CCDC22 Shrna (H) Lentiviral Particles: Sc-91292-V
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Transcriptome-Wide Profiling of Multiple RNA Modifications Simultaneously at Single-Base Resolution,” by Vahid Khoddami, Archana Yerra, Timothy L
Correction BIOCHEMISTRY, CHEMISTRY Correction for “Transcriptome-wide profiling of multiple RNA modifications simultaneously at single-base resolution,” by Vahid Khoddami, Archana Yerra, Timothy L. Mosbruger, Aaron M. Fleming, Cynthia J. Burrows, and Bradley R. Cairns, which was first published March 14, 2019; 10.1073/pnas.1817334116 (Proc Natl Acad Sci USA 116:6784–6789). The authors note that the following statement should be added to the Acknowledgments: “This work was also supported by Grant R01 GM093099 from the NIH/National Institute of General Medical Sciences (to C.J.B.).” Published under the PNAS license. Published online April 22, 2019. www.pnas.org/cgi/doi/10.1073/pnas.1905628116 9136 | PNAS | April 30, 2019 | vol. 116 | no. 18 www.pnas.org Downloaded by guest on October 2, 2021 Transcriptome-wide profiling of multiple RNA modifications simultaneously at single-base resolution Vahid Khoddamia,b,c,1,2, Archana Yerrab,c,1, Timothy L. Mosbrugerd, Aaron M. Fleminge, Cynthia J. Burrowse,3, and Bradley R. Cairnsb,c,3 aDepartment of Cell Biology, Harvard Medical School, Boston, MA 02115; bHoward Hughes Medical Institute, University of Utah School of Medicine, Salt Lake City, UT 84112; cDepartment of Oncological Sciences, Huntsman Cancer Institute, University of Utah School of Medicine, Salt Lake City, UT 84112; dBioinformatics Shared Resource, Huntsman Cancer Institute, University of Utah School of Medicine, Salt Lake City, UT 84112; and eDepartment of Chemistry, University of Utah, Salt Lake City, UT 84112 Contributed by Cynthia J. Burrows, January 25, 2019 (sent for review October 9, 2018; reviewed by Juan D. Alfonzo, Thomas Carell, and Peter C. -
Endosomal PI(3)P Regulation by the COMMD/CCDC22/CCDC93
ARTICLE https://doi.org/10.1038/s41467-019-12221-6 OPEN Endosomal PI(3)P regulation by the COMMD/ CCDC22/CCDC93 (CCC) complex controls membrane protein recycling Amika Singla 1,5, Alina Fedoseienko2,5, Sai S.P. Giridharan3, Brittany L. Overlee2, Adam Lopez1, Da Jia 4, Jie Song1, Kayci Huff-Hardy1, Lois Weisman3, Ezra Burstein 1,6 & Daniel D. Billadeau2,6 1234567890():,; Protein recycling through the endolysosomal system relies on molecular assemblies that interact with cargo proteins, membranes, and effector molecules. Among them, the COMMD/CCDC22/CCDC93 (CCC) complex plays a critical role in recycling events. While CCC is closely associated with retriever, a cargo recognition complex, its mechanism of action remains unexplained. Herein we show that CCC and retriever are closely linked through sharing a common subunit (VPS35L), yet the integrity of CCC, but not retriever, is required to maintain normal endosomal levels of phosphatidylinositol-3-phosphate (PI(3)P). CCC complex depletion leads to elevated PI(3)P levels, enhanced recruitment and activation of WASH (an actin nucleation promoting factor), excess endosomal F-actin and trapping of internalized receptors. Mechanistically, we find that CCC regulates the phosphorylation and endosomal recruitment of the PI(3)P phosphatase MTMR2. Taken together, we show that the regulation of PI(3)P levels by the CCC complex is critical to protein recycling in the endosomal compartment. 1 Department of Internal Medicine, and Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA. 2 Division of Oncology Research and Department of Biochemistry and Molecular Biology, College of Medicine, Mayo Clinic, Rochester, MN 55905, USA. -
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DEVELOPMENT OF HUMAN-COMPUTER INTERACTIVE APPROACHES FOR RARE DISEASE GENOMICS by Jessica J. Y. Lee B.Sc., The University of British Columbia, 2013 A THESIS SUBMITTED IN PARTIAL FULFILLMENT OF THE REQUIREMENTS FOR THE DEGREE OF DOCTOR OF PHILOSOPHY in THE FACULTY OF GRADUATE AND POSTDOCTORAL STUDIES (Genome Science and Technology) THE UNIVERSITY OF BRITISH COLUMBIA (Vancouver) November 2018 © Jessica J. Y. Lee, 2018 The following individuals certify that they have read, and recommend to the Faculty of Graduate and Postdoctoral Studies for acceptance, the dissertation entitled: Development of Human-Computer Interactive Approaches for Rare Disease Genomics submitted by Jessica J. Y. Lee in partial fulfillment of the requirements for the degree of Doctor of Philosophy in Genome Science and Technology Examining Committee: Clara van Karnebeek, Pediatrics; Genome Science and Technology Co-supervisor Wyeth Wasserman, Medical Genetics Co-supervisor William Hsiao, Pathology and Laboratory Medicine Supervisory Committee Member Martin Dawes, Family Practice University Examiner Sabrina Wong, Nursing University Examiner Additional Supervisory Committee Members: Sara Mostafavi, Statistics Supervisory Committee Member Raymond Ng, Computer Science Supervisory Committee Member ii Abstract Clinical genome sequencing is becoming a tool for standard clinical practice. Many studies have presented sequencing as effective for both diagnosing and informing the management of genetic diseases. However, the task of finding the causal variant(s) of a rare genetic disease within an individual is often difficult due to the large number of identified variants and lack of direct evidence of causality. Current computational solutions harness existing genetic knowledge in order to infer the pathogenicity of the variant(s), as well as filter those unlikely to be pathogenic. -
Evidence for Induction of the Ornithine Transcarbamylase Expression in Alzheimer's Disease
Molecular Psychiatry (2009) 14, 106–116 & 2009 Nature Publishing Group All rights reserved 1359-4184/09 $32.00 www.nature.com/mp ORIGINAL ARTICLE Evidence for induction of the ornithine transcarbamylase expression in Alzheimer’s disease F Bensemain1, D Hot2, S Ferreira1,3, J Dumont1, S Bombois4, C-A Maurage5, L Huot2, X Hermant1, E Levillain2, C Hubans2,3, F Hansmannel1, J Chapuis1, J-J Hauw6, S Schraen5, Y Lemoine2, L Bue´e5, C Berr7, D Mann8, F Pasquier4, P Amouyel1 and J-C Lambert1 1INSERM, U744, Institut Pasteur de Lille, Universite´ de Lille 2, Lille, France; 2Laboratoire des Biopuces, Institut Pasteur de Lille, Lille, France; 3Ge´noscreen, Lille, France; 4EA2691 Memory Clinic, University Hospital of Lille, Lille, France; 5INSERM, U837, Universite´ de Lille 2, Lille, France; 6APHP, GH Pı¨tie´-Salpeˆtrie`re, Laboratoire de Neuropathologie R Escourolle, INSERM, IFR 70, Paris, France; 7INSERM, U888, Universite´ de Montpellier I, Hoˆpital La Colombie`re, Montpellier, France and 8Greater Manchester Neurosciences Centre, University of Manchester, Manchester, UK To more rapidly identify candidate genes located within chromosomal regions of interest defined by genome scan studies in Alzheimer’s disease (AD), we have developed a customized microarray containing all the ORFs (n = 2741) located within nine of these regions. Levels of gene expression were assessed in total RNA from brain tissue of 12 controls and 12 AD patients. Of all genes showing differential expression, we focused on the ornithine transcarbamylase (OTC) gene on Xp21.1., a key enzyme of the urea cycle which we found to be expressed in AD brains but not in controls, as confirmed by RT–PCR. -
Investigating Common Pathogenic Mechanisms Between Homo Sapiens and Different Strains of Candida Albicans for Drug Design
toxins Article Investigating Common Pathogenic Mechanisms between Homo sapiens and Different Strains of Candida albicans for Drug Design: Systems Biology Approach via Two-Sided NGS Data Identification Shan-Ju Yeh 1, Chun-Chieh Yeh 1, Chung-Yu Lan 2,3 and Bor-Sen Chen 1,4,* 1 Laboratory of Control and Systems Biology, Department of Electrical Engineering, National Tsing Hua University, Hsinchu 30013, Taiwan; [email protected] (S.-J.Y.); [email protected] (C.-C.Y.) 2 Institute of Molecular and Cellular Biology, National Tsing Hua University, Hsinchu 30013, Taiwan; [email protected] 3 Department of Life Science, National Tsing Hua University, Hsinchu 30013, Taiwan 4 Department of Electrical Engineering, Yuan Ze University, Chungli 32003, Taiwan * Correspondence: [email protected] Received: 31 December 2018; Accepted: 11 February 2019; Published: 15 February 2019 Abstract: Candida albicans (C. albicans) is the most prevalent fungal species. Although it is a healthy microbiota, genetic and epigenetic alterations in host and pathogen, and microenvironment changes would lead to thrush, vaginal yeast infection, and even hematogenously disseminated infection. Despite the fact that cytotoxicity is well-characterized, few studies discuss the genome-wide genetic and epigenetic molecular mechanisms between host and C. albicans. The aim of this study is to identify drug targets and design a multiple-molecule drug to prevent the infection from C. albicans. To investigate the common and specific pathogenic mechanisms in human oral epithelial OKF6/TERT-2 cells during the C. albicans infection in different strains, systems modeling and big databases mining were used to construct candidate host–pathogen genetic and epigenetic interspecies network (GEIN). -
COMMD1 Is Linked to the WASH Complex and Regulates Endosomal Trafficking of the Copper Transporter ATP7A
M BoC | ARTICLE COMMD1 is linked to the WASH complex and regulates endosomal trafficking of the copper transporter ATP7A Christine A. Phillips-Krawczaka,*, Amika Singlab,*, Petro Starokadomskyyb, Zhihui Denga,c, Douglas G. Osbornea, Haiying Lib, Christopher J. Dicka, Timothy S. Gomeza, Megan Koeneckeb, Jin-San Zhanga,d, Haiming Daie, Luis F. Sifuentes-Dominguezb, Linda N. Gengb, Scott H. Kaufmanne, Marco Y. Heinf, Mathew Wallisg, Julie McGaughrang,h, Jozef Geczi,j, Bart van de Sluisk, Daniel D. Billadeaua,l, and Ezra Bursteinb,m aDepartment of Immunology, eDepartment of Molecular Pharmacology and Experimental Therapeutics, and lDepartment of Biochemistry and Molecular Biology, Mayo Clinic College of Medicine, Mayo Clinic, Rochester, MN 55905; bDepartment of Internal Medicine and mDepartment of Molecular Biology, UT Southwestern Medical Center, Dallas, TX 75390-9151; cDepartment of Pathophysiology, Qiqihar Medical University, Qiqihar, Heilongjiang 161006, China; dSchool of Pharmaceutical Sciences and Key Laboratory of Biotechnology and Pharmaceutical Engineering, Wenzhou Medical University, Wenzhou, Zhejiang 325035, China; fMax Planck Institute of Biochemistry, 82152 Martinsried, Germany; gGenetic Health Queensland at the Royal Brisbane and Women’s Hospital, Herston, Queensland 4029, Australia; hSchool of Medicine, University of Queensland, Brisbane, Queensland 4072, Australia; iRobinson Institute and jDepartment of Paediatrics, University of Adelaide, Adelaide, South Australia 5005, Australia; kSection of Molecular Genetics at the Department of Pediatrics, University Medical Center Groningen, University of Groningen, 9713 Groningen, Netherlands ABSTRACT COMMD1 deficiency results in defective copper homeostasis, but the mecha- Monitoring Editor nism for this has remained elusive. Here we report that COMMD1 is directly linked to early Jean E. Gruenberg endosomes through its interaction with a protein complex containing CCDC22, CCDC93, and University of Geneva C16orf62. -
Dynamic Erasure of Random X-Chromosome Inactivation During Ipsc Reprogramming
bioRxiv preprint doi: https://doi.org/10.1101/545558; this version posted February 9, 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-NC 4.0 International license. Dynamic Erasure of Random X-Chromosome Inactivation during iPSC Reprogramming Adrian Janiszewski1,*, Irene Talon1,*, Juan Song1, Natalie De Geest1, San Kit To1, Greet Bervoets2,3, Jean-Christophe Marine2,3, Florian Rambow2,3, Vincent Pasque1,✉. 1 KU Leuven - University of Leuven, Department of Development and Regeneration, Herestraat 49, B-3000 Leuven, Belgium. 2 Laboratory for Molecular Cancer Biology, VIB Center for Cancer Biology 3 Department of Oncology, KU Leuven, Belgium ✉ Correspondence to: [email protected] (V.P.) * These authors contributed equally Format: Research paper ABSTRACT Background: Induction and reversal of chromatin silencing is critical for successful development, tissue homeostasis and the derivation of induced pluripotent stem cells (iPSCs). X-chromosome inactivation (XCI) and reactivation (XCR) in female cells represent chromosome-wide transitions between active and inactive chromatin states. While XCI has long been studied and provided important insights into gene regulation, the dynamics and mechanisms underlying the reversal of stable chromatin silencing of X-linked genes are much less understood. Here, we use allele- specific transcriptomic approaches to study XCR during mouse iPSC reprogramming in order to elucidate the timing and mechanisms of chromosome-wide reversal of gene silencing. Results: We show that XCR is hierarchical, with subsets of genes reactivating early, late and very late. -
Targeted Next-Generation Sequencing in Patients with Suggestive X-Linked Intellectual Disability
G C A T T A C G G C A T genes Article Targeted Next-Generation Sequencing in Patients with Suggestive X-Linked Intellectual Disability Nekane Ibarluzea 1,2 , Ana Belén de la Hoz 1,2, Olatz Villate 1,2,3, Isabel Llano 1,2,3 , Intzane Ocio 4, Itxaso Martí 5, Miriam Guitart 6, Elisabeth Gabau 6, Fernando Andrade 1,2, Blanca Gener 1,2,3 and María-Isabel Tejada 1,2,3,* 1 Biocruces Bizkaia Health Research Institute, 48903 Barakaldo, Spain; [email protected] (N.I.); [email protected] (A.B.d.l.H.); [email protected] (O.V.); [email protected] (I.L.); [email protected] (F.A.); [email protected] (B.G.) 2 Spanish Consortium for Research on Rare Diseases (CIBERER), 28029 Madrid, Spain 3 Genetics Service, Cruces University Hospital, Osakidetza Basque Health Service, 48903 Barakaldo, Spain 4 Department of Paediatric Neurology, Araba University Hospital, Osakidetza Basque Health Service, 01009 Gasteiz, Spain; [email protected] 5 Department of Paediatric Neurology, Donostia University Hospital, Osakidetza Basque Health Service, 20014 Donostia, Spain; [email protected] 6 Genetics Laboratory, Paediatric Unit, Parc Taulí Hospital Universitari, Institut d’Investigació i Innovació Parc Taulí I3PT, Universitat Autònoma de Barcelona, 08208 Sabadell, Spain; [email protected] (M.G.); [email protected] (E.G.) * Correspondence: [email protected] Received: 3 December 2019; Accepted: 30 December 2019; Published: 2 January 2020 Abstract: X-linked intellectual disability (XLID) is known to contribute up to 10% of intellectual disability (ID) in males and could explain the increased ratio of affected males observed in patients with ID. -
Understanding Regulatory Mechanisms Underlying Stem Cells Helps to Identify Cancer Biomarkers
Understanding Regulatory Mechanisms Underlying Stem Cells Helps to Identify Cancer Biomarkers A dissertation submitted towards the degree Doctor of Engineering (Dr.-Ing) of the Faculty of Mathematics and Computer Science of Saarland University by Maryam Nazarieh Saarbrücken, June 2018 i iii Day of Colloquium Jun 28, 2018 Dean of the Faculty Prof. Dr. Sebastian Hack Chair of the Committee Prof. Dr. Hans-Peter Lenhof Reporters First reviewer Prof. Dr. Volkhard Helms Second reviewer Prof. Dr. Dr. Thomas Lengauer Academic Assistant Dr. Christina Backes Acknowledgements Firstly, I would like to thank Prof. Volkhard Helms for offering me a position at his group and for his supervision and support on the SFB 1027 project. I am grateful to Prof. Thomas Lengauer for his helpful comments. I am thankful to Prof. Andreas Wiese for his contribution and discussion. I would like to thank Prof. Jan Baumbach that allowed me to spend a training phase in his group during my PhD preparatory phase and the collaborative work which I performed with his PhD student Rashid Ibragimov where I proposed a heuristic algorithm based on the characteristics of protein-protein interaction networks for solving the graph edit dis- tance problem. I would like to thank Graduate School of Computer Science and Center for Bioinformatics at Saarland University, especially Prof. Raimund Seidel and Dr. Michelle Carnell for giving me an opportunity to carry out my PhD studies. Furthermore, I would like to thank to Prof. Helms for enhancing my experience by intro- ducing master students and working as their advisor for successfully accomplishing their master projects. -
Milger Et Al. Pulmonary CCR2+CD4+ T Cells Are Immune Regulatory And
Milger et al. Pulmonary CCR2+CD4+ T cells are immune regulatory and attenuate lung fibrosis development Supplemental Table S1 List of significantly regulated mRNAs between CCR2+ and CCR2- CD4+ Tcells on Affymetrix Mouse Gene ST 1.0 array. Genewise testing for differential expression by limma t-test and Benjamini-Hochberg multiple testing correction (FDR < 10%). Ratio, significant FDR<10% Probeset Gene symbol or ID Gene Title Entrez rawp BH (1680) 10590631 Ccr2 chemokine (C-C motif) receptor 2 12772 3.27E-09 1.33E-05 9.72 10547590 Klrg1 killer cell lectin-like receptor subfamily G, member 1 50928 1.17E-07 1.23E-04 6.57 10450154 H2-Aa histocompatibility 2, class II antigen A, alpha 14960 2.83E-07 1.71E-04 6.31 10590628 Ccr3 chemokine (C-C motif) receptor 3 12771 1.46E-07 1.30E-04 5.93 10519983 Fgl2 fibrinogen-like protein 2 14190 9.18E-08 1.09E-04 5.49 10349603 Il10 interleukin 10 16153 7.67E-06 1.29E-03 5.28 10590635 Ccr5 chemokine (C-C motif) receptor 5 /// chemokine (C-C motif) receptor 2 12774 5.64E-08 7.64E-05 5.02 10598013 Ccr5 chemokine (C-C motif) receptor 5 /// chemokine (C-C motif) receptor 2 12774 5.64E-08 7.64E-05 5.02 10475517 AA467197 expressed sequence AA467197 /// microRNA 147 433470 7.32E-04 2.68E-02 4.96 10503098 Lyn Yamaguchi sarcoma viral (v-yes-1) oncogene homolog 17096 3.98E-08 6.65E-05 4.89 10345791 Il1rl1 interleukin 1 receptor-like 1 17082 6.25E-08 8.08E-05 4.78 10580077 Rln3 relaxin 3 212108 7.77E-04 2.81E-02 4.77 10523156 Cxcl2 chemokine (C-X-C motif) ligand 2 20310 6.00E-04 2.35E-02 4.55 10456005 Cd74 CD74 antigen -
Genetic Testing for Developmental Disabilities, Intellectual Disability, and Autism Spectrum Disorder Technical Brief Number 23
Technical Brief Number 23 Genetic Testing for Developmental Disabilities, Intellectual Disability, and Autism Spectrum Disorder Technical Brief Number 23 Genetic Testing for Developmental Disabilities, Intellectual Disability, and Autism Spectrum Disorder Prepared for: Agency for Healthcare Research and Quality U.S. Department of Health and Human Services 540 Gaither Road Rockville, MD 20850 www.ahrq.gov Contract No. 290-2012-00011-I Prepared by: ECRI Institute–Penn Medicine Evidence-based Practice Center Plymouth Meeting, PA Investigators: Fang Sun, M.D., Ph.D. Jeff Oristaglio, Ph.D. Susan E. Levy, M.D., M.P.H. Hakon Hakonarson, M.D., Ph.D. Nancy Sullivan, B.A. Joann Fontanarosa, Ph.D. Karen M. Schoelles, M.D., M.S., FACP AHRQ Publication No. 15-EHC024-EF June 2015 This report is based on research conducted by the ECRI–Penn Medicine AHRQ Evidence-based Practice Center (EPC) under contract to the Agency for Healthcare Research and Quality (AHRQ), Rockville, MD (290-2012-00011-I). The findings and conclusions in this document are those of the authors, who are responsible for its contents; the findings and conclusions do not necessarily represent the views of AHRQ. Therefore, no statement in this report should be construed as an official position of AHRQ or of the U.S. Department of Health and Human Services. The information in this report is intended to help health care decisionmakers—patients and clinicians, health system leaders, and policymakers, among others—make well-informed decisions and thereby improve the quality of health care services. This report is not intended to be a substitute for the application of clinical judgment. -
Genetic Disruption of WASHC4 Drives Endo-Lysosomal Dysfunction
RESEARCH ARTICLE Genetic disruption of WASHC4 drives endo-lysosomal dysfunction and cognitive-movement impairments in mice and humans Jamie L Courtland1†, Tyler WA Bradshaw1†, Greg Waitt2, Erik J Soderblom2,3, Tricia Ho2, Anna Rajab4, Ricardo Vancini5, Il Hwan Kim3,6*, Scott H Soderling1,3* 1Department of Neurobiology, Duke University School of Medicine, Durham, United States; 2Proteomics and Metabolomics Shared Resource, Duke University School of Medicine, Durham, United States; 3Department of Cell Biology, Duke University School of Medicine, Durham, United States; 4Burjeel Hospital, VPS Healthcare, Muscat, Oman; 5Department of Pathology, Duke University School of Medicine, Durham, United States; 6Department of Anatomy and Neurobiology, University of Tennessee Heath Science Center, Memphis, United States Abstract Mutation of the Wiskott–Aldrich syndrome protein and SCAR homology (WASH) complex subunit, SWIP, is implicated in human intellectual disability, but the cellular etiology of this association is unknown. We identify the neuronal WASH complex proteome, revealing a network of endosomal proteins. To uncover how dysfunction of endosomal SWIP leads to disease, we c.3056C>G generate a mouse model of the human WASHC4 mutation. Quantitative spatial proteomics analysis of SWIPP1019R mouse brain reveals that this mutation destabilizes the WASH complex and *For correspondence: uncovers significant perturbations in both endosomal and lysosomal pathways. Cellular and [email protected] (IHK); histological analyses confirm that SWIPP1019R results in endo-lysosomal disruption and uncover [email protected] (SHS) indicators of neurodegeneration. We find that SWIPP1019R not only impacts cognition, but also P1019R †These authors contributed causes significant progressive motor deficits in mice. A retrospective analysis of SWIP equally to this work patients reveals similar movement deficits in humans.