DOCSLIB.ORG

Transcriptome of the Eastern Oyster Crassostrea Virginica in Response to Bacterial Challenge

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Transcriptome of the Eastern Oyster Crassostrea Virginica in Response to Bacterial Challenge University of Rhode Island DigitalCommons@URI Open Access Master's Theses 2013 Transcriptome of the Eastern Oyster Crassostrea Virginica in Response to Bacterial Challenge Ian McDowell University of Rhode Island, [email protected] Follow this and additional works at: https://digitalcommons.uri.edu/theses Recommended Citation McDowell, Ian, "Transcriptome of the Eastern Oyster Crassostrea Virginica in Response to Bacterial Challenge" (2013). Open Access Master's Theses. Paper 19. https://digitalcommons.uri.edu/theses/19 This Thesis is brought to you for free and open access by DigitalCommons@URI. It has been accepted for inclusion in Open Access Master's Theses by an authorized administrator of DigitalCommons@URI. For more information, please contact [email protected]. TRANSCRIPTOME OF THE EASTERN OYSTER CRASSOSTREA VIRGINICA IN RESPONSE TO BACTERIAL CHALLENGE BY IAN MCDOWELL A THESIS SUBMITTED IN PARTIAL FULFILLMENT OF THE REQUIREMENTS FOR THE DEGREE OF MASTER OF SCIENCE IN BIOLOGICAL AND ENVIRONMENTAL SCIENCES UNIVERSITY OF RHODE ISLAND 2013 ! MASTER OF SCIENCE THESIS OF IAN MCDOWELL APPROVED: Thesis Committee: Major Professor Marta Gomez-Chiarri Chris E. Lane Matt P. Hare Jason J. Kolbe Nasser H. Zawia DEAN OF THE GRADUATE SCHOOL ! UNIVERSITY OF RHODE ISLAND 2013 ABSTRACT The Eastern oyster Crassostrea virginica, an ecologically and economically important estuarine organism, suffers mortalities as high as 90-100% in affected areas due to Roseovarius Oyster Disease (ROD), caused by the bacterial pathogen, Roseovarius crassostreae. Advanced genotypic breeding techniques necessitate information regarding markers and genes associated with disease resistance. As yet, the host-pathogen interaction between C. virginica and R. crassostreae is poorly understood at the molecular level. The identification of potential genes and pathways responsible for an effective host defense response in the Eastern oyster to R. crassostreae is important not only to provide a basis for enhanced breeding techniques, but also to enhance understanding of innate immunity in a broader, evolutionary sense. The present study proposed to uncover not only genes and general processes potentially involved in disease resistance to ROD in the Eastern oyster, but also diversified gene families. To that end the present study entailed a disease challenge exposing ROD- resistant and ROD-susceptible families of oysters to R. crassostreae, high- throughput cDNA sequencing of samples from several timepoints throughout the disease challenge, assembly of sequence data into a reference transcriptome, analysis of the transcriptome through differential gene expression and gene family similarity clustering, and single nucleotide polymorphism (SNP) detection to identify candidate gene markers. Oyster resistance to R. crassostreae was found to involve extracellular matrix remodeling, cell adhesion, inflammation, metabolism, and other processes. Several gene families identified as putatively diversified and important in the oyster host defense response were enumerated and described, including serine proteases, serine protease inhibitors, c-type lectins, C1q domain-containing proteins, fibrinogen domain-containing proteins, scavenger receptors with class B SRCR domains, interferon-induced protein 44 (IFI44) family proteins, and GTPase of the immunity associated protein (GIMAP) family proteins. Further, similarity clustering of proteins and translated transcripts from diverse invertebrates suggested that GIMAP proteins are expanded in molluscs and IFI44 proteins are expanded in bivalves. ACKNOWLEDGEMENTS I thank my major professor, Marta Gomez-Chiarri, for her guidance, patience and expertise. I thank all of my labmates who have helped with this project and have helped to guide me in the lab including Chamilani Nikapitiya, Jess Piesz, Murni Karim, and Sae Bohm Sohn. I thank Ian Misner and Chris Lane who helped me greatly on the computational aspects of this project. I also thank the staff at Brown University’s Center for Computing and Visualization, especially Lingsheng Dong and Mark Howison, for their timely and immensely helpful support. I thank my family, friends, and very supportive girlfriend, Stacey McMillin. "#! TABLE OF CONTENTS ! ABSTRACT!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!""! ACKNOWLEDGEMENTS !!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!"#! TABLE OF CONTENTS!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!#! LIST OF TABLES !!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!#"! LIST OF FIGURES !!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!#"""! INTRODUCTION !!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!$ METHODS!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!%! RESULTS !!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!! &'! DISCUSSION !!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!! ()! TABLES!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!! '*! FIGURES !!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!! +'! APPENDIX !!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!! *%, BIBLIOGRAPHY !!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!$)-! , #! LIST OF TABLES Table 1. Assembly metrics for transcriptome assembly$$$$$$$$$$%59 Table 2. Top 50 most highly differentially expressed genes (DEGs) unique to GX_early up-regulated relative to control pool (CGX_late)$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$60 Table 3. Differentially expressed genes (DEGs) unique to GX_early down- regulated relative to control pool$$$$$$$$$$$%%%$$$$$$$$$$$$&' Table 4. Top 50 most highly differentially expressed genes (DEGs) among GX_early shared with F3L_early and/or F3L_late up-regulated relative to control pool $$$$$$$$$$$$$$$$$$$$$$$$%%$$$$$$$$$$$66 Table 5. Top 50 most highly differentially expressed genes (DEGs) among GX_early DEGs shared with F3L_early and/or F3L_late down-regulated relative to control pool $$$$$$$$$$$$$$%$$$$$%$$$$$$$$$%%%69 Table 6. Pfam families enriched among the differentially expressed genes (DEGs) from resistant (GX) and susceptible (F3L) oysters at early (1 and 5 d) and late (15 and 30 d) timepoints compared to control (CGX) oysters, with rank order of significance of enrichment and significance of enrichment (p-value)%%$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$72 Table 7. Pfam domains enriched among the differentially expressed genes #"! (DEGs) from resistant (GX) and susceptible (F3L) oysters at early (1 and 5 d) and late (15 and 30 d) timepoints compared to control (CGX) oysters, with rank order of significance of enrichment and significance of enrichment (p-value)$$$$$$$$$$$$$$$$$$$$$$$%%$$$$$$..74 Table 8. TribeMCL clusters enriched for differentially expressed genes (DEGs) from resistant (GX) and susceptible (F3L) oysters at early (1 and 5 d) and late (15 and 30 d) timepoints, with rank order of significance of enrichment and significance of enrichment (p-value)$$$$$%%$$$$%%$$76 Table 9. Comparison of select “diversified” groups of genes in the Eastern oyster to the Pacific oyster C.gigas genome and differential expression$$$$$$$$$$$$$$$$$$$$..$$$$$$$%$$$$$$$%$() #""! LIST OF FIGURES Figure 1. Cumulative percent mortality in two families of oysters challenged with the bacterial pathogen Roseovarius crassostreae (F3L and GX) and in unchallenged controls (CF3L and CGX).$$$$$$$$$%85 Figure 2. Heatmap of all differentially expressed genes (DEGs) in two oyster families experimentally challenged with the bacterial pathogen Roseovarius crassostreae (GX and F3L) and unchallenged controls$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$%$$%%$..86 Figure 3. Numbers of differentially expressed contigs (DEGs) shared and unique between GX_early (resistant oysters – days 1 and 5), F3L_early (susceptible oysters – days 1 and 5), and F3L_late (susceptible oysters – days 15 and 30)%%$$$$$$$$$$$$$$%$$$$$$$$$$$%%$$$$$$.87 Figure 4. Functionally enriched Gene Ontology terms among DEGs from resistant (GX) and susceptible (F3L) oysters at early (1 and 5 d) and late (15 and 30 d) time points compared to control (CGX) oysters mapped by semantic similarity using SimRel method and REViGO$$$$$$$$%$$88 Figure 5. Numbers of non-redundant transcripts/proteins and gene models in selected putative diversified gene families in multiple organisms from diverse taxa!$$$$%$$$$$$$$$$$$%%%$$$$$$$$$$$$$$$$$..90 #"""! Figure 6. C. virginica GIMAP translated transcripts clustered by similarity with color and size reflective of differential expression$$$$$$$$%%$$.91 Figure 7. C. virginica IFI44 translated transcripts clustered by similarity with color and size reflective of differential
Load more

Recommended publications
  • 1 Vitamins D2 and D3 Have Overlapping but Different Effects On
    medRxiv preprint doi: https://doi.org/10.1101/2020.12.16.20247700; this version posted February 22, 2021. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY 4.0 International license . Vitamins D2 and D3 have overlapping but different effects on human gene expression revealed through analysis of blood transcriptomes in a randomised double-blind placebo-controlled food-fortification trial Louise R. Durrant,1, 2, Giselda Buccaa,b, 1,3, Andrew Heskethb, 1, Carla Möller-Leveta, Laura Tripkovica, Huihai Wua, Kathryn H. Harta, John C. Mathersc, Ruan M. Elliotta, Susan A. Lanham-Newa & Colin P. Smitha,b, 3* a Department of Nutritional Sciences, School of Biosciences and Medicine, Faculty of Health and Medical Sciences, University of Surrey, Guildford, UK b School of Pharmacy and Biomolecular Sciences, University of Brighton, Brighton, UK c Human Nutrition Research Centre, Population Health Sciences Institute, Newcastle University, UK 1 These authors contributed equally 2 Current address: Yakult UK Ltd., Anteros, Odyssey Business Park, West End Road, South Ruislip, HA4 6QQ; formerly known as Louise Wilson. 3 Current address: School of Pharmacy and Biomolecular Sciences, University of Brighton, Brighton, UK *For correspondence: Prof Colin P. Smith, School of Pharmacy and Biomolecular Sciences, University of Brighton, Huxley Building, Moulsecoomb, Brighton, BN2 4GJ, UK; Tel. +44 (0)1273 642048. Email: [email protected] Key words: Vitamin D3, vitamin D2, 25-hydroxyvitamin D, human transcriptome, immunity, ethnic differences, Covid-19 Abstract For the first time, we report the influence of vitamin D2 and vitamin D3 on genome- wide gene expression in whole blood from healthy women representing two ethnic groups, white European and South Asian.
    [Show full text]
  • Meta-Analysis of Nasopharyngeal Carcinoma
    BMC Genomics BioMed Central Research article Open Access Meta-analysis of nasopharyngeal carcinoma microarray data explores mechanism of EBV-regulated neoplastic transformation Xia Chen†1,2, Shuang Liang†1, WenLing Zheng1,3, ZhiJun Liao1, Tao Shang1 and WenLi Ma*1 Address: 1Institute of Genetic Engineering, Southern Medical University, Guangzhou, PR China, 2Xiangya Pingkuang associated hospital, Pingxiang, Jiangxi, PR China and 3Southern Genomics Research Center, Guangzhou, Guangdong, PR China Email: Xia Chen - [email protected]; Shuang Liang - [email protected]; WenLing Zheng - [email protected]; ZhiJun Liao - [email protected]; Tao Shang - [email protected]; WenLi Ma* - [email protected] * Corresponding author †Equal contributors Published: 7 July 2008 Received: 16 February 2008 Accepted: 7 July 2008 BMC Genomics 2008, 9:322 doi:10.1186/1471-2164-9-322 This article is available from: http://www.biomedcentral.com/1471-2164/9/322 © 2008 Chen et al; licensee BioMed Central Ltd. This 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. Abstract Background: Epstein-Barr virus (EBV) presumably plays an important role in the pathogenesis of nasopharyngeal carcinoma (NPC), but the molecular mechanism of EBV-dependent neoplastic transformation is not well understood. The combination of bioinformatics with evidences from biological experiments paved a new way to gain more insights into the molecular mechanism of cancer. Results: We profiled gene expression using a meta-analysis approach. Two sets of meta-genes were obtained. Meta-A genes were identified by finding those commonly activated/deactivated upon EBV infection/reactivation.
    [Show full text]
  • Supplementary Table 1: Adhesion Genes Data Set
    Supplementary Table 1: Adhesion genes data set PROBE Entrez Gene ID Celera Gene ID Gene_Symbol Gene_Name 160832 1 hCG201364.3 A1BG alpha-1-B glycoprotein 223658 1 hCG201364.3 A1BG alpha-1-B glycoprotein 212988 102 hCG40040.3 ADAM10 ADAM metallopeptidase domain 10 133411 4185 hCG28232.2 ADAM11 ADAM metallopeptidase domain 11 110695 8038 hCG40937.4 ADAM12 ADAM metallopeptidase domain 12 (meltrin alpha) 195222 8038 hCG40937.4 ADAM12 ADAM metallopeptidase domain 12 (meltrin alpha) 165344 8751 hCG20021.3 ADAM15 ADAM metallopeptidase domain 15 (metargidin) 189065 6868 null ADAM17 ADAM metallopeptidase domain 17 (tumor necrosis factor, alpha, converting enzyme) 108119 8728 hCG15398.4 ADAM19 ADAM metallopeptidase domain 19 (meltrin beta) 117763 8748 hCG20675.3 ADAM20 ADAM metallopeptidase domain 20 126448 8747 hCG1785634.2 ADAM21 ADAM metallopeptidase domain 21 208981 8747 hCG1785634.2|hCG2042897 ADAM21 ADAM metallopeptidase domain 21 180903 53616 hCG17212.4 ADAM22 ADAM metallopeptidase domain 22 177272 8745 hCG1811623.1 ADAM23 ADAM metallopeptidase domain 23 102384 10863 hCG1818505.1 ADAM28 ADAM metallopeptidase domain 28 119968 11086 hCG1786734.2 ADAM29 ADAM metallopeptidase domain 29 205542 11085 hCG1997196.1 ADAM30 ADAM metallopeptidase domain 30 148417 80332 hCG39255.4 ADAM33 ADAM metallopeptidase domain 33 140492 8756 hCG1789002.2 ADAM7 ADAM metallopeptidase domain 7 122603 101 hCG1816947.1 ADAM8 ADAM metallopeptidase domain 8 183965 8754 hCG1996391 ADAM9 ADAM metallopeptidase domain 9 (meltrin gamma) 129974 27299 hCG15447.3 ADAMDEC1 ADAM-like,
    [Show full text]
  • Analysis of the Dynamics of Limb Transcriptomes During Mouse Development Istvan Gyurján1, Bernhard Sonderegger1, Felix Naef1,2 and Denis Duboule1,3*
    Gyurján et al. BMC Developmental Biology 2011, 11:47 http://www.biomedcentral.com/1471-213X/11/47 RESEARCH ARTICLE Open Access Analysis of the dynamics of limb transcriptomes during mouse development Istvan Gyurján1, Bernhard Sonderegger1, Felix Naef1,2 and Denis Duboule1,3* Abstract Background: The development of vertebrate limbs has been a traditional system to study fundamental processes at work during ontogenesis, such as the establishment of spatial cellular coordinates, the effect of diffusible morphogenetic molecules or the translation between gene activity and morphogenesis. In addition, limbs are amongst the first targets of malformations in human and they display a huge realm of evolutionary variations within tetrapods, which make them a paradigm to study the regulatory genome. Results: As a reference resource for future biochemical and genetic analyses, we used genome-wide tiling arrays to establish the transcriptomes of mouse limb buds at three different stages, during which major developmental events take place. We compare the three time-points and discuss some aspects of these datasets, for instance related to transcriptome dynamics or to the potential association between active genes and the distribution of intergenic transcriptional activity. Conclusions: These datasets provide a valuable resource, either for research projects involving gene expression and regulation in developing mouse limbs, or as examples of tissue-specific, genome-wide transcriptional activities. Background regulators of the dorso-ventral (DV) patterning are Limb development has fascinated biologists for a cen- Wnt7a, expressed in dorsal ectoderm, and Engrailed,in tury, mostly because of the importance of these struc- ventral ectoderm, as well as Lmxb1,agenetranscribed tures in the evolution of land vertebrates and due to in dorsal mesenchyme.
    [Show full text]
  • Detailed Characterization of Human Induced Pluripotent Stem Cells Manufactured for Therapeutic Applications
    Stem Cell Rev and Rep DOI 10.1007/s12015-016-9662-8 Detailed Characterization of Human Induced Pluripotent Stem Cells Manufactured for Therapeutic Applications Behnam Ahmadian Baghbaderani 1 & Adhikarla Syama2 & Renuka Sivapatham3 & Ying Pei4 & Odity Mukherjee2 & Thomas Fellner1 & Xianmin Zeng3,4 & Mahendra S. Rao5,6 # The Author(s) 2016. This article is published with open access at Springerlink.com Abstract We have recently described manufacturing of hu- help determine which set of tests will be most useful in mon- man induced pluripotent stem cells (iPSC) master cell banks itoring the cells and establishing criteria for discarding a line. (MCB) generated by a clinically compliant process using cord blood as a starting material (Baghbaderani et al. in Stem Cell Keywords Induced pluripotent stem cells . Embryonic stem Reports, 5(4), 647–659, 2015). In this manuscript, we de- cells . Manufacturing . cGMP . Consent . Markers scribe the detailed characterization of the two iPSC clones generated using this process, including whole genome se- quencing (WGS), microarray, and comparative genomic hy- Introduction bridization (aCGH) single nucleotide polymorphism (SNP) analysis. We compare their profiles with a proposed calibra- Induced pluripotent stem cells (iPSCs) are akin to embryonic tion material and with a reporter subclone and lines made by a stem cells (ESC) [2] in their developmental potential, but dif- similar process from different donors. We believe that iPSCs fer from ESC in the starting cell used and the requirement of a are likely to be used to make multiple clinical products. We set of proteins to induce pluripotency [3]. Although function- further believe that the lines used as input material will be used ally identical, iPSCs may differ from ESC in subtle ways, at different sites and, given their immortal status, will be used including in their epigenetic profile, exposure to the environ- for many years or even decades.
    [Show full text]
  • Shk Toxin: History, Structure and Therapeutic Applications for Autoimmune Diseases
    ShK toxin: history, structure and therapeutic applications for autoimmune diseases WikiJournal of Science Search this Journal Search Open access • Publication charge free • Public peer review Submit Authors Reviewers Editors About Journal Issues Resources CURRENT Editorial In preparation guidelines Upcoming This is an unpublished pre-print. It is undergoing peer review. articles Authors: Shih Chieh Chang, Saumya Bajaj, K. George Chandy Ethics statement This pre-print is undergoing public peer review Laboratory of Molecular Physiology, Infection Immunity Theme, Lee Kong Chian School of Medicine, Nanyang Technological Bylaws University, Singapore First submitted: 04 January 2018 Financials Author correspondence: [email protected] Last updated: 05 January 2018 Contact Reviewer comments Last reviewed version Abstract Stichodactyla toxin (ShK) is a 35-residue basic peptide from the sea anemone Stichodactyla helianthus that blocks a number of potassium channels. An analogue of ShK called ShK-186 or Dalazatide is in human trials as Licensing: This is an open access article distributed under the Creative a therapeutic for autoimmune diseases. Commons Attribution License, which permits unrestricted use, distribution, and reproduction, provided the original author and source are credited. Key words: ShK peptide, autoimmune diseases, T cells, Kv1.3, ShK domains History Contents Stichodactyla helianthus is a sea anemone of the family Stichodactylidae. Abstract Helianthus comes from the Greek words Helios meaning sun, and anthos meaning History flower. S. helianthus is also referred to as the 'sun anemone'. It is sessile and uses potent neurotoxins for defense against its primary predator, the spiny lobster. The Structure venom contains, among other components, numerous ion channel-blocking Phylogenetic relationships of ShK and ShK domains peptides.
    [Show full text]
  • Brain Region-Specific Gene Signatures Revealed by Distinct Astrocyte Subpopulations Unveil Links to Glioma and Neurodegenerative
    New Research Disorders of the Nervous System Brain Region-Specific Gene Signatures Revealed by Distinct Astrocyte Subpopulations Unveil Links to Glioma and Neurodegenerative Diseases Raquel Cuevas-Diaz Duran,1,2,3 Chih-Yen Wang,4 Hui Zheng,5,6,7 Benjamin Deneen,8,9,10,11 and Jia Qian Wu1,2 https://doi.org/10.1523/ENEURO.0288-18.2019 1The Vivian L. Smith Department of Neurosurgery, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, Texas 77030, 2Center for Stem Cell and Regenerative Medicine, UT Brown Foundation Institute of Molecular Medicine, Houston, Texas 77030, 3Tecnologico de Monterrey, Escuela de Medicina y Ciencias de la Salud, Monterrey NL 64710, Mexico, 4Department of Life Sciences, National Cheng Kung University, Tainan City 70101, Taiwan, 5Huffington Center on Aging, 6Medical Scientist Training Program, 7Department of Molecular and Human Genetics, 8Center for Cell and Gene Therapy, 9Department of Neuroscience, 10Neurological Research Institute at Texas’ Children’s Hospital, and 11Program in Developmental Biology, Baylor College of Medicine, Houston, Texas 77030 Abstract Currently, there are no effective treatments for glioma or for neurodegenerative diseases because of, in part, our limited understanding of the pathophysiology and cellular heterogeneity of these diseases. Mounting evidence suggests that astrocytes play an active role in the pathogenesis of these diseases by contributing to a diverse range of pathophysiological states. In a previous study, five molecularly distinct astrocyte subpopulations from three different brain regions were identified. To further delineate the underlying diversity of these populations, we obtained mouse brain region-specific gene signatures for both protein-coding and long non-coding RNA and found that these astrocyte subpopulations are endowed with unique molecular signatures across diverse brain regions.
    [Show full text]
  • Design of a Truncated Cardiotoxin‑I Analogue with Potent Insulinotropic
    Design of a Truncated Cardiotoxin‑I Analogue with Potent Insulinotropic Activity Thi Tuyet Nhung Nguyen, Benjamin Folch, Myriam Letourneau, Nam Hai Truong, Nicolas Doucet, Alain Fournier, David Chatenet To cite this version: Thi Tuyet Nhung Nguyen, Benjamin Folch, Myriam Letourneau, Nam Hai Truong, Nicolas Doucet, et al.. Design of a Truncated Cardiotoxin‑I Analogue with Potent Insulinotropic Activity. Journal of Medicinal Chemistry, American Chemical Society, 2014, 57 (6), pp.2623-33. 10.1021/jm401904q. hal-01177382 HAL Id: hal-01177382 https://hal.archives-ouvertes.fr/hal-01177382 Submitted on 14 Sep 2015 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. Design of a Truncated Cardiotoxin-I Analogue with Potent Insulinotropic Activity Thi Tuyet Nhung Nguyen†‡§, Benjamin Folch†∥⊥, Myriam Létourneau†§, Nam Hai Truong‡, Nicolas Doucet†∥⊥, Alain Fournier*†§, and David Chatenet*†§ † INRS−Institut Armand-Frappier, Université du Québec, 531 Boulevard des Prairies Ville de Laval, Québec H7 V 1B7, QuébecCanada ‡ Vietnam Academy of Science and Technology, Institute
    [Show full text]
  • Identification of Shared and Unique Gene Families Associated with Oral
    International Journal of Oral Science (2017) 9, 104–109 OPEN www.nature.com/ijos ORIGINAL ARTICLE Identification of shared and unique gene families associated with oral clefts Noriko Funato and Masataka Nakamura Oral clefts, the most frequent congenital birth defects in humans, are multifactorial disorders caused by genetic and environmental factors. Epidemiological studies point to different etiologies underlying the oral cleft phenotypes, cleft lip (CL), CL and/or palate (CL/P) and cleft palate (CP). More than 350 genes have syndromic and/or nonsyndromic oral cleft associations in humans. Although genes related to genetic disorders associated with oral cleft phenotypes are known, a gap between detecting these associations and interpretation of their biological importance has remained. Here, using a gene ontology analysis approach, we grouped these candidate genes on the basis of different functional categories to gain insight into the genetic etiology of oral clefts. We identified different genetic profiles and found correlations between the functions of gene products and oral cleft phenotypes. Our results indicate inherent differences in the genetic etiologies that underlie oral cleft phenotypes and support epidemiological evidence that genes associated with CL/P are both developmentally and genetically different from CP only, incomplete CP, and submucous CP. The epidemiological differences among cleft phenotypes may reflect differences in the underlying genetic causes. Understanding the different causative etiologies of oral clefts is
    [Show full text]
  • 1 1 2 3 Cell Type-Specific Transcriptomics of Hypothalamic
    1 2 3 4 Cell type-specific transcriptomics of hypothalamic energy-sensing neuron responses to 5 weight-loss 6 7 Fredrick E. Henry1,†, Ken Sugino1,†, Adam Tozer2, Tiago Branco2, Scott M. Sternson1,* 8 9 1Janelia Research Campus, Howard Hughes Medical Institute, 19700 Helix Drive, Ashburn, VA 10 20147, USA. 11 2Division of Neurobiology, Medical Research Council Laboratory of Molecular Biology, 12 Cambridge CB2 0QH, UK 13 14 †Co-first author 15 *Correspondence to: [email protected] 16 Phone: 571-209-4103 17 18 Authors have no competing interests 19 1 20 Abstract 21 Molecular and cellular processes in neurons are critical for sensing and responding to energy 22 deficit states, such as during weight-loss. AGRP neurons are a key hypothalamic population 23 that is activated during energy deficit and increases appetite and weight-gain. Cell type-specific 24 transcriptomics can be used to identify pathways that counteract weight-loss, and here we 25 report high-quality gene expression profiles of AGRP neurons from well-fed and food-deprived 26 young adult mice. For comparison, we also analyzed POMC neurons, an intermingled 27 population that suppresses appetite and body weight. We find that AGRP neurons are 28 considerably more sensitive to energy deficit than POMC neurons. Furthermore, we identify cell 29 type-specific pathways involving endoplasmic reticulum-stress, circadian signaling, ion 30 channels, neuropeptides, and receptors. Combined with methods to validate and manipulate 31 these pathways, this resource greatly expands molecular insight into neuronal regulation of 32 body weight, and may be useful for devising therapeutic strategies for obesity and eating 33 disorders.
    [Show full text]
  • Bioactive Mimetics of Conotoxins and Other Venom Peptides
    Toxins 2015, 7, 4175-4198; doi:10.3390/toxins7104175 OPEN ACCESS toxins ISSN 2072-6651 www.mdpi.com/journal/toxins Review Bioactive Mimetics of Conotoxins and other Venom Peptides Peter J. Duggan 1,2,* and Kellie L. Tuck 3,* 1 CSIRO Manufacturing, Bag 10, Clayton South, VIC 3169, Australia 2 School of Chemical and Physical Sciences, Flinders University, Adelaide, SA 5042, Australia 3 School of Chemistry, Monash University, Clayton, VIC 3800, Australia * Authors to whom correspondence should be addressed; E-Mails: [email protected] (P.J.D.); [email protected] (K.L.T.); Tel.: +61-3-9545-2560 (P.J.D.); +61-3-9905-4510 (K.L.T.); Fax: +61-3-9905-4597 (K.L.T.). Academic Editors: Macdonald Christie and Luis M. Botana Received: 2 September 2015 / Accepted: 8 October 2015 / Published: 16 October 2015 Abstract: Ziconotide (Prialt®), a synthetic version of the peptide ω-conotoxin MVIIA found in the venom of a fish-hunting marine cone snail Conus magnus, is one of very few drugs effective in the treatment of intractable chronic pain. However, its intrathecal mode of delivery and narrow therapeutic window cause complications for patients. This review will summarize progress in the development of small molecule, non-peptidic mimics of Conotoxins and a small number of other venom peptides. This will include a description of how some of the initially designed mimics have been modified to improve their drug-like properties. Keywords: venom peptides; toxins; conotoxins; peptidomimetics; N-type calcium channel; Cav2.2 1. Introduction A wide range of species from the animal kingdom produce venom for use in capturing prey or for self-defense.
    [Show full text]
  • Regulation of Muscle Stem Cell Function by the Transcription Factor Pax7
    Regulation of Muscle Stem Cell Function by the Transcription Factor Pax7 Alessandra Pasut Thesis submitted to the Faculty of Graduate and Postdoctoral Studies in partial fulfillment of the requirements for the Doctorate in Philosophy degree in Cellular and Molecular Medicine Department of Cellular and Molecular Medicine Faculty of Medicine University of Ottawa © Alessandra Pasut, Ottawa, Canada, 2015 ...above all don’t fear difficult moments, the best comes out from them. [Rita Levi Montalcini-Nobel laureate, 1909-2012] ii Abstract Pax7 is a paired box transcription factor expressed by all satellite cells which are critically required for muscle regeneration and growth. The absolute requirements of Pax7 in the maintenance of the satellite cell pool are widely acknowledged. However the mechanisms by which Pax7 executes muscle regeneration or contributes to satellite cell homeostasis remain elusive. We performed cell and molecular analysis of Pax7 null satellite cells to investigate muscle stem cell function. Through genome wide studies, we found that genes involved in cell- cell interactions, regulation of migration, control of lipid metabolism and inhibition of myogenic differentiation were significantly perturbed in Pax7 null satellite cells. Analysis of satellite cells in vitro showed that Pax7 null satellite cells undergo precocious myogenic differentiation and have perturbed expression of genes involved in the Notch signaling pathway. We showed that Notch 1 is a novel Pax7 target gene and by using a genetic approach we demonstrate that ectopic expression of the constitutively active intracellular domain of Notch1 (NICD1) in Pax7 null satellite cells is sufficient to maintain the satellite cell pool as well as to restore their proliferation.
    [Show full text]