Systematic Genetic Analysis of the MHC Region Reveals Mechanistic
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Decreased Plasma Concentrations of Apolipoprotein M in Sepsis And
Kumaraswamy et al. Critical Care 2012, 16:R60 http://ccforum.com/content/16/2/R60 RESEARCH Open Access Decreased plasma concentrations of apolipoprotein M in sepsis and systemic inflammatory response syndromes Sunil B Kumaraswamy1, Adam Linder2, Per Åkesson2 and Björn Dahlbäck1* Abstract Introduction: Apolipoprotein M (apoM) is present in 5% of high-density lipoprotein (HDL) particles in plasma. It is a carrier of sphingosine-1-phosphate (S1P), which is important for vascular barrier protection. The aim was to determine the plasma concentrations of apoM during sepsis and systemic inflammatory response syndrome (SIRS) and correlate them to levels of apolipoprotein A-I (apoA1), apolipoprotein B (apoB), HDL-, and low-density lipoprotein (LDL)-cholesterol. Methods: Plasma samples from patients with (1), severe sepsis with shock (n = 26); (2), severe sepsis without shock (n = 44); (3), sepsis (n = 100); (4), infections without SIRS (n = 43); and (5) SIRS without infection (n = 20) were analyzed. The concentrations of apoM, apoA1, and apoB were measured with enzyme-linked immunosorbent assays (ELISAs). Total, HDL-, and LDL-cholesterol concentrations were measured with a commercial HDL/LDL cholesterol test. Results: ApoM concentrations correlated negatively to acute-phase markers. Thus, apoM behaved as a negative acute-phase protein. Decreased values were observed in all patient groups (P < 0.0001), with the most drastic decreases observed in the severely sick patients. ApoM levels correlated strongly to those of apoA1, apoB, HDL, and LDL cholesterol. The HDL and LDL cholesterol levels were low in all patient groups, as compared with controls (P < 0.0001), in particular, HDL cholesterol. ApoA1 and apoB concentrations were low only in the more severely affected patients. -
Genetic Inhibition of the Ubiquitin Ligase Rnf5 Attenuates Phenotypes
www.nature.com/scientificreports OPEN Genetic Inhibition Of The Ubiquitin Ligase Rnf5 Attenuates Phenotypes Associated To F508del Received: 02 February 2015 Accepted: 17 June 2015 Cystic Fibrosis Mutation Published: 17 July 2015 Valeria Tomati1, Elvira Sondo1, Andrea Armirotti2, Emanuela Caci1, Emanuela Pesce1, Monica Marini1, Ambra Gianotti1, Young Ju Jeon3, Michele Cilli4, Angela Pistorio1, Luca Mastracci4,5, Roberto Ravazzolo1,6, Bob Scholte7, Ze’ev Ronai3, Luis J. V. Galietta1 & Nicoletta Pedemonte1 Cystic fibrosis (CF) is caused by mutations in the CFTR chloride channel. Deletion of phenylalanine 508 (F508del), the most frequent CF mutation, impairs CFTR trafficking and gating. F508del- CFTR mistrafficking may be corrected by acting directly on mutant CFTR itself or by modulating expression/activity of CFTR-interacting proteins, that may thus represent potential drug targets. To evaluate possible candidates for F508del-CFTR rescue, we screened a siRNA library targeting known CFTR interactors. Our analysis identified RNF5 as a protein whose inhibition promoted significant F508del-CFTR rescue and displayed an additive effect with the investigational drug VX-809. Significantly, RNF5 loss in F508del-CFTR transgenic animals ameliorated intestinal malabsorption and concomitantly led to an increase in CFTR activity in intestinal epithelial cells. In addition, we found that RNF5 is differentially expressed in human bronchial epithelia from CF vs. control patients. Our results identify RNF5 as a target for therapeutic modalities to antagonize mutant CFTR proteins. Cystic Fibrosis (CF), one of the most common inherited diseases (~1/3000 in Caucasian populations), is caused by mutations in the gene encoding the CF transmembrane conductance regulator (CFTR), a cAMP-regulated chloride channel expressed at the apical membrane of many types of epithelial cells1,2. -
RNF5 Antibody
RNF5 Antibody CATALOG NUMBER: 27-144 Antibody used in WB on Human HeLa at 0.2-1 ug/ml. Specifications APPLICATIONS: RNF5 antibody can be used for detection of RNF5 by ELISA at 1:12500. RNF5 antibody can be used for detection of RNF5 by western blot at 1 ug/mL, and HRP conjugated secondary antibody should be diluted 1:50,000 - 100,000. USER NOTE: Optimal dilutions for each application to be determined by the researcher. POSITIVE CONTROL: 1) Cat. No. 1201 - HeLa Cell Lysate PREDICTED MOLECULAR 20 kDa WEIGHT: IMMUNOGEN: Antibody produced in rabbits immunized with a synthetic peptide corresponding a region of human RNF5. HOST SPECIES: Rabbit Properties PURIFICATION: Antibody is purified by peptide affinity chromatography method. PHYSICAL STATE: Lyophilized BUFFER: Antibody is lyophilized in PBS buffer with 2% sucrose. Add 50 uL of distilled water. Final antibody concentration is 1 mg/mL. CONCENTRATION: 1 mg/ml STORAGE CONDITIONS: For short periods of storage (days) store at 4˚C. For longer periods of storage, store RNF5 antibody at -20˚C. As with any antibody avoid repeat freeze-thaw cycles. CLONALITY: Polyclonal CONJUGATE: Unconjugated Additional Info ALTERNATE NAMES: RNF5, RING5, RMA1 ACCESSION NO.: NP_008844 PROTEIN GI NO.: 5902054 OFFICIAL SYMBOL: RNF5 GENE ID: 6048 Background BACKGROUND: RNF5 contains a RING finger, which is a motif known to be involved in protein-protein interactions. This protein is a membrane-bound ubiquitin ligase. It can regulate cell motility by targeting paxillin ubiquitination and altering the distribution and localization of paxillin in cytoplasm and cell focal adhesions.The protein encoded by this gene contains a RING finger, which is a motif known to be involved in protein-protein interactions. -
1 Supporting Information for a Microrna Network Regulates
Supporting Information for A microRNA Network Regulates Expression and Biosynthesis of CFTR and CFTR-ΔF508 Shyam Ramachandrana,b, Philip H. Karpc, Peng Jiangc, Lynda S. Ostedgaardc, Amy E. Walza, John T. Fishere, Shaf Keshavjeeh, Kim A. Lennoxi, Ashley M. Jacobii, Scott D. Rosei, Mark A. Behlkei, Michael J. Welshb,c,d,g, Yi Xingb,c,f, Paul B. McCray Jr.a,b,c Author Affiliations: Department of Pediatricsa, Interdisciplinary Program in Geneticsb, Departments of Internal Medicinec, Molecular Physiology and Biophysicsd, Anatomy and Cell Biologye, Biomedical Engineeringf, Howard Hughes Medical Instituteg, Carver College of Medicine, University of Iowa, Iowa City, IA-52242 Division of Thoracic Surgeryh, Toronto General Hospital, University Health Network, University of Toronto, Toronto, Canada-M5G 2C4 Integrated DNA Technologiesi, Coralville, IA-52241 To whom correspondence should be addressed: Email: [email protected] (M.J.W.); yi- [email protected] (Y.X.); Email: [email protected] (P.B.M.) This PDF file includes: Materials and Methods References Fig. S1. miR-138 regulates SIN3A in a dose-dependent and site-specific manner. Fig. S2. miR-138 regulates endogenous SIN3A protein expression. Fig. S3. miR-138 regulates endogenous CFTR protein expression in Calu-3 cells. Fig. S4. miR-138 regulates endogenous CFTR protein expression in primary human airway epithelia. Fig. S5. miR-138 regulates CFTR expression in HeLa cells. Fig. S6. miR-138 regulates CFTR expression in HEK293T cells. Fig. S7. HeLa cells exhibit CFTR channel activity. Fig. S8. miR-138 improves CFTR processing. Fig. S9. miR-138 improves CFTR-ΔF508 processing. Fig. S10. SIN3A inhibition yields partial rescue of Cl- transport in CF epithelia. -
Download Thesis
This electronic thesis or dissertation has been downloaded from the King’s Research Portal at https://kclpure.kcl.ac.uk/portal/ The Genetics and Spread of Amyotrophic Lateral Sclerosis Jones, Ashley Richard Awarding institution: King's College London The copyright of this thesis rests with the author and no quotation from it or information derived from it may be published without proper acknowledgement. END USER LICENCE AGREEMENT Unless another licence is stated on the immediately following page this work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International licence. https://creativecommons.org/licenses/by-nc-nd/4.0/ You are free to copy, distribute and transmit the work Under the following conditions: Attribution: You must attribute the work in the manner specified by the author (but not in any way that suggests that they endorse you or your use of the work). Non Commercial: You may not use this work for commercial purposes. No Derivative Works - You may not alter, transform, or build upon this work. Any of these conditions can be waived if you receive permission from the author. Your fair dealings and other rights are in no way affected by the above. Take down policy If you believe that this document breaches copyright please contact [email protected] providing details, and we will remove access to the work immediately and investigate your claim. Download date: 07. Oct. 2021 THE GENETICS AND SPREAD OF AMYOTROPHIC LATERAL SCLEROSIS Ashley Richard Jones PhD in Clinical Neuroscience - 1 - Abstract Our knowledge of the genetic contribution to Amyotrophic Lateral Sclerosis (ALS) is rapidly growing, and there is increasing research into how ALS spreads through the motor system and beyond. -
Role of Genomic Variants in the Response to Biologics Targeting Common Autoimmune Disorders
Role of genomic variants in the response to biologics targeting common autoimmune disorders by Gordana Lenert, PhD The thesis submitted to the Faculty of Graduate and Postdoctoral Affairs in partial fulfillment of the requirements for the degree of Master of Science Ottawa-Carleton Joint Program in Bioinformatics Carleton University Ottawa, Canada © 2016 Gordana Lenert Abstract Autoimmune diseases (AID) are common chronic inflammatory conditions initiated by the loss of the immunological tolerance to self-antigens. Chronic immune response and uncontrolled inflammation provoke diverse clinical manifestations, causing impairment of various tissues, organs or organ systems. To avoid disability and death, AID must be managed in clinical practice over long periods with complex and closely controlled medication regimens. The anti-tumor necrosis factor biologics (aTNFs) are targeted therapeutic drugs used for AID management. However, in spite of being very successful therapeutics, aTNFs are not able to induce remission in one third of AID phenotypes. In our research, we investigated genomic variability of AID phenotypes in order to explain unpredictable lack of response to aTNFs. Our hypothesis is that key genetic factors, responsible for the aTNFs unresponsiveness, are positioned at the crossroads between aTNF therapeutic processes that generate remission and pathogenic or disease processes that lead to AID phenotypes expression. In order to find these key genetic factors at the intersection of the curative and the disease pathways, we combined genomic variation data collected from publicly available curated AID genome wide association studies (AID GWAS) for each disease. Using collected data, we performed prioritization of genes and other genomic structures, defined the key disease pathways and networks, and related the results with the known data by the bioinformatics approaches. -
1 Characterizing the Emergence of Liver and Gallbladder
bioRxiv preprint doi: https://doi.org/10.1101/718775; this version posted July 30, 2019. 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. Page 1 Characterizing the Emergence of Liver and Gallbladder from the Embryonic Endoderm through Single-Cell RNA-Seq Tianhao Mu1,2,3,4§, Liqin Xu5,6,7§, Yu Zhong5,6,8§, Xinyu Liu4,9§, Zhikun Zhao5,6, Chaoben Huang3, Xiaofeng Lan3, Chengchen Lufei4,9, Yi Zhou4,9, Yixun Su1,3, Luang Xu9, Miaomiao Jiang5,6, Hongpo Zhou5,6, Xinxin Lin5,6, Liang Wu5,6, Siqi Peng5,6, Shiping Liu5,6, Susanne Brix7, Michael Dean10, Norris R. Dunn11, Kenneth S. Zaret12, Xin-Yuan Fu1,2,3,4,9,13*& Yong Hou5,6* 1 Department of Biochemistry, YLL School of Medicine, National University of Singapore, Singapore 119615, Singapore. 2 Laboratory of Human Diseases and Immunotherapies, West China Hospital, Sichuan University, Chengdu 610041, China. 3 Department of Biology, Southern University of Science and Technology, Shenzhen 518055, China. 4 GenEros Biopharma, Hangzhou 310018, China. 5 BGI-Shenzhen, Shenzhen 518083, China. 6 China National GeneBank, BGI-Shenzhen, Shenzhen 518120, China. 7 Department of Biotechnology and Biomedicine, Technical University of Denmark, Soltofts Plads, 2800 Kongens Lyngby, Denmark. 8 School of Biology and Biological Engineering, South China University of Technology, Guangzhou 510006, China. 1 bioRxiv preprint doi: https://doi.org/10.1101/718775; this version posted July 30, 2019. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. -
(LCN) Gene Family, Including Evidence the Mouse Mup Cluster Is Result of an “Evolutionary Bloom” Georgia Charkoftaki1, Yewei Wang1, Monica Mcandrews2, Elspeth A
Charkoftaki et al. Human Genomics (2019) 13:11 https://doi.org/10.1186/s40246-019-0191-9 REVIEW Open Access Update on the human and mouse lipocalin (LCN) gene family, including evidence the mouse Mup cluster is result of an “evolutionary bloom” Georgia Charkoftaki1, Yewei Wang1, Monica McAndrews2, Elspeth A. Bruford3, David C. Thompson4, Vasilis Vasiliou1* and Daniel W. Nebert5 Abstract Lipocalins (LCNs) are members of a family of evolutionarily conserved genes present in all kingdoms of life. There are 19 LCN-like genes in the human genome, and 45 Lcn-like genes in the mouse genome, which include 22 major urinary protein (Mup)genes.TheMup genes, plus 29 of 30 Mup-ps pseudogenes, are all located together on chromosome (Chr) 4; evidence points to an “evolutionary bloom” that resulted in this Mup cluster in mouse, syntenic to the human Chr 9q32 locus at which a single MUPP pseudogene is located. LCNs play important roles in physiological processes by binding and transporting small hydrophobic molecules —such as steroid hormones, odorants, retinoids, and lipids—in plasma and other body fluids. LCNs are extensively used in clinical practice as biochemical markers. LCN-like proteins (18–40 kDa) have the characteristic eight β-strands creating a barrel structure that houses the binding-site; LCNs are synthesized in the liver as well as various secretory tissues. In rodents, MUPs are involved in communication of information in urine-derived scent marks, serving as signatures of individual identity, or as kairomones (to elicit fear behavior). MUPs also participate in regulation of glucose and lipid metabolism via a mechanism not well understood. -
Isolation, Tissue Expression, and Chromosomal Assignment of a Novel Human Gene Which Encodes a Protein with RING finger Motif
272J Hum Genet (1998) 43:272–274N. Matsuda et al.: © Jpn EGF Soc receptor Hum Genet and osteoblastic and Springer-Verlag differentiation 1998 SHORT COMMUNICATION Naohiko Seki · Atsushi Hattori · Sumio Sugano Yutaka Suzuki · Akira Nakagawara Miki Ohhira · Masa-aki Muramatsu · Tada-aki Hori Toshiyuki Saito Isolation, tissue expression, and chromosomal assignment of a novel human gene which encodes a protein with RING finger motif Received: June 22, 1998 / Accepted: July 31, 1998 Abstract We identified a novel gene encoding a RING and spacing of their zinc-chelating residues (Schwabe finger (C3HC4-type zinc finger) protein from a human neu- and Klug 1994; Mackay and Crossley 1998). It is estimated roblastoma full-length enriched cDNA library. This cDNA that there are 500 zinc-finger proteins encoded in the clone consists of 1919 nucleotides with an open reading yeast genome and that approximately 1% of all mammalian frame of a 485-amino acid protein. From reverse transcrip- genes encode zinc fingers (Mackay and Crossley 1998). The tion (RT)-polymerase chain reaction (PCR) analysis, the RING finger is a C3HC4-type zinc finger motif, and mem- messenger RNA was ubiquitously expressed in various hu- bers of the RING finger family are mostly nuclear proteins; man adult tissues. The chromosomal location of the gene this motif is involved in both protein-DNA and protein- was determined on the chromosome 6p21.3 region by PCR- protein interactions (Freemont et al. 1991, Saurin et al. based analyses with both a human/rodent mono- 1996). chromosomal hybrid cell panel and a radiation hybrid mapping panel. Key words RING finger · Full-Length enriched cDNA Isolation of cDNA clone for novel RING finger protein library · Chromosome 6p21.3 · RH mapping A cDNA clone for a novel RING finger protein was iso- lated from a full-length enriched cDNA library constructed Introduction from a neuroblastoma (NB) sample, using the oligo-capping method, as described previously (Maruyama and Sugano 1994; Suzuki et al. -
Increased Expression of the E3 Ubiquitin Ligase RNF5 Is Associated with Decreased Survival in Breast Cancer
Research Article Increased Expression of the E3 Ubiquitin Ligase RNF5 Is Associated with Decreased Survival in Breast Cancer Kenneth D. Bromberg,2 Harriet M. Kluger,3 Agnes Delaunay,1 Sabiha Abbas,1 Kyle A. DiVito,3 Stan Krajewski,1 andZe’ev Ronai 1 1Signal Transduction Program, The Burnham Institute for Medical Research, La Jolla, California; 2Department of Oncological Sciences, Mount Sinai School of Medicine, New York, New York; and 3Department of Pathology, Yale University School of Medicine, New Haven, Connecticut Abstract cancer development. For example, the MDM2 oncogene, which The selective ubiquitination of proteins by ubiquitin E3 ligases targets p53 for ubiquitination-dependent degradation, is overex- plays an important regulatory role in control of cell pressed in human tumors (6). In contrast, the tumor suppressors differentiation, growth, and transformation and their dysre- BRCA1 and BRCA2 and von Hippel-Lindau are frequently mutated gulation is often associated with pathologic outcomes, or deleted in human tumors (7, 8). RNF5 is an 18-kDa RING including tumorigenesis. RNF5is an E3 ubiquitin ligase that finger E3 ligase that is important for development in Caeno- has been implicated in motility and endoplasmic reticulum rhabditis elegans by regulating proper formation of muscle stress response. Here, we show that RNF5expression is up- attachment sites (9). In mammalian cells, RNF5 regulates cell regulated in breast cancer tumors and related cell lines. motility by ubiquitinating the focal adhesion protein paxillin (10), which triggers the exclusion of paxillin from the focal adhesions. Elevated expression of RNF5was seen in breast cancer cell lines that became more sensitive to cytochalasin D– and RNF5 (a.k.a. -
Supporting Information
Supporting Information Poulogiannis et al. 10.1073/pnas.1009941107 SI Materials and Methods Loss of Heterozygosity (LOH) Analysis of PARK2. Seven microsatellite Bioinformatic Analysis of Genome and Transcriptome Data. The markers (D6S1550, D6S253, D6S305, D6S955, D6S980, D6S1599, aCGH package in R was used to identify significant DNA copy and D6S396) were amplified for LOH analysis within the PARK2 number (DCN) changes in our collection of 100 sporadic CRCs locus using primers that were previously described (8). (1) (Gene Expression Omnibus, accession no. GSE12520). The MSP of the PARK2 Promoter. CpG sites within the PARK2 promoter aCGH analysis of cell lines and liver metastases was derived region were detected using the Methprimer software (http://www. from published data (2, 3). Chromosome 6 tiling-path array- urogene.org/methprimer/index.html). Methylation-specificand CGH was used to identify the smallest and most frequently al- control primers were designed using the Primo MSP software tered regions of DNA copy number change on chromosome 6. (http://www.changbioscience.com/primo/primom.html); bisulfite An integrative approach was used to correlate expression pro- modification of genomic DNA was performed as described pre- files with genomic copy number data from a SNP array from the viously (9). All tumor DNA samples from primary CRC tumors same tumors (n = 48) (4) (GSE16125), using Pearson’s corre- (n = 100) and CRC lines (n = 5), as well as those from the leukemia lation coefficient analysis to identify the relationships between cell lines KG-1a (acute myeloid leukemia, AML), U937 (acute DNA copy number changes and gene expression of those genes lymphoblastic leukemia, ALL), and Raji (Burkitt lymphoma, BL) SssI located within the small frequently altered regions of DCN were screened as part of this analysis. -
WO 2016/103269 Al 30 June 2016 (30.06.2016) P O P C T
(12) INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT) (19) World Intellectual Property Organization I International Bureau (10) International Publication Number (43) International Publication Date WO 2016/103269 Al 30 June 2016 (30.06.2016) P O P C T (51) International Patent Classification: AO, AT, AU, AZ, BA, BB, BG, BH, BN, BR, BW, BY, C12N 5/0793 (2010.01) CI2N 5/079 (2010.01) BZ, CA, CH, CL, CN, CO, CR, CU, CZ, DE, DK, DM, DO, DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, (21) International Application Number: HN, HR, HU, ID, IL, IN, IR, IS, JP, KE, KG, KN, KP, KR, PCT/IL2015/05 1253 KZ, LA, LC, LK, LR, LS, LU, LY, MA, MD, ME, MG, (22) International Filing Date: MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, OM, 23 December 2015 (23. 12.2015) PA, PE, PG, PH, PL, PT, QA, RO, RS, RU, RW, SA, SC, SD, SE, SG, SK, SL, SM, ST, SV, SY, TH, TJ, TM, TN, (25) Filing Language: English TR, TT, TZ, UA, UG, US, UZ, VC, VN, ZA, ZM, ZW. (26) Publication Language: English (84) Designated States (unless otherwise indicated, for every (30) Priority Data: kind of regional protection available): ARIPO (BW, GH, 62/096,184 23 December 2014 (23. 12.2014) US GM, KE, LR, LS, MW, MZ, NA, RW, SD, SL, ST, SZ, TZ, UG, ZM, ZW), Eurasian (AM, AZ, BY, KG, KZ, RU, (71) Applicant: RAMOT AT TEL-AVIV UNIVERSITY TJ, TM), European (AL, AT, BE, BG, CH, CY, CZ, DE, LTD.