scale microcantilever- and RNAi-based approach to phenotype the contribution of > 1000 genes to the rounding of single mitotic cells against confinement. Our screen analyzes the rounding force, pressure and volume of mitotic cells and localizes selected proteins. We identify 49 genes relevant for mitotic rounding, a large portion of which have not previously been linked to mitosis or cell mechanics. Among these, depleting the endoplasmic reticulum-localized protein FAM134A impairs mitotic progression by affecting metaphase plate alignment and pressure generation by delocalizing cortical myosin II. Furthermore, silencing the DJ-1 gene uncovers a link between mitochondria-associated Parkinson’s disease and mitotic pressure. We conclude that mechanical phenotyping is a powerful approach to study the mechanisms governing cell shape. 1 Max Planck Institute of Molecular Cell Biology and Genetics, Pfotenhauerstrasse 108, 01307 Dresden, Germany. 2 Division of Cell Biology, Life Science Institute, Kurume University, Hyakunen-Kohen 1-1, Kurume, Fukuoka 839-0864, Japan. 3 Department of Biosystems Science and Engineering (D-BSSE), Eidgenössische Technische Hochschule (ETH) Zurich, Mattenstrasse 26, 4058 Basel, Switzerland. -
The Transcriptional and Epigenetic Role of Brd4 in the Regulation of the Cellular Stress Response
THE TRANSCRIPTIONAL AND EPIGENETIC ROLE OF BRD4 IN THE REGULATION OF THE CELLULAR STRESS RESPONSE INAUGURAL-DISSERTATION to obtain the academic degree Doctor rerum naturalium (Dr. rer. nat.) submitted to the Department of Biology, Chemistry and Pharmacy of Freie Universität Berlin by Michelle Hussong from Zweibrücken 2015 Die vorliegende Arbeit wurde im Zeitraum von Juli 2012 bis September 2015 am Max- Planck-Institut für Molekulare Genetik in Berlin sowie an der Universität zu Köln unter der Leitung von Frau Prof. Dr. Dr. Michal-Ruth Schweiger angefertigt. 1. Gutachter: Prof. Dr. Dr. Michal-Ruth Schweiger 2. Gutachter: Prof. Dr. Rupert Mutzel Disputation am 07.12.2015 ACKNOWLEDGMENT ACKNOWLEDGMENT This dissertation would not have been possible without the guidance and the help of many people who in one way or another contributed to the preparation and completion of this study. Firstly, I would like to express my sincere gratitude to my advisor Prof. Dr. Dr. Michal-Ruth Schweiger, for her continuous support throughout my PhD study, for her patience, motivation, and immense knowledge. I am eminently thankful for the multiple possibilities she gave me to work on this interesting and challenging field of research. I also want to thank Professor Dr. Rupert Mutzel for taking the time of being my second supervisor. My sincere thanks also goes to Prof. Dr. Hans Lehrach for having given me the opportunity to do my PhD thesis in the extraordinary and inspiring environment at the Max-Planck- Institute for Molecular Genetics in Berlin. Especially, the multitude of technologies and knowledge in his department made my work successful. -
Nº Ref Uniprot Proteína Péptidos Identificados Por MS/MS 1 P01024
Document downloaded from http://www.elsevier.es, day 26/09/2021. This copy is for personal use. Any transmission of this document by any media or format is strictly prohibited. Nº Ref Uniprot Proteína Péptidos identificados 1 P01024 CO3_HUMAN Complement C3 OS=Homo sapiens GN=C3 PE=1 SV=2 por 162MS/MS 2 P02751 FINC_HUMAN Fibronectin OS=Homo sapiens GN=FN1 PE=1 SV=4 131 3 P01023 A2MG_HUMAN Alpha-2-macroglobulin OS=Homo sapiens GN=A2M PE=1 SV=3 128 4 P0C0L4 CO4A_HUMAN Complement C4-A OS=Homo sapiens GN=C4A PE=1 SV=1 95 5 P04275 VWF_HUMAN von Willebrand factor OS=Homo sapiens GN=VWF PE=1 SV=4 81 6 P02675 FIBB_HUMAN Fibrinogen beta chain OS=Homo sapiens GN=FGB PE=1 SV=2 78 7 P01031 CO5_HUMAN Complement C5 OS=Homo sapiens GN=C5 PE=1 SV=4 66 8 P02768 ALBU_HUMAN Serum albumin OS=Homo sapiens GN=ALB PE=1 SV=2 66 9 P00450 CERU_HUMAN Ceruloplasmin OS=Homo sapiens GN=CP PE=1 SV=1 64 10 P02671 FIBA_HUMAN Fibrinogen alpha chain OS=Homo sapiens GN=FGA PE=1 SV=2 58 11 P08603 CFAH_HUMAN Complement factor H OS=Homo sapiens GN=CFH PE=1 SV=4 56 12 P02787 TRFE_HUMAN Serotransferrin OS=Homo sapiens GN=TF PE=1 SV=3 54 13 P00747 PLMN_HUMAN Plasminogen OS=Homo sapiens GN=PLG PE=1 SV=2 48 14 P02679 FIBG_HUMAN Fibrinogen gamma chain OS=Homo sapiens GN=FGG PE=1 SV=3 47 15 P01871 IGHM_HUMAN Ig mu chain C region OS=Homo sapiens GN=IGHM PE=1 SV=3 41 16 P04003 C4BPA_HUMAN C4b-binding protein alpha chain OS=Homo sapiens GN=C4BPA PE=1 SV=2 37 17 Q9Y6R7 FCGBP_HUMAN IgGFc-binding protein OS=Homo sapiens GN=FCGBP PE=1 SV=3 30 18 O43866 CD5L_HUMAN CD5 antigen-like OS=Homo -
Identification of Growth Trait Related Genes in a Yorkshire Purebred Pig Population by Genome-Wide Association Studies
Open Access Asian-Australas J Anim Sci Vol. 30, No. 4:462-469 April 2017 https://doi.org/10.5713/ajas.16.0548 pISSN 1011-2367 eISSN 1976-5517 Identification of growth trait related genes in a Yorkshire purebred pig population by genome-wide association studies Qingli Meng1,a, Kejun Wang2,a, Xiaolei Liu3, Haishen Zhou1, Li Xu1, Zhaojun Wang1,*, and Meiying Fang2,* * Corresponding Authors: Zhaojun Wang Objective: The aim of this study is to identify genomic regions or genes controlling growth Tel: +86-010-82475589, Fax: +86-010-82475589, E-mail: [email protected] traits in pigs. Meiying Fang Methods: Using a panel of 54,148 single nucleotide polymorphisms (SNPs), we performed a Tel: +86-010-62734943, Fax: +86-010-62734943, genome-wide Association (GWA) study in 562 pure Yorshire pigs with four growth traits: average E-mail: [email protected] daily gain from 30 kg to 100 kg or 115 kg, and days to 100 kg or 115 kg. Fixed and random model 1 Beijing Breeding Swine Center, Beijing 100194, China Circulating Probability Unification method was used to identify the associations between 2 Department of Animal Genetics and Breeding, 54,148 SNPs and these four traits. SNP annotations were performed through the Sus scrofa data National Engineering Laboratory for Animal Breeding, MOA Laboratory of Animal Genetics and Breeding, set from Ensembl. Bioinformatics analysis, including gene ontology analysis, pathway analysis College of Animal Science and Technology, China and network analysis, was used to identify the candidate genes. Agricultural University, -
Genome-Wide Assessment of DNA Methylation in Mouse Oocytes Reveals Effects Associated with in Vitro Growth, Superovulation
Saenz-de-Juano et al. Clinical Epigenetics (2019) 11:197 https://doi.org/10.1186/s13148-019-0794-y RESEARCH Open Access Genome-wide assessment of DNA methylation in mouse oocytes reveals effects associated with in vitro growth, superovulation, and sexual maturity Maria Desemparats Saenz-de-Juano1,2, Elena Ivanova3, Katy Billooye1, Anamaria-Cristina Herta1, Johan Smitz1, Gavin Kelsey3,4 and Ellen Anckaert1* Abstract Background: In vitro follicle culture (IFC), as applied in the mouse system, allows the growth and maturation of a large number of immature preantral follicles to become mature and competent oocytes. In the human oncofertility clinic, there is increasing interest in developing this technique as an alternative to ovarian cortical tissue transplantation and to preserve the fertility of prepubertal cancer patients. However, the effect of IFC and hormonal stimulation on DNA methylation in the oocyte is not fully known, and there is legitimate concern over epigenetic abnormalities that could be induced by procedures applied during assisted reproductive technology (ART). Results: In this study, we present the first genome-wide analysis of DNA methylation in MII oocytes obtained after natural ovulation, after IFC and after superovulation. We also performed a comparison between prepubertal and adult hormonally stimulated oocytes. Globally, the distinctive methylation landscape of oocytes, comprising alternating hyper- and hypomethylated domains, is preserved irrespective of the procedure. The conservation of methylation extends to the germline differential methylated regions (DMRs) of imprinted genes, necessary for their monoallelic expression in the embryo. However, we do detect specific, consistent, and coherent differences in DNA methylation in IFC oocytes, and between oocytes obtained after superovulation from prepubertal compared with sexually mature females. -
Development of Novel Analysis and Data Integration Systems to Understand Human Gene Regulation
Development of novel analysis and data integration systems to understand human gene regulation Dissertation zur Erlangung des Doktorgrades Dr. rer. nat. der Fakult¨atf¨urMathematik und Informatik der Georg-August-Universit¨atG¨ottingen im PhD Programme in Computer Science (PCS) der Georg-August University School of Science (GAUSS) vorgelegt von Raza-Ur Rahman aus Pakistan G¨ottingen,April 2018 Prof. Dr. Stefan Bonn, Zentrum f¨urMolekulare Neurobiologie (ZMNH), Betreuungsausschuss: Institut f¨urMedizinische Systembiologie, Hamburg Prof. Dr. Tim Beißbarth, Institut f¨urMedizinische Statistik, Universit¨atsmedizin, Georg-August Universit¨at,G¨ottingen Prof. Dr. Burkhard Morgenstern, Institut f¨urMikrobiologie und Genetik Abtl. Bioinformatik, Georg-August Universit¨at,G¨ottingen Pr¨ufungskommission: Prof. Dr. Stefan Bonn, Zentrum f¨urMolekulare Neurobiologie (ZMNH), Referent: Institut f¨urMedizinische Systembiologie, Hamburg Prof. Dr. Tim Beißbarth, Institut f¨urMedizinische Statistik, Universit¨atsmedizin, Korreferent: Georg-August Universit¨at,G¨ottingen Prof. Dr. Burkhard Morgenstern, Weitere Mitglieder Institut f¨urMikrobiologie und Genetik Abtl. Bioinformatik, der Pr¨ufungskommission: Georg-August Universit¨at,G¨ottingen Prof. Dr. Carsten Damm, Institut f¨urInformatik, Georg-August Universit¨at,G¨ottingen Prof. Dr. Florentin W¨org¨otter, Physikalisches Institut Biophysik, Georg-August-Universit¨at,G¨ottingen Prof. Dr. Stephan Waack, Institut f¨urInformatik, Georg-August Universit¨at,G¨ottingen Tag der m¨undlichen Pr¨ufung: der 30. M¨arz2018 -
A Study of Alterations in DNA Epigenetic Modifications (5Mc and 5Hmc) and Gene Expression Influenced by Simulated Microgravity I
View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by Digital Repository @ Iowa State University Genome Informatics Facility Publications Genome Informatics Facility 1-28-2016 A Study of Alterations in DNA Epigenetic Modifications (5mC and 5hmC) and Gene Expression Influenced by Simulated Microgravity in Human Lymphoblastoid Cells Basudev Chowdhury Purdue University Arun S. Seetharam Iowa State University, [email protected] Zhiping Wang Indiana University School of Medicine Yunlong Liu Indiana University School of Medicine Amy C. Lossie Purdue University See next page for additional authors Follow this and additional works at: https://lib.dr.iastate.edu/genomeinformatics_pubs Part of the Bioinformatics Commons, Genetics Commons, and the Genomics Commons Recommended Citation Chowdhury, Basudev; Seetharam, Arun S.; Wang, Zhiping; Liu, Yunlong; Lossie, Amy C.; Thimmapuram, Jyothi; and Irudayaraj, Joseph, "A Study of Alterations in DNA Epigenetic Modifications (5mC and 5hmC) and Gene Expression Influenced by Simulated Microgravity in Human Lymphoblastoid Cells" (2016). Genome Informatics Facility Publications. 4. https://lib.dr.iastate.edu/genomeinformatics_pubs/4 This Article is brought to you for free and open access by the Genome Informatics Facility at Iowa State University Digital Repository. It has been accepted for inclusion in Genome Informatics Facility Publications by an authorized administrator of Iowa State University Digital Repository. For more information, please contact [email protected]. A Study of Alterations in DNA Epigenetic Modifications (5mC and 5hmC) and Gene Expression Influenced by Simulated Microgravity in Human Lymphoblastoid Cells Abstract Cells alter their gene expression in response to exposure to various environmental changes. Epigenetic mechanisms such as DNA methylation are believed to regulate the alterations in gene expression patterns.