DOCSLIB.ORG

Proteomic Analysis of Ascending Colon Biopsies from a Paediatric

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Proteomic Analysis of Ascending Colon Biopsies from a Paediatric Gut Online First, published on May 23, 2016 as 10.1136/gutjnl-2015-310705 Inflammatory bowel disease ORIGINAL ARTICLE Proteomic analysis of ascending colon biopsies from Gut: first published as 10.1136/gutjnl-2015-310705 on 23 May 2016. Downloaded from a paediatric inflammatory bowel disease inception cohort identifies protein biomarkers that differentiate Crohn’s disease from UC Amanda E Starr,1 Shelley A Deeke,1 Zhibin Ning,1 Cheng-Kang Chiang,1 Xu Zhang,1 Walid Mottawea,1,2 Ruth Singleton,3 Eric I Benchimol,3,4,5 Ming Wen,1 David R Mack,3,4 Alain Stintzi,1 Daniel Figeys1,6 ▸ Additional material is ABSTRACT published online only. To view Objective Accurate differentiation between Crohn’s Significance of this study please visit the journal online (http://dx.doi.org/10.1136/ disease (CD) and UC is important to ensure early and gutjnl-2015-310705). appropriate therapeutic intervention. We sought to identify proteins that enable differentiation between CD 1Department of Biochemistry, What is already known on this subject? Microbiology and Immunology, and UC in children with new onset IBD. ▸ Accurate diagnosis of Crohn’s disease (CD) and Ottawa Institute of Systems Design Mucosal biopsies were obtained from children UC is important, so appropriate therapy can be Biology, University of Ottawa, undergoing baseline diagnostic endoscopy prior to initiated to reduce disease progression, Ottawa, Ontario, Canada therapeutic interventions. Using a super-stable isotope complications of disease related to permanent 2Department of Microbiology and Immunology, Mansoura labeling with amino acids in cell culture (SILAC)-based bowel damage and avoid unnecessary adverse University, Mansoura, Egypt approach, the proteomes of 99 paediatric control and drug events. 3Children’s Hospital of Eastern biopsies of patients with CD and UC were compared. ▸ Differentiation through clinical symptoms, site fl Ontario (CHEO) In ammatory Multivariate analysis of a subset of these (n=50) was of disease, presence of granulomas, genetics Bowel Disease Centre and applied to identify novel biomarkers, which were CHEO Research Institute, and current serological tests each have University of Ottawa, Ottawa, validated in a second subset (n=49). limitations. Ontario, Canada Results In the discovery cohort, a panel of five proteins ▸ Proteomic analyses are powerful tools to assess 4 Department of Pediatrics, was sufficient to distinguish control from IBD-affected quantitative and qualitative data about University of Ottawa, Ottawa, tissue biopsies with an AUC of 1.0 (95% CI 0.99 to biological systems. http://gut.bmj.com/ Ontario, Canada fl 5School of Epidemiology, 1.0); a second panel of 12 proteins segregated in amed CD from UC within an AUC of 0.95 (95% CI 0.86 to What are the new findings? Public Health and Preventive ▸ Medicine, University of Ottawa, 1.0). Application of the two panels to the validation An unbiased proteomics screen of biopsies Ottawa, Ontario, Canada fi from an inception cohort of patients with IBD 6 cohort resulted in accurate classi cation of 95.9% (IBD Department of Chemistry and from control) and 80% (CD from UC) of patients. 116 led to the identification of a panel of proteins Biomolecular Sciences, fi that can be used to differentiate patients with University of Ottawa, Ottawa, proteins were identi ed to have correlation with the Ontario, Canada severity of disease, four of which were components of CD from those with UC. on September 27, 2021 by guest. Protected copyright. the two panels, including visfatin and metallothionein-2. ▸ Candidate biomarkers suggest elevated fatty Correspondence to Conclusions This study has identified two panels of acid metabolism in paediatric CD and elevated Dr Daniel Figeys, Department protein metabolism in paediatric UC. of Biochemistry, Microbiology candidate biomarkers for the diagnosis of IBD and the and Immunology, Ottawa differentiation of IBD subtypes to guide appropriate How might it impact on clinical practice in Institute of Systems Biology, therapeutic interventions in paediatric patients. the foreseeable future? University of Ottawa, Roger ▸ Guidon Hall, 451 Smyth Road, The utilisation of these protein biomarkers into University of Ottawa, Ottawa, the clinical setting could improve accuracy of the Ontario, Canada K1H 8M5; current methods used to differentiate subtypes dfi[email protected] INTRODUCTION of IBD and do so in a rapid time frame. Further Received 10 September 2015 The IBDs are chronic, relapsing and remitting, GI understanding of the pathogenesis of paediatric Revised 10 March 2016 inflammatory conditions that affect over 4 million IBD may also be realised. Accepted 25 April 2016 people worldwide.1 In Canada, over 230 000 indi- viduals suffer from IBD, with an additional 10 000 cases diagnosed each year.2 IBD includes Crohn’s symptoms, and instead have a range of presenting disease (CD) and UC, which differ in clinical pres- features including atypical symptoms such as short entation and complications and may have different stature or weight loss leading to delayed recogni- – responses to treatment.3 5 Paediatric patients, tion and diagnosis.9 Generally, CD is characterised To cite: Starr AE, Deeke SA, 10%–25% of the IBD population,67often present by discreet mucosal and submucosal lesions, which Ning Z, et al. Gut Published Online First: [please include with different features from adult patients with can occur anywhere throughout the GI tract, and Day Month Year] IBD, and have more aggressive and extensive are transmural in nature. In contrast, UC extends – doi:10.1136/gutjnl-2015- disease and more long-term severe outcomes.4 8 proximally from the rectum, with contiguous, but 310705 Fewer children have the so-called classical generally superficial inflammation. However, non- Starr AE, et al. Gut 2016;0:1–11. doi:10.1136/gutjnl-2015-310705 1 Copyright Article author (or their employer) 2016. Produced by BMJ Publishing Group Ltd (& BSG) under licence. Inflammatory bowel disease specific gastric involvement, relative rectal sparing and periap- patient biopsies, for which the variance of the proteomic data pendiceal patch involvement in UC10 can add to diagnostic con- were <2.0, were randomly divided into equal groups between fusion and misclassification of disease. Differential diagnosis is the discovery and the validation phase using a balanced stratifi- Gut: first published as 10.1136/gutjnl-2015-310705 on 23 May 2016. Downloaded from important for the induction and maintenance of appropriate cation approach for gender and diagnosis (Etcetera in WinPepi, therapy, which can differ between CD and UC. In the paediatric BixtonHealth.ca). The study was approved by the Children’s population, exclusive enteral nutrition is an effective induction Hospital of Eastern Ontario (CHEO) Research Ethics Board. therapy in CD but not in UC.11 For maintenance therapy, Study data were collected and managed using Research methotrexate is established for CD,12 but not for UC,13 whereas Electronic Data Capture (REDCap), hosted at the CHEO mesalamine is not.14 Furthermore, complications related to the Research Institute. REDCap is a secure, web-based application diseases are very different. For those unfortunate patients who designed to support data capture for research studies.31 do not respond to therapy, surgical options are very different with surgery for UC offering the end of the UC disease process Study population and the opportunity for reservoir formation and reconstitution All patients under 18 years of age and scheduled to undergo of the bowel continuity. For CD, with the very real possibility of diagnostic colonoscopy between October 2011 and February recurrence elsewhere in the GI tract, surgery to remove inflamed 2015 were considered eligible for recruitment. Exclusion cri- segments of inflamed mucosa is generally not offered unless teria, related to conditions known to affect the intestinal micro- disease complications necessitate such action. Thus, for both biome and mucosal gene expression, included (1) a body mass consideration of therapeutic options and discussion of out- index >95th percentile for age; (2) diabetes mellitus (insulin comes, correct diagnosis is an important factor in effective treat- and non-insulin-dependent); (3) infectious gastroenteritis within ment in IBD. the preceding 2 months or (4) use of any antibiotics, probiotics Genome-wide association studies have identified nearly 170 or immunomodulatory agents within the preceding 4 weeks. All susceptibility loci associated with IBD, including many loci that IBD cases met the standard diagnostic criteria for either UC or – overlap in CD and UC,15 17 yet disease manifestation due to CD following thorough clinical, microbiological, endoscopic, these variants is less than 15%.17 Biomarkers have been sought histological and radiological evaluation.32 Phenotyping of to complement current IBD diagnostic tools such as endoscopy, disease was based on endoscopy and radiological findings and imaging and histology to reduce ambiguous diagnosis of IBD, based on the Paris modification of the Montreal Classification assist in subtype differentiation and provide objective measures for IBD.33 Clinical disease activity of CD or UC was determined of disease. Previous studies have identified proteins that are ele- using the Pediatric Crohn’s Disease Activity Index (PCDAI)34 or vated and measurable in serum or stool;3 however, these pro- the Pediatric UC Activity Index (PUCAI),35 respectively. Since teins have been found to perform best in the more obvious ascending
Load more

Recommended publications
  • Molecular Profile of Tumor-Specific CD8+ T Cell Hypofunction in a Transplantable Murine Cancer Model
    Downloaded from http://www.jimmunol.org/ by guest on September 25, 2021 T + is online at: average * The Journal of Immunology , 34 of which you can access for free at: 2016; 197:1477-1488; Prepublished online 1 July from submission to initial decision 4 weeks from acceptance to publication 2016; doi: 10.4049/jimmunol.1600589 http://www.jimmunol.org/content/197/4/1477 Molecular Profile of Tumor-Specific CD8 Cell Hypofunction in a Transplantable Murine Cancer Model Katherine A. Waugh, Sonia M. Leach, Brandon L. Moore, Tullia C. Bruno, Jonathan D. Buhrman and Jill E. Slansky J Immunol cites 95 articles Submit online. Every submission reviewed by practicing scientists ? is published twice each month by Receive free email-alerts when new articles cite this article. Sign up at: http://jimmunol.org/alerts http://jimmunol.org/subscription Submit copyright permission requests at: http://www.aai.org/About/Publications/JI/copyright.html http://www.jimmunol.org/content/suppl/2016/07/01/jimmunol.160058 9.DCSupplemental This article http://www.jimmunol.org/content/197/4/1477.full#ref-list-1 Information about subscribing to The JI No Triage! Fast Publication! Rapid Reviews! 30 days* Why • • • Material References Permissions Email Alerts Subscription Supplementary The Journal of Immunology The American Association of Immunologists, Inc., 1451 Rockville Pike, Suite 650, Rockville, MD 20852 Copyright © 2016 by The American Association of Immunologists, Inc. All rights reserved. Print ISSN: 0022-1767 Online ISSN: 1550-6606. This information is current as of September 25, 2021. The Journal of Immunology Molecular Profile of Tumor-Specific CD8+ T Cell Hypofunction in a Transplantable Murine Cancer Model Katherine A.
    [Show full text]
  • Epidermal Fatty Acid-Binding Protein 5 (FABP5) Involvement in Alpha-Synuclein-Induced Mitochondrial Injury Under Oxidative Stress
    biomedicines Article Epidermal Fatty Acid-Binding Protein 5 (FABP5) Involvement in Alpha-Synuclein-Induced Mitochondrial Injury under Oxidative Stress Yifei Wang , Yasuharu Shinoda , An Cheng , Ichiro Kawahata and Kohji Fukunaga * Department of Pharmacology, Graduate School of Pharmaceutical Sciences, Tohoku University, 6–3 Aramaki-Aoba, Aoba-ku, Sendai 980-8578, Japan; [email protected] (Y.W.); [email protected] (Y.S.); [email protected] (A.C.); [email protected] (I.K.) * Correspondence: [email protected]; Tel.: +81-22-795-6836 Abstract: The accumulation of α-synuclein (αSyn) has been implicated as a causal factor in the pathogenesis of Parkinson’s disease (PD). There is growing evidence that supports mitochondrial dysfunction as a potential primary cause of dopaminergic neuronal death in PD. Here, we focused on reciprocal interactions between αSyn aggregation and mitochondrial injury induced by oxidative stress. We further investigated whether epidermal fatty acid-binding protein 5 (FABP5) is related to αSyn oligomerization/aggregation and subsequent disturbances in mitochondrial function in neuronal cells. In the presence of rotenone, a mitochondrial respiratory chain complex I inhibitor, co- overexpression of FABP5 with αSyn significantly decreased the viability of Neuro-2A cells compared to that of αSyn alone. Under these conditions, FABP5 co-localized with αSyn in the mitochondria, thereby reducing mitochondrial membrane potential. Furthermore, we confirmed that pharmacologi- cal inhibition of FABP5 by its ligand prevented αSyn accumulation in mitochondria, which led to cell death rescue. These results suggested that FABP5 is crucial for mitochondrial dysfunction related to Citation: Wang, Y.; Shinoda, Y.; αSyn oligomerization/aggregation in the mitochondria induced by oxidative stress in neurons.
    [Show full text]
  • An Amplified Fatty Acid-Binding Protein Gene Cluster In
    cancers Review An Amplified Fatty Acid-Binding Protein Gene Cluster in Prostate Cancer: Emerging Roles in Lipid Metabolism and Metastasis Rong-Zong Liu and Roseline Godbout * Department of Oncology, Cross Cancer Institute, University of Alberta, Edmonton, AB T6G 1Z2, Canada; [email protected] * Correspondence: [email protected]; Tel.: +1-780-432-8901 Received: 6 November 2020; Accepted: 16 December 2020; Published: 18 December 2020 Simple Summary: Prostate cancer is the second most common cancer in men. In many cases, prostate cancer grows very slowly and remains confined to the prostate. These localized cancers can usually be cured. However, prostate cancer can also metastasize to other organs of the body, which often results in death of the patient. We found that a cluster of genes involved in accumulation and utilization of fats exists in multiple copies and is expressed at much higher levels in metastatic prostate cancer compared to localized disease. These genes, called fatty acid-binding protein (or FABP) genes, individually and collectively, promote properties associated with prostate cancer metastasis. We propose that levels of these FABP genes may serve as an indicator of prostate cancer aggressiveness, and that inhibiting the action of FABP genes may provide a new approach to prevent and/or treat metastatic prostate cancer. Abstract: Treatment for early stage and localized prostate cancer (PCa) is highly effective. Patient survival, however, drops dramatically upon metastasis due to drug resistance and cancer recurrence. The molecular mechanisms underlying PCa metastasis are complex and remain unclear. It is therefore crucial to decipher the key genetic alterations and relevant molecular pathways driving PCa metastatic progression so that predictive biomarkers and precise therapeutic targets can be developed.
    [Show full text]
  • Single-Cell RNA Sequencing Demonstrates the Molecular and Cellular Reprogramming of Metastatic Lung Adenocarcinoma
    ARTICLE https://doi.org/10.1038/s41467-020-16164-1 OPEN Single-cell RNA sequencing demonstrates the molecular and cellular reprogramming of metastatic lung adenocarcinoma Nayoung Kim 1,2,3,13, Hong Kwan Kim4,13, Kyungjong Lee 5,13, Yourae Hong 1,6, Jong Ho Cho4, Jung Won Choi7, Jung-Il Lee7, Yeon-Lim Suh8,BoMiKu9, Hye Hyeon Eum 1,2,3, Soyean Choi 1, Yoon-La Choi6,10,11, Je-Gun Joung1, Woong-Yang Park 1,2,6, Hyun Ae Jung12, Jong-Mu Sun12, Se-Hoon Lee12, ✉ ✉ Jin Seok Ahn12, Keunchil Park12, Myung-Ju Ahn 12 & Hae-Ock Lee 1,2,3,6 1234567890():,; Advanced metastatic cancer poses utmost clinical challenges and may present molecular and cellular features distinct from an early-stage cancer. Herein, we present single-cell tran- scriptome profiling of metastatic lung adenocarcinoma, the most prevalent histological lung cancer type diagnosed at stage IV in over 40% of all cases. From 208,506 cells populating the normal tissues or early to metastatic stage cancer in 44 patients, we identify a cancer cell subtype deviating from the normal differentiation trajectory and dominating the metastatic stage. In all stages, the stromal and immune cell dynamics reveal ontological and functional changes that create a pro-tumoral and immunosuppressive microenvironment. Normal resident myeloid cell populations are gradually replaced with monocyte-derived macrophages and dendritic cells, along with T-cell exhaustion. This extensive single-cell analysis enhances our understanding of molecular and cellular dynamics in metastatic lung cancer and reveals potential diagnostic and therapeutic targets in cancer-microenvironment interactions. 1 Samsung Genome Institute, Samsung Medical Center, Seoul 06351, Korea.
    [Show full text]
  • Understanding the Transport Mechanism of BBB Peptide Shuttles: Thrre and Miniap-4 As Case Studies
    Understanding the transport mechanism of BBB peptide shuttles: THRre and MiniAp-4 as case studies Cristina Fuster Juncà ADVERTIMENT. La consulta d’aquesta tesi queda condicionada a l’acceptació de les següents condicions d'ús: La difusió d’aquesta tesi per mitjà del servei TDX (www.tdx.cat) i a través del Dipòsit Digital de la UB (diposit.ub.edu) ha estat autoritzada pels titulars dels drets de propietat intel·lectual únicament per a usos privats emmarcats en activitats d’investigació i docència. No s’autoritza la seva reproducció amb finalitats de lucre ni la seva difusió i posada a disposició des d’un lloc aliè al servei TDX ni al Dipòsit Digital de la UB. No s’autoritza la presentació del seu contingut en una finestra o marc aliè a TDX o al Dipòsit Digital de la UB (framing). Aquesta reserva de drets afecta tant al resum de presentació de la tesi com als seus continguts. En la utilització o cita de parts de la tesi és obligat indicar el nom de la persona autora. ADVERTENCIA. La consulta de esta tesis queda condicionada a la aceptación de las siguientes condiciones de uso: La difusión de esta tesis por medio del servicio TDR (www.tdx.cat) y a través del Repositorio Digital de la UB (diposit.ub.edu) ha sido autorizada por los titulares de los derechos de propiedad intelectual únicamente para usos privados enmarcados en actividades de investigación y docencia. No se autoriza su reproducción con finalidades de lucro ni su difusión y puesta a disposición desde un sitio ajeno al servicio TDR o al Repositorio Digital de la UB.
    [Show full text]
  • The Temporal Mutational and Immune Tumour Microenvironment
    www.nature.com/npjbcancer ARTICLE OPEN The temporal mutational and immune tumour microenvironment remodelling of HER2-negative primary breast cancers ✉ Leticia De Mattos-Arruda 1,2,3 , Javier Cortes 4,5,6,7,8, Juan Blanco-Heredia1,2, Daniel G. Tiezzi 3,9, Guillermo Villacampa10, Samuel Gonçalves-Ribeiro 10, Laia Paré11,12,13, Carla Anjos Souza1,2, Vanesa Ortega7, Stephen-John Sammut3,14, Pol Cusco10, Roberta Fasani10, Suet-Feung Chin 3, Jose Perez-Garcia4,5,6, Rodrigo Dienstmann10, Paolo Nuciforo10, Patricia Villagrasa12, Isabel T. Rubio10, Aleix Prat 11,12,13 and Carlos Caldas 3,14 The biology of breast cancer response to neoadjuvant therapy is underrepresented in the literature and provides a window-of- opportunity to explore the genomic and microenvironment modulation of tumours exposed to therapy. Here, we characterised the mutational, gene expression, pathway enrichment and tumour-infiltrating lymphocytes (TILs) dynamics across different timepoints of 35 HER2-negative primary breast cancer patients receiving neoadjuvant eribulin therapy (SOLTI-1007 NEOERIBULIN- NCT01669252). Whole-exome data (N = 88 samples) generated mutational profiles and candidate neoantigens and were analysed along with RNA-Nanostring 545-gene expression (N = 96 samples) and stromal TILs (N = 105 samples). Tumour mutation burden varied across patients at baseline but not across the sampling timepoints for each patient. Mutational signatures were not always conserved across tumours. There was a trend towards higher odds of response and less hazard to relapse when the percentage of 1234567890():,; subclonal mutations was low, suggesting that more homogenous tumours might have better responses to neoadjuvant therapy. Few driver mutations (5.1%) generated putative neoantigens.
    [Show full text]
  • Biological Role of Conceptus Derived Factors During Early Pregnancy In
    Biological Role of Conceptus Derived Factors During Early Pregnancy in Ruminants A dissertation submitted in partial fulfillment of the requirements for the degree of DOCTOR OF PHILOSOPHY IN ANIMAL SCIENCES UNIVERSITY OF MISSOURI- COLUMBIA Division of Animal Science By KELSEY BROOKS Dr. Thomas Spencer, Dissertation Supervisor August 2016 The undersigned have examined the dissertation entitled, BIOLOGICAL ROLE OF CONCEPTUS DERIVED FACTORS DURING EARLY PREGNANCY IN RUMINANTS presented by Kelsey Brooks, a candidate for the degree of doctor of philosophy, and hereby certify that, in their opinion, it is worthy of acceptance. __________________________________ Chair, Dr. Thomas Spencer ___________________________________ Dr. Rodney Geisert ___________________________________ Dr. Randall Prather ___________________________________ Dr. Laura Schulz ACKNOWLEDGMENTS I would like to acknowledge all the students, faculty and staff at Washington State University and the University of Missouri for their help and support throughout my doctoral program. I am grateful for the opportunity to work with Dr. Thomas Spencer, and thank him for his input and guidance not only in planning experiments and completing projects but for helping me turn my love of science into a career in research. I would also like to acknowledge the members of my graduate committee at Washington State University for their help and input during the first 3 years of my studies. A special thanks to Dr. Jim Pru and Cindy Pru for providing unlimited entertainment, and the occasional missing reagent. Thank you to my committee members at the University of Missouri for adopting me late in my program and helping shape my future as an independent scientist. Thanks are also extended to members of the Prather lab and Wells lab for letting me in on the secrets of success using the CRISPR/Cas9 system.
    [Show full text]
  • Development and Validation of a Protein-Based Risk Score for Cardiovascular Outcomes Among Patients with Stable Coronary Heart Disease
    Supplementary Online Content Ganz P, Heidecker B, Hveem K, et al. Development and validation of a protein-based risk score for cardiovascular outcomes among patients with stable coronary heart disease. JAMA. doi: 10.1001/jama.2016.5951 eTable 1. List of 1130 Proteins Measured by Somalogic’s Modified Aptamer-Based Proteomic Assay eTable 2. Coefficients for Weibull Recalibration Model Applied to 9-Protein Model eFigure 1. Median Protein Levels in Derivation and Validation Cohort eTable 3. Coefficients for the Recalibration Model Applied to Refit Framingham eFigure 2. Calibration Plots for the Refit Framingham Model eTable 4. List of 200 Proteins Associated With the Risk of MI, Stroke, Heart Failure, and Death eFigure 3. Hazard Ratios of Lasso Selected Proteins for Primary End Point of MI, Stroke, Heart Failure, and Death eFigure 4. 9-Protein Prognostic Model Hazard Ratios Adjusted for Framingham Variables eFigure 5. 9-Protein Risk Scores by Event Type This supplementary material has been provided by the authors to give readers additional information about their work. Downloaded From: https://jamanetwork.com/ on 10/02/2021 Supplemental Material Table of Contents 1 Study Design and Data Processing ......................................................................................................... 3 2 Table of 1130 Proteins Measured .......................................................................................................... 4 3 Variable Selection and Statistical Modeling ........................................................................................
    [Show full text]
  • Urinary Proteomics for the Early Diagnosis of Diabetic Nephropathy in Taiwanese Patients Authors
    Urinary Proteomics for the Early Diagnosis of Diabetic Nephropathy in Taiwanese Patients Authors: Wen-Ling Liao1,2, Chiz-Tzung Chang3,4, Ching-Chu Chen5,6, Wen-Jane Lee7,8, Shih-Yi Lin3,4, Hsin-Yi Liao9, Chia-Ming Wu10, Ya-Wen Chang10, Chao-Jung Chen1,9,+,*, Fuu-Jen Tsai6,10,11,+,* 1 Graduate Institute of Integrated Medicine, China Medical University, Taichung, 404, Taiwan 2 Center for Personalized Medicine, China Medical University Hospital, Taichung, 404, Taiwan 3 Division of Nephrology and Kidney Institute, Department of Internal Medicine, China Medical University Hospital, Taichung, 404, Taiwan 4 Institute of Clinical Medical Science, China Medical University College of Medicine, Taichung, 404, Taiwan 5 Division of Endocrinology and Metabolism, Department of Medicine, China Medical University Hospital, Taichung, 404, Taiwan 6 School of Chinese Medicine, China Medical University, Taichung, 404, Taiwan 7 Department of Medical Research, Taichung Veterans General Hospital, Taichung, 404, Taiwan 8 Department of Social Work, Tunghai University, Taichung, 404, Taiwan 9 Proteomics Core Laboratory, Department of Medical Research, China Medical University Hospital, Taichung, 404, Taiwan 10 Human Genetic Center, Department of Medical Research, China Medical University Hospital, China Medical University, Taichung, 404, Taiwan 11 Department of Health and Nutrition Biotechnology, Asia University, Taichung, 404, Taiwan + Fuu-Jen Tsai and Chao-Jung Chen contributed equally to this work. Correspondence: Fuu-Jen Tsai, MD, PhD and Chao-Jung Chen, PhD FJ Tsai: Genetic Center, China Medical University Hospital, No.2 Yuh-Der Road, 404 Taichung, Taiwan; Telephone: 886-4-22062121 Ext. 2041; Fax: 886-4-22033295; E-mail: [email protected] CJ Chen: Graduate Institute of Integrated Medicine, China Medical University, No.91, Hsueh-Shih Road, 404, Taichung, Taiwan; Telephone: 886-4-22053366 Ext.
    [Show full text]
  • Neural Progenitor Fate Decision Defects, Cortical Hypoplasia and Behavioral Impairment in Celsr1-Deficient Mice
    OPEN Molecular Psychiatry (2018) 23, 723–734 www.nature.com/mp ORIGINAL ARTICLE Neural progenitor fate decision defects, cortical hypoplasia and behavioral impairment in Celsr1-deficient mice C Boucherie1, C Boutin1,5, Y Jossin2, O Schakman3, AM Goffinet1,LRis4, P Gailly3 and F Tissir1 The development of the cerebral cortex is a tightly regulated process that relies on exquisitely coordinated actions of intrinsic and extrinsic cues. Here, we show that the communication between forebrain meninges and apical neural progenitor cells (aNPC) is essential to cortical development, and that the basal compartment of aNPC is key to this communication process. We found that Celsr1, a cadherin of the adhesion G protein coupled receptor family, controls branching of aNPC basal processes abutting the meninges and thereby regulates retinoic acid (RA)-dependent neurogenesis. Loss-of-function of Celsr1 results in a decreased number of endfeet, modifies RA-dependent transcriptional activity and biases aNPC commitment toward self-renewal at the expense of basal progenitor and neuron production. The mutant cortex has a reduced number of neurons, and Celsr1 mutant mice exhibit microcephaly and behavioral abnormalities. Our results uncover an important role for Celsr1 protein and for the basal compartment of neural progenitor cells in fate decision during the development of the cerebral cortex. Molecular Psychiatry (2018) 23, 723–734; doi:10.1038/mp.2017.236; published online 19 December 2017 INTRODUCTION germinal zones,13 its function, after neural tube closure, has not The cerebral cortex is the seat of higher brain functions and its been assessed. formation requires the production and positioning of a right Here, we report that at the onset of neurogenesis, the Celsr1 number and diversity of neurons for intricate circuits assembly.
    [Show full text]
  • Expression of Genes Encoding Igfbps, SNARK, CD36, and PECAM1 in the Liver of Mice Treated with Chromium Disilicide and Titanium Nitride Nanoparticles
    Th is is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/ licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. 84 ENDOCRINE REGULATIONS, Vol. 51, No. 2, 84–95, 2017 doi:10.1515/enr-2017-0008 Expression of genes encoding IGFBPs, SNARK, CD36, and PECAM1 in the liver of mice treated with chromium disilicide and titanium nitride nanoparticles 1,2Minchenko DO, 1Tsymbal DO, 2Yavorovsky OP, 2Solokha NV, 1Minchenko OH 1Department of Molecular Biology, Palladin Institute of Biochemistry, National Academy of Sciences of Ukraine, Kyiv, Ukraine; 2Department of Pediatric and Department of Hygiene and Occupational Pathology, National Bohomolets Medical University, Kyiv, Ukraine E-mail: [email protected] Objective. Th e aim of the present study was to examine the eff ect of chromium disilicide and titanium nitride nanoparticles on the expression level of genes encoding important regulatory fac- tors (IGFBP1, IGFBP2, IGFBP3, IGFBP4, IGFBP5, SNARK/NUAK2, CD36, and PECAM1/CD31) in mouse liver for evaluation of possible toxic eff ects of these nanoparticles. Methods. Male mice received 20 mg chromium disilicide nanoparticles (45 nm) and titani- um nitride nanoparticles (20 nm) with food every working day for 2 months. Th e expression of IGFBP1, IGFBP2, IGFBP3, IGFBP4, IGFBP5, SNARK, CD36, and PECAM1 genes in mouse liver was studied by quantitative polymerase chain reaction. Results. Treatment of mice with chromium disilicide nanoparticles led to down-regulation of the expression of IGFBP2, IGFBP5, PECAM1, and SNARK genes in the liver in comparison with control mice, with more prominent changes for SNARK gene.
    [Show full text]
  • Dietary Effects of Arachidonate-Rich
    Lipids in Health and Disease BioMed Central Research1 Lipids2002, in Health and Disease x Open Access Dietary effects of arachidonate-rich fungal oil and fish oil on murine hepatic and hippocampal gene expression Alvin Berger1,5, David M Mutch1,3, J Bruce German2,4 and Matthew A Roberts*1 Address: 1Metabolic and Genomic Regulation, Nestlé Research Center, Vers-chez-les-Blanc, CH-1000 Lausanne 26, Switzerland, 2External Scientific Network, Nestlé Research Center, Vers-chez-les-Blanc, CH-1000 Lausanne 26, Switzerland, 3Institut de Biologie Animale, Université de Lausanne, CH-1015 Lausanne, Switzerland, 4Department of Food Science, University of California, Davis, CA 95616, USA and 5Current Address: Cytochroma, Inc., Manager Lipidomics™, 330 Cochrane Drive, Markham, Ontario, Canada E-mail: Alvin Berger - [email protected]; David M Mutch - [email protected]; J Bruce German - [email protected]; Matthew A Roberts* - [email protected] *Corresponding author Published: 21 October 2002 Received: 10 October 2002 Accepted: 21 October 2002 Lipids in Health and Disease 2002, 1:2 This article is available from: http://www.Lipidworld.com/content/1/1/2 © 2002 Berger et al; licensee BioMed Central Ltd. This article is published in Open Access: verbatim copying and redistribution of this article are permitted in all media for any purpose, provided this notice is preserved along with the article's original URL. Keywords: arachidonic acid, docosahexaenoic acid, fatty acid, hippocampus, liver, mice, microarray, PPAR, SREBP, transcription Abstract Background: The functions, actions, and regulation of tissue metabolism affected by the consumption of long chain polyunsaturated fatty acids (LC-PUFA) from fish oil and other sources remain poorly understood; particularly how LC-PUFAs affect transcription of genes involved in regulating metabolism.
    [Show full text]