Clinical Features Patient Report Introduction Skeletal Dysplasia With

Total Page:16

File Type:pdf, Size:1020Kb

Clinical Features Patient Report Introduction Skeletal Dysplasia With Skeletal Dysplasia with short stature and a Larsen-like Phenotype due to a homozygous mutation in B3GAT3 Elisabeth Steichen-Gersdorf, Department of Pediatrics 1, Medical University of Innsbruck Franco Laccone, Institute of Medical Genetics, Vienna, Austria E-mail: Elisabeth.steichen@i- med.ac.at Introduction Patient Report Clinical features Proteoglycans are We report on a girl with important components of disproportionate short stature cell plasma membranes and joint laxity with pes planus and extracellular matrices and radial head dislocation. The of connective tissues. girl is the 1st child of a The basic structure of each consanguinous turkish mating, proteoglyan consists of a born at 37 weeks, BW 2140g, L gylcosaminoglycan side 43cm (<P3rd), mildly delayed chain attached to a core motor devellopement and normal protein via a intelligence. She was previously Patient at 13 years, dysproportionate short Hypermobile finger joints, spatulate tetrasaccharide linker assigned to Spondylo- stature, round flat face, prominent eyes, distal phalages, pes planus, halux region . The first sugar is a epimetaphyseal dysplasia with radial head dyslocation, genu valgum valgus Xylose unit enzymatically joint laxity type 1 (SEMDJL1), a added onto the serine similar phenotype with residue of the core protein. progressive severe Subsequent addition of two kyphoscoliosis, thoracic galactose and one asymmetry, and respiratory glucuronic acid completes compromise resulting in early the process. The specific death. A novel homozygous enzymes that catalyze each mutation in B3GAT3 was Short femoral neck, radial head dyslocation, subluxation of knee of the steps have well been detected by whole-exome- joint, irregular carpal bones, halux valgus characterized and defects sequencing causing a Larsen-like Fig.1 have been asigned to a phenotype with skeletal pleiotropic spectrum of involvement including elbow connective tissue disorders deformities with radial head (Fig2). Most of them with dislocation, genu valgum, Glycosaminoglycan Synthesis short stature, dislocation of hypermobile joints, flat feet, and large joints, joint laxity tapered fingers with spatulate and/or skoliosis. distal phalanges. The girl had a B3GAT3- c.416C>T, B3GAT3 mutations are round face, bifid uvula, high p.Thr139Met Glucoronyltransferase 1 rare and have been arched palate, flat midface, deficiency reported previously in two prominent eyes with blue sclerae, Arabian families with short and a long philtrum. Bone density stature and joint laxity. The (BMD) at the age of 18 years was female patient with a novel low with L1-4 ,Z score-1,8. Final homozygous mutation height was 129,5 cm (-5,3 expands the spectrum of SDS),weight 37kg (<3rd centile) the impaired proteoglycan synthesis. Malfait et al Am J Hum Genet 2013 Fig. 2 Whole Exome Sequencing Discussion Whole Exome Sequencing by SOLID 5500 We add an additional case with a spondyloepimetaphyseal (ThermoFIsher) revealed a homozygous dysplasia to a group of patients with features of Ehlers-Danlos or missense mutation in B3GAT3-gene Larsen-like phenotype with a unique combination of multiple coding for Glucoronyl-transferase I dyslocations and joint laxity, caused by mutations in the linker (enzymatic step in the Golgi apparatus for region of glycosaminoglycans (GAG). This includes syndromes with a linkage region synthesis of proteoglycans mutations of enzymes in the GAG side chain polymerization such i.e heparan sulfate) c.416C>T, as B3GAT3, B3GALT6 (Ehlers-Danlos- like), B4GALT6 (Ehlers- p.Thr139Met. (Fig2): This residue is highly Danlos-like syndrome with kyphoskoliosis), B4GALT7 (Larsen of conserved and predicted as pathogenic by Reunion Island Syndrome) and XYLT1 (Desbuquois Dysplasia Type Polyphen-2 and MutationTaster. 2). Glucoronosyl-transferase deficiency 1, encoded by B3GAT3 is References: supposed to result in defects in collagen supramolecular organisation, which is responsible for several of the observed 1. Von Oettingen J, Tan WH, Dauber A. 2014: Am.J. Med. Genet clinical features. Bone mineral density was in the lower range, 164A,1580-6 however compared to Galactosyl-transferase II (B3GALT6) 2. Baasanjav S, Al-Gazali L, Hashiguchi T et al. , Am J Hum Genet 89:15-27 mutations, early onset fractures did not occur in this patient. 3. Malfait F, Kariminejad A, Van Damme T et al 2013, Am J Hum Genet 92,935-45 The authors declare no conflict of interests 452-P2 Growth Poster presented at: Elisabeth Steichen-Gersdorf DOI: 10.3252/pso.eu.54espe.2015 ESPE 2015 ESPE.
Recommended publications
  • Supp Material.Pdf
    Simon et al. Supplementary information: Table of contents p.1 Supplementary material and methods p.2-4 • PoIy(I)-poly(C) Treatment • Flow Cytometry and Immunohistochemistry • Western Blotting • Quantitative RT-PCR • Fluorescence In Situ Hybridization • RNA-Seq • Exome capture • Sequencing Supplementary Figures and Tables Suppl. items Description pages Figure 1 Inactivation of Ezh2 affects normal thymocyte development 5 Figure 2 Ezh2 mouse leukemias express cell surface T cell receptor 6 Figure 3 Expression of EZH2 and Hox genes in T-ALL 7 Figure 4 Additional mutation et deletion of chromatin modifiers in T-ALL 8 Figure 5 PRC2 expression and activity in human lymphoproliferative disease 9 Figure 6 PRC2 regulatory network (String analysis) 10 Table 1 Primers and probes for detection of PRC2 genes 11 Table 2 Patient and T-ALL characteristics 12 Table 3 Statistics of RNA and DNA sequencing 13 Table 4 Mutations found in human T-ALLs (see Fig. 3D and Suppl. Fig. 4) 14 Table 5 SNP populations in analyzed human T-ALL samples 15 Table 6 List of altered genes in T-ALL for DAVID analysis 20 Table 7 List of David functional clusters 31 Table 8 List of acquired SNP tested in normal non leukemic DNA 32 1 Simon et al. Supplementary Material and Methods PoIy(I)-poly(C) Treatment. pIpC (GE Healthcare Lifesciences) was dissolved in endotoxin-free D-PBS (Gibco) at a concentration of 2 mg/ml. Mice received four consecutive injections of 150 μg pIpC every other day. The day of the last pIpC injection was designated as day 0 of experiment.
    [Show full text]
  • 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
    [Show full text]
  • Curcumin Alters Gene Expression-Associated DNA Damage, Cell Cycle, Cell Survival and Cell Migration and Invasion in NCI-H460 Human Lung Cancer Cells in Vitro
    ONCOLOGY REPORTS 34: 1853-1874, 2015 Curcumin alters gene expression-associated DNA damage, cell cycle, cell survival and cell migration and invasion in NCI-H460 human lung cancer cells in vitro I-TSANG CHIANG1,2, WEI-SHU WANG3, HSIN-CHUNG LIU4, SU-TSO YANG5, NOU-YING TANG6 and JING-GUNG CHUNG4,7 1Department of Radiation Oncology, National Yang‑Ming University Hospital, Yilan 260; 2Department of Radiological Technology, Central Taiwan University of Science and Technology, Taichung 40601; 3Department of Internal Medicine, National Yang‑Ming University Hospital, Yilan 260; 4Department of Biological Science and Technology, China Medical University, Taichung 404; 5Department of Radiology, China Medical University Hospital, Taichung 404; 6Graduate Institute of Chinese Medicine, China Medical University, Taichung 404; 7Department of Biotechnology, Asia University, Taichung 404, Taiwan, R.O.C. Received March 31, 2015; Accepted June 26, 2015 DOI: 10.3892/or.2015.4159 Abstract. Lung cancer is the most common cause of cancer CARD6, ID1 and ID2 genes, associated with cell survival and mortality and new cases are on the increase worldwide. the BRMS1L, associated with cell migration and invasion. However, the treatment of lung cancer remains unsatisfactory. Additionally, 59 downregulated genes exhibited a >4-fold Curcumin has been shown to induce cell death in many human change, including the DDIT3 gene, associated with DNA cancer cells, including human lung cancer cells. However, the damage; while 97 genes had a >3- to 4-fold change including the effects of curcumin on genetic mechanisms associated with DDIT4 gene, associated with DNA damage; the CCPG1 gene, these actions remain unclear. Curcumin (2 µM) was added associated with cell cycle and 321 genes with a >2- to 3-fold to NCI-H460 human lung cancer cells and the cells were including the GADD45A and CGREF1 genes, associated with incubated for 24 h.
    [Show full text]
  • New Insight on FGFR3-Related Chondrodysplasias Molecular Physiopathology Revealed by Human Chondrocyte Gene Expression Profiling
    New insight on FGFR3-related chondrodysplasias molecular physiopathology revealed by human chondrocyte gene expression profiling Laurent Schibler, Linda Gibbs, Catherine Benoist-Lasselin, Charles Decraene, Jelena Martinovic, Philippe Loget, Anne-Lise Delezoide, Marie Gonzales, Arnold Munnich, Jean-Philippe Jais, et al. To cite this version: Laurent Schibler, Linda Gibbs, Catherine Benoist-Lasselin, Charles Decraene, Jelena Martinovic, et al.. New insight on FGFR3-related chondrodysplasias molecular physiopathology revealed by human chondrocyte gene expression profiling. PLoS ONE, Public Library of Science, 2009, 4, online (10), Non paginé. 10.1371/journal.pone.0007633. hal-01193364 HAL Id: hal-01193364 https://hal.archives-ouvertes.fr/hal-01193364 Submitted on 30 May 2020 HAL is a multi-disciplinary open access L’archive ouverte pluridisciplinaire HAL, est archive for the deposit and dissemination of sci- destinée au dépôt et à la diffusion de documents entific research documents, whether they are pub- scientifiques de niveau recherche, publiés ou non, lished or not. The documents may come from émanant des établissements d’enseignement et de teaching and research institutions in France or recherche français ou étrangers, des laboratoires abroad, or from public or private research centers. publics ou privés. New Insight on FGFR3-Related Chondrodysplasias Molecular Physiopathology Revealed by Human Chondrocyte Gene Expression Profiling Laurent Schibler1,2, Linda Gibbs1,3, Catherine Benoist-Lasselin1, Charles Decraene4, Jelena Martinovic5,
    [Show full text]
  • The Clinical and Mutational Spectrum of B3GAT3 Linkeropathy
    Colman et al. Orphanet Journal of Rare Diseases (2019) 14:138 https://doi.org/10.1186/s13023-019-1110-9 RESEARCH Open Access The clinical and mutational spectrum of B3GAT3 linkeropathy: two case reports and literature review Marlies Colman1, Tim Van Damme1, Elisabeth Steichen-Gersdorf2, Franco Laccone3, Sheela Nampoothiri4, Delfien Syx1, Brecht Guillemyn1, Sofie Symoens1 and Fransiska Malfait1* Abstract Background: Proteoglycans are large and structurally complex macromolecules which can be found in abundancy in the extracellular matrix and on the surface of all animal cells. Mutations in the genes encoding the enzymes responsible for the formation of the tetrasaccharide linker region between the proteoglycan core protein and the glycosaminoglycan side chains lead to a spectrum of severe and overlapping autosomal recessive connective tissue disorders, collectively coined the ‘glycosaminoglycan linkeropathies’. Results: We report the clinical findings of two novel patients with a complex linkeropathy due to biallelic mutations in B3GAT3, the gene that encodes glucuronosyltransferase I, which catalyzes the addition of the ultimate saccharide to the linker region. We identified a previously reported c.667G > A missense mutation and an unreported homozygous c.416C > T missense mutation. We also performed a genotype and phenotype-oriented literature overview of all hitherto reported patients harbouring B3GAT3 mutations. A total of 23 patients from 10 families harbouring bi-allelic mutations and one patient with a heterozygeous splice-site mutation in B3GAT3 have been reported. They all display a complex phenotype characterized by consistent presence of skeletal dysplasia (including short stature, kyphosis, scoliosis and deformity of the long bones), facial dysmorphology, and spatulate distal phalanges.
    [Show full text]
  • Glycosaminoglycan Biosynthesis in Zebrafish
    Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine 1143 Glycosaminoglycan Biosynthesis in Zebrafish BEATA FILIPEK-GÓRNIOK ACTA UNIVERSITATIS UPSALIENSIS ISSN 1651-6206 ISBN 978-91-554-9368-4 UPPSALA urn:nbn:se:uu:diva-264269 2015 Dissertation presented at Uppsala University to be publicly examined in C8:305, BMC, Husargatan 3, Uppsala, Friday, 27 November 2015 at 13:15 for the degree of Doctor of Philosophy (Faculty of Medicine). The examination will be conducted in English. Faculty examiner: Associate Professor Kay Grobe (Institute for Physiological Chemistry and Pathobiochemistry, University of Münster). Abstract Filipek-Górniok, B. 2015. Glycosaminoglycan Biosynthesis in Zebrafish. Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine 1143. 54 pp. Uppsala: Acta Universitatis Upsaliensis. ISBN 978-91-554-9368-4. Proteoglycans (PGs) are composed of highly sulfated glycosaminoglycans chains (GAGs) attached to specific core proteins. They are present in extracellular matrices, on the cell surface and in storage granules of hematopoietic cells. Heparan sulfate (HS) and chondroitin/dermatan sulfate (CS/DS) GAGs play indispensable roles in a wide range of biological processes, where they can serve as protein carriers, be involved in growth factor or morphogen gradient formation and act as co-receptors in signaling processes. Protein binding abilities of GAGs are believed to be predominantly dependent on the arrangement of the sugar modifications, sulfation and epimerization, into specific oligosaccharide sequences. Although the process of HS and CS/DS assembly and modification is not fully understood, a set of GAG biosynthetic enzymes have been fairly well studied and several mutations in genes encoding for this Golgi machinery have been linked to human genetic disorders.
    [Show full text]
  • Heparan Sulfate Glycosaminoglycans in Glioblastoma Promote Tumor Invasion Vy M
    Published OnlineFirst August 4, 2017; DOI: 10.1158/1541-7786.MCR-17-0352 Signal Transduction Molecular Cancer Research Heparan Sulfate Glycosaminoglycans in Glioblastoma Promote Tumor Invasion Vy M. Tran1, Anna Wade1, Andrew McKinney1, Katharine Chen1, Olle R. Lindberg1, Jane R. Engler1, Anders I. Persson1,2,3, and Joanna J. Phillips1,2,4 Abstract Glioblastoma (GBM) is the most common primary malignant heterogeneous HS content and structure across patient-derived brain tumor of adults and confers a poor prognosis due, in part, to tumorsphere lines suggested diverse functions in the GBM tumor diffuse invasion of tumor cells. Heparan sulfate (HS) glycosami- microenvironment. In GBM5 and mPN, elevated expression of noglycans, present on the cell surface and in the extracellular sulfatase 2 (SULF2), an extracellular enzyme that alters ligand matrix, regulate cell signaling pathways and cell–microenviron- binding to HS, was associated with low trisulfated HS disacchar- ment interactions. In GBM, the expression of HS glycosamino- ides, a substrate of SULF2. In contrast, other primary tumorsphere glycans and the enzymes that regulate their function are altered, lines had elevated expression of the HS-modifying enzyme hepar- but the actual HS content and structure are unknown. However, anase (HPSE). Using gene editing strategies to inhibit HPSE, a role inhibition of HS glycosaminoglycan function is emerging as a for HPSE in promoting tumor cell adhesion and invasion was promising therapeutic strategy for some cancers. In this study, we identified. These studies characterize the heterogeneity in HS use liquid chromatography–mass spectrometry analysis to dem- glycosaminoglycan content and structure across GBM and reveal onstrate differences in HS disaccharide content and structure their role in tumor cell invasion.
    [Show full text]
  • Multiplexed Surrogate Analysis of Glycotransferase Activity in Whole Biospecimens † † ‡ Chad R
    Article pubs.acs.org/ac Multiplexed Surrogate Analysis of Glycotransferase Activity in Whole Biospecimens † † ‡ Chad R. Borges, ,* Douglas S. Rehder, and Paolo Boffetta † Molecular Biomarkers Unit, The Biodesign Institute at Arizona State University, Tempe, Arizona 85287, United States ‡ Institute for Translational Epidemiology and Tisch Cancer Institute, Mount Sinai School of Medicine, New York, New York 10029, United States *S Supporting Information ABSTRACT: Dysregulated glycotransferase enzymes in can- cer cells produce aberrant glycanssome of which can help facilitate metastases. Within a cell, individual glycotransferases promiscuously help to construct dozens of unique glycan structures, making it difficult to comprehensively track their activity in biospecimensespecially where they are absent or inactive. Here, we describe an approach to deconstruct glycans in whole biospecimens then analytically pool together resulting monosaccharide-and-linkage-specific degradation products (“glycan nodes”) that directly represent the activities of specific glycotransferases. To implement this concept, a reproducible, relative quantitation-based glycan methylation analysis methodology was developed that simultaneously captures information from N-, O-, and lipid linked glycans and is compatible with whole biofluids and homogenized tissues; in total, over 30 different glycan nodes are detectable per gas chromatography−mass spectrometry (GC-MS) run. Numerous nonliver organ cancers are known to induce the production of abnormally glycosylated serum proteins. Thus, following analytical validation, in blood plasma, the technique was applied to a group of 59 lung cancer patient plasma samples and age/gender/ smoking-status-matched non-neoplastic controls from the Lung Cancer in Central and Eastern Europe (CEE) study to gauge the clinical utility of the approach toward the detection of lung cancer.
    [Show full text]
  • Investigating the Role of the O-Glcnac Modification During the Neural Differentiation of Human Embryonic Stem Cells
    Investigating the role of the O-GlcNAc modification during the neural differentiation of human embryonic stem cells By Lissette Andres A dissertation submitted in partial satisfaction of the requirements for the degree of Doctor of Philosophy in Molecular and Cell Biology in the Graduate Division of the University of California, Berkeley Committee in charge: Professor Carolyn R. Bertozzi, Chair Professor Michael Rape Professor Ellen Robey Professor David V. Schaffer Fall 2014 Investigating the role of the O-GlcNAc modification during the neural differentiation of human embryonic stem cells © 2014 by Lissette Andres ! ! Abstract Investigating the role of the O-GlcNAc modification during the neural differentiation of human embryonic stem cells by Lissette Andres Doctor of Philosophy in Molecular and Cell Biology University of California, Berkeley Professor Carolyn R. Bertozzi, Chair Human embryonic stem cells (hESCs) have the ability of propagating indefinitely and can be induced to differentiate into specialized cell types; however, the molecular mechanisms that govern the self-renewal and conversion of hESCs into a variety of cell types are not well understood. In order to understand the molecular mechanisms involved in the modulation of these processes it is necessary to look beyond what is encoded in the genome, and look into other forms of cellular regulation such as post- translational modifications. The addition of a single monosaccharide, !-N- acetylglucosamine (O-GlcNAc), to the hydroxy side chain of serine or threonine residues of protein is an intracellular, post-translational modification that shares qualities with phosphorylation. The enzymes involved in the addition and removal of O-GlcNAc, O-GlcNAc transferase and O-GlcNAcase, respectively, have been shown to target key transcriptional and epigenetic regulators.
    [Show full text]
  • Lineage-Specific Effector Signatures of Invariant NKT Cells Are Shared Amongst Δγ T, Innate Lymphoid, and Th Cells
    Downloaded from http://www.jimmunol.org/ by guest on September 26, 2021 δγ is online at: average * The Journal of Immunology , 10 of which you can access for free at: 2016; 197:1460-1470; Prepublished online 6 July from submission to initial decision 4 weeks from acceptance to publication 2016; doi: 10.4049/jimmunol.1600643 http://www.jimmunol.org/content/197/4/1460 Lineage-Specific Effector Signatures of Invariant NKT Cells Are Shared amongst T, Innate Lymphoid, and Th Cells You Jeong Lee, Gabriel J. Starrett, Seungeun Thera Lee, Rendong Yang, Christine M. Henzler, Stephen C. Jameson and Kristin A. Hogquist J Immunol cites 41 articles Submit online. Every submission reviewed by practicing scientists ? is published twice each month by Submit copyright permission requests at: http://www.aai.org/About/Publications/JI/copyright.html Receive free email-alerts when new articles cite this article. Sign up at: http://jimmunol.org/alerts http://jimmunol.org/subscription http://www.jimmunol.org/content/suppl/2016/07/06/jimmunol.160064 3.DCSupplemental This article http://www.jimmunol.org/content/197/4/1460.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 © 2016 by The American Association of Immunologists, Inc. All rights reserved. Print ISSN: 0022-1767 Online ISSN: 1550-6606. This information is current as of September 26, 2021. The Journal of Immunology Lineage-Specific Effector Signatures of Invariant NKT Cells Are Shared amongst gd T, Innate Lymphoid, and Th Cells You Jeong Lee,* Gabriel J.
    [Show full text]
  • Autocrine IFN Signaling Inducing Profibrotic Fibroblast Responses By
    Downloaded from http://www.jimmunol.org/ by guest on September 23, 2021 Inducing is online at: average * The Journal of Immunology , 11 of which you can access for free at: 2013; 191:2956-2966; Prepublished online 16 from submission to initial decision 4 weeks from acceptance to publication August 2013; doi: 10.4049/jimmunol.1300376 http://www.jimmunol.org/content/191/6/2956 A Synthetic TLR3 Ligand Mitigates Profibrotic Fibroblast Responses by Autocrine IFN Signaling Feng Fang, Kohtaro Ooka, Xiaoyong Sun, Ruchi Shah, Swati Bhattacharyya, Jun Wei and John Varga J Immunol cites 49 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/2013/08/20/jimmunol.130037 6.DC1 This article http://www.jimmunol.org/content/191/6/2956.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 © 2013 by The American Association of Immunologists, Inc. All rights reserved. Print ISSN: 0022-1767 Online ISSN: 1550-6606. This information is current as of September 23, 2021. The Journal of Immunology A Synthetic TLR3 Ligand Mitigates Profibrotic Fibroblast Responses by Inducing Autocrine IFN Signaling Feng Fang,* Kohtaro Ooka,* Xiaoyong Sun,† Ruchi Shah,* Swati Bhattacharyya,* Jun Wei,* and John Varga* Activation of TLR3 by exogenous microbial ligands or endogenous injury-associated ligands leads to production of type I IFN.
    [Show full text]
  • 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.
    [Show full text]