DOCSLIB.ORG

Genes Involved in DNA Repair and Nitrosamine Metabolism and Those Located on Chromosome 14Q32 Are Dysregulated in Nasopharyngeal Carcinoma

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Genes Involved in DNA Repair and Nitrosamine Metabolism and Those Located on Chromosome 14Q32 Are Dysregulated in Nasopharyngeal Carcinoma 2216 Genes Involved in DNA Repair and Nitrosamine Metabolism and Those Located on Chromosome 14q32 Are Dysregulated in Nasopharyngeal Carcinoma Lori E. Dodd,1 Srikumar Sengupta,4 I-How Chen,7 Johan A. den Boon,4 Yu-Juen Cheng,8 William Westra,9 Michael A. Newton,5 Beth F. Mittl,3 Lisa McShane,1 Chien-Jen Chen,8 Paul Ahlquist,4,6 and Allan Hildesheim2 1Biometric Research Branch, Division of Cancer Treatment and Diagnosis and 2Hormonal and Reproductive Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute; 3Westat, Inc., Rockville, Maryland; 4Institute for Molecular Virology, 5Department of Statistics and of Biostatistics and Medical Informatics, and 6McArdle Laboratory for Cancer Research and Howard Hughes Medical Institute, University of Wisconsin, Madison, Wisconsin; 7Department of Otolaryngology, McKay Memorial Hospital; 8Graduate Institute of Epidemiology, College of Public Health, National Taiwan University, Taipei, Taiwan; and 9Department of Pathology, Johns Hopkins University, School of Medicine, Baltimore, Maryland Abstract Polymorphisms in nitrosamine metabolism, DNA repair, and Differentially expressed probe sets within the nitrosamine immune response genes have been associated with nasopha- metabolism pathway were consistently underexpressed ryngeal carcinoma (NPC). Studies have suggested chromo- (100%), with strong effects observed for NQ01, CYP2B6, somal regions involved in NPC. To shed light on NPC and CYP2E1. No significant evidence of increases in rate of etiology, we evaluated host gene expression patterns in 31 differential expression was seen within the immune/inflam- NPC and 10 normal nasopharyngeal tissue specimens using matory pathway. A significant elevation in rate of differential the Affymetrix Human Genome U133 Plus 2.0 Array. We expression was noted for chromosome 4p15.1-4q12 (13.0%; focused on genes in five a priori biological pathways and P = 0.04); both overexpression and underexpression were chromosomal locations. Rates of differential expression evident (38% and 62%, respectively). An elevation in the rate of within these prespecified lists and overall were tested using differential expression on chromosome 14q32 was observed a bootstrap method. Differential expression was observed for (11.3%; P = 0.06) with a consistent pattern of gene under- 7.6% of probe sets overall. Elevations in rate of differential expression (100%; P < 0.0001). These effects were similar when expression were observed within the DNA repair (13.7%; excluding late-stage tumors. Our results suggest that nitrosa- P = 0.01) and nitrosamine metabolism (17.5%; P = 0.04) mine activation and DNA repair are important in NPC. The pathways. Differentially expressed probe sets within the consistent down-regulation of expression on chromosome DNA repair pathway were consistently overexpressed (93%), 14q32 suggests loss of heterozygosity in this region. (Cancer with strong effects observed for PRKDC, PCNA, and CHEK1. Epidemiol Biomarkers Prev 2006;15(11):2216–25) Introduction EBV is a ubiquitous DNA virus with worldwide distribution an early age. In a study of the association between dietary known to be associated with the development of f100% of nitrosamine levels and NPC risk in Taiwan, individuals in the nasopharyngeal carcinomas (NPC), particularly in southeast- upper quartile of consumption of nitrosamines during child- ern Asia and among those of Chinese descent (1, 2). In addition hood had a 2.6-fold increased risk of NPC (3). Smoking of to EBV infection, numerous environmental and host factors cigarettes, which contain nitrosamines and other agents have been suggested to be associated with NPC in epidemi- capable of DNA damage, has also been shown to be associated ologic studies. with NPC, particularly when smoking occurs for a prolonged Exogenous exposures associated with NPC previously period (4). include sources of nitrosamines (dietary and other), nitrosa- Host factors believed to be associated with NPC tend to fall mine precursors, and other agents involved in damage to into two biological categories: factors linked to DNA damage DNA. Studies have shown an association between dietary and repair and those linked to immunologic control of EBV. consumption of salted fish and other preserved foods rich in Data available to date suggest that polymorphisms in genes nitrosamines and their precursors and NPC risk (1). Such involved in the activation of nitrosamines into reactive exposures seem to be particularly important when occurring at intermediates capable of DNA damage or in the repair of damage are associated with NPC (5-7). In particular, CYP2E1 variants have been associated with NPC (5, 6), and specific Received 6/14/06; revised 8/4/06; accepted 9/11/06. polymorphisms in the DNA repair genes XRCC1 and hOGG1 Grant support: National Cancer Institute Intramural Research Program and NIH grants have been suggested to affect NPC risk (7). CA2243, CA97944, and CA64364. P. Ahlquist is an investigator of the Howard Hughes Medical Immunologic factors have been hypothesized to be associ- Institute. ated with NPC development because interindividual differ- The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. ences in immunologic control of the ubiquitous EBV infection Section 1734 solely to indicate this fact. are likely important determinants of NPC risk. In this Note: Current address for I. Chen: College of Medicine, Chang Gung University, respect, genes that encode for human leukocyte antigens Taipei, Taiwan. Analyses were done using BRB ArrayTools developed by Dr. Richard Simon and Amy Peng. (HLA) responsible for the presentation of viruses, such as This study used the high-performance computational capabilities of the Biowulf PC/Linux EBV, to the immune system have been studied. Studies to cluster at the NIH, Bethesda, MD (http://biowulf.nih.gov). date have consistently shown an association between specific Requests for reprints: Allan Hildesheim, National Cancer Institute, 6120 Executive Boulevard, Room 7062, Rockville, MD 20852. Phone: 301-435-3984. E-mail: [email protected] HLA alleles and haplotypes and risk of NPC (8, 9). Among Copyright D 2006 American Association for Cancer Research. others, HLA-A*0207, HLA-A*1101, HLA-B*4601, and HLA- doi:10.1158/1055-9965.EPI-06-0455 B*5801 are associated with NPC risk. In addition to HLA gene Cancer Epidemiol Biomarkers Prev 2006;15(11). November 2006 Downloaded from cebp.aacrjournals.org on September 25, 2021. © 2006 American Association for Cancer Research. Cancer Epidemiology,Biomarkers & Prevention 2217 polymorphisms that might affect the adaptive immune were evaluated by wide-spectrum cytokeratin immunohisto- response, recent studies have begun to evaluate the role of chemistry using monoclonal mouse anti-human cytokeratin innate immune responses in NPC pathogenesis through the primary antibody (AE1/AE3; 1:20 dilution) from DAKO and evaluation of KIR genes and their HLA ligands (10). DAKO EnVision+ System, Peroxidase (3,3¶-Diaminobenzidine) Most recently, studies of multiplex families at high risk of Mouse (DAKO Corp., Carpinteria, CA) as per manufacturer’s NPC have been conducted. Initial reports from these family- protocol, and in situ hybridization for EBV EBERs was done based studies have suggested linkage of several chromosomal using EBV Probe ISH kit (NCL-EBV-K) from Novocastra regions (including 4p15.1-4q12 and 14q32) with NPC in these Laboratories Ltd. (Newcastle upon Tyne, United Kingdom) families10 (11). following manufacturer’s protocol. As summarized above, data point to the involvement of Tumor tissue was defined as section areas that stained multiple factors in NPC pathogenesis. However, other than positive for both cytokeratins and EBV EBERs. the evaluation and localization of EBV in tumor cells of the Laser Capture Microdissection. For tumor enrichment from nasopharynx, little is known about events occurring locally at NPC sections containing <70% tumor tissue as well as to the nasopharynx that might support any of the hypotheses isolate epithelial compartment from normal healthy nasopha- mentioned above. ryngeal tissue specimens, we used laser capture microdissec- Herein, we describe results of a study in which expression tion (LCM). Most of the adjacent matched nontumor biopsies levels of a priori–defined genes were evaluated using micro- were found to harbor tumor cells and were not included array technology (Affymetrix array) and compared between for further study. To prepare and orient the sections for tissues obtained from NPC lesions and normal nasopharyngeal LCM, serial adjacent sections were briefly hematoxylin stained, tissue. Our results provide important evidence linking the dehydrated through graded ethanol, and air dried. Tumor expression of genes involved in nitrosamine metabolism and identification and mapping were aided by referring to the DNA repair to NPC. The results also provide evidence for adjacent slides evaluated by cytokeratin immunohistochemis- the involvement of a gene(s) on the telomeric end of the long try and EBV in situ hybridization. LCM was done using an arm of chromosome 14 in the etiology of NPC. A separate Arcturus PixCell II laser dissecting microscope and CapSure report from this study has evaluated expression levels in genes Macro LCM caps (Arcturus Bioscience, Mountain View, CA). included on the Affymetrix array and related them to levels of expression
Load more

Recommended publications
  • Supplementary Materials
    DEPs in osteosarcoma cells comparing to osteoblastic cells Biological Process Protein Percentage of Hits metabolic process (GO:0008152) 29.3 29.3% cellular process (GO:0009987) 20.2 20.2% localization (GO:0051179) 9.4 9.4% biological regulation (GO:0065007) 8 8.0% developmental process (GO:0032502) 7.8 7.8% response to stimulus (GO:0050896) 5.6 5.6% cellular component organization (GO:0071840) 5.6 5.6% multicellular organismal process (GO:0032501) 4.4 4.4% immune system process (GO:0002376) 4.2 4.2% biological adhesion (GO:0022610) 2.7 2.7% apoptotic process (GO:0006915) 1.6 1.6% reproduction (GO:0000003) 0.8 0.8% locomotion (GO:0040011) 0.4 0.4% cell killing (GO:0001906) 0.1 0.1% 100.1% Genes 2179Hits 3870 biological adhesion apoptotic process … reproduction (GO:0000003) , 0.8% (GO:0022610) , 2.7% locomotion (GO:0040011) ,… immune system process cell killing (GO:0001906) , 0.1% (GO:0002376) , 4.2% multicellular organismal process (GO:0032501) , metabolic process 4.4% (GO:0008152) , 29.3% cellular component organization (GO:0071840) , 5.6% response to stimulus (GO:0050896), 5.6% developmental process (GO:0032502) , 7.8% biological regulation (GO:0065007) , 8.0% cellular process (GO:0009987) , 20.2% localization (GO:0051179) , 9.
    [Show full text]
  • Y Chromosomal Noncoding Rnas Regulate Autosomal Gene Expression Via Pirnas in Mouse Testis Hemakumar M
    bioRxiv preprint doi: https://doi.org/10.1101/285429; this version posted January 15, 2021. 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. Y chromosomal noncoding RNAs regulate autosomal gene expression via piRNAs in mouse testis Hemakumar M. Reddy1,2,16, Rupa Bhattacharya1,3,16, Zeenath Jehan1,4, Kankadeb Mishra1,5, Pranatharthi Annapurna1,6, Shrish Tiwari1, Nissankararao Mary Praveena1, Jomini Liza Alex1, Vishnu M Dhople1,7, Lalji Singh8, Mahadevan Sivaramakrishnan1,9, Anurag Chaturvedi1,10, Nandini Rangaraj1, Thomas Michael Shiju1,11, Badanapuram Sridevi1, Sachin Kumar1, Ram Reddy Dereddi1,12, Sunayana M Rayabandla1,13, Rachel A. Jesudasan1,14*, 15* 1Centre for Cellular and Molecular Biology (CCMB), Uppal Road, Hyderabad, Telengana – 500007, India. Present address: 2Brown University BioMed Division, Department of Molecular Biology, Cell Biology and Biochemistry, 185 Meeting Street room 260, Sidney Frank Life Sciences Building, Providence, RI 02912, USA. 3 Pennington NJ 08534, USA. 4Department of Genetics and Molecular Medicines, Vasavi Medical and Research Centre, 6- 1-91 Khairatabad, Hyderabad 500 004 India. 5Department of Cell Biology, Memorial Sloan Kettering Cancer Centre, Rockefeller Research Laboratory, 430 East 67th Street, RRL 445, New York, NY 10065, USA. 6Departments of Orthopaedic Surgery & Bioengineering, University of Pennsylvania, 376A Stemmler Hall, 36th Street & Hamilton Walk, Philadelphia, PA 19104.USA. 7Ernst-Moritz-Arndt-University of Greifswald Interfaculty Institute for Genetics and Functional Genomics, Department of Functional Genomics, Friedrich-Ludwig-Jahn-Straße 15 a, 17487 Greifswald, Germany. 8 Deceased. 9Jubilant Biosystems Ltd., #96, Industrial Suburb, 2nd Stage, Yeshwantpur, Bangalore- 560022, Karnataka, India.
    [Show full text]
  • Protein Interaction Networks and Their Applications to Protein Characterization and Cancer Genes Prediction
    Ramón Aragüés Peleato Protein interaction networks and their applications to protein characterization and cancer genes prediction PhD Thesis Barcelona, May 2007 1 The image of the cover shows the happiness protein interaction network (i.e. the protein interaction network for proteins involved in the serotonin pathway) ii Protein Interaction Networks and their Applications to Protein Characterization and Cancer Genes Prediction Ramón Aragüés Peleato Memòria presentada per optar al grau de Doctor en Biologia per la Universitat Pompeu Fabra. Aquesta Tesi Doctoral ha estat realitzada sota la direcció del Dr. Baldo Oliva al Departament de Ciències Experimentals i de la Salut de la Universitat Pompeu Fabra Baldo Oliva Miguel Ramón Aragüés Peleato Barcelona, Maig 2007 The research in this thesis has been carried out at the Structural Bioinformatics Lab (SBI) within the Grup de Recerca en Informàtica Biomèdica at the Parc de Recerca Biomèdica de Barcelona (PRBB). The research carried out in this thesis has been supported by a “Formación de Personal Investigador (FPI)” grant from the Ministerio de Educación y Ciencia awarded to Dr. Baldo Oliva. A mis padres, que me hicieron querer conseguirlo A Natalia, que me ayudó a conseguir hacerlo ii TABLE OF CONTENTS TABLE OF CONTENTS................................................................................................................................... I ACKNOWLEDGEMENTS...........................................................................................................................
    [Show full text]
  • WO 2015/065964 Al 7 May 2015 (07.05.2015) W P O P C T
    (12) INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT) (19) World Intellectual Property Organization International Bureau (10) International Publication Number (43) International Publication Date WO 2015/065964 Al 7 May 2015 (07.05.2015) W P O P C T (51) International Patent Classification: (74) Agents: KOWALSKI, Thomas, J. et al; Vedder Price C12N 15/90 (2006.01) C12N 15/113 (2010.01) P.C., 1633 Broadway, New York, NY 1001 9 (US). C12N 15/10 (2006.01) C12N 15/63 (2006.01) (81) Designated States (unless otherwise indicated, for every (21) International Application Number: kind of national protection available): AE, AG, AL, AM, PCT/US2014/062558 AO, AT, AU, AZ, BA, BB, BG, BH, BN, BR, BW, BY, BZ, CA, CH, CL, CN, CO, CR, CU, CZ, DE, DK, DM, (22) International Filing Date: DO, DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, 28 October 2014 (28.10.2014) HN, HR, HU, ID, IL, IN, IR, IS, JP, KE, KG, KN, KP, KR, (25) Filing Language: English KZ, LA, LC, LK, LR, LS, LU, LY, MA, MD, ME, MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, OM, (26) Publication Language: English PA, PE, PG, PH, PL, PT, QA, RO, RS, RU, RW, SA, SC, (30) Priority Data: SD, SE, SG, SK, SL, SM, ST, SV, SY, TH, TJ, TM, TN, 61/96 1,980 28 October 20 13 (28. 10.20 13) US TR, TT, TZ, UA, UG, US, UZ, VC, VN, ZA, ZM, ZW. 61/963,643 9 December 2013 (09.
    [Show full text]
  • S41467-020-18249-3.Pdf
    ARTICLE https://doi.org/10.1038/s41467-020-18249-3 OPEN Pharmacologically reversible zonation-dependent endothelial cell transcriptomic changes with neurodegenerative disease associations in the aged brain Lei Zhao1,2,17, Zhongqi Li 1,2,17, Joaquim S. L. Vong2,3,17, Xinyi Chen1,2, Hei-Ming Lai1,2,4,5,6, Leo Y. C. Yan1,2, Junzhe Huang1,2, Samuel K. H. Sy1,2,7, Xiaoyu Tian 8, Yu Huang 8, Ho Yin Edwin Chan5,9, Hon-Cheong So6,8, ✉ ✉ Wai-Lung Ng 10, Yamei Tang11, Wei-Jye Lin12,13, Vincent C. T. Mok1,5,6,14,15 &HoKo 1,2,4,5,6,8,14,16 1234567890():,; The molecular signatures of cells in the brain have been revealed in unprecedented detail, yet the ageing-associated genome-wide expression changes that may contribute to neurovas- cular dysfunction in neurodegenerative diseases remain elusive. Here, we report zonation- dependent transcriptomic changes in aged mouse brain endothelial cells (ECs), which pro- minently implicate altered immune/cytokine signaling in ECs of all vascular segments, and functional changes impacting the blood–brain barrier (BBB) and glucose/energy metabolism especially in capillary ECs (capECs). An overrepresentation of Alzheimer disease (AD) GWAS genes is evident among the human orthologs of the differentially expressed genes of aged capECs, while comparative analysis revealed a subset of concordantly downregulated, functionally important genes in human AD brains. Treatment with exenatide, a glucagon-like peptide-1 receptor agonist, strongly reverses aged mouse brain EC transcriptomic changes and BBB leakage, with associated attenuation of microglial priming. We thus revealed tran- scriptomic alterations underlying brain EC ageing that are complex yet pharmacologically reversible.
    [Show full text]
  • SLFN11 Promotes CDT1 Degradation by CUL4 in Response to Replicative DNA Damage, While Its Absence Leads to Synthetic Lethality with ATR/CHK1 Inhibitors
    SLFN11 promotes CDT1 degradation by CUL4 in response to replicative DNA damage, while its absence leads to synthetic lethality with ATR/CHK1 inhibitors Ukhyun Joa,1, Yasuhisa Muraia, Sirisha Chakkab, Lu Chenb, Ken Chengb, Junko Muraic, Liton Kumar Sahaa, Lisa M. Miller Jenkinsd, and Yves Pommiera,1 aDevelopmental Therapeutics Branch, Laboratory of Molecular Pharmacology, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20814; bNational Center for Advancing Translational Sciences, Functional Genomics Laboratory, NIH, Rockville, MD 20850; cInstitute for Advanced Biosciences, Keio University, 997-0052 Yamagata, Japan; and dLaboratory of Cell Biology, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD 20892 Edited by Richard D. Kolodner, Ludwig Institute for Cancer Research, La Jolla, CA, and approved December 8, 2020 (received for review July 29, 2020) Schlafen-11 (SLFN11) inactivation in ∼50% of cancer cells confers condensation related to deposition of H3K27me3 in the gene broad chemoresistance. To identify therapeutic targets and under- body of SLFN11 by EZH2, a histone methyltransferase (11). lying molecular mechanisms for overcoming chemoresistance, we Targeting epigenetic regulators is therefore an attractive com- performed an unbiased genome-wide RNAi screen in SLFN11-WT bination strategy to overcome chemoresistance of SLFN11- and -knockout (KO) cells. We found that inactivation of Ataxia deficient cancers (10, 25, 26). An alternative approach is to at- Telangiectasia- and Rad3-related (ATR), CHK1, BRCA2, and RPA1 tack SLFN11-negative cancer cells by targeting the essential SLFN11 overcome chemoresistance to camptothecin (CPT) in -KO pathways that cells use to overcome replicative damage and cells. Accordingly, we validate that clinical inhibitors of ATR replication stress.
    [Show full text]
  • (12) United States Patent (10) Patent No.: US 7,799,528 B2 Civin Et Al
    US007799528B2 (12) United States Patent (10) Patent No.: US 7,799,528 B2 Civin et al. (45) Date of Patent: Sep. 21, 2010 (54) THERAPEUTIC AND DIAGNOSTIC Al-Hajj et al., “Prospective identification of tumorigenic breast can APPLICATIONS OF GENES cer cells.” Proc. Natl. Acad. Sci. U.S.A., 100(7):3983-3988 (2003). DIFFERENTIALLY EXPRESSED IN Bhatia et al., “A newly discovered class of human hematopoietic cells LYMPHO-HEMATOPOETC STEM CELLS with SCID-repopulating activity.” Nat. Med. 4(9)1038-45 (1998). (75) Inventors: Curt I. Civin, Baltimore, MD (US); Bonnet, D., “Normal and leukemic CD35-negative human Robert W. Georgantas, III, Towson, hematopoletic stem cells.” Rev. Clin. Exp. Hematol. 5:42-61 (2001). Cambot et al., “Human Immune Associated Nucleotide 1: a member MD (US) of a new guanosine triphosphatase family expressed in resting T and (73) Assignee: The Johns Hopkins University, B cells.” Blood, 99(9):3293-3301 (2002). Baltimore, MD (US) Chen et al., “Kruppel-like Factor 4 (Gut-enriched Kruppel-like Fac tor) Inhibits Cell Proliferation by Blocking G1/S Progression of the *) NotOt1Ce: Subjubject to anyy d1Sclaimer,disclai theh term off thisthi Cell Cycle.” J. Biol. Chem., 276(32):30423-30428 (2001). patent is extended or adjusted under 35 Chen et al., “Transcriptional profiling of Kurppel-like factor 4 reveals U.S.C. 154(b) by 168 days. a function in cell cycle regulation and epithelial differentiation.” J. Mol. Biol. 326(3):665-677 (2003). (21) Appl. No.: 11/199.665 Civin et al., “Highly purified CD34-positive cells reconstitute (22) Filed: Aug. 9, 2005 hematopoiesis,” J.
    [Show full text]
  • Supplementary Materials
    Supplementary Materials COMPARATIVE ANALYSIS OF THE TRANSCRIPTOME, PROTEOME AND miRNA PROFILE OF KUPFFER CELLS AND MONOCYTES Andrey Elchaninov1,3*, Anastasiya Lokhonina1,3, Maria Nikitina2, Polina Vishnyakova1,3, Andrey Makarov1, Irina Arutyunyan1, Anastasiya Poltavets1, Evgeniya Kananykhina2, Sergey Kovalchuk4, Evgeny Karpulevich5,6, Galina Bolshakova2, Gennady Sukhikh1, Timur Fatkhudinov2,3 1 Laboratory of Regenerative Medicine, National Medical Research Center for Obstetrics, Gynecology and Perinatology Named after Academician V.I. Kulakov of Ministry of Healthcare of Russian Federation, Moscow, Russia 2 Laboratory of Growth and Development, Scientific Research Institute of Human Morphology, Moscow, Russia 3 Histology Department, Medical Institute, Peoples' Friendship University of Russia, Moscow, Russia 4 Laboratory of Bioinformatic methods for Combinatorial Chemistry and Biology, Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry of the Russian Academy of Sciences, Moscow, Russia 5 Information Systems Department, Ivannikov Institute for System Programming of the Russian Academy of Sciences, Moscow, Russia 6 Genome Engineering Laboratory, Moscow Institute of Physics and Technology, Dolgoprudny, Moscow Region, Russia Figure S1. Flow cytometry analysis of unsorted blood sample. Representative forward, side scattering and histogram are shown. The proportions of negative cells were determined in relation to the isotype controls. The percentages of positive cells are indicated. The blue curve corresponds to the isotype control. Figure S2. Flow cytometry analysis of unsorted liver stromal cells. Representative forward, side scattering and histogram are shown. The proportions of negative cells were determined in relation to the isotype controls. The percentages of positive cells are indicated. The blue curve corresponds to the isotype control. Figure S3. MiRNAs expression analysis in monocytes and Kupffer cells. Full-length of heatmaps are presented.
    [Show full text]
  • Chloride Channels Regulate Differentiation and Barrier Functions
    RESEARCH ARTICLE Chloride channels regulate differentiation and barrier functions of the mammalian airway Mu He1†*, Bing Wu2†, Wenlei Ye1, Daniel D Le2, Adriane W Sinclair3,4, Valeria Padovano5, Yuzhang Chen6, Ke-Xin Li1, Rene Sit2, Michelle Tan2, Michael J Caplan5, Norma Neff2, Yuh Nung Jan1,7,8, Spyros Darmanis2*, Lily Yeh Jan1,7,8* 1Department of Physiology, University of California, San Francisco, San Francisco, United States; 2Chan Zuckerberg Biohub, San Francisco, United States; 3Department of Urology, University of California, San Francisco, San Francisco, United States; 4Division of Pediatric Urology, University of California, San Francisco, Benioff Children’s Hospital, San Francisco, United States; 5Department of Cellular and Molecular Physiology, Yale University School of Medicine, New Heaven, United States; 6Department of Anesthesia and Perioperative Care, University of California, San Francisco, San Francisco, United States; 7Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, United States; 8Howard Hughes Medical Institute, University of California, San Francisco, San Francisco, United States *For correspondence: Abstract The conducting airway forms a protective mucosal barrier and is the primary target of [email protected] (MH); [email protected] airway disorders. The molecular events required for the formation and function of the airway (SD); mucosal barrier, as well as the mechanisms by which barrier dysfunction leads to early onset airway [email protected] (LYJ) diseases,
    [Show full text]
  • Exploring the Relationship Between Gut Microbiota and Major Depressive Disorders
    E3S Web of Conferences 271, 03055 (2021) https://doi.org/10.1051/e3sconf/202127103055 ICEPE 2021 Exploring the Relationship between Gut Microbiota and Major Depressive Disorders Catherine Tian1 1Shanghai American School, Shanghai, China Abstract. Major Depressive Disorder (MDD) is a psychiatric disorder accompanied with a high rate of suicide, morbidity and mortality. With the symptom of an increasing or decreasing appetite, there is a possibility that MDD may have certain connections with gut microbiota, the colonies of microbes which reside in the human digestive system. In recent years, more and more studies started to demonstrate the links between MDD and gut microbiota from animal disease models and human metabolism studies. However, this relationship is still largely understudied, but it is very innovative since functional dissection of this relationship would furnish a new train of thought for more effective treatment of MDD. In this study, by using multiple genetic analytic tools including Allen Brain Atlas, genetic function analytical tools, and MicrobiomeAnalyst, I explored the genes that shows both expression in the brain and the digestive system to affirm that there is a connection between gut microbiota and the MDD. My approach finally identified 7 MDD genes likely to be associated with gut microbiota, implicating 3 molecular pathways: (1) Wnt Signaling, (2) citric acid cycle in the aerobic respiration, and (3) extracellular exosome signaling. These findings may shed light on new directions to understand the mechanism of MDD, potentially facilitating the development of probiotics for better psychiatric disorder treatment. 1 Introduction 1.1 Major Depressive Disorder Major Depressive Disorder (MDD) is a mood disorder that will affect the mood, behavior and other physical parts.
    [Show full text]
  • Genomic Deregulation During Renal Cell Carcinoma Metastasis Implements a Myofibroblast-Like Gene Expression Program
    Author Manuscript Published OnlineFirst on October 15, 2010; DOI: 10.1158/0008-5472.CAN-10-2279 AuthorPublished manuscripts OnlineFirst have been onpeer October reviewed and15, accepted2010 as for 10.1158/0008-5472.CAN-10-2279 publication but have not yet been edited. López-Lago et al. 1 Genomic Deregulation during Renal Cell Carcinoma Metastasis Implements a Myofibroblast-Like Gene Expression Program Miguel A. López-Lago1, Venkata J. Thodima1, Asha Guttapalli1, Timothy Chan2, Adriana Heguy2, Ana M. Molina4, Victor E. Reuter3, Robert J. Motzer4, and Raju S. K. Chaganti1,3, Author’s affiliation: 1. Cell Biology Program, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York NY, 01121 2. Human Oncology and Pathogenesis Program, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021 3. Department of Pathology, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021 4. Department of Medicine, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021 Corresponding Author: R. S. K. Chaganti, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY. Tel: 212/639-8121; FAX; 212/717-3541; E-mail: [email protected] Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Copyright © 2010 American Association for Cancer Research Downloaded from cancerres.aacrjournals.org on October 4, 2021. © 2010 American Association for Cancer Research. Author Manuscript Published OnlineFirst on October 15, 2010; DOI: 10.1158/0008-5472.CAN-10-2279 Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. López-Lago et al.
    [Show full text]
  • Spink2 Modulates Apoptotic Susceptibility and Is a Candidate Gene in the Rgcs1 QTL That Affects Retinal Ganglion Cell Death After Optic Nerve Damage
    Spink2 Modulates Apoptotic Susceptibility and Is a Candidate Gene in the Rgcs1 QTL That Affects Retinal Ganglion Cell Death after Optic Nerve Damage Joel A. Dietz1., Margaret E. Maes1., Shuang Huang2, Brian S. Yandell2, Cassandra L. Schlamp1, Angela D. Montgomery1, R. Rand Allingham3, Michael A. Hauser3, Robert W. Nickells1* 1 Department of Ophthalmology and Visual Sciences, University of Wisconsin, Madison, Wisconsin, United States of America, 2 Department of Biostatistics, University of Wisconsin, Madison, Wisconsin, United States of America, 3 Center for Human Genetics, Department of Medicine, Duke University Medical Center, Durham, North Carolina, United States of America Abstract The Rgcs1 quantitative trait locus, on mouse chromosome 5, influences susceptibility of retinal ganglion cells to acute damage of the optic nerve. Normally resistant mice (DBA/2J) congenic for the susceptible allele from BALB/cByJ mice exhibit susceptibility to ganglion cells, not only in acute optic nerve crush, but also to chronic inherited glaucoma that is characteristic of the DBA/2J strain as they age. SNP mapping of this QTL has narrowed the region of interest to 1 Mb. In this region, a single gene (Spink2) is the most likely candidate for this effect. Spink2 is expressed in retinal ganglion cells and is increased after optic nerve damage. This gene is also polymorphic between resistant and susceptible strains, containing a single conserved amino acid change (threonine to serine) and a 220 bp deletion in intron 1 that may quantitatively alter endogenous expression levels between strains. Overexpression of the different variants of Spink2 in D407 tissue culture cells also increases their susceptibility to the apoptosis-inducing agent staurosporine in a manner consistent with the differential susceptibility between the DBA/2J and BALB/cByJ strains.
    [Show full text]