Structure-Based Targeting of Transcriptional Regulatory Complexes Implicated in Human Disease: a Dissertation
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A Case of Mistaken Identity…
Gastroenterology & Hepatology: Open Access Case Report Open Access A case of mistaken identity… Abstract Volume 5 Issue 8 - 2016 Paragangliomas are rare tumors of the autonomic nervous system, which may origin from Marina Morais,1,2 Marinho de Almeida,1,2 virtually any part of the body containing embryonic neural crest tissue. Catarina Eloy,2,3 Renato Bessa Melo,1,2 Luís A 60year-old old female, with a history of resistant hypertension and constitutional Graça,1 J Costa Maia1 symptoms, was hospitalized for acute renal failure. In the investigation, a CT scan revealed 1General Surgery Department, Portugal a 63x54mm hepatic nodule in the caudate lobe. Intraoperatively, the tumor was closely 2University of Porto Medical School, Portugal attached to segment 1, but not depending directly on the hepatic parenchyma or any other 3Instituto de Patologia e Imunologia Molecular da Universidade adjacent structure, and it was resected. Histology reported a paraganglioma. Postoperative do Porto (IPATIMUP), Portugal period was uneventful. Correspondence: J Costa Maia, Sao Joao Medical Center, A potentially functional PG was mistaken for an incidentaloma, due to its location, General Surgery Department, Portugal, interrelated illnesses and unspecific symptoms. PG may mimic primary liver tumors and Email therefore should be a differential diagnosis for tumors in this location. Received: August 29, 2016 | Published: December 30, 2016 Background and hydrochlorothiazide), was admitted to the Internal Medicine Department due to gastroenteritis and dehydration-associated acute Paragangliomas (PG) are rare tumors of the autonomic nervous renal failure (ARF). She reported weight loss (more than 15%), system. Their origin takes part in the neural crest cells, which produce anorexia, asthenia, polydipsia, polyuria and frequent episodes of 1 neuropeptides and catecholamines. -
Activation of the STAT3 Signaling Pathway by the RNA-Dependent RNA Polymerase Protein of Arenavirus
viruses Article Activation of the STAT3 Signaling Pathway by the RNA-Dependent RNA Polymerase Protein of Arenavirus Qingxing Wang 1,2 , Qilin Xin 3 , Weijuan Shang 1, Weiwei Wan 1,2, Gengfu Xiao 1,2,* and Lei-Ke Zhang 1,2,* 1 State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan 430071, hubei, China; [email protected] (Q.W.); [email protected] (W.S.); [email protected] (W.W.) 2 University of Chinese Academy of Sciences, Beijing 100049, China 3 UMR754, Viral Infections and Comparative Pathology, 50 Avenue Tony Garnier, CEDEX 07, 69366 Lyon, France; [email protected] * Correspondence: [email protected] (G.X.); [email protected] (L.-K.Z.) Abstract: Arenaviruses cause chronic and asymptomatic infections in their natural host, rodents, and several arenaviruses cause severe hemorrhagic fever that has a high mortality in infected humans, seriously threatening public health. There are currently no FDA-licensed drugs available against arenaviruses; therefore, it is important to develop novel antiviral strategies to combat them, which would be facilitated by a detailed understanding of the interactions between the viruses and their hosts. To this end, we performed a transcriptomic analysis on cells infected with arenavirus lymphocytic choriomeningitis virus (LCMV), a neglected human pathogen with clinical significance, and found that the signal transducer and activator of transcription 3 (STAT3) signaling pathway was activated. A further investigation indicated that STAT3 could be activated by the RNA-dependent RNA polymerase L protein (Lp) of LCMV. Our functional analysis found that STAT3 cannot affect Citation: Wang, Q.; Xin, Q.; Shang, LCMV multiplication in A549 cells. -
DISSERTATION PROTEOMIC PROFILING of the RAT RENAL PROXIMAL CONVOLUTED TUBULE in RESPONSE to CHRONIC METABOLIC ACIDOSIS Submitted
DISSERTATION PROTEOMIC PROFILING OF THE RAT RENAL PROXIMAL CONVOLUTED TUBULE IN RESPONSE TO CHRONIC METABOLIC ACIDOSIS Submitted by Dana Marie Freund Department of Biochemistry and Molecular Biology In partial fulfillment of the requirements For the Degree of Doctor of Philosophy Colorado State University Fort Collins, Colorado Spring 2013 Doctoral Committee: Advisor: Norman Curthoys Co-Advisor: Jessica Prenni Jennifer Nyborg Olve Peersen Karen Dobos ABSTRACT PROTEOMIC PROFILING OF THE RAT RENAL PROXIMAL CONVOLUTED TUBULE IN RESPONSE TO CHRONIC METABOLIC ACIDOSIS The human kidneys contain more than one million glomeruli which filter nearly 200 liters of plasma per day. The proximal tubule is the segment of the nephron that immediately follows the glomeruli. This portion of the nephron contributes to fluid, electrolyte and nutrient homeostasis by reabsorbing 60-70% of the filtered water and NaCl and an even greater proportion of NaHCO3. The initial or convoluted portion of the proximal tubule reabsorbs nearly all of the nutrients in the glomerular filtrate and is the site of active secretion and many of the metabolic functions of the kidney. For example, the proximal convoluted tubule is the primary site of renal ammoniagenesis and gluconeogenesis, processes that are significantly activated during metabolic acidosis. Metabolic acidosis is a common clinical condition that is characterized by a decrease in blood pH and bicarbonate concentration. Metabolic acidosis also occurs frequently as a secondary complication, which adversely affects the outcome of patients with various life- threatening conditions. This type of acidosis can occur acutely, lasting for a few hours to a day, or as a chronic condition where acid-base balance is not fully restored. -
Interferon Regulatory Factor 3-CL, an Isoform of IRF3, Antagonizes Activity of IRF3
Cellular & Molecular Immunology (2011) 8, 67–74 ß 2011 CSI and USTC. All rights reserved 1672-7681/11 $32.00 www.nature.com/cmi RESEARCH ARTICLE Interferon regulatory factor 3-CL, an isoform of IRF3, antagonizes activity of IRF3 Chunhua Li1,2,3, Lixin Ma2 and Xinwen Chen1 Interferon regulatory factor 3 (IRF3), one member of the IRF family, plays a central role in induction of type I interferon (IFN) and regulation of apoptosis. Controlled activity of IRF3 is essential for its functions. During reverse transcription (RT)-PCR to clone the full-length open reading frame (ORF) of IRF3, we cloned a full-length ORF encoding an isoform of IRF3, termed as IRF3-CL, and has a unique carboxyl-terminus of 125 amino acids. IRF3-CL is ubiquitously expressed in distinct cell lines. Overexpression of IRF3-CL inhibits Sendai virus (SeV)-triggered induction of IFN-b and SeV-induced and inhibitor of NF-kB kinase-e (IKKe)-mediated nuclear translocation of IRF3. When IKKe is overexpressed, IRF3-CL is associated with IRF3. These results suggest that IRF3-CL, the alternative splicing isoform of IRF-3, may function as a negative regulator of IRF3. Cellular & Molecular Immunology (2011) 8, 67–74; doi:10.1038/cmi.2010.55; published online 6 December 2010 Keywords: interferon regulatory factor 3; negative regulation; splicing variant INTRODUCTION A single gene is capable of generating multiple transcripts from a The interferon regulatory factor (IRF) family of transcriptional factors common mRNA precursor through alternative splicing, which may plays versatile roles in many biological processes, including innate and produce distinct protein isoforms with diverse and even antagonistic adaptive immune responses, cell growth control, apoptosis and functions. -
IRF8 Regulates Gram-Negative Bacteria–Mediated NLRP3 Inflammasome Activation and Cell Death
IRF8 Regulates Gram-Negative Bacteria− Mediated NLRP3 Inflammasome Activation and Cell Death This information is current as Rajendra Karki, Ein Lee, Bhesh R. Sharma, Balaji Banoth of September 25, 2021. and Thirumala-Devi Kanneganti J Immunol published online 23 March 2020 http://www.jimmunol.org/content/early/2020/03/20/jimmun ol.1901508 Downloaded from Supplementary http://www.jimmunol.org/content/suppl/2020/03/20/jimmunol.190150 Material 8.DCSupplemental http://www.jimmunol.org/ Why The JI? Submit online. • Rapid Reviews! 30 days* from submission to initial decision • No Triage! Every submission reviewed by practicing scientists • Fast Publication! 4 weeks from acceptance to publication by guest on September 25, 2021 *average Subscription Information about subscribing to The Journal of Immunology is online at: http://jimmunol.org/subscription Permissions Submit copyright permission requests at: http://www.aai.org/About/Publications/JI/copyright.html Email Alerts Receive free email-alerts when new articles cite this article. Sign up at: http://jimmunol.org/alerts The Journal of Immunology is published twice each month by The American Association of Immunologists, Inc., 1451 Rockville Pike, Suite 650, Rockville, MD 20852 Copyright © 2020 by The American Association of Immunologists, Inc. All rights reserved. Print ISSN: 0022-1767 Online ISSN: 1550-6606. Published March 23, 2020, doi:10.4049/jimmunol.1901508 The Journal of Immunology IRF8 Regulates Gram-Negative Bacteria–Mediated NLRP3 Inflammasome Activation and Cell Death Rajendra Karki,*,1 Ein Lee,*,†,1 Bhesh R. Sharma,*,1 Balaji Banoth,* and Thirumala-Devi Kanneganti* Inflammasomes are intracellular signaling complexes that are assembled in response to a variety of pathogenic or physiologic stimuli to initiate inflammatory responses. -
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. -
Grhpr Gene, Full Gene Analysis
TEST ID: GRHPZ GRHPR GENE, FULL GENE ANALYSIS CLINICAL INFORMATION MOBILE APPS FROM MAYO MEDICAL LABORATORIES Primary hyperoxaluria type 2 (PH2) is a hereditary disorder of glyoxylate metabolism caused by deficiency of the hepatic enzyme glyoxylate reductase/hydroxypyruvate reductase (GRHPR). Lab Catalog for iPad and Absence of GRHPR activity results in excess oxalate and usually L-glycerate excreted in the Lab Reference for iPhone urine leading to nephrolithiasis (kidney stones) and sometimes renal failure. and iPod Touch Onset of PH2 is typically in childhood or adolescence with symptoms related to kidney stones. In some cases, kidney failure may be the initial presenting feature. Nephrocalcinosis, as seen by renal ultrasound, is observed less frequently in individuals with PH2 than primary Requires iOS 5.1+ hyperoxaluria type 1 (PH1). End-stage renal disease (ESRD) is also less common and of later onset than PH1; however, once ESRD develops, oxalate deposition in other organs such as REFERENCE VALUES bone, retina, and myocardium can occur. An interpretive report will be While the exact prevalence and incidence of PH2 are not known, it is thought that PH2 is less provided. common than PH1, which has an estimated prevalence rate of 1 to 3 per million population and an incidence of 0.1 per million/year. ANALYTIC TIME Biochemical testing is indicated in patients with possible primary hyperoxaluria. Measurement 14 days of urinary oxalate in a timed, 24-hour urine collection is strongly preferred, with correction to adult body surface area in pediatric patients (HYOX / Hyperoxaluria Panel, Urine; OXU / Oxalate, Urine). In very young children (incapable of performing a timed collection), random urine oxalate to creatinine ratios may be used for determination of oxalate excretion. -
RNF11 at the Crossroads of Protein Ubiquitination
biomolecules Review RNF11 at the Crossroads of Protein Ubiquitination Anna Mattioni, Luisa Castagnoli and Elena Santonico * Department of Biology, University of Rome Tor Vergata, Via della ricerca scientifica, 00133 Rome, Italy; [email protected] (A.M.); [email protected] (L.C.) * Correspondence: [email protected] Received: 29 September 2020; Accepted: 8 November 2020; Published: 11 November 2020 Abstract: RNF11 (Ring Finger Protein 11) is a 154 amino-acid long protein that contains a RING-H2 domain, whose sequence has remained substantially unchanged throughout vertebrate evolution. RNF11 has drawn attention as a modulator of protein degradation by HECT E3 ligases. Indeed, the large number of substrates that are regulated by HECT ligases, such as ITCH, SMURF1/2, WWP1/2, and NEDD4, and their role in turning off the signaling by ubiquitin-mediated degradation, candidates RNF11 as the master regulator of a plethora of signaling pathways. Starting from the analysis of the primary sequence motifs and from the list of RNF11 protein partners, we summarize the evidence implicating RNF11 as an important player in modulating ubiquitin-regulated processes that are involved in transforming growth factor beta (TGF-β), nuclear factor-κB (NF-κB), and Epidermal Growth Factor (EGF) signaling pathways. This connection appears to be particularly significant, since RNF11 is overexpressed in several tumors, even though its role as tumor growth inhibitor or promoter is still controversial. The review highlights the different facets and peculiarities of this unconventional small RING-E3 ligase and its implication in tumorigenesis, invasion, neuroinflammation, and cancer metastasis. Keywords: Ring Finger Protein 11; HECT ligases; ubiquitination 1. -
Application of an LC–MS/MS Method for the Simultaneous Quantification
molecules Article Application of an LC–MS/MS Method for the Simultaneous Quantification of Homovanillic Acid and Vanillylmandelic Acid for the Diagnosis and Follow-Up of Neuroblastoma in 357 Patients Narae Hwang 1,† , Eunbin Chong 1,†, Hyeonju Oh 1, Hee Won Cho 2, Ji Won Lee 2 , Ki Woong Sung 2,* and Soo-Youn Lee 1,3,4,* 1 Department of Laboratory Medicine and Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351, Korea; [email protected] (N.H.); [email protected] (E.C.); [email protected] (H.O.) 2 Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351, Korea; [email protected] (H.W.C.); [email protected] (J.W.L.) 3 Department of Clinical Pharmacology & Therapeutics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351, Korea 4 Department of Health Science and Technology, Samsung Advanced Institute of Health Science and Technology, Sungkyunkwan University, Seoul 06351, Korea * Correspondence: [email protected] (K.W.S.); [email protected] (S.-Y.L.); Tel.: +82-2-3410-3529 (K.W.S.); Citation: Hwang, N.; Chong, E.; Oh, +82-2-3410-1834 (S.-Y.L.); Fax: +82-2-3410-0043 (K.W.S.); +82-2-3410-2719 (S.Y.L.) H.; Cho, H.W.; Lee, J.W.; Sung, K.W.; † These authors contributed equally to this work. Lee, S.-Y. Application of an LC–MS/MS Method for the Abstract: Homovanillic acid (HVA) and vanillylmandelic acid (VMA) are end-stage metabolites of Simultaneous Quantification of catecholamine and are clinical biomarkers for the diagnosis of neuroblastoma. -
October 2019
Cleveland Clinic Laboratories Technical Update • October 2019 Cleveland Clinic Laboratories is dedicated to keeping you updated and informed about recent testing changes. This Technical Update is provided on a monthly basis to notify you of any changes to the tests in our catalog. Recently changed tests are bolded, and they could include revisions to methodology, reference range, days performed, or CPT code. Deleted tests and new tests are listed separately. For your convenience, tests are listed alphabetically and order codes are provided. To compare the new information with previous test information, refer to the online Test Directory at clevelandcliniclabs. com. Test information is updated in the online Test Directory on the Effective Date stated in the Technical Update. Please update your database as necessary. For additional detail, contact Client Services at 216.444.5755 or 800.628.6816, or via email at [email protected]. Days Performed/Reported Specimen Requirement Component Change(s) Special Information Test Discontinued Reference Range Name Change Test Update Methodology Order Code New Test Stability Page # CPT Summary of Changes Fee by Test Name 6 Allergen, Ampicilloyl (IgE) 6 Allergen, Cashew Component IgE 2–3, 9 Allergen, Peanut Components IgE 7 Allergen, Tree, Hackberry IgE 7 Allergen, Weed, Careless Weed IgE 8 Allergen, Weed, Yellow Dock (Rumex crispus) IgE 3 ALL NGS Panel Bone Marrow 3 ALL NGS Panel Peripheral Blood 3, 9 Bone Marrow Chromosome Analysis with Reflex SNP Array 3 CA 125 3, 9 Chromosome Analysis, Blood -
Supplementary Materials
Supplementary Materials COMPARATIVE ANALYSIS OF THE TRANSCRIPTOME, PROTEOME AND miRNA PROFILE OF KUPFFER CELLS AND MONOCYTES Andrey Elchaninov1,3*, Anastasiya Lokhonina1,3, Maria Nikitina2, Polina Vishnyakova1,3, Andrey Makarov1, Irina Arutyunyan1, Anastasiya Poltavets1, Evgeniya Kananykhina2, Sergey Kovalchuk4, Evgeny Karpulevich5,6, Galina Bolshakova2, Gennady Sukhikh1, Timur Fatkhudinov2,3 1 Laboratory of Regenerative Medicine, National Medical Research Center for Obstetrics, Gynecology and Perinatology Named after Academician V.I. Kulakov of Ministry of Healthcare of Russian Federation, Moscow, Russia 2 Laboratory of Growth and Development, Scientific Research Institute of Human Morphology, Moscow, Russia 3 Histology Department, Medical Institute, Peoples' Friendship University of Russia, Moscow, Russia 4 Laboratory of Bioinformatic methods for Combinatorial Chemistry and Biology, Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry of the Russian Academy of Sciences, Moscow, Russia 5 Information Systems Department, Ivannikov Institute for System Programming of the Russian Academy of Sciences, Moscow, Russia 6 Genome Engineering Laboratory, Moscow Institute of Physics and Technology, Dolgoprudny, Moscow Region, Russia Figure S1. Flow cytometry analysis of unsorted blood sample. Representative forward, side scattering and histogram are shown. The proportions of negative cells were determined in relation to the isotype controls. The percentages of positive cells are indicated. The blue curve corresponds to the isotype control. Figure S2. Flow cytometry analysis of unsorted liver stromal cells. Representative forward, side scattering and histogram are shown. The proportions of negative cells were determined in relation to the isotype controls. The percentages of positive cells are indicated. The blue curve corresponds to the isotype control. Figure S3. MiRNAs expression analysis in monocytes and Kupffer cells. Full-length of heatmaps are presented. -
Supplementary Table S4. FGA Co-Expressed Gene List in LUAD
Supplementary Table S4. FGA co-expressed gene list in LUAD tumors Symbol R Locus Description FGG 0.919 4q28 fibrinogen gamma chain FGL1 0.635 8p22 fibrinogen-like 1 SLC7A2 0.536 8p22 solute carrier family 7 (cationic amino acid transporter, y+ system), member 2 DUSP4 0.521 8p12-p11 dual specificity phosphatase 4 HAL 0.51 12q22-q24.1histidine ammonia-lyase PDE4D 0.499 5q12 phosphodiesterase 4D, cAMP-specific FURIN 0.497 15q26.1 furin (paired basic amino acid cleaving enzyme) CPS1 0.49 2q35 carbamoyl-phosphate synthase 1, mitochondrial TESC 0.478 12q24.22 tescalcin INHA 0.465 2q35 inhibin, alpha S100P 0.461 4p16 S100 calcium binding protein P VPS37A 0.447 8p22 vacuolar protein sorting 37 homolog A (S. cerevisiae) SLC16A14 0.447 2q36.3 solute carrier family 16, member 14 PPARGC1A 0.443 4p15.1 peroxisome proliferator-activated receptor gamma, coactivator 1 alpha SIK1 0.435 21q22.3 salt-inducible kinase 1 IRS2 0.434 13q34 insulin receptor substrate 2 RND1 0.433 12q12 Rho family GTPase 1 HGD 0.433 3q13.33 homogentisate 1,2-dioxygenase PTP4A1 0.432 6q12 protein tyrosine phosphatase type IVA, member 1 C8orf4 0.428 8p11.2 chromosome 8 open reading frame 4 DDC 0.427 7p12.2 dopa decarboxylase (aromatic L-amino acid decarboxylase) TACC2 0.427 10q26 transforming, acidic coiled-coil containing protein 2 MUC13 0.422 3q21.2 mucin 13, cell surface associated C5 0.412 9q33-q34 complement component 5 NR4A2 0.412 2q22-q23 nuclear receptor subfamily 4, group A, member 2 EYS 0.411 6q12 eyes shut homolog (Drosophila) GPX2 0.406 14q24.1 glutathione peroxidase