Mouse Slc12a9 Knockout Project (CRISPR/Cas9)
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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. -
9-Azido Analogs of Three Sialic Acid Forms for Metabolic Remodeling Of
Supporting Information 9-Azido Analogs of Three Sialic Acid Forms for Metabolic Remodeling of Cell-Surface Sialoglycans Bo Cheng,†,‡ Lu Dong,†,§ Yuntao Zhu,†,‡ Rongbing Huang,†,‡ Yuting Sun,†,‖ Qiancheng You,†,‡ Qitao Song,†,§ James C. Paton, ∇ Adrienne W. Paton,∇ and Xing Chen*,†,‡,§,⊥,# †College of Chemistry and Molecular Engineering, ‡Beijing National Laboratory for Molecular Sciences, §Peking−Tsinghua Center for Life Sciences,‖Academy for Advanced Interdisciplinary Studies, ⊥Synthetic and Functional Biomolecules Center, and #Key Laboratory of Bioorganic Chemistry and Molecular Engineering of Ministry of Education, Peking University, Beijing 100871, China ∇Research Centre for Infectious Diseases, Department of Molecular and Biomedical Science, University of Adelaide, Adelaide SA 5005, Australia Page S1 Table of Contents: Scheme S1.……………………………………………………….........……………. S3 Figure S1……………………………………………………..………..……………. S3 Figure S2……………………………………………………..………..…………… S4 Figure S3……………………………………………………..………..…………… S4 Figure S4……………………………………………………..………..…………… S5 Figure S5……………………………………………………..………..…………… S6 Figure S6……………………………………………………..………..…………….S7 Figure S7……………………………………………………..………..…………….S8 Figure S8……………………………………………………..………..…………….S9 Experimental Procedures……………………………….…........…………....S10-S27 Table S1………………………………………………..………..…………….S28-S48 Supporting Reference……………………………………………….......………...S49 Page S2 Scheme S1. Synthesis of 9AzNeu5Gc Figure S1: a, b, c, d) Representative scatter plots (FSC vs. SSC) and histograms of flow cytometry analysis -
Supplementary Material
BMJ Publishing Group Limited (BMJ) disclaims all liability and responsibility arising from any reliance Supplemental material placed on this supplemental material which has been supplied by the author(s) J Neurol Neurosurg Psychiatry Page 1 / 45 SUPPLEMENTARY MATERIAL Appendix A1: Neuropsychological protocol. Appendix A2: Description of the four cases at the transitional stage. Table A1: Clinical status and center proportion in each batch. Table A2: Complete output from EdgeR. Table A3: List of the putative target genes. Table A4: Complete output from DIANA-miRPath v.3. Table A5: Comparison of studies investigating miRNAs from brain samples. Figure A1: Stratified nested cross-validation. Figure A2: Expression heatmap of miRNA signature. Figure A3: Bootstrapped ROC AUC scores. Figure A4: ROC AUC scores with 100 different fold splits. Figure A5: Presymptomatic subjects probability scores. Figure A6: Heatmap of the level of enrichment in KEGG pathways. Kmetzsch V, et al. J Neurol Neurosurg Psychiatry 2021; 92:485–493. doi: 10.1136/jnnp-2020-324647 BMJ Publishing Group Limited (BMJ) disclaims all liability and responsibility arising from any reliance Supplemental material placed on this supplemental material which has been supplied by the author(s) J Neurol Neurosurg Psychiatry Appendix A1. Neuropsychological protocol The PREV-DEMALS cognitive evaluation included standardized neuropsychological tests to investigate all cognitive domains, and in particular frontal lobe functions. The scores were provided previously (Bertrand et al., 2018). Briefly, global cognitive efficiency was evaluated by means of Mini-Mental State Examination (MMSE) and Mattis Dementia Rating Scale (MDRS). Frontal executive functions were assessed with Frontal Assessment Battery (FAB), forward and backward digit spans, Trail Making Test part A and B (TMT-A and TMT-B), Wisconsin Card Sorting Test (WCST), and Symbol-Digit Modalities test. -
Characterization of the Ion Transporter NKCC1 in the Field of Chemosensation
Characterization of the Ion Transporter NKCC1 in the Field of Chemosensation Dissertation to obtain the degree Doctor Rerum Naturalium (Dr.rer.nat.) at the Faculty of Biology and Biotechnology Ruhr-University Bochum International Graduate School of Biosciences Ruhr-University Bochum (Department of Cellphysiology) submitted by Claudia Haering from Dortmund, Germany Bochum (April, 2015) First Referee: Prof. Dr. Dr. Dr. Hatt Second Referee: Prof. Dr. Wiese Charakterisierung des Ionentransporters NKCC1 in der Chemosensorik Dissertation zur Erlangung des Grades eines Doktors der Naturwissenschaften der Fakultät Biologie und Biotechnologie an der Internationalen Graduiertenschule Biowissenschaften der Ruhr-Universität Bochum angefertigt im Lehrstuhl für Zellphysiologie vorgelegt von Claudia Haering aus Dortmund, Deutschland Bochum (April, 2015) Referent: Prof. Dr. Dr. Dr. Hatt Korreferent: Prof. Dr. Wiese ERKLÄRUNG Hiermit erkläre ich, dass ich die Arbeit selbständig verfasst und bei keiner anderen Fakultät eingereicht und dass ich keine anderen als die angegebenen Hilfsmittel verwendet habe. Es handelt sich bei der heute von mir eingereichten Dissertation um sechs in Wort und Bild völlig übereinstimmende Exemplare. Weiterhin erkläre ich, dass digitale Abbildungen nur die originalen Daten enthalten und in keinem Fall inhaltsverändernde Bildbearbeitung vorgenommen wurde. Bochum, den (Claudia Haering) Table of contents 1. Introduction __________________________________________________________ 1 1.1 General introduction - Olfaction_________________________________________ -
Epistasis-Driven Identification of SLC25A51 As a Regulator of Human
ARTICLE https://doi.org/10.1038/s41467-020-19871-x OPEN Epistasis-driven identification of SLC25A51 as a regulator of human mitochondrial NAD import Enrico Girardi 1, Gennaro Agrimi 2, Ulrich Goldmann 1, Giuseppe Fiume1, Sabrina Lindinger1, Vitaly Sedlyarov1, Ismet Srndic1, Bettina Gürtl1, Benedikt Agerer 1, Felix Kartnig1, Pasquale Scarcia 2, Maria Antonietta Di Noia2, Eva Liñeiro1, Manuele Rebsamen1, Tabea Wiedmer 1, Andreas Bergthaler1, ✉ Luigi Palmieri2,3 & Giulio Superti-Furga 1,4 1234567890():,; About a thousand genes in the human genome encode for membrane transporters. Among these, several solute carrier proteins (SLCs), representing the largest group of transporters, are still orphan and lack functional characterization. We reasoned that assessing genetic interactions among SLCs may be an efficient way to obtain functional information allowing their deorphanization. Here we describe a network of strong genetic interactions indicating a contribution to mitochondrial respiration and redox metabolism for SLC25A51/MCART1, an uncharacterized member of the SLC25 family of transporters. Through a combination of metabolomics, genomics and genetics approaches, we demonstrate a role for SLC25A51 as enabler of mitochondrial import of NAD, showcasing the potential of genetic interaction- driven functional gene deorphanization. 1 CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria. 2 Laboratory of Biochemistry and Molecular Biology, Department of Biosciences, Biotechnologies and Biopharmaceutics, -
Integrative Analysis of Disease Signatures Shows Inflammation Disrupts Juvenile Experience-Dependent Cortical Plasticity
New Research Development Integrative Analysis of Disease Signatures Shows Inflammation Disrupts Juvenile Experience- Dependent Cortical Plasticity Milo R. Smith1,2,3,4,5,6,7,8, Poromendro Burman1,3,4,5,8, Masato Sadahiro1,3,4,5,6,8, Brian A. Kidd,2,7 Joel T. Dudley,2,7 and Hirofumi Morishita1,3,4,5,8 DOI:http://dx.doi.org/10.1523/ENEURO.0240-16.2016 1Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, New York 10029, 2Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York 10029, 3Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, New York 10029, 4Department of Ophthalmology, Icahn School of Medicine at Mount Sinai, New York, New York 10029, 5Mindich Child Health and Development Institute, Icahn School of Medicine at Mount Sinai, New York, New York 10029, 6Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai, New York, New York 10029, 7Icahn Institute for Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai, New York, New York 10029, and 8Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, New York 10029 Visual Abstract Throughout childhood and adolescence, periods of heightened neuroplasticity are critical for the development of healthy brain function and behavior. Given the high prevalence of neurodevelopmental disorders, such as autism, identifying disruptors of developmental plasticity represents an essential step for developing strategies for prevention and intervention. Applying a novel computational approach that systematically assessed connections between 436 transcriptional signatures of disease and multiple signatures of neuroplasticity, we identified inflammation as a common pathological process central to a diverse set of diseases predicted to dysregulate Significance Statement During childhood and adolescence, heightened neuroplasticity allows the brain to reorganize and adapt to its environment. -
Chloride Homeostasis in Neurons with Special Emphasis on the Olivocerebellar System: Differential Roles for Transporters and Channels
View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by Erasmus University Digital Repository REVIEW published: 01 May 2018 doi: 10.3389/fncel.2018.00101 Chloride Homeostasis in Neurons With Special Emphasis on the Olivocerebellar System: Differential Roles for Transporters and Channels Negah Rahmati 1*†, Freek E. Hoebeek 1,2, Saša Peter 1 and Chris I. De Zeeuw 1,3 1 Department of Neuroscience, Erasmus Medical Center, Rotterdam, Netherlands, 2 NIDOD Institute, Wilhelmina Children’s Hospital, University Medical Center Utrecht and Brain Center Rudolf Magnus, Utrecht, Netherlands, 3 Netherlands Institute for Neuroscience, Royal Dutch Academy for Arts and Sciences, Amsterdam, Netherlands The intraneuronal ionic composition is an important determinant of brain functioning. There is growing evidence that aberrant homeostasis of the intracellular concentration of − − + 2+ Cl ([Cl ]i) evokes, in addition to that of Na and Ca , robust impairments of neuronal excitability and neurotransmission and thereby neurological conditions. More specifically, − Edited by: understanding the mechanisms underlying regulation of [Cl ]i is crucial for deciphering Jonathan Mapelli, the variability in GABAergic and glycinergic signaling of neurons, in both health and University of Modena and Reggio − Emilia, Italy disease. The homeostatic level of [Cl ]i is determined by various regulatory mechanisms, − Reviewed by: including those mediated by plasma membrane Cl channels and transporters. This Mauricio Di Fulvio, review focuses -
RNA-Seq Reveals Conservation of Function Among the Yolk Sacs Of
RNA-seq reveals conservation of function among the PNAS PLUS yolk sacs of human, mouse, and chicken Tereza Cindrova-Daviesa, Eric Jauniauxb, Michael G. Elliota,c, Sungsam Gongd,e, Graham J. Burtona,1, and D. Stephen Charnock-Jonesa,d,e,1,2 aCentre for Trophoblast Research, Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, CB2 3EG, United Kingdom; bElizabeth Garret Anderson Institute for Women’s Health, Faculty of Population Health Sciences, University College London, London, WC1E 6BT, United Kingdom; cSt. John’s College, University of Cambridge, Cambridge, CB2 1TP, United Kingdom; dDepartment of Obstetrics and Gynaecology, University of Cambridge, Cambridge, CB2 0SW, United Kingdom; and eNational Institute for Health Research, Cambridge Comprehensive Biomedical Research Centre, Cambridge, CB2 0QQ, United Kingdom Edited by R. Michael Roberts, University of Missouri-Columbia, Columbia, MO, and approved May 5, 2017 (received for review February 14, 2017) The yolk sac is phylogenetically the oldest of the extraembryonic yolk sac plays a critical role during organogenesis (3–5, 8–10), membranes. The human embryo retains a yolk sac, which goes there are limited data to support this claim. Obtaining experi- through primary and secondary phases of development, but its mental data for the human is impossible for ethical reasons, and importance is controversial. Although it is known to synthesize thus we adopted an alternative strategy. Here, we report RNA proteins, its transport functions are widely considered vestigial. sequencing (RNA-seq) data derived from human and murine yolk Here, we report RNA-sequencing (RNA-seq) data for the human sacs and compare them with published data from the yolk sac of and murine yolk sacs and compare those data with data for the the chicken. -
Program in Human Neutrophils Fails To
Downloaded from http://www.jimmunol.org/ by guest on September 25, 2021 is online at: average * The Journal of Immunology Anaplasma phagocytophilum , 20 of which you can access for free at: 2005; 174:6364-6372; ; from submission to initial decision 4 weeks from acceptance to publication J Immunol doi: 10.4049/jimmunol.174.10.6364 http://www.jimmunol.org/content/174/10/6364 Insights into Pathogen Immune Evasion Mechanisms: Fails to Induce an Apoptosis Differentiation Program in Human Neutrophils Dori L. Borjesson, Scott D. Kobayashi, Adeline R. Whitney, Jovanka M. Voyich, Cynthia M. Argue and Frank R. DeLeo cites 28 articles Submit online. Every submission reviewed by practicing scientists ? is published twice each month by Receive free email-alerts when new articles cite this article. Sign up at: http://jimmunol.org/alerts http://jimmunol.org/subscription Submit copyright permission requests at: http://www.aai.org/About/Publications/JI/copyright.html http://www.jimmunol.org/content/suppl/2005/05/03/174.10.6364.DC1 This article http://www.jimmunol.org/content/174/10/6364.full#ref-list-1 Information about subscribing to The JI No Triage! Fast Publication! Rapid Reviews! 30 days* • Why • • Material References Permissions Email Alerts Subscription Supplementary The Journal of Immunology The American Association of Immunologists, Inc., 1451 Rockville Pike, Suite 650, Rockville, MD 20852 Copyright © 2005 by The American Association of Immunologists All rights reserved. Print ISSN: 0022-1767 Online ISSN: 1550-6606. This information is current as of September 25, 2021. The Journal of Immunology Insights into Pathogen Immune Evasion Mechanisms: Anaplasma phagocytophilum Fails to Induce an Apoptosis Differentiation Program in Human Neutrophils1 Dori L. -
Wo 2008/156655 A9
(12) INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT) CORRECTED VERSION (19) World Intellectual Property Organization International Bureau (43) International Publication Date (10) International Publication Number 24 December 2008 (24.12.2008) PCT WO 2008/156655 A9 (51) International Patent Classification: (81) Designated States (unless otherwise indicated, for every C07K 14/00 (2006.01) kind of national protection available): AE, AG, AL, AM, AO, AT,AU, AZ, BA, BB, BG, BH, BR, BW, BY, BZ, CA, (21) International Application Number: CH, CN, CO, CR, CU, CZ, DE, DK, DM, DO, DZ, EC, EE, PCT/US2008/007377 EG, ES, FI, GB, GD, GE, GH, GM, GT, HN, HR, HU, ID, IL, IN, IS, JP, KE, KG, KM, KN, KP, KR, KZ, LA, LC, (22) International Filing Date: 13 June 2008 (13.06.2008) LK, LR, LS, LT, LU, LY, MA, MD, ME, MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, OM, PG, PH, (25) Filing Language: English PL, PT, RO, RS, RU, SC, SD, SE, SG, SK, SL, SM, SV, SY, TJ, TM, TN, TR, TT, TZ, UA, UG, US, UZ, VC, VN, (26) Publication Language: English ZA, ZM, ZW (30) Priority Data: (84) Designated States (unless otherwise indicated, for every kind of regional protection available): ARIPO (BW, GH, 60/934,768 15 June 2007 (15.06.2007) US GM, KE, LS, MW, MZ, NA, SD, SL, SZ, TZ, UG, ZM, ZW), Eurasian (AM, AZ, BY, KG, KZ, MD, RU, TJ, TM), (71) Applicants (for all designated States except US): European (AT,BE, BG, CH, CY, CZ, DE, DK, EE, ES, FI, GENELUX CORPORATION [US/US]; 3030 Bunker FR, GB, GR, HR, HU, IE, IS, IT, LT,LU, LV,MC, MT, NL, Hill Street, Suite 310, San Diego, CA 92109 (US). -
Supplemental Figures 04 12 2017
Jung et al. 1 SUPPLEMENTAL FIGURES 2 3 Supplemental Figure 1. Clinical relevance of natural product methyltransferases (NPMTs) in brain disorders. (A) 4 Table summarizing characteristics of 11 NPMTs using data derived from the TCGA GBM and Rembrandt datasets for 5 relative expression levels and survival. In addition, published studies of the 11 NPMTs are summarized. (B) The 1 Jung et al. 6 expression levels of 10 NPMTs in glioblastoma versus non‐tumor brain are displayed in a heatmap, ranked by 7 significance and expression levels. *, p<0.05; **, p<0.01; ***, p<0.001. 8 2 Jung et al. 9 10 Supplemental Figure 2. Anatomical distribution of methyltransferase and metabolic signatures within 11 glioblastomas. The Ivy GAP dataset was downloaded and interrogated by histological structure for NNMT, NAMPT, 12 DNMT mRNA expression and selected gene expression signatures. The results are displayed on a heatmap. The 13 sample size of each histological region as indicated on the figure. 14 3 Jung et al. 15 16 Supplemental Figure 3. Altered expression of nicotinamide and nicotinate metabolism‐related enzymes in 17 glioblastoma. (A) Heatmap (fold change of expression) of whole 25 enzymes in the KEGG nicotinate and 18 nicotinamide metabolism gene set were analyzed in indicated glioblastoma expression datasets with Oncomine. 4 Jung et al. 19 Color bar intensity indicates percentile of fold change in glioblastoma relative to normal brain. (B) Nicotinamide and 20 nicotinate and methionine salvage pathways are displayed with the relative expression levels in glioblastoma 21 specimens in the TCGA GBM dataset indicated. 22 5 Jung et al. 23 24 Supplementary Figure 4. -
Conserved Genes from Simon's Simplex Collection in Drosoph Human Gene HGNC Flybaseid Fly Gene A2M 7 Fbgn00
Supplemental Table 1: Conserved genes from Simon's Simplex Collection in Drosophila melanogaster Human Gene HGNC FlyBaseID Fly Gene A2M 7 FBgn0041181 Tep3 A2ML1 23336 FBgn0041180 Tep4 AASS 17366 FBgn0286198 LKRSDH ABCA1 29 FBgn0083956 CG34120 ABCA13 14638 FBgn0083956 CG34120 ABCA2 32 FBgn0031171 CG1801 ABCA7 37 FBgn0083956 CG34120 ABCA8 38 FBgn0034493 CG8908 ABCB6 47 FBgn0038376 Hmt-1 ABCC4 55 FBgn0038740 CG4562 ABCC5 56 FBgn0039644 rdog ABCG1 73 FBgn0020762 Atet ABCG2 74 FBgn0003996 w ABHD12 15868 FBgn0034419 CG15111 ABI2 24011 FBgn0020510 Abi ABL1 76 FBgn0000017 Abl ABL2 77 FBgn0000017 Abl ABR 81 FBgn0025836 RhoGAP1A ACACB 85 FBgn0033246 ACC ACE 2707 FBgn0012037 Ance ACHE 108 FBgn0000024 Ace ACP2 123 FBgn0000032 Acph-1 ACTN4 166 FBgn0000667 Actn ACTR6 24025 FBgn0011741 Arp6 ACTRT3 24022 FBgn0000045 Act79B ADAM18 196 FBgn0259110 mmd ADAMTS7 223 FBgn0029791 CG4096 ADAMTSL1 14632 FBgn0051619 nolo ADAMTSL4 19706 FBgn0032252 loh ADCY5 236 FBgn0263131 CG43373 ADD3 245 FBgn0263391 hts ADRBK2 290 FBgn0260798 Gprk1 AEBP2 24051 FBgn0086655 jing AGAP1 16922 FBgn0028509 CenG1A AGAP2 16921 FBgn0028509 CenG1A AGK 21869 FBgn0260750 Mulk AGO1 3262 FBgn0262739 AGO1 AGTRAP 13539 FBgn0052638 CG32638 AK1 361 FBgn0022709 Adk1 AKAP1 367 FBgn0263987 spoon AKAP9 379 FBgn0086690 Plp AKR1B15 37281 FBgn0086254 CG6084 AKR1C2 385 FBgn0086254 CG6084 AKR1D1 388 FBgn0086254 CG6084 AKT2 392 FBgn0010379 Akt1 ALDH18A1 9722 FBgn0037146 CG7470 ALDH1L1 3978 FBgn0032945 CG8665 ALDH3A1 405 FBgn0010548 Aldh-III ALDH5A1 408 FBgn0039349 Ssadh ALS2 443 FBgn0037116 Als2 AMPD2 469