DOCSLIB.ORG

Novel O-Glycan Arrays to Characterize Human Cancer-Associated Epithelial Antigens

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Novel O-Glycan Arrays to Characterize Human Cancer-Associated Epithelial Antigens Novel O-glycan arrays to characterize human cancer-associated epithelial antigens A thesis submitted for the degree of Doctor of Philosophy at Imperial College London by Chao Gao Glycosciences Laboratory Division of Immunology and Inflammation Department of Medicine Faculty of Medicine Imperial College London February 2015 ABSTRACT Aberrantly expressed carbohydrates occur on cancer cells and are antigenic. This thesis is focused on studies to elucidate two elusive hybridoma-defined, cancer- associated carbohydrate antigens: a prostate cancer-associated antigen F77 and a broadly distributed epithelial cancer-associated antigen AE3. The key experiments performed are microarray analyses with mucin-type glycoproteins and generation of designer arrays, multidimensional chromatographies and mass spectrometry of O-glycomes. Antigen-positive sequences assigned are corroborated with focused arrays of natural and chemically synthetized oligosaccharides or glycolipids and products of glycosidase treatments. The F77 antigen is assigned as blood group H type 2 on a 6-linked branch of a poly- N-acetyllactosamine backbone (structure a). This sequence is shown to occur on O- glycans and on glycolipids. The F77 antibody can bind, with lower intensities, to the blood group A and B analogues of structure a. The minimum F77 antigenic sequence is shown to be a pentasaccharide (underlined in structure a). The close association of F77 antigen with prostate cancer is proposed to be a consequence of up- regulation of branching enzymes together with persistent expression of H antigen. This may account for the prevalence of F77 antigen in prostate cancers irrespective of the patients‘ ABO blood group status. There appear to be two distinct forms of AE3 antigen as evidenced by the ability of AE3 antibody to bind: (i) the O-glycan structure b, known as T antigen, which is joined by α-linkage to serine on mucin-type glycoproteins, and (ii) a sulphated glycolipid known as SM1a (structure c) in which ―T‖ sequence is joined by β-linkage to galactose. An O-glycan analogue of structure c (structure d), has not been 2 reported so far. Chemo-enzymatic synthesis of structure d will shortly be attempted for antigenic analysis. With knowledge of details of these two antigens, the biosynthetic pathways, the biological functions and clinical applications can now be rationally pursued. 3 DECARATION OF ORIGINALITY I, Chao Gao, hereby declare that the work presented in this thesis is my own work. Where I have used materials and results from other sources, this is clearly stated. This thesis has not been submitted for a degree to any other academic institution. Most of the results in Chapter 3 of this thesis have been published in the two papers below. Gao, C., Liu, Y., Zhang, H., Zhang, Y., Fukuda, M. N., Palma, A. S., Kozak, R. P., Childs, R. A., Nonaka, M., Li, Z., Siegel, D. L., Hanfland, P., Peehl, D. M., Chai, W., Greene, M. I., and Feizi, T. (2014) Carbohydrate Sequence of the Prostate Cancer- associated Antigen F77 Assigned by a Mucin O-Glycome Designer Array. J Biol Chem 289, 16462-16477 Nonaka, M., Fukuda, M. N., Gao, C., Li, Z., Zhang, H., Greene, M. I., Peehl, D. M., Feizi, T., and Fukuda, M. (2014) Determination of Carbohydrate Structure Recognized by Prostate-specific F77 Monoclonal Antibody through Expression Analysis of Glycosyltransferase Genes. J Biol Chem 289, 16478-16486 The work described in Section 3.8 has been presented at the 2014 Meeting of the Society for Glycobiology and the abstract has been published as below. Gao, C., Imamura, A., Liu, Y., Zhang, H., Zhang, Y., Chai, W., Kiso, M., Greene, M., and Feizi, T. (2014) Clinching the elusive prostate cancer antigen F77. in 2014 Joint Meeting of the Society for Glycobiology and the Japanese Society of Carbohydrate Research, Glycobiology 24, 1195 Chao Gao 4 COPYRIGHT DECLARATION The copyright of this thesis rests with the author and is made available under a Creative Commons Attribution Non-Commercial No Derivatives license. Researchers are free to copy, distribute or transmit the thesis on the condition that they attribute it, that they do not use it for commercial purposes and that they do not alter, transform or build upon it. For any reuse or redistribution, researchers must make clear to others the license terms of this work. 5 ACKNOWLEDGEMENTS I would like to express my utmost gratitude to my supervisor Professor Ten Feizi for her constant patience and guidance in so many aspects of my study at Imperial College. She led me to into the field of glycobiology, which is a fast growing area with great potential opportunities. Her broad knowledge of carbohydrate sequences and functions is of great value to a PhD student who is starting and willing to devote himself to this field. Professor Feizi is also a good model of scientist, always energetic, sharp and enthusiastic in addressing scientific problems and observations. More importantly, Professor Feizi spends time with her students. My whole PhD progressed with valuable discussions with her on writing reports, manuscripts and my thesis, and in preparing presentations. Her mentoring was remarkable and I have benefited a lot from her training. I would take this opportunity also to thank Dr Wengang Chai, who introduced me to the Glycosciences Laboratory at the very beginning. A short conversation in China opened a brand new avenue to me in 2010. Dr Chai is an excellent scientist with strong determination. He is very well organised and he always thinks ahead of time. I have received tremendously valuable advice from him on how to perform good experiments and how to organise my tasks in the most efficient way. He generously shared with me his great experience in experimental procedures, especially in O- glycan release, oligosaccharide fractionation, all steps in making neoglycolipids and performing analyses by mass spectrometry (MS). I appreciate his comments and suggestions. Dr Yan Liu is a great scientist I admire very much. She is a good teacher and has offered great help and guidance in my microarray experiments, from the planning, the probe preparation to arraying, binding experiments and data analysis. She started the F77 project and made a great contribution throughout the project. She has also guided me in my writing and presentations. I would like to express my sincere gratitude to Dr Liu (who is now a great mother as well as a scientist). 6 Special thanks to Dr Yibing Zhang. He helped me to do the MS analysis each time, and I ―happened to‖ have so many samples every time. I was always eager to know the results and he was always so prompt in running my samples. Dr Zhang is a great friend. He walked me through in each step when I met problems. I would like to thank my colleagues who provided teaching and help during my studies in the Glycosciences Laboratory, Dr Robert A Childs, Dr Mark S Stoll, Dr Colin Herbert and Dr Barbara Molloy. I should particularly thank Dr Angelina Palma, who prepared the first mucin array and gave me important advice on the design of microarray experiments. She initiated the AE3 project. Dr. Juthathip Mongkolsapaya has special thanks from me for resurrecting the AE3 hybridoma clone received from venerable Dr. John Codington, and providing no less than 1 litre of potent culture supernatant. This was most welcome at a time when the AE3 antibody had become scarce. Many thanks go to the PhD students in the laboratory, Frederick Gyapon Quast and Zhen Li. I would like to thank our external collaborators who generously provided precious antibodies, glycolipids, oligosaccharides and enzymes, and contributed to the discussions in the course of my PhD project. Due to the space limit, I am only able to list their names here: Drs. Mark Greene, Hongtao Zhang, Don Siegel, Nonaka Motohiro, Michiko Fukuda, Minoru Fukuda, Donna Peehl, Peter Hanfland, Radoslaw P. Kozak, Makoto Kiso, Akihiro Imamura, Ando Hiromune, Susann Teneberg, Henrik Clausen, Ola Blixt, Joy Burchell and Joyce Taylor-Papadimitriou. I would like to thank my parents for being tolerant and patient although they are not scientists. They are the best parents one could ever have. They have, with their love, built the warmest and coziest home, where I dream of going back to, almost every day. It is a shelter where I can go whenever I have troubles and difficulties. I love my parents. When I look back at these four years, I feel so lucky to have made so many good friends from every corner of the world. I should thank my dearest friends for their great support and advice on all aspects of my PhD studies: Drs Yaozu Xiang, Hua Zhang, Jiaying Tang, Bo Han, Yichen Xu, Chuncheng Guo, Yuepeng Wang, Wei Dai, 7 Hongbo Zhou, Lan Wei, Xue Yang, Zhongping Xiao, Chuncui Huang and Hongtao Zhang; Lei Cheng Lit, Lei Wang, Chenjing Shang, Qize Ding, Nan Jia, Qiushi Chen, Ningyu Xiao, Chengli Zong, Fan Zhang, Xiangpeng Li and Xia Wu. I also want to give my special thanks to my flatmate Jin Ma. I will never forget the delicious meals you cooked at home and the fancy restaurants we went to together. More importantly, I will remember forever the days and nights we spent together studying at home. I overcame my laziness each time I saw how diligent and focused you were during your studying. My gratitude is to all my teachers and colleagues at Ocean University of China, especially my forever mentor Professor Huashi Guan for his support and encouragement since my master‘s studies. Also I want to thank my teachers Professors Guangli Yu, Hongbing Liu and Chunxia Li, and my colleagues and friends in Ocean University of China. Last but not least, I would like to thank the China Scholarship Council, the Henry Lester Trust, and Professor Ten Feizi for supporting my studies at Imperial College and making all of the above-mentioned stories possible.
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]
  • Fucosyltransferase Genes on Porcine Chromosome 6Q11 Are Closely Linked to the Blood Group Inhibitor (S) and Escherichia Coli F18 Receptor (ECF18R) Loci
    Mammalian Genome 8, 736–741 (1997). © Springer-Verlag New York Inc. 1997 Two a(1,2) fucosyltransferase genes on porcine Chromosome 6q11 are closely linked to the blood group inhibitor (S) and Escherichia coli F18 receptor (ECF18R) loci E. Meijerink,1 R. Fries,1,*P.Vo¨geli,1 J. Masabanda,1 G. Wigger,1 C. Stricker,1 S. Neuenschwander,1 H.U. Bertschinger,2 G. Stranzinger1 1Institute of Animal Science, Swiss Federal Institute of Technology, ETH-Zentrum, CH-8092 Zurich, Switzerland 2Institute of Veterinary Bacteriology, University of Zurich, CH 8057 Zurich, Switzerland Received: 17 February 1997 / Accepted: 30 May 1997 Abstract. The Escherichia coli F18 receptor locus (ECF18R) has fimbriae F107, has been shown to be genetically controlled by the been genetically mapped to the halothane linkage group on porcine host and is inherited as a dominant trait (Bertschinger et al. 1993) Chromosome (Chr) 6. In an attempt to obtain candidate genes for with B being the susceptibility allele and b the resistance allele. this locus, we isolated 5 cosmids containing the a(1,2)fucosyl- The genetic locus for this E. coli F18 receptor (ECF18R) has been transferase genes FUT1, FUT2, and the pseudogene FUT2P from mapped to porcine Chr 6 (SSC6), based on its close linkage to the a porcine genomic library. Mapping by fluorescence in situ hy- S locus and other loci of the halothane (HAL) linkage group (Vo¨- bridization placed all these clones in band q11 of porcine Chr 6 geli et al. 1996). The epistatic S locus suppresses the phenotypic (SSC6q11). Sequence analysis of the cosmids resulted in the char- expression of the A-0 blood group system when being SsSs (Vo¨geli acterization of an open reading frame (ORF), 1098 bp in length, et al.
    [Show full text]
  • Circular RNA Circ 0128846 Promotes the Progression of Osteoarthritis By
    Liu et al. Journal of Orthopaedic Surgery and Research (2021) 16:307 https://doi.org/10.1186/s13018-021-02428-z RESEARCH ARTICLE Open Access Circular RNA circ_0128846 promotes the progression of osteoarthritis by regulating miR-127-5p/NAMPT axis Chao Liu1, Ping Cheng2, Jianjun Liang1, Xiaoming Zhao3 and Wei Du3* Abstract Background: Mounting evidence indicates that circular RNAs (circRNAs) participate in the occurrence and development of various diseases, including osteoarthritis (OA). However, the effects and molecular mechanism of circ_0128846 in OA have not been reported. Methods: The expression levels of circ_0128846, microRNA-127-5p (miR-127-5p), and nicotinamide phosphoribosyltransferase (NAMPT) were determined by quantitative real-time polymerase chain reaction (qRT-PCR) or western blot assay. Cell viability was determined by Cell Counting Kit-8 (CCK-8) assay. Cell apoptosis was examined by flow cytometry and western blot assay. Inflammatory response and cartilage extracellular matrix (ECM) degradation were evaluated by western blot assay. The relationship between miR-127-5p and circ_0128846 or NAMPT was predicted by bioinformatics tools and verified by dual-luciferase reporter and RNA Immunoprecipitation (RIP) assays. Results: Circ_0128846 and NAMPT were upregulated and miR-127-5p was downregulated in OA cartilage tissues. Knockdown of circ_0128846 increased cell viability and inhibited apoptosis, inflammation and ECM degradation in OA chondrocytes, while these effects were reversed by downregulating miR-127-5p. Moreover, circ_0128846 positively regulated NAMPT expression by sponging miR-127-5p. Furthermore, miR-127-5p promoted cell viability and suppressed apoptosis, inflammation, and ECM degradation in OA chondrocytes by directly targeting NAMPT. Conclusion: Circ_0128846 knockdown might inhibit the progression of OA by upregulating miR-127-5p and downregulating NAMPT, offering a new insight into the potential application of circ_0128846 in OA treatment.
    [Show full text]
  • Endometrial Gene Expression in the Early Luteal Phase Is Impacted By
    Human Reproduction, Vol.27, No.11 pp. 3259–3272, 2012 Advanced Access publication on August 28, 2012 doi:10.1093/humrep/des279 ORIGINAL ARTICLE Reproductive biology Endometrial gene expression in the early luteal phase is impacted by mode of triggering final oocyte maturation in recFSH stimulated and GnRH antagonist co-treated IVF cycles P. Humaidan1,*, I. Van Vaerenbergh2, C. Bourgain2, B. Alsbjerg3, Downloaded from C. Blockeel4, F. Schuit5, L. Van Lommel5, P. Devroey4, and H. Fatemi4 1The Fertility Clinic, Department D, Odense University Hospital, OHU, Entrance 55, Odense C 5000, Denmark 2Reproductive Immunology and Implantation Unit, Dutch-speaking Free University of Brussels, Brussels, Belgium 3The Fertility Clinic, Skive Regional Hospital, Skive, Denmark 4Centre for Reproductive Medicine, Dutch-speaking Free University of Brussels, Brussels, Belgium 5Gene Expression Unit, KU Leuven, Leuven, Belgium http://humrep.oxfordjournals.org/ *Correspondence address. Tel: +45-20-34-26-87; E-mail: [email protected] Submitted on March 9, 2012; resubmitted on June 3, 2012; accepted on June 22, 2012 study question: Do differences in endometrial gene expression exist after ovarian stimulation with four different regimens of triggering final oocyte maturation and luteal phase support in the same patient? summary answer: Significant differences in the expression of genes involved in receptivity and early implantation were seen between by greta verheyen on June 5, 2013 the four protocols. what is known already: GnRH agonist triggering
    [Show full text]
  • Genetic Testing Policy Number: PG0041 ADVANTAGE | ELITE | HMO Last Review: 04/11/2021
    Genetic Testing Policy Number: PG0041 ADVANTAGE | ELITE | HMO Last Review: 04/11/2021 INDIVIDUAL MARKETPLACE | PROMEDICA MEDICARE PLAN | PPO GUIDELINES This policy does not certify benefits or authorization of benefits, which is designated by each individual policyholder terms, conditions, exclusions and limitations contract. It does not constitute a contract or guarantee regarding coverage or reimbursement/payment. Paramount applies coding edits to all medical claims through coding logic software to evaluate the accuracy and adherence to accepted national standards. This medical policy is solely for guiding medical necessity and explaining correct procedure reporting used to assist in making coverage decisions and administering benefits. SCOPE X Professional X Facility DESCRIPTION A genetic test is the analysis of human DNA, RNA, chromosomes, proteins, or certain metabolites in order to detect alterations related to a heritable or acquired disorder. This can be accomplished by directly examining the DNA or RNA that makes up a gene (direct testing), looking at markers co-inherited with a disease-causing gene (linkage testing), assaying certain metabolites (biochemical testing), or examining the chromosomes (cytogenetic testing). Clinical genetic tests are those in which specimens are examined and results reported to the provider or patient for the purpose of diagnosis, prevention or treatment in the care of individual patients. Genetic testing is performed for a variety of intended uses: Diagnostic testing (to diagnose disease) Predictive
    [Show full text]
  • The Expression of Genes Contributing to Pancreatic Adenocarcinoma Progression Is Influenced by the Respective Environment – Sagini Et Al
    The expression of genes contributing to pancreatic adenocarcinoma progression is influenced by the respective environment – Sagini et al Supplementary Figure 1: Target genes regulated by TGM2. Figure represents 24 genes regulated by TGM2, which were obtained from Ingenuity Pathway Analysis. As indicated, 9 genes (marked red) are down-regulated by TGM2. On the contrary, 15 genes (marked red) are up-regulated by TGM2. Supplementary Table 1: Functional annotations of genes from Suit2-007 cells growing in pancreatic environment Categoriesa Diseases or p-Valuec Predicted Activation Number of genesf Functions activationd Z-scoree Annotationb Cell movement Cell movement 1,56E-11 increased 2,199 LAMB3, CEACAM6, CCL20, AGR2, MUC1, CXCL1, LAMA3, LCN2, COL17A1, CXCL8, AIF1, MMP7, CEMIP, JUP, SOD2, S100A4, PDGFA, NDRG1, SGK1, IGFBP3, DDR1, IL1A, CDKN1A, NREP, SEMA3E SERPINA3, SDC4, ALPP, CX3CL1, NFKBIA, ANXA3, CDH1, CDCP1, CRYAB, TUBB2B, FOXQ1, SLPI, F3, GRINA, ITGA2, ARPIN/C15orf38- AP3S2, SPTLC1, IL10, TSC22D3, LAMC2, TCAF1, CDH3, MX1, LEP, ZC3H12A, PMP22, IL32, FAM83H, EFNA1, PATJ, CEBPB, SERPINA5, PTK6, EPHB6, JUND, TNFSF14, ERBB3, TNFRSF25, FCAR, CXCL16, HLA-A, CEACAM1, FAT1, AHR, CSF2RA, CLDN7, MAPK13, FERMT1, TCAF2, MST1R, CD99, PTP4A2, PHLDA1, DEFB1, RHOB, TNFSF15, CD44, CSF2, SERPINB5, TGM2, SRC, ITGA6, TNC, HNRNPA2B1, RHOD, SKI, KISS1, TACSTD2, GNAI2, CXCL2, NFKB2, TAGLN2, TNF, CD74, PTPRK, STAT3, ARHGAP21, VEGFA, MYH9, SAA1, F11R, PDCD4, IQGAP1, DCN, MAPK8IP3, STC1, ADAM15, LTBP2, HOOK1, CST3, EPHA1, TIMP2, LPAR2, CORO1A, CLDN3, MYO1C,
    [Show full text]
  • 10Th Anniversary of the Human Genome Project
    Grand Celebration: 10th Anniversary of the Human Genome Project Volume 3 Edited by John Burn, James R. Lupski, Karen E. Nelson and Pabulo H. Rampelotto Printed Edition of the Special Issue Published in Genes www.mdpi.com/journal/genes John Burn, James R. Lupski, Karen E. Nelson and Pabulo H. Rampelotto (Eds.) Grand Celebration: 10th Anniversary of the Human Genome Project Volume 3 This book is a reprint of the special issue that appeared in the online open access journal Genes (ISSN 2073-4425) in 2014 (available at: http://www.mdpi.com/journal/genes/special_issues/Human_Genome). Guest Editors John Burn University of Newcastle UK James R. Lupski Baylor College of Medicine USA Karen E. Nelson J. Craig Venter Institute (JCVI) USA Pabulo H. Rampelotto Federal University of Rio Grande do Sul Brazil Editorial Office Publisher Assistant Editor MDPI AG Shu-Kun Lin Rongrong Leng Klybeckstrasse 64 Basel, Switzerland 1. Edition 2016 MDPI • Basel • Beijing • Wuhan ISBN 978-3-03842-123-8 complete edition (Hbk) ISBN 978-3-03842-169-6 complete edition (PDF) ISBN 978-3-03842-124-5 Volume 1 (Hbk) ISBN 978-3-03842-170-2 Volume 1 (PDF) ISBN 978-3-03842-125-2 Volume 2 (Hbk) ISBN 978-3-03842-171-9 Volume 2 (PDF) ISBN 978-3-03842-126-9 Volume 3 (Hbk) ISBN 978-3-03842-172-6 Volume 3 (PDF) © 2016 by the authors; licensee MDPI, Basel, Switzerland. All articles in this volume are Open Access distributed under the Creative Commons License (CC-BY), which allows users to download, copy and build upon published articles even for commercial purposes, as long as the author and publisher are properly credited, which ensures maximum dissemination and a wider impact of our publications.
    [Show full text]
  • Differential Mucosal Gene Expression Modulates the Development of Murine Colitis Zhiping Liu Iowa State University
    Iowa State University Capstones, Theses and Retrospective Theses and Dissertations Dissertations 2008 Differential mucosal gene expression modulates the development of murine colitis Zhiping Liu Iowa State University Follow this and additional works at: https://lib.dr.iastate.edu/rtd Part of the Allergy and Immunology Commons, and the Medical Immunology Commons Recommended Citation Liu, Zhiping, "Differential mucosal gene expression modulates the development of murine colitis" (2008). Retrospective Theses and Dissertations. 15866. https://lib.dr.iastate.edu/rtd/15866 This Dissertation is brought to you for free and open access by the Iowa State University Capstones, Theses and Dissertations at Iowa State University Digital Repository. It has been accepted for inclusion in Retrospective Theses and Dissertations by an authorized administrator of Iowa State University Digital Repository. For more information, please contact [email protected]. Differential mucosal gene expression modulates the development of murine colitis by Zhiping Liu A dissertation submitted to the graduate faculty in partial fulfillment of the requirements for the degree of DOCTOR OF PHILOSOPHY Major: Immunobiology Program of Study Committee: Michael J. Wannemuehler, Major Professor Randy E. Sacco Jesse M. Hostetter Douglas E. Jones Eileen L. Thacker Iowa State University Ames, Iowa 2008 Copyright © Zhiping Liu, 2008. All rights reserved. UMI Number: 3299613 UMI Microform 3299613 Copyright 2008 by ProQuest Information and Learning Company. All rights reserved. This microform edition is protected against unauthorized copying under Title 17, United States Code. ProQuest Information and Learning Company 300 North Zeeb Road P.O. Box 1346 Ann Arbor, MI 48106-1346 ii DEDICATION This dissertation is dedicated to: My daughter Zoe Liu, who was two years old on December 16, 2007; And my son Gavin Liu, who will be born on February 2008; And my wife Jun Jiang.
    [Show full text]
  • Normal Development and Fertility of Fut1, Fut2, and Sec1 Triple Knockout Mice Jiaxi Chen1*, Zhipeng Su2*, Chunlei Zhang3,4*
    bioRxiv preprint doi: https://doi.org/10.1101/615070; this version posted April 21, 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. Normal development and fertility of Fut1, Fut2, and Sec1 triple knockout mice Jiaxi Chen1*, Zhipeng Su2*, Chunlei Zhang3,4*, Fenge Li4, Patrick Hwu4, Zhen Wang2, Yanping Wang2, Yunsen Li2, Jiao Tong1, Chunchao Chen1, Dapeng Zhou1 1, School of Medicine, Tongji University, Shanghai 200092, China. 2, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA. 3, Shenzhen Hospital of Chinese Medicine, Shenzhen, Guangdong 518033, P.R. China. 4, Laboratory of Cellular and Molecular Tumor Immunology, Institutes of Biology and Medical Sciences, Jiangsu Laboratory of Infection Immunity, Soochow University, Suzhou, 215123, China. *These authors contributed equally to this study. Correspondence author: Tongji University School of Medicine, 1239 Siping Road, Shanghai, 200092, China. Tel: +86-21-65987589, Dr. Dapeng Zhou, E-mail address: [email protected] bioRxiv preprint doi: https://doi.org/10.1101/615070; this version posted April 21, 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. Abbreviations: Fut1, a-2 fucosyltransferase I; Fut2, a-2 fucosyltransferase II; Sec1, a-2 fucosyltransferase III; Blood group H, Fuc a2 Gal b; Blood group A, GalNAc a3 Fuc a2 Gal b; Blood group B, Gal a3 Fuc a2 Gal b; CFG, consortium of functional glycomics; Lewis y, Fuc a2 Gal b4 (a3) GlcNAc b; Type I H, Fuc a2 Gal b3 GlcNAc b; Type II H, Fuc a2 Gal b4 GlcNAc b; Type III H, Fuc a2 Gal b3 GalNAc a; Type IV H, Fuc a2 Gal b3 GalNAc b; Type V H, Fuc a2 Gal b3 Ga b; Type VI H, Fuc a2 Gal b4 Glc b bioRxiv preprint doi: https://doi.org/10.1101/615070; this version posted April 21, 2019.
    [Show full text]
  • The Interaction of the Gut Microbiota with the Mucus Barrier in Health and Disease in Human
    Review The Interaction of the Gut Microbiota with the Mucus Barrier in Health and Disease in Human Anthony P. Corfield Mucin Research Group, School of Clinical Sciences, Bristol Royal Infirmary, Level 7, Marlborough Street, Bristol BS2 8HW, UK; [email protected] Received: 29 June 2018; Accepted: 30 July 2018; Published: 2 August 2018 Abstract: Glycoproteins are major players in the mucus protective barrier in the gastrointestinal and other mucosal surfaces. In particular the mucus glycoproteins, or mucins, are responsible for the protective gel barrier. They are characterized by their high carbohydrate content, present in their variable number, tandem repeat domains. Throughout evolution the mucins have been maintained as integral components of the mucosal barrier, emphasizing their essential biological status. The glycosylation of the mucins is achieved through a series of biosynthetic pathways processes, which generate the wide range of glycans found in these molecules. Thus mucins are decorated with molecules having information in the form of a glycocode. The enteric microbiota interacts with the mucosal mucus barrier in a variety of ways in order to fulfill its many normal processes. How bacteria read the glycocode and link to normal and pathological processes is outlined in the review. Keywords: gastrointestinal; glycoprotein; glycosylation; glycan; glycocode; microbiota; mucus; mucin; mucosal 1. Introduction The mucosal protective barrier is a feature of higher animals and has been developed and maintained throughout evolution [1,2]. The family of mucus glycoproteins, the mucins, are an integral part of this barrier and also feature throughout evolution [3,4]. A principal character of the mucins is their glycosylation, a high proportion of their molecular weight consists of carbohydrate in the form of oligosaccharides, or glycan chains [5–8].
    [Show full text]
  • A Personalised Dietary Approach—A Way Forward to Manage Nutrient Deficiency, Effects of the Western Diet, and Food Intolerance
    nutrients Review A Personalised Dietary Approach—A Way Forward to Manage Nutrient Deficiency, Effects of the Western Diet, and Food Intolerances in Inflammatory Bowel Disease Bobbi B Laing 1,2 , Anecita Gigi Lim 1 and Lynnette R Ferguson 1,* 1 Faculty of Medical and Health Sciences, University of Auckland, Auckland 1023, New Zealand 2 Nutrition Society of New Zealand, Palmerston North 4444, New Zealand * Correspondence: [email protected] Received: 7 May 2019; Accepted: 2 July 2019; Published: 5 July 2019 Abstract: This review discusses the personalised dietary approach with respect to inflammatory bowel disease (IBD). It identifies gene–nutrient interactions associated with the nutritional deficiencies that people with IBD commonly experience, and the role of the Western diet in influencing these. It also discusses food intolerances and how particular genotypes can affect these. It is well established that with respect to food there is no “one size fits all” diet for those with IBD. Gene–nutrient interactions may help explain this variability in response to food that is associated with IBD. Nutrigenomic research, which examines the effects of food and its constituents on gene expression, shows that—like a number of pharmaceutical products—food can have beneficial effects or have adverse (side) effects depending on a person’s genotype. Pharmacogenetic research is identifying gene variants with adverse reactions to drugs, and this is modifying clinical practice and allowing individualised treatment. Nutrigenomic research could enable individualised treatment in persons with IBD and enable more accurate tailoring of food intake, to avoid exacerbating malnutrition and to counter some of the adverse effects of the Western diet.
    [Show full text]
  • The H Blood Group System
    R EVIEW The H blood group system E.A. Scharberg, C. Olsen, and P. Bugert The H blood group system, ISBT symbol H (018), consists of a types (Fig. 1). The H antigen on the type 1 precursor is single antigen (H) defined by a terminal fucose residue found predominantly produced by the α-1,2-fucosyltransferase on red blood cells and in secretions formed by the action 2 (α2FucT2) enzyme in secretory cells of the digestive and of α-1,2-fucosyltransferases 1 (α2FucT1) and 2 (α2FucT2), respectively. Mutant alleles of the corresponding FUT1 and FUT2 respiratory tracts. The α-1,2-fucosyltransferase 1 (α2FucT1) genes result in either a H– phenotype (Bombay phenotype, Oh) enzyme is a single-pass type II transmembrane glycoprotein w or a weak H phenotype (para-Bombay, H+ ). In addition, the found in the Golgi apparatus that forms the H antigen on type 2 FUT2 gene is the molecular basis of the secretor (Se) status, and homozygosity or compound heterozygosity for null alleles precursor chains in erythroid tissues and vascular endothelial is associated with the nonsecretor (se) status. H– individuals cells.6,7 The carbohydrate chain including the H antigen is then have natural anti-H (mostly IgM), which can cause severe the substrate of the glycosyltransferases encoded by the ABO hemolytic transfusion reactions with intravascular hemolysis. gene to produce A and/or B antigens. Subsequently, in blood Immunohematology 2016;32:112–118. group O individuals, the H antigen is not converted to A or B Key Words: H antigen, Bombay phenotype, Oh, FUT1, FUT2 and is strongly detectable on RBCs.
    [Show full text]