Risk Variants Disrupting Enhancers of TH1 and TREG Cells in Type 1 Diabetes
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Educational Paper Ciliopathies
Eur J Pediatr (2012) 171:1285–1300 DOI 10.1007/s00431-011-1553-z REVIEW Educational paper Ciliopathies Carsten Bergmann Received: 11 June 2011 /Accepted: 3 August 2011 /Published online: 7 September 2011 # The Author(s) 2011. This article is published with open access at Springerlink.com Abstract Cilia are antenna-like organelles found on the (NPHP) . Ivemark syndrome . Meckel syndrome (MKS) . surface of most cells. They transduce molecular signals Joubert syndrome (JBTS) . Bardet–Biedl syndrome (BBS) . and facilitate interactions between cells and their Alstrom syndrome . Short-rib polydactyly syndromes . environment. Ciliary dysfunction has been shown to Jeune syndrome (ATD) . Ellis-van Crefeld syndrome (EVC) . underlie a broad range of overlapping, clinically and Sensenbrenner syndrome . Primary ciliary dyskinesia genetically heterogeneous phenotypes, collectively (Kartagener syndrome) . von Hippel-Lindau (VHL) . termed ciliopathies. Literally, all organs can be affected. Tuberous sclerosis (TSC) . Oligogenic inheritance . Modifier. Frequent cilia-related manifestations are (poly)cystic Mutational load kidney disease, retinal degeneration, situs inversus, cardiac defects, polydactyly, other skeletal abnormalities, and defects of the central and peripheral nervous Introduction system, occurring either isolated or as part of syn- dromes. Characterization of ciliopathies and the decisive Defective cellular organelles such as mitochondria, perox- role of primary cilia in signal transduction and cell isomes, and lysosomes are well-known -
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. -
Snps Related to Vitamin D and Breast Cancer Risk
Huss et al. Breast Cancer Research (2018) 20:1 DOI 10.1186/s13058-017-0925-3 RESEARCHARTICLE Open Access SNPs related to vitamin D and breast cancer risk: a case-control study Linnea Huss1* , Salma Tunå Butt1, Peter Almgren 2, Signe Borgquist3,4, Jasmine Brandt1, Asta Försti5,6, Olle Melander2 and Jonas Manjer1 Abstract Background: It has been suggested that vitamin D might protect from breast cancer, although studies on levels of vitamin D in association with breast cancer have been inconsistent. Genome-wide association studies (GWASs) have identified several single-nucleotide polymorphisms (SNPs) to be associated with vitamin D. The aim of this study was to investigate such vitamin D-SNP associations in relation to subsequent breast cancer risk. A first step included verification of these SNPs as determinants of vitamin D levels. Methods: The Malmö Diet and Cancer Study included 17,035 women in a prospective cohort. Genotyping was performed and was successful in 4058 nonrelated women from this cohort in which 865 were diagnosed with breast cancer. Levels of vitamin D (25-hydroxyvitamin D) were available for 700 of the breast cancer cases and 643 of unaffected control subjects. SNPs previously associated with vitamin D in GWASs were identified. Logistic regression analyses yielding ORs with 95% CIs were performed to investigate selected SNPs in relation to low levels of vitamin D (below median) as well as to the risk of breast cancer. Results: The majority of SNPs previously associated with levels of vitamin D showed a statistically significant association with circulating vitamin D levels. Heterozygotes of one SNP (rs12239582) were found to have a statistically significant association with a low risk of breast cancer (OR 0.82, 95% CI 0.68–0.99), and minor homozygotes of the same SNP were found to have a tendency towards a low risk of being in the group with low vitamin D levels (OR 0.72, 95% CI 0.52–1.00). -
Ciliopathies Gene Panel
Ciliopathies Gene Panel Contact details Introduction Regional Genetics Service The ciliopathies are a heterogeneous group of conditions with considerable phenotypic overlap. Levels 4-6, Barclay House These inherited diseases are caused by defects in cilia; hair-like projections present on most 37 Queen Square cells, with roles in key human developmental processes via their motility and signalling functions. Ciliopathies are often lethal and multiple organ systems are affected. Ciliopathies are London, WC1N 3BH united in being genetically heterogeneous conditions and the different subtypes can share T +44 (0) 20 7762 6888 many clinical features, predominantly cystic kidney disease, but also retinal, respiratory, F +44 (0) 20 7813 8578 skeletal, hepatic and neurological defects in addition to metabolic defects, laterality defects and polydactyly. Their clinical variability can make ciliopathies hard to recognise, reflecting the ubiquity of cilia. Gene panels currently offer the best solution to tackling analysis of genetically Samples required heterogeneous conditions such as the ciliopathies. Ciliopathies affect approximately 1:2,000 5ml venous blood in plastic EDTA births. bottles (>1ml from neonates) Ciliopathies are generally inherited in an autosomal recessive manner, with some autosomal Prenatal testing must be arranged dominant and X-linked exceptions. in advance, through a Clinical Genetics department if possible. Referrals Amniotic fluid or CV samples Patients presenting with a ciliopathy; due to the phenotypic variability this could be a diverse set should be sent to Cytogenetics for of features. For guidance contact the laboratory or Dr Hannah Mitchison dissecting and culturing, with ([email protected]) / Prof Phil Beales ([email protected]) instructions to forward the sample to the Regional Molecular Genetics Referrals will be accepted from clinical geneticists and consultants in nephrology, metabolic, laboratory for analysis respiratory and retinal diseases. -
Cellular and Molecular Signatures in the Disease Tissue of Early
Cellular and Molecular Signatures in the Disease Tissue of Early Rheumatoid Arthritis Stratify Clinical Response to csDMARD-Therapy and Predict Radiographic Progression Frances Humby1,* Myles Lewis1,* Nandhini Ramamoorthi2, Jason Hackney3, Michael Barnes1, Michele Bombardieri1, Francesca Setiadi2, Stephen Kelly1, Fabiola Bene1, Maria di Cicco1, Sudeh Riahi1, Vidalba Rocher-Ros1, Nora Ng1, Ilias Lazorou1, Rebecca E. Hands1, Desiree van der Heijde4, Robert Landewé5, Annette van der Helm-van Mil4, Alberto Cauli6, Iain B. McInnes7, Christopher D. Buckley8, Ernest Choy9, Peter Taylor10, Michael J. Townsend2 & Costantino Pitzalis1 1Centre for Experimental Medicine and Rheumatology, William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, Charterhouse Square, London EC1M 6BQ, UK. Departments of 2Biomarker Discovery OMNI, 3Bioinformatics and Computational Biology, Genentech Research and Early Development, South San Francisco, California 94080 USA 4Department of Rheumatology, Leiden University Medical Center, The Netherlands 5Department of Clinical Immunology & Rheumatology, Amsterdam Rheumatology & Immunology Center, Amsterdam, The Netherlands 6Rheumatology Unit, Department of Medical Sciences, Policlinico of the University of Cagliari, Cagliari, Italy 7Institute of Infection, Immunity and Inflammation, University of Glasgow, Glasgow G12 8TA, UK 8Rheumatology Research Group, Institute of Inflammation and Ageing (IIA), University of Birmingham, Birmingham B15 2WB, UK 9Institute of -
Nicotinamide Riboside Kinases Display Redundancy in Mediating Nicotinamide Mononucleotide and Nicotinamide Riboside Metabolism in Skeletal Muscle Cells
Original Article Nicotinamide riboside kinases display redundancy in mediating nicotinamide mononucleotide and nicotinamide riboside metabolism in skeletal muscle cells Rachel S. Fletcher 1,2, Joanna Ratajczak 3,4, Craig L. Doig 1,2, Lucy A. Oakey 2, Rebecca Callingham 5, Gabriella Da Silva Xavier 5, Antje Garten 1,6, Yasir S. Elhassan 1,2, Philip Redpath 7, Marie E. Migaud 7, Andrew Philp 8, Charles Brenner 9, Carles Canto 3,4, Gareth G. Lavery 1,2,* ABSTRACT þ Objective: Augmenting nicotinamide adenine dinucleotide (NAD ) availability may protect skeletal muscle from age-related metabolic decline. þ Dietary supplementation of NAD precursors nicotinamide mononucleotide (NMN) and nicotinamide riboside (NR) appear efficacious in elevating þ þ muscle NAD . Here we sought to identify the pathways skeletal muscle cells utilize to synthesize NAD from NMN and NR and provide insight into mechanisms of muscle metabolic homeostasis. þ Methods: We exploited expression profiling of muscle NAD biosynthetic pathways, single and double nicotinamide riboside kinase 1/2 (NRK1/ þ 2) loss-of-function mice, and pharmacological inhibition of muscle NAD recycling to evaluate NMN and NR utilization. Results: Skeletal muscle cells primarily rely on nicotinamide phosphoribosyltransferase (NAMPT), NRK1, and NRK2 for salvage biosynthesis of þ þ NAD . NAMPT inhibition depletes muscle NAD availability and can be rescued by NR and NMN as the preferred precursors for elevating muscle þ cell NAD in a pathway that depends on NRK1 and NRK2. Nrk2 knockout mice develop normally and show subtle alterations to their NADþ metabolome and expression of related genes. NRK1, NRK2, and double KO myotubes revealed redundancy in the NRK dependent þ metabolism of NR to NAD . -
Análise Integrativa De Perfis Transcricionais De Pacientes Com
UNIVERSIDADE DE SÃO PAULO FACULDADE DE MEDICINA DE RIBEIRÃO PRETO PROGRAMA DE PÓS-GRADUAÇÃO EM GENÉTICA ADRIANE FEIJÓ EVANGELISTA Análise integrativa de perfis transcricionais de pacientes com diabetes mellitus tipo 1, tipo 2 e gestacional, comparando-os com manifestações demográficas, clínicas, laboratoriais, fisiopatológicas e terapêuticas Ribeirão Preto – 2012 ADRIANE FEIJÓ EVANGELISTA Análise integrativa de perfis transcricionais de pacientes com diabetes mellitus tipo 1, tipo 2 e gestacional, comparando-os com manifestações demográficas, clínicas, laboratoriais, fisiopatológicas e terapêuticas Tese apresentada à Faculdade de Medicina de Ribeirão Preto da Universidade de São Paulo para obtenção do título de Doutor em Ciências. Área de Concentração: Genética Orientador: Prof. Dr. Eduardo Antonio Donadi Co-orientador: Prof. Dr. Geraldo A. S. Passos Ribeirão Preto – 2012 AUTORIZO A REPRODUÇÃO E DIVULGAÇÃO TOTAL OU PARCIAL DESTE TRABALHO, POR QUALQUER MEIO CONVENCIONAL OU ELETRÔNICO, PARA FINS DE ESTUDO E PESQUISA, DESDE QUE CITADA A FONTE. FICHA CATALOGRÁFICA Evangelista, Adriane Feijó Análise integrativa de perfis transcricionais de pacientes com diabetes mellitus tipo 1, tipo 2 e gestacional, comparando-os com manifestações demográficas, clínicas, laboratoriais, fisiopatológicas e terapêuticas. Ribeirão Preto, 2012 192p. Tese de Doutorado apresentada à Faculdade de Medicina de Ribeirão Preto da Universidade de São Paulo. Área de Concentração: Genética. Orientador: Donadi, Eduardo Antonio Co-orientador: Passos, Geraldo A. 1. Expressão gênica – microarrays 2. Análise bioinformática por module maps 3. Diabetes mellitus tipo 1 4. Diabetes mellitus tipo 2 5. Diabetes mellitus gestacional FOLHA DE APROVAÇÃO ADRIANE FEIJÓ EVANGELISTA Análise integrativa de perfis transcricionais de pacientes com diabetes mellitus tipo 1, tipo 2 e gestacional, comparando-os com manifestações demográficas, clínicas, laboratoriais, fisiopatológicas e terapêuticas. -
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 -
Human Lectins, Their Carbohydrate Affinities and Where to Find Them
biomolecules Review Human Lectins, Their Carbohydrate Affinities and Where to Review HumanFind Them Lectins, Their Carbohydrate Affinities and Where to FindCláudia ThemD. Raposo 1,*, André B. Canelas 2 and M. Teresa Barros 1 1, 2 1 Cláudia D. Raposo * , Andr1 é LAQVB. Canelas‐Requimte,and Department M. Teresa of Chemistry, Barros NOVA School of Science and Technology, Universidade NOVA de Lisboa, 2829‐516 Caparica, Portugal; [email protected] 12 GlanbiaLAQV-Requimte,‐AgriChemWhey, Department Lisheen of Chemistry, Mine, Killoran, NOVA Moyne, School E41 of ScienceR622 Co. and Tipperary, Technology, Ireland; canelas‐ [email protected] NOVA de Lisboa, 2829-516 Caparica, Portugal; [email protected] 2* Correspondence:Glanbia-AgriChemWhey, [email protected]; Lisheen Mine, Tel.: Killoran, +351‐212948550 Moyne, E41 R622 Tipperary, Ireland; [email protected] * Correspondence: [email protected]; Tel.: +351-212948550 Abstract: Lectins are a class of proteins responsible for several biological roles such as cell‐cell in‐ Abstract:teractions,Lectins signaling are pathways, a class of and proteins several responsible innate immune for several responses biological against roles pathogens. such as Since cell-cell lec‐ interactions,tins are able signalingto bind to pathways, carbohydrates, and several they can innate be a immuneviable target responses for targeted against drug pathogens. delivery Since sys‐ lectinstems. In are fact, able several to bind lectins to carbohydrates, were approved they by canFood be and a viable Drug targetAdministration for targeted for drugthat purpose. delivery systems.Information In fact, about several specific lectins carbohydrate were approved recognition by Food by andlectin Drug receptors Administration was gathered for that herein, purpose. plus Informationthe specific organs about specific where those carbohydrate lectins can recognition be found by within lectin the receptors human was body. -
Early Growth Response 1 Regulates Hematopoietic Support and Proliferation in Human Primary Bone Marrow Stromal Cells
Hematopoiesis SUPPLEMENTARY APPENDIX Early growth response 1 regulates hematopoietic support and proliferation in human primary bone marrow stromal cells Hongzhe Li, 1,2 Hooi-Ching Lim, 1,2 Dimitra Zacharaki, 1,2 Xiaojie Xian, 2,3 Keane J.G. Kenswil, 4 Sandro Bräunig, 1,2 Marc H.G.P. Raaijmakers, 4 Niels-Bjarne Woods, 2,3 Jenny Hansson, 1,2 and Stefan Scheding 1,2,5 1Division of Molecular Hematology, Department of Laboratory Medicine, Lund University, Lund, Sweden; 2Lund Stem Cell Center, Depart - ment of Laboratory Medicine, Lund University, Lund, Sweden; 3Division of Molecular Medicine and Gene Therapy, Department of Labora - tory Medicine, Lund University, Lund, Sweden; 4Department of Hematology, Erasmus MC Cancer Institute, Rotterdam, the Netherlands and 5Department of Hematology, Skåne University Hospital Lund, Skåne, Sweden ©2020 Ferrata Storti Foundation. This is an open-access paper. doi:10.3324/haematol. 2019.216648 Received: January 14, 2019. Accepted: July 19, 2019. Pre-published: August 1, 2019. Correspondence: STEFAN SCHEDING - [email protected] Li et al.: Supplemental data 1. Supplemental Materials and Methods BM-MNC isolation Bone marrow mononuclear cells (BM-MNC) from BM aspiration samples were isolated by density gradient centrifugation (LSM 1077 Lymphocyte, PAA, Pasching, Austria) either with or without prior incubation with RosetteSep Human Mesenchymal Stem Cell Enrichment Cocktail (STEMCELL Technologies, Vancouver, Canada) for lineage depletion (CD3, CD14, CD19, CD38, CD66b, glycophorin A). BM-MNCs from fetal long bones and adult hip bones were isolated as reported previously 1 by gently crushing bones (femora, tibiae, fibulae, humeri, radii and ulna) in PBS+0.5% FCS subsequent passing of the cell suspension through a 40-µm filter. -
TULP1 Mutations Causing Early-Onset Retinal Degeneration: Preserved but Insensitive Macular Cones
Retina TULP1 Mutations Causing Early-Onset Retinal Degeneration: Preserved but Insensitive Macular Cones Samuel G. Jacobson,1 Artur V. Cideciyan,1 Wei Chieh Huang,1 Alexander Sumaroka,1 Alejandro J. Roman,1 Sharon B. Schwartz,1 Xunda Luo,1 Rebecca Sheplock,1 Joanna M. Dauber,1 Malgorzata Swider,1 and Edwin M. Stone2,3 1Scheie Eye Institute, Department of Ophthalmology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States 2Department of Ophthalmology, University of Iowa Carver College of Medicine, Iowa City, Iowa, United States 3Howard Hughes Medical Institute, Iowa City, Iowa, United States Correspondence: Samuel G. Jacob- PURPOSE. To investigate visual function and outer and inner retinal structure in the rare form of son, Scheie Eye Institute, University retinal degeneration (RD) caused by TULP1 (tubby-like protein 1) mutations. of Pennsylvania, 51 N. 39th Street, Philadelphia, PA 19104, USA; METHODS. Retinal degeneration patients with TULP1 mutations (n ¼ 5; age range, 5–36 years) [email protected]. were studied by kinetic and chromatic static perimetry, en face autofluorescence imaging, and spectral-domain optical coherence tomography (OCT) scans. Outer and inner retinal Submitted: April 10, 2014 Accepted: July 13, 2014 laminar thickness were measured and mapped across the central retina. Comparisons were made with results from patients with RD associated with four ciliopathy genotypes (MAK, Citation: Jacobson SG, Cideciyan AV, RPGR, BBS1, and USH2A). Huang WC, et al. TULP1 mutations causing early-onset retinal degenera- RESULTS. The TULP1-RD patients were severely affected already in the first decade of life and tion: preserved but insensitive macu- there was rapidly progressive visual loss. -
Direct Interaction Between Hnrnp-M and CDC5L/PLRG1 Proteins Affects Alternative Splice Site Choice
Direct interaction between hnRNP-M and CDC5L/PLRG1 proteins affects alternative splice site choice David Llères, Marco Denegri, Marco Biggiogera, Paul Ajuh, Angus Lamond To cite this version: David Llères, Marco Denegri, Marco Biggiogera, Paul Ajuh, Angus Lamond. Direct interaction be- tween hnRNP-M and CDC5L/PLRG1 proteins affects alternative splice site choice. EMBO Reports, EMBO Press, 2010, 11 (6), pp.445 - 451. 10.1038/embor.2010.64. hal-03027049 HAL Id: hal-03027049 https://hal.archives-ouvertes.fr/hal-03027049 Submitted on 26 Nov 2020 HAL is a multi-disciplinary open access L’archive ouverte pluridisciplinaire HAL, est archive for the deposit and dissemination of sci- destinée au dépôt et à la diffusion de documents entific research documents, whether they are pub- scientifiques de niveau recherche, publiés ou non, lished or not. The documents may come from émanant des établissements d’enseignement et de teaching and research institutions in France or recherche français ou étrangers, des laboratoires abroad, or from public or private research centers. publics ou privés. scientificscientificreport report Direct interaction between hnRNP-M and CDC5L/ PLRG1 proteins affects alternative splice site choice David Lle`res1*, Marco Denegri1*w,MarcoBiggiogera2,PaulAjuh1z & Angus I. Lamond1+ 1Wellcome Trust Centre for Gene Regulation & Expression, College of Life Sciences, University of Dundee, Dundee, UK, and 2LaboratoriodiBiologiaCellulareandCentrodiStudioperl’IstochimicadelCNR,DipartimentodiBiologiaAnimale, Universita’ di Pavia, Pavia, Italy Heterogeneous nuclear ribonucleoprotein-M (hnRNP-M) is an and affect the fate of heterogeneous nuclear RNAs by influencing their abundant nuclear protein that binds to pre-mRNA and is a structure and/or by facilitating or hindering the interaction of their component of the spliceosome complex.