Insights from Proteomics and Enteric Innervation Analysis
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Pathophysiology and Management of Diabetic Gastroenteropathy
Pathophysiology and management of diabetic gastroenteropathy Meldgaard, Theresa; Keller, Jutta; Olesen, Anne Estrup; Olesen, Søren Schou; Krogh, Klaus; Borre, Mette; Farmer, Adam; Brock, Birgitte; Brock, Christina; Drewes, Asbjørn Mohr Published in: Therapeutic Advances in Gastroenterology DOI: 10.1177/1756284819852047 Publication date: 2019 Document version Publisher's PDF, also known as Version of record Document license: CC BY-NC Citation for published version (APA): Meldgaard, T., Keller, J., Olesen, A. E., Olesen, S. S., Krogh, K., Borre, M., Farmer, A., Brock, B., Brock, C., & Drewes, A. M. (2019). Pathophysiology and management of diabetic gastroenteropathy. Therapeutic Advances in Gastroenterology, 12, 1-17. https://doi.org/10.1177/1756284819852047 Download date: 01. Oct. 2021 TAG0010.1177/1756284819852047Therapeutic Advances in GastroenterologyT Meldgaard, J Keller 852047review-article20192019 Therapeutic Advances in Gastroenterology Review Ther Adv Gastroenterol Pathophysiology and management of 2019, Vol. 12: 1–17 DOI:https://doi.org/10.1177/1756284819852047 10.1177/ diabetic gastroenteropathy 1756284819852047https://doi.org/10.1177/1756284819852047 © The Author(s), 2019. Article reuse guidelines: Theresa Meldgaard, Jutta Keller, Anne Estrup Olesen, Søren Schou Olesen, Klaus Krogh, sagepub.com/journals- Mette Borre, Adam Farmer, Birgitte Brock, Christina Brock and Asbjørn Mohr Drewes permissions Abstract: Polyneuropathy is a common complication to diabetes. Neuropathies within the Correspondence to: Theresa Meldgaard enteric nervous system are associated with gastroenteropathy and marked symptoms that Mech-Sense, Department of Gastroenterology and severely reduce quality of life. Symptoms are pleomorphic but include nausea, vomiting, Hepatology, Aalborg dysphagia, dyspepsia, pain, bloating, diarrhoea, constipation and faecal incontinence. The University Hospital, aims of this review are fourfold. First, to provide a summary of the pathophysiology underlying Denmark Department of Clinical diabetic gastroenteropathy. -
PARSANA-DISSERTATION-2020.Pdf
DECIPHERING TRANSCRIPTIONAL PATTERNS OF GENE REGULATION: A COMPUTATIONAL APPROACH by Princy Parsana A dissertation submitted to The Johns Hopkins University in conformity with the requirements for the degree of Doctor of Philosophy Baltimore, Maryland July, 2020 © 2020 Princy Parsana All rights reserved Abstract With rapid advancements in sequencing technology, we now have the ability to sequence the entire human genome, and to quantify expression of tens of thousands of genes from hundreds of individuals. This provides an extraordinary opportunity to learn phenotype relevant genomic patterns that can improve our understanding of molecular and cellular processes underlying a trait. The high dimensional nature of genomic data presents a range of computational and statistical challenges. This dissertation presents a compilation of projects that were driven by the motivation to efficiently capture gene regulatory patterns in the human transcriptome, while addressing statistical and computational challenges that accompany this data. We attempt to address two major difficulties in this domain: a) artifacts and noise in transcriptomic data, andb) limited statistical power. First, we present our work on investigating the effect of artifactual variation in gene expression data and its impact on trans-eQTL discovery. Here we performed an in-depth analysis of diverse pre-recorded covariates and latent confounders to understand their contribution to heterogeneity in gene expression measurements. Next, we discovered 673 trans-eQTLs across 16 human tissues using v6 data from the Genotype Tissue Expression (GTEx) project. Finally, we characterized two trait-associated trans-eQTLs; one in Skeletal Muscle and another in Thyroid. Second, we present a principal component based residualization method to correct gene expression measurements prior to reconstruction of co-expression networks. -
Universidade Estadual De Campinas Instituto De Biologia
UNIVERSIDADE ESTADUAL DE CAMPINAS INSTITUTO DE BIOLOGIA VERÔNICA APARECIDA MONTEIRO SAIA CEREDA O PROTEOMA DO CORPO CALOSO DA ESQUIZOFRENIA THE PROTEOME OF THE CORPUS CALLOSUM IN SCHIZOPHRENIA CAMPINAS 2016 1 VERÔNICA APARECIDA MONTEIRO SAIA CEREDA O PROTEOMA DO CORPO CALOSO DA ESQUIZOFRENIA THE PROTEOME OF THE CORPUS CALLOSUM IN SCHIZOPHRENIA Dissertação apresentada ao Instituto de Biologia da Universidade Estadual de Campinas como parte dos requisitos exigidos para a obtenção do Título de Mestra em Biologia Funcional e Molecular na área de concentração de Bioquímica. Dissertation presented to the Institute of Biology of the University of Campinas in partial fulfillment of the requirements for the degree of Master in Functional and Molecular Biology, in the area of Biochemistry. ESTE ARQUIVO DIGITAL CORRESPONDE À VERSÃO FINAL DA DISSERTAÇÃO DEFENDIDA PELA ALUNA VERÔNICA APARECIDA MONTEIRO SAIA CEREDA E ORIENTADA PELO DANIEL MARTINS-DE-SOUZA. Orientador: Daniel Martins-de-Souza CAMPINAS 2016 2 Agência(s) de fomento e nº(s) de processo(s): CNPq, 151787/2F2014-0 Ficha catalográfica Universidade Estadual de Campinas Biblioteca do Instituto de Biologia Mara Janaina de Oliveira - CRB 8/6972 Saia-Cereda, Verônica Aparecida Monteiro, 1988- Sa21p O proteoma do corpo caloso da esquizofrenia / Verônica Aparecida Monteiro Saia Cereda. – Campinas, SP : [s.n.], 2016. Orientador: Daniel Martins de Souza. Dissertação (mestrado) – Universidade Estadual de Campinas, Instituto de Biologia. 1. Esquizofrenia. 2. Espectrometria de massas. 3. Corpo caloso. -
Noninvasive Sleep Monitoring in Large-Scale Screening of Knock-Out Mice
bioRxiv preprint doi: https://doi.org/10.1101/517680; this version posted January 11, 2019. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-ND 4.0 International license. Noninvasive sleep monitoring in large-scale screening of knock-out mice reveals novel sleep-related genes Shreyas S. Joshi1*, Mansi Sethi1*, Martin Striz1, Neil Cole2, James M. Denegre2, Jennifer Ryan2, Michael E. Lhamon3, Anuj Agarwal3, Steve Murray2, Robert E. Braun2, David W. Fardo4, Vivek Kumar2, Kevin D. Donohue3,5, Sridhar Sunderam6, Elissa J. Chesler2, Karen L. Svenson2, Bruce F. O'Hara1,3 1Dept. of Biology, University of Kentucky, Lexington, KY 40506, USA, 2The Jackson Laboratory, Bar Harbor, ME 04609, USA, 3Signal solutions, LLC, Lexington, KY 40503, USA, 4Dept. of Biostatistics, University of Kentucky, Lexington, KY 40536, USA, 5Dept. of Electrical and Computer Engineering, University of Kentucky, Lexington, KY 40506, USA. 6Dept. of Biomedical Engineering, University of Kentucky, Lexington, KY 40506, USA. *These authors contributed equally Address for correspondence and proofs: Shreyas S. Joshi, Ph.D. Dept. of Biology University of Kentucky 675 Rose Street 101 Morgan Building Lexington, KY 40506 U.S.A. Phone: (859) 257-2805 FAX: (859) 257-1717 Email: [email protected] Running title: Sleep changes in knockout mice bioRxiv preprint doi: https://doi.org/10.1101/517680; this version posted January 11, 2019. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. -
Supplemental Information
Supplemental information Dissection of the genomic structure of the miR-183/96/182 gene. Previously, we showed that the miR-183/96/182 cluster is an intergenic miRNA cluster, located in a ~60-kb interval between the genes encoding nuclear respiratory factor-1 (Nrf1) and ubiquitin-conjugating enzyme E2H (Ube2h) on mouse chr6qA3.3 (1). To start to uncover the genomic structure of the miR- 183/96/182 gene, we first studied genomic features around miR-183/96/182 in the UCSC genome browser (http://genome.UCSC.edu/), and identified two CpG islands 3.4-6.5 kb 5’ of pre-miR-183, the most 5’ miRNA of the cluster (Fig. 1A; Fig. S1 and Seq. S1). A cDNA clone, AK044220, located at 3.2-4.6 kb 5’ to pre-miR-183, encompasses the second CpG island (Fig. 1A; Fig. S1). We hypothesized that this cDNA clone was derived from 5’ exon(s) of the primary transcript of the miR-183/96/182 gene, as CpG islands are often associated with promoters (2). Supporting this hypothesis, multiple expressed sequences detected by gene-trap clones, including clone D016D06 (3, 4), were co-localized with the cDNA clone AK044220 (Fig. 1A; Fig. S1). Clone D016D06, deposited by the German GeneTrap Consortium (GGTC) (http://tikus.gsf.de) (3, 4), was derived from insertion of a retroviral construct, rFlpROSAβgeo in 129S2 ES cells (Fig. 1A and C). The rFlpROSAβgeo construct carries a promoterless reporter gene, the β−geo cassette - an in-frame fusion of the β-galactosidase and neomycin resistance (Neor) gene (5), with a splicing acceptor (SA) immediately upstream, and a polyA signal downstream of the β−geo cassette (Fig. -
Primary Structure of Tektin Al
Proc. Nati. Acad. Sci. USA Vol. 89, pp. 8567-8571, September 1992 Cell Biology Primary structure of tektin Al: Comparison with intermediate- filament proteins and a model for its association with tubulin (basal body/centriole/dlia/flageila/microtubule) J. M. NORRANDER*, L. A. AMOSt, AND R. W. LINCK* *Department of Cell Biology and Neuroanatomy, University of Minnesota, Minneapolis, MN 55455; and tLaboratory of Molecular Biology, Medical Research Center, Hills Road, Cambridge, CB2 2QH, United Kingdom Communicated by M. F. Perutz, May 19, 1992 (receivedfor review January 22, 1992) ABSTRACT Tektins are proteins that form rilamentous MATERIALS AND METHODS polymers in the walls of ciliary and flagellar microtubules and that have biochemical and immunological properties similar to S. purpuratus gametes were collected, handled, and cultured those of intermediate-filament proteins. We report here the at 16'C, as described (14). At desired times, aliquots of sequence of a cDNA for tektin Al, one of the main tektins from eggs/embryos were isolated and frozen in liquid N2. Total Strongylocentrotus purpuratus sea urchin embryos. By hybrid- RNA and poly(A)+ mRNA were isolated (15). A Agtll cDNA ization analysis, tektin A mRNA appears maximally at cilio- expression library, constructed from blastulae (gift of T. L. genesis. The predicted structure of tektin Al (Mr 52,955) is a Thomas, Texas A & M, College Station, TX), was screened series of a-helical rod segments separated by nonhelical link- with polyclonal antibodies (16) against S. purpuratus sperm ers. The two halves of the rod appear homologous and are flagellar tektin A (11). The largest clone isolated, tekA10-2, probably related by gene duplication. -
Fluoroscopic Characterization of Colonic Dysmotility Associated to Opioid and Cannabinoid Agonists in Conscious Rats
J Neurogastroenterol Motil, Vol. 25 No. 2 April, 2019 pISSN: 2093-0879 eISSN: 2093-0887 https://doi.org/10.5056/jnm18202 JNM Journal of Neurogastroenterology and Motility Original Article Fluoroscopic Characterization of Colonic Dysmotility Associated to Opioid and Cannabinoid Agonists in Conscious Rats Susana Díaz-Ruano,1 Ana E López-Pérez,1,5 Rocío Girón,2,3,4,5 Irene Pérez-García,2 María I Martín-Fontelles,2,3,4,5 and Raquel Abalo2,3,4,5* 1Unidad de Dolor, Servicio de Anestesiología, Hospital General Universitario Gregorio Marañón, Madrid, Spain; 2Departamento de Ciencias Básicas de la Salud, Facultad de Ciencias de la Salud, Universidad Rey Juan Carlos, Alcorcón, Madrid, Spain; 3Unidad Asociada I+D+i al Instituto de Investigación en Ciencias de la Alimentación, CIAL (CSIC), Madrid, Spain; 4Unidad Asociada I+D+i al Instituto de Química Médica, IQM (CSIC), Madrid, Spain; and 5Grupo de Excelencia Investigadora URJC-Banco de Santander-Grupo Multidisciplinar de Investigación y Tratamiento del Dolor (i+DOL), Madrid, Spain Background/Aims Gastrointestinal adverse effects have a major impact on health and quality of life in analgesics users. Non-invasive methods to study gastrointestinal motility are of high interest. Fluoroscopy has been previously used to study gastrointestinal motility in small experimental animals, but they were generally anesthetized and anesthesia itself may alter motility. In this study, our aim is to determine, in conscious rats, the effect of increasing doses of 2 opioid (morphine and loperamide) and 1 cannabinoid (WIN 55,212-2) agonists on colonic motility using fluoroscopic recordings and spatio-temporal maps. Methods Male Wistar rats received barium sulfate intragastrically, 20-22 hours before fluoroscopy, so that stained fecal pellets could be seen at the time of recording. -
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 -
Identification of Candidate Genes and Pathways Associated with Obesity
animals Article Identification of Candidate Genes and Pathways Associated with Obesity-Related Traits in Canines via Gene-Set Enrichment and Pathway-Based GWAS Analysis Sunirmal Sheet y, Srikanth Krishnamoorthy y , Jihye Cha, Soyoung Choi and Bong-Hwan Choi * Animal Genome & Bioinformatics, National Institute of Animal Science, RDA, Wanju 55365, Korea; [email protected] (S.S.); [email protected] (S.K.); [email protected] (J.C.); [email protected] (S.C.) * Correspondence: [email protected]; Tel.: +82-10-8143-5164 These authors contributed equally. y Received: 10 October 2020; Accepted: 6 November 2020; Published: 9 November 2020 Simple Summary: Obesity is a serious health issue and is increasing at an alarming rate in several dog breeds, but there is limited information on the genetic mechanism underlying it. Moreover, there have been very few reports on genetic markers associated with canine obesity. These studies were limited to the use of a single breed in the association study. In this study, we have performed a GWAS and supplemented it with gene-set enrichment and pathway-based analyses to identify causative loci and genes associated with canine obesity in 18 different dog breeds. From the GWAS, the significant markers associated with obesity-related traits including body weight (CACNA1B, C22orf39, U6, MYH14, PTPN2, SEH1L) and blood sugar (PRSS55, GRIK2), were identified. Furthermore, the gene-set enrichment and pathway-based analysis (GESA) highlighted five enriched pathways (Wnt signaling pathway, adherens junction, pathways in cancer, axon guidance, and insulin secretion) and seven GO terms (fat cell differentiation, calcium ion binding, cytoplasm, nucleus, phospholipid transport, central nervous system development, and cell surface) which were found to be shared among all the traits. -
Derived Neural Stem Cells Exposed to Alcohol with Strain-Specific Cross
www.nature.com/scientificreports OPEN Genome-Wide Transcriptome Landscape of Embryonic Brain- Derived Neural Stem Cells Exposed Received: 26 July 2018 Accepted: 14 November 2018 to Alcohol with Strain-Specifc Cross- Published: xx xx xxxx Examination in BL6 and CD1 Mice Wayne Xu1,2, Vichithra R. B. Liyanage1,3, Aaron MacAulay1,3, Romina D. Levy1,3, Kyle Curtis1,3, Carl O. Olson1,3, Robby M. Zachariah1,3, Shayan Amiri1,3, Marjorie Buist1,3, Geofrey G. Hicks1,3, James R. Davie1 & Mojgan Rastegar1,3 We have previously reported the deregulatory impact of ethanol on global DNA methylation of brain- derived neural stem cells (NSC). Here, we conducted a genome-wide RNA-seq analysis in diferentiating NSC exposed to diferent modes of ethanol exposure. RNA-seq results showed distinct gene expression patterns and canonical pathways induced by ethanol exposure and withdrawal. Short-term ethanol exposure caused abnormal up-regulation of synaptic pathways, while continuous ethanol treatment profoundly afected brain cells’ morphology. Ethanol withdrawal restored the gene expression profle of diferentiating NSC without rescuing impaired expression of epigenetics factors. Ingenuity Pathway Analysis (IPA) analysis predicated that ethanol may impact synaptic functions via GABA receptor signalling pathway and afects neural system and brain morphology. We identifed Sptbn2, Dcc, and Scn3a as candidate genes which may link alcohol-induced neuronal morphology to brain structural abnormalities, predicted by IPA analysis. Cross-examination of Scn3a and As3mt in diferentiated NSC from two diferent mouse strains (BL6 and CD1) showed a consistent pattern of induction and reduction, respectively. Collectively, our study identifes genetic networks, which may contribute to alcohol-mediated cellular and brain structural dysmorphology, contributing to our knowledge of alcohol-mediated damage to central nervous system, paving the path for better understanding of FASD pathobiology. -
Differential Expression of ZWINT in Cancers of the Breast
Differential expression of ZW10 interacting kinetochore protein in cancers of the breast. Shahan Mamoor, MS1 [email protected] East Islip, NY 11730 Breast cancer affects women at relatively high frequency1. We mined published microarray datasets2,3 to determine in an unbiased fashion and at the systems level genes most differentially expressed in the primary tumors of patients with breast cancer. We report here significant differential expression of the gene encoding the ZW10 interacting kinetochore protein, ZWINT, when comparing primary tumors of the breast to the tissue of origin, the normal breast. ZWINT was also differentially expressed in the tumor cells of patients with triple negative breast cancer. ZWINT mRNA was present at significantly higher quantities in tumors of the breast as compared to normal breast tissue. Analysis of human survival data revealed that expression of ZWINT in primary tumors of the breast was correlated with overall survival in patients with basal and luminal A subtype cancer, but in a contrary manner, demonstrating a complex relationship between correlation of primary tumor expression with overall survival based on molecular subtype. ZWINT may be of relevance to initiation, maintenance or progression of cancers of the female breast. Keywords: breast cancer, ZWINT, ZW10 interacting kinetochore protein, systems biology of breast cancer, targeted therapeutics in breast cancer. 1 Invasive breast cancer is diagnosed in over a quarter of a million women in the United States each year1 and in 2018, breast cancer was the leading cause of cancer death in women worldwide4. While patients with localized breast cancer are provided a 99% 5-year survival rate, patients with regional breast cancer, cancer that has spread to lymph nodes or nearby structures, are provided an 86% 5-year survival rate5,6. -
Akt Phosphorylation of Neuronal Nitric Oxide Synthase Regulates Gastrointestinal Motility in Mouse Ileum
Akt phosphorylation of neuronal nitric oxide synthase regulates gastrointestinal motility in mouse ileum Damian D. Guerraa, Rachael Boka, Vibhuti Vyasa, David J. Orlickyb, Ramón A. Lorcaa, and K. Joseph Hurta,c,1 aDivision of Reproductive Sciences, Department of Obstetrics and Gynecology, University of Colorado Anschutz Medical Campus, Aurora, CO 80045; bDepartment of Pathology, University of Colorado Anschutz Medical Campus, Aurora, CO 80045; and cDivision of Maternal Fetal Medicine, Department of Obstetrics and Gynecology, University of Colorado Anschutz Medical Campus, Aurora, CO 80045 Edited by Solomon H. Snyder, Johns Hopkins University School of Medicine, Baltimore, MD, and approved July 15, 2019 (received for review April 5, 2019) Nitric oxide (NO) is a major inhibitory neurotransmitter that mediates receptor activation (18–20). Some evidence suggests that phosphor- nonadrenergic noncholinergic (NANC) signaling. Neuronal NO syn- ylation of the equivalent Akt/PKA consensus site in nNOS, ser- + thase (nNOS) is activated by Ca2 /calmodulin to produce NO, which ine1412 (S1412), also stimulates neuronal NO synthesis (21). Because + causes smooth muscle relaxation to regulate physiologic tone. nNOS nNOS activity is more sensitive to [Ca2 ](21),andnNOSismore serine1412 (S1412) phosphorylation may reduce the activating rapidly dephosphorylated than eNOS (22), it is technically difficult to 2+ Ca requirement and sustain NO production. We developed and evaluate nNOS S1412 phosphorylation in vivo. Nonetheless, studies S1412A characterized a nonphosphorylatable nNOS knock-in mouse implicate nNOS S1412 phosphorylation in hippocampal excitotoxicity and evaluated its enteric neurotransmission and gastrointestinal (4), penile erection (22), and luteinizing hormone release (23). (GI) motility to understand the physiologic significance of nNOS Enteric neurons express high levels of nNOS, Akt, and PKA S1412 phosphorylation.