Supplementary Materials for Volumetric Alteration of Olfactory
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Supplementary Table S1. Upregulated Genes Differentially
Supplementary Table S1. Upregulated genes differentially expressed in athletes (p < 0.05 and 1.3-fold change) Gene Symbol p Value Fold Change 221051_s_at NMRK2 0.01 2.38 236518_at CCDC183 0.00 2.05 218804_at ANO1 0.00 2.05 234675_x_at 0.01 2.02 207076_s_at ASS1 0.00 1.85 209135_at ASPH 0.02 1.81 228434_at BTNL9 0.03 1.81 229985_at BTNL9 0.01 1.79 215795_at MYH7B 0.01 1.78 217979_at TSPAN13 0.01 1.77 230992_at BTNL9 0.01 1.75 226884_at LRRN1 0.03 1.74 220039_s_at CDKAL1 0.01 1.73 236520_at 0.02 1.72 219895_at TMEM255A 0.04 1.72 201030_x_at LDHB 0.00 1.69 233824_at 0.00 1.69 232257_s_at 0.05 1.67 236359_at SCN4B 0.04 1.64 242868_at 0.00 1.63 1557286_at 0.01 1.63 202780_at OXCT1 0.01 1.63 1556542_a_at 0.04 1.63 209992_at PFKFB2 0.04 1.63 205247_at NOTCH4 0.01 1.62 1554182_at TRIM73///TRIM74 0.00 1.61 232892_at MIR1-1HG 0.02 1.61 204726_at CDH13 0.01 1.6 1561167_at 0.01 1.6 1565821_at 0.01 1.6 210169_at SEC14L5 0.01 1.6 236963_at 0.02 1.6 1552880_at SEC16B 0.02 1.6 235228_at CCDC85A 0.02 1.6 1568623_a_at SLC35E4 0.00 1.59 204844_at ENPEP 0.00 1.59 1552256_a_at SCARB1 0.02 1.59 1557283_a_at ZNF519 0.02 1.59 1557293_at LINC00969 0.03 1.59 231644_at 0.01 1.58 228115_at GAREM1 0.01 1.58 223687_s_at LY6K 0.02 1.58 231779_at IRAK2 0.03 1.58 243332_at LOC105379610 0.04 1.58 232118_at 0.01 1.57 203423_at RBP1 0.02 1.57 AMY1A///AMY1B///AMY1C///AMY2A///AMY2B// 208498_s_at 0.03 1.57 /AMYP1 237154_at LOC101930114 0.00 1.56 1559691_at 0.01 1.56 243481_at RHOJ 0.03 1.56 238834_at MYLK3 0.01 1.55 213438_at NFASC 0.02 1.55 242290_at TACC1 0.04 1.55 ANKRD20A1///ANKRD20A12P///ANKRD20A2/// -
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. -
MBNL1 Regulates Essential Alternative RNA Splicing Patterns in MLL-Rearranged Leukemia
ARTICLE https://doi.org/10.1038/s41467-020-15733-8 OPEN MBNL1 regulates essential alternative RNA splicing patterns in MLL-rearranged leukemia Svetlana S. Itskovich1,9, Arun Gurunathan 2,9, Jason Clark 1, Matthew Burwinkel1, Mark Wunderlich3, Mikaela R. Berger4, Aishwarya Kulkarni5,6, Kashish Chetal6, Meenakshi Venkatasubramanian5,6, ✉ Nathan Salomonis 6,7, Ashish R. Kumar 1,7 & Lynn H. Lee 7,8 Despite growing awareness of the biologic features underlying MLL-rearranged leukemia, 1234567890():,; targeted therapies for this leukemia have remained elusive and clinical outcomes remain dismal. MBNL1, a protein involved in alternative splicing, is consistently overexpressed in MLL-rearranged leukemias. We found that MBNL1 loss significantly impairs propagation of murine and human MLL-rearranged leukemia in vitro and in vivo. Through transcriptomic profiling of our experimental systems, we show that in leukemic cells, MBNL1 regulates alternative splicing (predominantly intron exclusion) of several genes including those essential for MLL-rearranged leukemogenesis, such as DOT1L and SETD1A.Wefinally show that selective leukemic cell death is achievable with a small molecule inhibitor of MBNL1. These findings provide the basis for a new therapeutic target in MLL-rearranged leukemia and act as further validation of a burgeoning paradigm in targeted therapy, namely the disruption of cancer-specific splicing programs through the targeting of selectively essential RNA binding proteins. 1 Division of Bone Marrow Transplantation and Immune Deficiency, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH 45229, USA. 2 Cancer and Blood Diseases Institute, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH 45229, USA. 3 Division of Experimental Hematology and Cancer Biology, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH 45229, USA. -
International Union of Pharmacology. XXXV. the Glucagon Receptor Family
0031-6997/03/5501-167–194$7.00 PHARMACOLOGICAL REVIEWS Vol. 55, No. 1 Copyright © 2003 by The American Society for Pharmacology and Experimental Therapeutics 30106/1047548 Pharmacol Rev 55:167–194, 2003 Printed in U.S.A International Union of Pharmacology. XXXV. The Glucagon Receptor Family KELLY E. MAYO, LAURENCE J. MILLER, DOMINIQUE BATAILLE, STEPHANE´ DALLE, BURKHARD GO¨ KE, BERNARD THORENS, AND DANIEL J. DRUCKER Department of Biochemistry, Molecular Biology and Cell Biology, Northwestern University, Evanston, Illinois (K.E.M.); Mayo Clinic and Foundation, Department of Molecular Pharmacology and Experimental Therapeutics, Rochester, Minnesota (L.J.M.); INSERM U 376, Montpellier, France (D.B., S.D.); Department of Medicine II, Grosshadern, Klinikum der Ludwig-Maximilians, University of Munich, Germany (B.G.); Institute of Pharmacology and Toxicology, University of Lausanne, Lausanne, Switzerland (B.T.); and Banting and Best Diabetes Centre, Toronto General Hospital, University of Toronto, Toronto, Ontario, Canada (D.J.D.) Abstract .............................................................................. 168 I. Introduction ........................................................................... 168 II. Secretin receptor....................................................................... 169 A. Molecular basis for receptor nomenclature ............................................ 169 B. Endogenous agonist................................................................. 169 C. Receptor structure ................................................................. -
C3orf70 Is Involved in Neural and Neurobehavioral Development
pharmaceuticals Article C3orf70 Is Involved in Neural and Neurobehavioral Development Yoshifumi Ashikawa 1, Takashi Shiromizu 1, Koki Miura 1, Yuka Adachi 1, Takaaki Matsui 2, Yasumasa Bessho 2, Toshio Tanaka 3 and Yuhei Nishimura 1,* 1 Department of Integrative Pharmacology, Mie University Graduate School of Medicine, Tsu, Mie 514-8507, Japan; [email protected] (Y.A.); [email protected] (T.S.); [email protected] (K.M.); [email protected] (Y.A.) 2 Gene Regulation Research, Graduate School of Biological Sciences, Nara Institute of Science and Technology, Takayama, Nara 630-0192, Japan; [email protected] (T.M.); [email protected] (Y.B.) 3 Department of Systems Pharmacology, Mie University Graduate School of Medicine, Tsu, Mie 514-8507, Japan; [email protected] * Correspondence: [email protected] Received: 10 October 2019; Accepted: 15 October 2019; Published: 16 October 2019 Abstract: Neurogenesis is the process by which undifferentiated progenitor cells develop into mature and functional neurons. Defects in neurogenesis are associated with neurodevelopmental and neuropsychiatric disorders; therefore, elucidating the molecular mechanisms underlying neurogenesis can advance our understanding of the pathophysiology of these disorders and facilitate the discovery of novel therapeutic targets. In this study, we performed a comparative transcriptomic analysis to identify common targets of the proneural transcription factors Neurog1/2 and Ascl1 during neurogenesis of human and mouse stem cells. We successfully identified C3orf70 as a novel common target gene of Neurog1/2 and Ascl1 during neurogenesis. Using in situ hybridization, we demonstrated that c3orf70a and c3orf70b, two orthologs of C3orf70, were expressed in the midbrain and hindbrain of zebrafish larvae. -
The Role of Cyclin B3 in Mammalian Meiosis
THE ROLE OF CYCLIN B3 IN MAMMALIAN MEIOSIS by Mehmet Erman Karasu A Dissertation Presented to the Faculty of the Louis V. Gerstner Jr. Graduate School of Biomedical Sciences, Memorial Sloan Kettering Cancer Center In Partial Fulfillment of the Requirements for the Degree of Doctor of Philosophy New York, NY November, 2018 Scott Keeney, PhD Date Dissertation Mentor Copyright © Mehmet Erman Karasu 2018 DEDICATION I would like to dedicate this thesis to my parents, Mukaddes and Mustafa Karasu. I have been so lucky to have their support and unconditional love in this life. ii ABSTRACT Cyclins and cyclin dependent kinases (CDKs) lie at the center of the regulation of the cell cycle. Cyclins as regulatory partners of CDKs control the switch-like cell cycle transitions that orchestrate orderly duplication and segregation of genomes. Similar to somatic cell division, temporal regulation of cyclin-CDK activity is also important in meiosis, which is the specialized cell division that generates gametes for sexual production by halving the genome. Meiosis does so by carrying out one round of DNA replication followed by two successive divisions without another intervening phase of DNA replication. In budding yeast, cyclin-CDK activity has been shown to have a crucial role in meiotic events such as formation of meiotic double-strand breaks that initiate homologous recombination. Mammalian cells express numerous cyclins and CDKs, but how these proteins control meiosis remains poorly understood. Cyclin B3 was previously identified as germ cell specific, and its restricted expression pattern at the beginning of meiosis made it an interesting candidate to regulate meiotic events. -
Accepted By:- Signature Redacted Department of Biology Graduate Co-Chair: Michael T
EXPLORING THE FUNCTIONAL CONSERVATION OF MUSCLEBLIND (MBL) PROTEINS by MASSACH USETTS INSTITUTE Julia C. Oddo d o ECHNOLOGY B.S. Molecular, Cellular, and Developmental Biology, SE 1 7 2015 Minor Biochemistry 2011 LIB RARIES SUBMITTED TO THE DEPARTMENT OF BIOLOGY IN PARTIAL FULFILLMENT OF THE REQUIREMENTS FOR THE DEGREE OF MASTERS OF SCIENCE IN BIOLOGY AT THE MASSACHUSETTS INSTITUTE OF TECHNOLOGY SEPTEMBER 2015 C 2015 Massachusetts Institute of Technology. All rights reserved. The author hereby grants to MIT permission to reproduce and to distribute publicly paper and electronic copies of this thesis document in whole or in part in any medium now known or hereafter created. Signature redacted Signature of Auth or:_ Department of Biology May 22, 2015 Certified by: Signature redacte Thesis Supervisor: Chris B. Burge Professor of Biology and Biological Engineering Director Program CSB Certified by: Signature redactec Thesis Co-Supervisor: Eric T. Wang Research Fellow Accepted by:- Signature redacted Department of Biology Graduate Co-Chair: Michael T. Hemann Associate Professor of Biology 1 EXPLORING THE FUNCTIONAL CONSERVATION OF MUSCLEBLIND (MBL) PROTEINS by Julia C. Oddo Submitted to the Department of Biology on September 8th, 2015 in Partial Fulfillment of the Requirements for the Degree of Master of Science in Biology ABSTRACT Muscleblind (Mbl) is an evolutionarily conserved family of proteins involved in many aspects of RNA metabolism, including alternative splicing. Disruption of Muscleblind in several animals lends to a variety of defects and disease, including the multi-systemic disorder Myotonic Dystrophy (DM). Though much is known about the involvement of Muscleblind in DM, there is much basic knowledge of the protein's function to be discovered. -
In-Depth Characterization of the Wnt-Signaling/Β-Catenin Pathway In
Götzel et al. BMC Gastroenterology (2019) 19:38 https://doi.org/10.1186/s12876-019-0957-5 RESEARCH ARTICLE Open Access In-depth characterization of the Wnt- signaling/β-catenin pathway in an in vitro model of Barrett’s sequence Katharina Götzel1, Olga Chemnitzer1, Luisa Maurer1, Arne Dietrich1,2, Uwe Eichfeld1, Orestis Lyros1, Yusef Moulla1, Stefan Niebisch1, Matthias Mehdorn1, Boris Jansen-Winkeln1, Michael Vieth3, Albrecht Hoffmeister4, Ines Gockel1 and René Thieme1* Abstract Background: An altered Wnt-signaling activation has been reported during Barrett’s esophagus progression, but with rarely detected mutations in APC and β-catenin (CTNNB1) genes. Methods: In this study, a robust in-depth expression pattern analysis of frizzled receptors, co-receptors, the Wnt- ligands Wnt3a and Wnt5a, the Wnt-signaling downstream targets Axin2, and CyclinD1, as well as the activation of the intracellular signaling kinases Akt and GSK3β was performed in an in vitro cell culture model of Barrett’s esophagus. Representing the Barrett’s sequence, we used normal esophageal squamous epithelium (EPC-1, EPC-2), metaplasia (CP-A) and dysplasia (CP-B) to esophageal adenocarcinoma (EAC) cell lines (OE33, OE19) and primary specimens of squamous epithelium, metaplasia and EAC. Results: A loss of Wnt3a expression was observed beginning from the metaplastic cell line CP-A towards dysplasia (CP-B) and EAC (OE33 and OE19), confirmed by a lower staining index of WNT3A in Barrett’s metaplasia and EAC, than in squamous epithelium specimens. Frizzled 1–10 expression analysis revealed a distinct expression pattern, showing the highest expression for Fzd2, Fzd3, Fzd4, Fzd5, Fzd7, and the co-receptor LRP5/6 in EAC cells, while Fzd3 and Fzd7 were rarely expressed in primary specimens from squamous epithelium. -
UNIVERSITY of CALIFORNIA RIVERSIDE Investigations Into The
UNIVERSITY OF CALIFORNIA RIVERSIDE Investigations into the Role of TAF1-mediated Phosphorylation in Gene Regulation A Dissertation submitted in partial satisfaction of the requirements for the degree of Doctor of Philosophy in Cell, Molecular and Developmental Biology by Brian James Gadd December 2012 Dissertation Committee: Dr. Xuan Liu, Chairperson Dr. Frank Sauer Dr. Frances M. Sladek Copyright by Brian James Gadd 2012 The Dissertation of Brian James Gadd is approved Committee Chairperson University of California, Riverside Acknowledgments I am thankful to Dr. Liu for her patience and support over the last eight years. I am deeply indebted to my committee members, Dr. Frank Sauer and Dr. Frances Sladek for the insightful comments on my research and this dissertation. Thanks goes out to CMDB, especially Dr. Bachant, Dr. Springer and Kathy Redd for their support. Thanks to all the members of the Liu lab both past and present. A very special thanks to the members of the Sauer lab, including Silvia, Stephane, David, Matt, Stephen, Ninuo, Toby, Josh, Alice, Alex and Flora. You have made all the years here fly by and made them so enjoyable. From the Sladek lab I want to thank Eugene, John, Linh and Karthi. Special thanks go out to all the friends I’ve made over the years here. Chris, Amber, Stephane and David, thank you so much for feeding me, encouraging me and keeping me sane. Thanks to the brothers for all your encouragement and prayers. To any I haven’t mentioned by name, I promise I haven’t forgotten all you’ve done for me during my graduate years. -
Kif9 Is an Active Kinesin Motor Required for Ciliary Beating and Proximodistal Patterning of Motile Axonemes
bioRxiv preprint doi: https://doi.org/10.1101/2021.08.26.457815; this version posted August 27, 2021. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. 1 Kif9 is an active kinesin motor required for ciliary beating and proximodistal patterning of motile axonemes Mia J. Konjikusic1,2,3, Chanjae Lee1, Yang Yue4, Bikram D. Shrestha5, Ange M. Nguimtsop1, Amjad Horani6, Steven Brody7,8, Vivek N. Prakash5,9, Ryan S. Gray2,3, Kristen J. Verhey4, John B. Wallingford1* 1 Department of Molecular Biosciences, University of Texas at Austin, Austin, TX, USA. 2 Department of Pediatrics, Dell Pediatric Research Institute, 1400 Barbara Jordan Blvd, The University of Texas at Austin, Dell Medical School, Austin, TX, USA. 3 Department of Nutritional Sciences, 200 W 24th Street, The University of Texas at Austin, Austin, TX 78712, USA. 4 Department of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, MI, 48109, USA. 5 Department of Physics, University of Miami, Coral Gables, FL, USA. 6 Department of Pediatrics, Washington University School of Medicine, St. Louis, MO, USA. 7 Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA. 8 Department of Cell Biology and Physiology, Washington University School of Medicine, St. Louis, MO, 63110 USA 9 Department of Biology and Department of Marine Biology and Ecology, University of Miami, Coral Gables, FL, USA. *Corresponding Author [email protected] Patterson Labs 2401 Speedway Austin, Tx 78712 bioRxiv preprint doi: https://doi.org/10.1101/2021.08.26.457815; this version posted August 27, 2021. -
HPV E2, E4, E5 Drive Alternative Carcinogenic Pathways in HPV Positive Cancers
Oncogene (2020) 39:6327–6339 https://doi.org/10.1038/s41388-020-01431-8 ARTICLE HPV E2, E4, E5 drive alternative carcinogenic pathways in HPV positive cancers 1,2 3 3 4,5 4 6 Shuling Ren ● Daria A. Gaykalova ● Theresa Guo ● Alexander V. Favorov ● Elana J. Fertig ● Pablo Tamayo ● 1,7 1 1 1 1 1 Juan Luis Callejas-Valera ● Mike Allevato ● Mara Gilardi ● Jessica Santos ● Takahito Fukusumi ● Akihiro Sakai ● 1 1 1 6 6 1 1 Mizuo Ando ● Sayed Sadat ● Chao Liu ● Guorong Xu ● Kathleen M. Fisch ● Zhiyong Wang ● Alfredo A. Molinolo ● 1 6 3 1,8 J. Silvio Gutkind ● Trey Ideker ● Wayne M. Koch ● Joseph A. Califano Received: 19 February 2020 / Revised: 19 July 2020 / Accepted: 13 August 2020 / Published online: 26 August 2020 © The Author(s) 2020. This article is published with open access Abstract The dominant paradigm for HPV carcinogenesis includes integration into the host genome followed by expression of E6 and E7 (E6/E7). We explored an alternative carcinogenic pathway characterized by episomal E2, E4, and E5 (E2/E4/E5) expression. Half of HPV positive cervical and pharyngeal cancers comprised a subtype with increase in expression of E2/E4/ E5, as well as association with lack of integration into the host genome. Models of the E2/E4/E5 carcinogenesis show p53 1234567890();,: 1234567890();,: dependent enhanced proliferation in vitro, as well as increased susceptibility to induction of cancer in vivo. Whole genomic expression analysis of the E2/E4/E5 pharyngeal cancer subtype is defined by activation of the fibroblast growth factor receptor (FGFR) pathway and this subtype is susceptible to combination FGFR and mTOR inhibition, with implications for targeted therapy. -
Construction of an Mirna‑Gene Regulatory Network in Colorectal Cancer Through Integrated Analysis of Mrna and Mirna Microarrays
MOLECULAR MEDICINE REPORTS 18: 5109-5116, 2018 Construction of an miRNA‑gene regulatory network in colorectal cancer through integrated analysis of mRNA and miRNA microarrays JUN HU, XIN YUE, JIANZHONG LIU and DALU KONG Department of Colorectal Cancer Surgery, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy of Tianjin, Tianjin's Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin 300060, P.R. China Received December 19, 2017; Accepted August 8, 2018 DOI: 10.3892/mmr.2018.9505 Abstract. The aim of the present study was to identify poten- Introduction tial biomarkers associated with colorectal cancer (CRC). The GSE32323 and GSE53592 mRNA and microRNA (miRNA) Colorectal cancer (CRC) is a common malignancy that ranks expression profiles were selected from the Gene Expression as the second leading cause of cancer-associated mortality in Omnibus database. The differentially expressed genes (DEGs) men and women in the USA (1). Despite improvements in CRC and differentially expressed miRNAs (DEMs) in CRC tissue therapy, CRC remains a major public health problem, and it is samples compared with surrounding control tissue samples estimated that there are 1,000,000 individuals suffering from (DEGs-CC), and DEGs in cells treated with 5-aza-2'-de- CRC worldwide, with the mortality rate is as high as ~50% in oxycitidine compared with untreated cells (DEGs-TC) certain developed countries (2). The tumor stage is the most were identified with the Limma package. The Database for important prognostic indicator for CRC. However, the tumors Annotation, Visualization and Integrated Discovery was used are often diagnosed at an intermediate or late stage, and the to conduct the functional and pathways enrichment analysis.