DOCSLIB.ORG

Mammalian O-Mannosyl Glycans: Biochemistry and Glycopathology

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Mammalian O-Mannosyl Glycans: Biochemistry and Glycopathology No. 1] Proc. Jpn. Acad., Ser. B 95 (2019) 39 Review Mammalian O-mannosyl glycans: Biochemistry and glycopathology † By Tamao ENDO*1, (Communicated by Kunihiko SUZUKI, M.J.A.) Abstract: Glycosylation is an important posttranslational modification in mammals. The glycans of glycoproteins are classified into two groups, namely, N-glycans and O-glycans, according to their glycan-peptide linkage regions. Recently, O-mannosyl glycan, an O-glycan, has been shown to be important in muscle and brain development. A clear relationship between O-mannosyl glycans and the pathomechanisms of some congenital muscular dystrophies has been established in humans. Ribitol-5-phosphate is a newly identified glycan component in mammals, and its biosynthetic pathway has been elucidated. The discovery of new glycan structures and the identification of highly regulated mechanisms of glycan processing will help researchers to understand glycan functions and develop therapeutic strategies. Keywords: O-mannosylation, congenital muscular dystrophy, dystroglycan, ribitol-5- phosphate altered glycosylation was published in this journal,3) Introduction including our pioneering findings of muscular dys- The major glycans of glycoproteins are classified trophy and glycosylation. Since then, many bio- into two groups according to their glycan-peptide chemists, molecular biologists, pediatricians, neurol- linkages. Glycans linked to asparagine (Asn) residues ogists, and geneticists have entered this new research of proteins are termed N-glycans, whereas glycans field. This review will describe recent progress in linked to serine (Ser) or threonine (Thr) residues are establishing the biochemistry and glycopathology of called O-glycans. In N-glycans, the reducing terminal O-Man glycans in mammals. N-acetylglucosamine (GlcNAc) is linked to the amide group of Asn via an aspartylglycosylamine linkage. Structure In O-glycans, the reducing terminal N-acetylgalactos- O-Mannosylation is known as a yeast-type amine (GalNAc) is attached to the hydroxyl group modification, and all O-Man glycan structures that of Ser and Thr residues. In addition to the abundant have been elucidated in yeast are neutral linear O-GalNAc forms, several unique types of protein O- structures consisting of only Man residues. O- glycosylation have been identified, such as O-linked Mannosylation of proteins is essential for viability fucose (Fuc), glucose (Glc), GlcNAc, and mannose in yeast, and its absence is thought to affect the cell (Man), which have been shown to mediate diverse wall structure and rigidity. On the other hand, physiological functions. We and other researchers mammalian O-Man glycan is a unique type of protein have shown that O-Man glycan is important in modification that is present in a limited number of muscle and brain development, and its deficiency glycoproteins in the brain, nerves, and skeletal leads to a group of congenital muscular dystrophies muscle.4) One of the best known O-Man-modified known as ,-dystroglycanopathies.1),2) In 2004, a glycoproteins is ,-dystroglycan (,-DG), which is a review of human genetic diseases characterized by central component of the dystrophin-glycoprotein complex (DGC) isolated from skeletal muscle mem- *1 Tokyo Metropolitan Institute of Gerontology, Tokyo, branes. ,-DG is heavily glycosylated, and its glycans Japan. † have an important role in binding to proteins such Correspondence should be addressed: T. Endo, Tokyo Metropolitan Institute of Gerontology, 35-2 Sakaecho, Itabashi-ku, as laminin, neurexin, perlecan, pikachurin, and agrin, Tokyo 173-0015, Japan (e-mail: [email protected]). which contain laminin G (LG) domains. Recently, doi: 10.2183/pjab.95.004 ©2019 The Japan Academy 40 T. ENDO [Vol. 95, the binding mode of the LG4 and LG5 domains of tion of core M3, and its defect causes ,-dystrogly- laminin-,2 with the GlcAO1-3Xyl disaccharide re- canopathy. peat was resolved using X-ray crystallography.5) Ribitol (Rbo) is a sugar alcohol, and the usage (1) Core M1 and core M2. We first iden- of Rbo or Rbo5P as a glycan component has not tified a sialylated O-Man glycan, Sia,2-3GalO1- been reported in mammals. However, Rbo5P is used 4GlcNAcO1-2Man, in ,-DG present in bovine pe- as a component of the teichoic acids present in the ripheral nerves6) and then in rabbit skeletal muscle.7) cell walls of most gram-positive bacteria.14) Rbo5P Subsequently, many studies of the O-Man glycan was first detected as a glycan component in the structure have been performed and various O-Man extended structure of core M3 by our group.15) glycan structures have been elucidated. Currently, Shortly thereafter, several groups independently these glycans are classified into three core O-Man reported that Rbo5P is a component of mammalian structures based on the linkage of GlcNAc to the glycans.16)–18) Man residue: core M1 (GlcNAcO1-2Man), core Before a detailed glycan structure was deter- M2 [GlcNAcO1-6(GlcNAcO1-2)Man], and core M3 mined, importance of the glycan moiety of ,-DG was (GalNAcO1-3GlcNAcO1-4Man).2) Furthermore, in well recognized by an antibody, IIH6, because the addition to Sia,2-3GalO1-4GlcNAc (sialyl glycan), IIH6 antibody recognizes glycosylated ,-DG and GalO1-4(Fuc,1-3)GlcNAc (Lewis X glycan) and functionally competes with DG-laminin binding. HSO3-3GlcAO1-3GalO1-4GlcNAc (HNK-1 epitope Thus, IIH6 was considered to recognize laminin- glycan) are exclusively attached to core M1 and binding epitopes on sugar chains. The IIH6 epitope core M2. Notably, the core M2 structure is present in has been proposed to attach to core M3 on ,-DG via the brain. HNK-1 and Lewis X glycans on core M1 the phosphodiester linkage because hydrogen fluoride and core M2 are thought to play important roles in (HF) treatment, which cleaves the phosphodiester brain development.8),9) bond, ablates the laminin-binding activity.19) Origi- (2) Core M3. The extended complete core M3 nally the IIH6 epitope glycan was thought to be structure is novel and has recently been revealed linked to the 6-position of Man in core M3 but the (bottom structure in Fig. 1).10) Characteristic fea- correct binding to the 3-position of GalNAc in tures include 1) the phosphorylation of the 6-position core M3 was subsequently reported.15) of Man; 2) a tandem ribitol-5-phosphate (Rbo5P) The glycosaminoglycan-like (-3GlcAO1-3Xyl,1-) structure; 3) a (-3GlcAO1-3Xyl,1-) repeat; and 4) a (GlcA-Xyl) repeat is unique. The GlcA-Xyl repeat single GlcAO1-4XylO1-4 unit. was identified to be assembled as a result of the The addition of a phosphate to the monosac- enzymatic activity of LARGE (like-acetylglucosami- charide of glycans is a glycan modification whose nyltransferase).20) LARGE overexpression drastically significance is partially understood. For example, enhances IIH6 reactivity and the laminin-binding Man 6-phosphate acts as a recognition marker of activity of ,-DG, whereas HF treatment induces the lysosomal enzymes.11) In mammalian cells, newly loss of IIH6 reactivity and laminin-binding activity of synthesized lysosomal enzymes are modified with a ,-DG, suggesting that the IIH6 epitope is probably phosphate and acquire the Man 6-phosphate marker. the same as the GlcA-Xyl repeat structure. However, These enzymes bind to the lumenal domains of extensive data suggested that the GlcA-Xyl repeat sorting receptors (Man 6-phosphate receptors) is not directly linked to the 6-position of Man in through their Man 6-phosphate recognition markers core M3. For example, mutations in FKTN (fukutin) in the trans-Golgi network and are targeted to and FKRP (fukutin-related protein) are responsible acidified endosomes and lysosomes. Another case is for ,-dystroglycanopathy, and these patients show a xylose (Xyl) 2-phosphate of glycosaminoglycan as dramatic reduction in the reactivity of IIH6, suggest- a common linkage tetrasaccharide. Phosphorylation ing the presence of an unknown “scaffold moiety” and de-phosphorylation of the 2-position of the Xyl between the phosphate and GlcA-Xyl repeat. We residue are an important modification that regulates used small recombinant ,-DG containing the first 20 the formation of the linkage region and glycosami- amino acids of the mucin-like domain to determine noglycan biosynthesis.12) This transient phosphoryl- the scaffold structure up to the GlcA-Xyl repeat. ation is performed by FAM20B,12) and its deletion in Finally, we proposed that the scaffold glycan was mice results in embryonic lethality.13) As will be “GlcA-Xyl-Rbo5P-Rbo5P”.15) Rbo is a pentose alco- described later, the 6-phosphate of Man attached hol (pentitol) and has never been reported in to core M3 is required for the glycan chain elonga- mammalian glycans. No. 1] Mammalian O-mannosyl glycans 41 Ser/Thr Dol-P-Man POMT1/POMT2 Manα1 Ser/Thr core M3 β α ER GlcNAc 1 4Man 1 Ser/Thr POMGNT2 Golgi B3GALNT2 core M1 POMGNT1 GlcNAcβ1 2Manα1 Ser/Thr GalNAcβ1 3GlcNAcβ1 4Manα1 Ser/Thr POMK core M2 GNT-IX (VB) GlcNAcβ1 PO4 6 6 Manα1 Ser/Thr 2 GalNAcβ1 3GlcNAcβ1 4 Manα1 Ser/Thr β GlcNAc 1 ER Golgi FKTN PO4 6 Rbo5P 3GalNAcβ1 3GlcNAcβ1 4 Manα1 Ser/Thr FKRP PO4 6 Rbo5P 1Rbo5P 3GalNAcβ1 3GlcNAcβ1 4 Manα1 Ser/Thr TMEM5 (RXYLT1) PO4 6 Xylβ1 4Rbo5P 1Rbo5P 3GalNAcβ1 3GlcNAcβ1 4 Manα1 Ser/Thr B4GAT1 PO4 6 GlcAβ1 4Xylβ1 4Rbo5P 1Rbo5P 3GalNAcβ1 3GlcNAcβ1 4 Manα1 Ser/Thr LARGE 3GlcAβ1 3Xylα1 n PO4 6 3GlcAβ1 4Xylβ1 4Rbo5P 1Rbo5P 3GalNAcβ1 3GlcNAcβ1 4 Manα1 Ser/Thr Fig. 1. Biosynthetic pathway of core M1, core M2, and core M3 O-Man glycans in the ER and Golgi. GalNAc, N-acetylgalactosamine; GlcNAc, N-acetylglucosamine; Man, mannose; GlcA, glucuronic acid; Rbo5P, ribitol-5-phosphate; Xyl, xylose; PO4, phosphate; POMT1, protein O-mannosyltransferase 1; POMT2, protein O-mannosyltransferase 2; B3GALNT2, O-1,3-N-acetylgalactosaminyl- transferase 2; B4GAT1, O-1,4-glucuronosyltransferase 1; Dol-P-Man, dolichol-phosphate-mannose; FKTN, fukutin; FKRP, fukutin- related protein; GNT-IX(VB), O-1,6-N-acetylglucosaminyltransferase IX(VB); LARGE, acetylglucosaminyltransferase-like; POMGNT1, protein O-linked mannose O-1,2-N-acetylglucosaminyltransferase 1; POMGNT2, protein O-linked mannose O-1,4-N- acetylglucosaminyltransferase 2; POMK, protein O-mannose kinase; TMEM5 (RXYLT1), transmembrane protein 5 (Rbo5PO1,4- xylosyltransferase).
Load more

Recommended publications
  • 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.
    [Show full text]
  • In Vivo Dual RNA-Seq Analysis Reveals the Basis for Differential Tissue Tropism of Clinical Isolates of Streptococcus Pneumoniae
    In Vivo Dual RNA-Seq Analysis Reveals the Basis for Differential Tissue Tropism of Clinical Isolates of Streptococcus pneumoniae Vikrant Minhas,1,4 Rieza Aprianto,2,4 Lauren J. McAllister,1 Hui Wang,1 Shannon C. David,1 Kimberley T. McLean,1 Iain Comerford,3 Shaun R. McColl,3 James C. Paton,1,5,6,* Jan-Willem Veening,2,5 and Claudia Trappetti,1,5 Supplementary Information Supplementary Table 1. Pneumococcal differential gene expression in the lungs 6 h post-infection, 9-47-Ear vs 9-47M. Genes with fold change (FC) greater than 2 and p < 0.05 are shown. FC values highlighted in blue = upregulated in 9-47-Ear, while values highlighted in red = upregulated in 9- 47M. Locus tag in 9-47- Product padj FC Ear Sp947_chr_00844 Sialidase B 3.08E-10 313.9807 Sp947_chr_02077 hypothetical protein 4.46E-10 306.9412 Sp947_chr_00842 Sodium/glucose cotransporter 2.22E-09 243.4822 Sp947_chr_00841 N-acetylneuraminate lyase 4.53E-09 227.7963 scyllo-inositol 2-dehydrogenase Sp947_chr_00845 (NAD(+)) 4.36E-09 221.051 Sp947_chr_00848 hypothetical protein 1.19E-08 202.7867 V-type sodium ATPase catalytic subunit Sp947_chr_00853 A 1.29E-06 100.5411 Sp947_chr_00846 Beta-glucoside kinase 3.42E-06 98.18951 Sp947_chr_00855 V-type sodium ATPase subunit D 8.34E-06 85.94879 Sp947_chr_00851 V-type sodium ATPase subunit C 2.50E-05 72.46612 Sp947_chr_00843 hypothetical protein 2.17E-05 65.97758 Sp947_chr_00839 HTH-type transcriptional regulator RpiR 3.09E-05 61.28171 Sp947_chr_00854 V-type sodium ATPase subunit B 1.32E-06 50.86992 Sp947_chr_00120 hypothetical protein 3.00E-04
    [Show full text]
  • Novel Cardiovascular Findings in Association with a POMT2
    European Journal of Human Genetics (2014) 22, 486–491 & 2014 Macmillan Publishers Limited All rights reserved 1018-4813/14 www.nature.com/ejhg ARTICLE Novel cardiovascular findings in association with a POMT2 mutation: three siblings with a-dystroglycanopathy Hugo R Martinez*,1, William J Craigen2, Monika Ummat3, Adekunle M Adesina4, Timothy E Lotze3 and John L Jefferies5 Dystroglycanopathies are a genetically heterogeneous subset of congenital muscular dystrophies that exhibit autosomal recessive inheritance and are characterized by abnormal glycosylation of a-dystroglycan. In particular, POMT2 (protein O-mannosyltransferase-2) mutations have been identified in congenital muscular dystrophy patients with a wide range of clinical involvement, ranging from the severe muscle-eye-brain disease and Walker–Warburg syndrome to limb girdle muscular dystrophy without structural brain or ocular involvement. Cardiovascular disease is thought to be uncommon in congenital muscular dystrophy, with rare reports of cardiac involvement. We describe three brothers aged 21, 19, and 17 years with an apparently homozygous POMT2 mutation who all presented with congenital muscular dystrophy, intellectual disabilities, and distinct cardiac abnormalities. All three brothers were homozygous for a p.Tyr666Cys missense mutation in exon 19 of the POMT2 gene. On screening echocardiograms, all siblings demonstrated significant dilatation of the aortic root and depressed left ventricular systolic function and/or left ventricular wall motion abnormalities. Our report is the first to document an association between POMT2 mutations and aortopathy with concomitant depressed left ventricular systolic function. On the basis of our findings, we suggest patients with POMT2 gene mutations be screened not only for myocardial dysfunction but also for aortopathy.
    [Show full text]
  • Congenital Disorders of Glycosylation from a Neurological Perspective
    brain sciences Review Congenital Disorders of Glycosylation from a Neurological Perspective Justyna Paprocka 1,* , Aleksandra Jezela-Stanek 2 , Anna Tylki-Szyma´nska 3 and Stephanie Grunewald 4 1 Department of Pediatric Neurology, Faculty of Medical Science in Katowice, Medical University of Silesia, 40-752 Katowice, Poland 2 Department of Genetics and Clinical Immunology, National Institute of Tuberculosis and Lung Diseases, 01-138 Warsaw, Poland; [email protected] 3 Department of Pediatrics, Nutrition and Metabolic Diseases, The Children’s Memorial Health Institute, W 04-730 Warsaw, Poland; [email protected] 4 NIHR Biomedical Research Center (BRC), Metabolic Unit, Great Ormond Street Hospital and Institute of Child Health, University College London, London SE1 9RT, UK; [email protected] * Correspondence: [email protected]; Tel.: +48-606-415-888 Abstract: Most plasma proteins, cell membrane proteins and other proteins are glycoproteins with sugar chains attached to the polypeptide-glycans. Glycosylation is the main element of the post- translational transformation of most human proteins. Since glycosylation processes are necessary for many different biological processes, patients present a diverse spectrum of phenotypes and severity of symptoms. The most frequently observed neurological symptoms in congenital disorders of glycosylation (CDG) are: epilepsy, intellectual disability, myopathies, neuropathies and stroke-like episodes. Epilepsy is seen in many CDG subtypes and particularly present in the case of mutations
    [Show full text]
  • Serum Albumin OS=Homo Sapiens
    Protein Name Cluster of Glial fibrillary acidic protein OS=Homo sapiens GN=GFAP PE=1 SV=1 (P14136) Serum albumin OS=Homo sapiens GN=ALB PE=1 SV=2 Cluster of Isoform 3 of Plectin OS=Homo sapiens GN=PLEC (Q15149-3) Cluster of Hemoglobin subunit beta OS=Homo sapiens GN=HBB PE=1 SV=2 (P68871) Vimentin OS=Homo sapiens GN=VIM PE=1 SV=4 Cluster of Tubulin beta-3 chain OS=Homo sapiens GN=TUBB3 PE=1 SV=2 (Q13509) Cluster of Actin, cytoplasmic 1 OS=Homo sapiens GN=ACTB PE=1 SV=1 (P60709) Cluster of Tubulin alpha-1B chain OS=Homo sapiens GN=TUBA1B PE=1 SV=1 (P68363) Cluster of Isoform 2 of Spectrin alpha chain, non-erythrocytic 1 OS=Homo sapiens GN=SPTAN1 (Q13813-2) Hemoglobin subunit alpha OS=Homo sapiens GN=HBA1 PE=1 SV=2 Cluster of Spectrin beta chain, non-erythrocytic 1 OS=Homo sapiens GN=SPTBN1 PE=1 SV=2 (Q01082) Cluster of Pyruvate kinase isozymes M1/M2 OS=Homo sapiens GN=PKM PE=1 SV=4 (P14618) Glyceraldehyde-3-phosphate dehydrogenase OS=Homo sapiens GN=GAPDH PE=1 SV=3 Clathrin heavy chain 1 OS=Homo sapiens GN=CLTC PE=1 SV=5 Filamin-A OS=Homo sapiens GN=FLNA PE=1 SV=4 Cytoplasmic dynein 1 heavy chain 1 OS=Homo sapiens GN=DYNC1H1 PE=1 SV=5 Cluster of ATPase, Na+/K+ transporting, alpha 2 (+) polypeptide OS=Homo sapiens GN=ATP1A2 PE=3 SV=1 (B1AKY9) Fibrinogen beta chain OS=Homo sapiens GN=FGB PE=1 SV=2 Fibrinogen alpha chain OS=Homo sapiens GN=FGA PE=1 SV=2 Dihydropyrimidinase-related protein 2 OS=Homo sapiens GN=DPYSL2 PE=1 SV=1 Cluster of Alpha-actinin-1 OS=Homo sapiens GN=ACTN1 PE=1 SV=2 (P12814) 60 kDa heat shock protein, mitochondrial OS=Homo
    [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]
  • Supplementary Materials
    Supplementary materials Supplementary Table S1: MGNC compound library Ingredien Molecule Caco- Mol ID MW AlogP OB (%) BBB DL FASA- HL t Name Name 2 shengdi MOL012254 campesterol 400.8 7.63 37.58 1.34 0.98 0.7 0.21 20.2 shengdi MOL000519 coniferin 314.4 3.16 31.11 0.42 -0.2 0.3 0.27 74.6 beta- shengdi MOL000359 414.8 8.08 36.91 1.32 0.99 0.8 0.23 20.2 sitosterol pachymic shengdi MOL000289 528.9 6.54 33.63 0.1 -0.6 0.8 0 9.27 acid Poricoic acid shengdi MOL000291 484.7 5.64 30.52 -0.08 -0.9 0.8 0 8.67 B Chrysanthem shengdi MOL004492 585 8.24 38.72 0.51 -1 0.6 0.3 17.5 axanthin 20- shengdi MOL011455 Hexadecano 418.6 1.91 32.7 -0.24 -0.4 0.7 0.29 104 ylingenol huanglian MOL001454 berberine 336.4 3.45 36.86 1.24 0.57 0.8 0.19 6.57 huanglian MOL013352 Obacunone 454.6 2.68 43.29 0.01 -0.4 0.8 0.31 -13 huanglian MOL002894 berberrubine 322.4 3.2 35.74 1.07 0.17 0.7 0.24 6.46 huanglian MOL002897 epiberberine 336.4 3.45 43.09 1.17 0.4 0.8 0.19 6.1 huanglian MOL002903 (R)-Canadine 339.4 3.4 55.37 1.04 0.57 0.8 0.2 6.41 huanglian MOL002904 Berlambine 351.4 2.49 36.68 0.97 0.17 0.8 0.28 7.33 Corchorosid huanglian MOL002907 404.6 1.34 105 -0.91 -1.3 0.8 0.29 6.68 e A_qt Magnogrand huanglian MOL000622 266.4 1.18 63.71 0.02 -0.2 0.2 0.3 3.17 iolide huanglian MOL000762 Palmidin A 510.5 4.52 35.36 -0.38 -1.5 0.7 0.39 33.2 huanglian MOL000785 palmatine 352.4 3.65 64.6 1.33 0.37 0.7 0.13 2.25 huanglian MOL000098 quercetin 302.3 1.5 46.43 0.05 -0.8 0.3 0.38 14.4 huanglian MOL001458 coptisine 320.3 3.25 30.67 1.21 0.32 0.9 0.26 9.33 huanglian MOL002668 Worenine
    [Show full text]
  • Molecular Diagnostic Requisition
    BAYLOR MIRACA GENETICS LABORATORIES SHIP TO: Baylor Miraca Genetics Laboratories 2450 Holcombe, Grand Blvd. -Receiving Dock PHONE: 800-411-GENE | FAX: 713-798-2787 | www.bmgl.com Houston, TX 77021-2024 Phone: 713-798-6555 MOLECULAR DIAGNOSTIC REQUISITION PATIENT INFORMATION SAMPLE INFORMATION NAME: DATE OF COLLECTION: / / LAST NAME FIRST NAME MI MM DD YY HOSPITAL#: ACCESSION#: DATE OF BIRTH: / / GENDER (Please select one): FEMALE MALE MM DD YY SAMPLE TYPE (Please select one): ETHNIC BACKGROUND (Select all that apply): UNKNOWN BLOOD AFRICAN AMERICAN CORD BLOOD ASIAN SKELETAL MUSCLE ASHKENAZIC JEWISH MUSCLE EUROPEAN CAUCASIAN -OR- DNA (Specify Source): HISPANIC NATIVE AMERICAN INDIAN PLACE PATIENT STICKER HERE OTHER JEWISH OTHER (Specify): OTHER (Please specify): REPORTING INFORMATION ADDITIONAL PROFESSIONAL REPORT RECIPIENTS PHYSICIAN: NAME: INSTITUTION: PHONE: FAX: PHONE: FAX: NAME: EMAIL (INTERNATIONAL CLIENT REQUIREMENT): PHONE: FAX: INDICATION FOR STUDY SYMPTOMATIC (Summarize below.): *FAMILIAL MUTATION/VARIANT ANALYSIS: COMPLETE ALL FIELDS BELOW AND ATTACH THE PROBAND'S REPORT. GENE NAME: ASYMPTOMATIC/POSITIVE FAMILY HISTORY: (ATTACH FAMILY HISTORY) MUTATION/UNCLASSIFIED VARIANT: RELATIONSHIP TO PROBAND: THIS INDIVIDUAL IS CURRENTLY: SYMPTOMATIC ASYMPTOMATIC *If family mutation is known, complete the FAMILIAL MUTATION/ VARIANT ANALYSIS section. NAME OF PROBAND: ASYMPTOMATIC/POPULATION SCREENING RELATIONSHIP TO PROBAND: OTHER (Specify clinical findings below): BMGL LAB#: A COPY OF ORIGINAL RESULTS ATTACHED IF PROBAND TESTING WAS PERFORMED AT ANOTHER LAB, CALL TO DISCUSS PRIOR TO SENDING SAMPLE. A POSITIVE CONTROL MAY BE REQUIRED IN SOME CASES. REQUIRED: NEW YORK STATE PHYSICIAN SIGNATURE OF CONSENT I certify that the patient specified above and/or their legal guardian has been informed of the benefits, risks, and limitations of the laboratory test(s) requested.
    [Show full text]
  • PROCEEDINGS of the XVI CONGRESS of the ITALIAN SOCIETY of MYOLOGY
    Acta Myologica • 2016; XXXV: p. 3-81 PROCEEDINGS OF THE XVI CONGRESS OF THE ITALIAN SOCIETY OF MYOLOGY Lecce, Italy June 8-11, 2016 3 PROCEEDINGS OF THE XVI CONGRESS OF THE ITALIAN SOCIETY OF MYOLOGY 5 PROCEEDINGS OF THE XVI CONGRESS OF THE ITALIAN SOCIETY OF MYOLOGY 6 PROCEEDINGS OF THE XVI CONGRESS OF THE ITALIAN SOCIETY OF MYOLOGY 7 PROCEEDINGS OF THE XVI CONGRESS OF THE ITALIAN SOCIETY OF MYOLOGY 8 PROCEEDINGS OF THE XVI CONGRESS OF THE ITALIAN SOCIETY OF MYOLOGY 9 PROCEEDINGS OF THE XVI CONGRESS OF THE ITALIAN SOCIETY OF MYOLOGY 10 PROCEEDINGS OF THE XVI CONGRESS OF THE ITALIAN SOCIETY OF MYOLOGY ABSTRACTS OF INVITED LECTURES (in alphabetical order of the first Author) Brain in muscle diseases ciency (CMD1A), also in the mildest cases with a LGMD Bertini E. phenotype. Moreover progressive brain MRI abnormali- Unit of Neuromuscular and Neurodegenerative Disorders, ties are observed in adult DM1 patients as white matter Laboratory of Molecular Medicine, Bambino Gesù Children’s involvement and brain atrophy, and some studies under- Hospital IRCCS, Rome line that WM damage is likely to be the major contributor It is well known that brain involvement is generally to cognitive impairment in DM1. unusual in muscle disease, and should be considered in the algorithm of the differential diagnosis of myopathies. Epigenetics in Myotonic Dystrophies Classification of brain involvement in myopathies, ex- Botta A. cluding mitochondrial encephalomyopathies, can be clas- Dept. of Biomedicine and Prevention, Tor Vergata University of sified for convenience in two main subgroups:1) those Rome, Italy conditions with mental disabilities that are not associated Myotonic dystrophy type 1 (DM1, Steinert’s disease, with brain malformations; and 2) those that are associated MIM#160900) is the most common form of adult-onset with malformations or peculiar brain abnormalities, and muscular dystrophy in humans, characterized by myoto- can be detected by MRI.
    [Show full text]
  • A Homozygous DPM3 Mutation in a Patient with Alpha-Dystroglycan-Related Limb Girdle Muscular Dystrophy P.Y.K
    Available online at www.sciencedirect.com ScienceDirect Neuromuscular Disorders 27 (2017) 1043–1046 www.elsevier.com/locate/nmd Case report A homozygous DPM3 mutation in a patient with alpha-dystroglycan-related limb girdle muscular dystrophy P.Y.K. Van den Bergh a,*, Y. Sznajer a,b, V. Van Parys a, W. va n To l c,d, R.A. Wevers d, D.J. Lefeber c,d, L. Xu e,f, M. Lek e,f, D.G. MacArthur e,f, K. Johnson g, L. Phillips g, A. Töpf g, V. Straub g a Neuromuscular Reference Centre, University Hospital St-Luc, University of Louvain, Brussels, Belgium b Centre for Human Genetics, University Hospital St-Luc, University of Louvain, Brussels, Belgium c Department of Neurology, Radboud University Medical Centre, Nijmegen, The Netherlands d Translational Metabolic Laboratory, Radboud University Medical Centre, Nijmegen, The Netherlands e Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, MA 02114, USA f Program in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA g The John Walton Muscular Dystrophy Research Centre, Institute of Genetic Medicine, Newcastle University, Newcastle upon-Tyne, United Kingdom Received 19 April 2017; received in revised form 27 June 2017; accepted 12 July 2017 Abstract Defects of O-linked glycosylation of alpha-dystroglycan cause a wide spectrum of muscular dystrophies ranging from severe congenital muscular dystrophy associated with abnormal brain and eye development to mild limb girdle muscular dystrophy. We report a female patient who developed isolated pelvic girdle muscle weakness and wasting, which became symptomatic at age 42. Exome sequencing uncovered a homozygous c.131T > G (p.Leu44Pro) substitution in DPM3, encoding dolichol-P-mannose (DPM) synthase subunit 3, leading to a 50% reduction of enzymatic activity.
    [Show full text]
  • Prenatal Testing Requisition Form
    BAYLOR MIRACA GENETICS LABORATORIES SHIP TO: Baylor Miraca Genetics Laboratories 2450 Holcombe, Grand Blvd. -Receiving Dock PHONE: 800-411-GENE | FAX: 713-798-2787 | www.bmgl.com Houston, TX 77021-2024 Phone: 713-798-6555 PRENATAL COMPREHENSIVE REQUISITION FORM PATIENT INFORMATION NAME (LAST,FIRST, MI): DATE OF BIRTH (MM/DD/YY): HOSPITAL#: ACCESSION#: REPORTING INFORMATION ADDITIONAL PROFESSIONAL REPORT RECIPIENTS PHYSICIAN: NAME: INSTITUTION: PHONE: FAX: PHONE: FAX: NAME: EMAIL (INTERNATIONAL CLIENT REQUIREMENT): PHONE: FAX: SAMPLE INFORMATION CLINICAL INDICATION FETAL SPECIMEN TYPE Pregnancy at risk for specific genetic disorder DATE OF COLLECTION: (Complete FAMILIAL MUTATION information below) Amniotic Fluid: cc AMA PERFORMING PHYSICIAN: CVS: mg TA TC Abnormal Maternal Screen: Fetal Blood: cc GESTATIONAL AGE (GA) Calculation for AF-AFP* NTD TRI 21 TRI 18 Other: SELECT ONLY ONE: Abnormal NIPT (attach report): POC/Fetal Tissue, Type: TRI 21 TRI 13 TRI 18 Other: Cultured Amniocytes U/S DATE (MM/DD/YY): Abnormal U/S (SPECIFY): Cultured CVS GA ON U/S DATE: WKS DAYS PARENTAL BLOODS - REQUIRED FOR CMA -OR- Maternal Blood Date of Collection: Multiple Pregnancy Losses LMP DATE (MM/DD/YY): Parental Concern Paternal Blood Date of Collection: Other Indication (DETAIL AND ATTACH REPORT): *Important: U/S dating will be used if no selection is made. Name: Note: Results will differ depending on method checked. Last Name First Name U/S dating increases overall screening performance. Date of Birth: KNOWN FAMILIAL MUTATION/DISORDER SPECIFIC PRENATAL TESTING Notice: Prior to ordering testing for any of the disorders listed, you must call the lab and discuss the clinical history and sample requirements with a genetic counselor.
    [Show full text]
  • Epigenetic Mechanisms Are Involved in the Oncogenic Properties of ZNF518B in Colorectal Cancer
    Epigenetic mechanisms are involved in the oncogenic properties of ZNF518B in colorectal cancer Francisco Gimeno-Valiente, Ángela L. Riffo-Campos, Luis Torres, Noelia Tarazona, Valentina Gambardella, Andrés Cervantes, Gerardo López-Rodas, Luis Franco and Josefa Castillo SUPPLEMENTARY METHODS 1. Selection of genomic sequences for ChIP analysis To select the sequences for ChIP analysis in the five putative target genes, namely, PADI3, ZDHHC2, RGS4, EFNA5 and KAT2B, the genomic region corresponding to the gene was downloaded from Ensembl. Then, zoom was applied to see in detail the promoter, enhancers and regulatory sequences. The details for HCT116 cells were then recovered and the target sequences for factor binding examined. Obviously, there are not data for ZNF518B, but special attention was paid to the target sequences of other zinc-finger containing factors. Finally, the regions that may putatively bind ZNF518B were selected and primers defining amplicons spanning such sequences were searched out. Supplementary Figure S3 gives the location of the amplicons used in each gene. 2. Obtaining the raw data and generating the BAM files for in silico analysis of the effects of EHMT2 and EZH2 silencing The data of siEZH2 (SRR6384524), siG9a (SRR6384526) and siNon-target (SRR6384521) in HCT116 cell line, were downloaded from SRA (Bioproject PRJNA422822, https://www.ncbi. nlm.nih.gov/bioproject/), using SRA-tolkit (https://ncbi.github.io/sra-tools/). All data correspond to RNAseq single end. doBasics = TRUE doAll = FALSE $ fastq-dump -I --split-files SRR6384524 Data quality was checked using the software fastqc (https://www.bioinformatics.babraham. ac.uk /projects/fastqc/). The first low quality removing nucleotides were removed using FASTX- Toolkit (http://hannonlab.cshl.edu/fastxtoolkit/).
    [Show full text]