DOCSLIB.ORG

Expression and Function of Npas4 During Early Development

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Expression and Function of Npas4 During Early Development Expression and function of Npas4 during early development THOMAS STEPHEN KLARIC A thesis submitted for the degree of Doctor of Philosophy DECEMBER 2011 Discipline of Genetics School of Molecular and Biomedical Science The University of Adelaide Table of contents Table of contents Table of contents ............................................................................................. i List of figures ............................................................................................... viii List of tables .................................................................................................. ix Declaration ..................................................................................................... x Acknowledgements ....................................................................................... xi Abbreviations ............................................................................................... xii Notes .......................................................................................................... xviii Abstract ........................................................................................................ xix 1 - Introduction............................................................................................... 1 1.1 Overview ................................................................................................................... 1 1.2 An introduction to Npas4 ........................................................................................... 1 1.2.1 Npas4 is a member of the bHLH PAS transcription factor family ..................................... 1 1.2.1.1 Transcription factors ........................................................................................................ 1 1.2.1.2 The bHLH PAS transcription factor family ........................................................................ 2 1.2.1.3 The newest member of the bHLH PAS family: Npas4 ...................................................... 6 1.2.2 Genomic organisation of the mouse Npas4 gene ............................................................ 7 1.2.3 Domain structure and sequence conservation within the Npas4 protein ......................... 7 1.2.4 Interaction with other bHLH PAS factors ......................................................................... 9 1.2.5 DNA binding specificity of Npas4 transcriptional complexes ........................................... 9 1.3 Expression of Npas4 ................................................................................................. 10 1.3.1 Tissue distribution of the Npas4 transcript in the adult organism .................................. 10 1.3.2 Npas4 expression in the adult brain ............................................................................... 11 1.3.3 Cellular distribution of Npas4 expression ....................................................................... 12 1.3.4 Subcellular localisation .................................................................................................. 12 1.3.5 Npas4 expression during development .......................................................................... 13 1.4 Regulation of Npas4 expression ............................................................................... 13 1.4.1 Npas4 is a stimulus-response transcription factor .......................................................... 13 1.4.1.1 Immediate-early genes .................................................................................................. 14 1.4.2 Regulation of Npas4 expression by neural activity ......................................................... 15 1.4.2.1 Neural activity and NMDAR-mediated Ca2+ signalling ................................................... 15 1.4.2.1.1 Neural activity ....................................................................................................................... 15 1.4.2.1.2 Neurotransmitters and their receptors ................................................................................. 15 i Table of contents 1.4.2.1.3 Excitatory synaptic transmission: glutamate and glutamate receptors ............................... 16 1.4.2.1.4 Glutamate receptor signalling and cation flux ...................................................................... 16 1.4.2.1.5 Ca2+ signalling ........................................................................................................................ 18 1.4.2.1.6 Creb: an example of a Ca2+-sensitive transcription factor .................................................... 20 1.4.2.2 Activity-dependent regulation of Npas4 expression in neurons ................................... 20 1.4.2.2.1 Neuronal depolarisation ....................................................................................................... 21 1.4.2.2.2 Nuclear Ca2+ signalling .......................................................................................................... 21 1.4.2.3 Excitotoxic brain injury and Npas4 expression .............................................................. 22 1.4.2.3.1 Seizure................................................................................................................................... 22 1.4.2.3.2 Cerebral ischaemia................................................................................................................ 22 1.4.2.4 Learning and synaptic plasticity ..................................................................................... 24 1.4.2.4.1 Long-term potentiation and long-term depression .............................................................. 24 1.4.2.4.2 Regulation of Npas4 by Chem-LTP and Chem-LTD ............................................................... 27 1.4.2.4.3 Npas4 expression in the context of learning and memory ................................................... 27 1.4.3 Regulation of Npas4 expression by neurotrophin signalling .......................................... 28 1.4.3.1 Neurotrophins ............................................................................................................... 28 1.4.3.2 Neurotrophin receptors ................................................................................................. 28 1.4.3.3 Neurotrophin-dependent Npas4 expression ................................................................. 30 1.4.3.4 Other growth factors ..................................................................................................... 31 1.4.4 Post-translational regulation of Npas4 expression and activity ..................................... 33 1.4.5 Npas4 expression in response to psychological stress ................................................... 34 1.4.5.1 Psychological stress ....................................................................................................... 34 1.4.5.2 Acute psychological stress ............................................................................................. 35 1.4.5.2.1 IEG expression in response to acute psychological stress .................................................... 35 1.4.5.3 Chronic psychological stress .......................................................................................... 35 1.4.5.3.1 Repression of IEGs in response to chronic psychological stress ........................................... 36 1.4.5.4 The effect of psychological stress on Npas4 expression ............................................... 37 1.4.6 Npas4 expression in response to cellular stress ............................................................. 38 1.4.6.1 Oxidative stress .............................................................................................................. 38 1.4.6.2 Osmotic stress ............................................................................................................... 39 1.4.7 The effect of drugs of abuse on Npas4 expression ......................................................... 40 1.4.7.1 Psychostimulants: cocaine and methamphetamine ..................................................... 40 1.4.7.2 Opioids: morphine and heroin ....................................................................................... 40 1.4.7.3 Other drugs of abuse: nicotine and ethanol .................................................................. 41 1.4.8 Circadian regulation of Npas4 expression...................................................................... 41 1.4.8.1 Circadian rhythm ........................................................................................................... 42 1.4.8.1.1 The biological clock of the suprachiasmatic nuclei ............................................................... 42 1.4.8.1.2 Clock output and circadian control of melatonin release ..................................................... 43 ii Table of contents 1.4.8.2 Melatonin and melatonin receptor signalling ................................................................ 43 1.4.8.2.1 Melatonin receptors .............................................................................................................. 44 1.4.8.2.2 Melatonin-dependent circadian regulation of gene expression in the pars tuberalis .......... 44 1.4.8.3 Circadian expression of Npas4 in the pars tuberalis ...................................................... 46 1.4.8.3.1 Possible mechanisms involved in circadian expression of Npas4 ......................................... 46 1.4.9 Post-transcriptional
Load more

Recommended publications
  • 1 Evidence for Gliadin Antibodies As Causative Agents in Schizophrenia
    1 Evidence for gliadin antibodies as causative agents in schizophrenia. C.J.Carter PolygenicPathways, 20 Upper Maze Hill, Saint-Leonard’s on Sea, East Sussex, TN37 0LG [email protected] Tel: 0044 (0)1424 422201 I have no fax Abstract Antibodies to gliadin, a component of gluten, have frequently been reported in schizophrenia patients, and in some cases remission has been noted following the instigation of a gluten free diet. Gliadin is a highly immunogenic protein, and B cell epitopes along its entire immunogenic length are homologous to the products of numerous proteins relevant to schizophrenia (p = 0.012 to 3e-25). These include members of the DISC1 interactome, of glutamate, dopamine and neuregulin signalling networks, and of pathways involved in plasticity, dendritic growth or myelination. Antibodies to gliadin are likely to cross react with these key proteins, as has already been observed with synapsin 1 and calreticulin. Gliadin may thus be a causative agent in schizophrenia, under certain genetic and immunological conditions, producing its effects via antibody mediated knockdown of multiple proteins relevant to the disease process. Because of such homology, an autoimmune response may be sustained by the human antigens that resemble gliadin itself, a scenario supported by many reports of immune activation both in the brain and in lymphocytes in schizophrenia. Gluten free diets and removal of such antibodies may be of therapeutic benefit in certain cases of schizophrenia. 2 Introduction A number of studies from China, Norway, and the USA have reported the presence of gliadin antibodies in schizophrenia 1-5. Gliadin is a component of gluten, intolerance to which is implicated in coeliac disease 6.
    [Show full text]
  • Disruption of the Neuronal PAS3 Gene in a Family Affected with Schizophrenia D Kamnasaran, W J Muir, M a Ferguson-Smith,Dwcox
    325 ORIGINAL ARTICLE J Med Genet: first published as 10.1136/jmg.40.5.325 on 1 May 2003. Downloaded from Disruption of the neuronal PAS3 gene in a family affected with schizophrenia D Kamnasaran, W J Muir, M A Ferguson-Smith,DWCox ............................................................................................................................. J Med Genet 2003;40:325–332 Schizophrenia and its subtypes are part of a complex brain disorder with multiple postulated aetiolo- gies. There is evidence that this common disease is genetically heterogeneous, with many loci involved. See end of article for In this report, we describe a mother and daughter affected with schizophrenia, who are carriers of a authors’ affiliations t(9;14)(q34;q13) chromosome. By mapping on flow sorted aberrant chromosomes isolated from lym- ....................... phoblast cell lines, both subjects were found to have a translocation breakpoint junction between the Correspondence to: markers D14S730 and D14S70, a 683 kb interval on chromosome 14q13. This interval was found to Dr D W Cox, 8-39 Medical contain the neuronal PAS3 gene (NPAS3), by annotating the genomic sequence for ESTs and perform- Sciences Building, ing RACE and cDNA library screenings. The NPAS3 gene was characterised with respect to the University of Alberta, genomic structure, human expression profile, and protein cellular localisation to gain insight into gene Edmonton, Alberta T6G function. The translocation breakpoint junction lies within the third intron of NPAS3, resulting in the dis- 2H7, Canada; [email protected] ruption of the coding potential. The fact that the bHLH and PAS domains are disrupted from the remain- ing parts of the encoded protein suggests that the DNA binding and dimerisation functions of this Revised version received protein are destroyed.
    [Show full text]
  • SHARP1 (BHLHE41) Mouse Monoclonal Antibody [Clone ID: OTI3H4] Product Data
    OriGene Technologies, Inc. 9620 Medical Center Drive, Ste 200 Rockville, MD 20850, US Phone: +1-888-267-4436 [email protected] EU: [email protected] CN: [email protected] Product datasheet for TA806354 SHARP1 (BHLHE41) Mouse Monoclonal Antibody [Clone ID: OTI3H4] Product data: Product Type: Primary Antibodies Clone Name: OTI3H4 Applications: IHC, WB Recommended Dilution: WB 1:2000, IHC 1:150 Reactivity: Human Host: Mouse Isotype: IgG1 Clonality: Monoclonal Immunogen: Human recombinant protein fragment corresponding to amino acids 1-297 of human BHLHE41(NP_110389) produced in E.coli. Formulation: PBS (PH 7.3) containing 1% BSA, 50% glycerol and 0.02% sodium azide. Concentration: 1 mg/ml Purification: Purified from mouse ascites fluids or tissue culture supernatant by affinity chromatography (protein A/G) Conjugation: Unconjugated Storage: Store at -20°C as received. Stability: Stable for 12 months from date of receipt. Predicted Protein Size: 50.3 kDa Gene Name: basic helix-loop-helix family member e41 Database Link: NP_110389 Entrez Gene 79365 Human Q9C0J9 Background: This gene encodes a basic helix-loop-helix protein expressed in various tissues. The encoded protein can interact with ARNTL or compete for E-box binding sites in the promoter of PER1 and repress CLOCK/ARNTL's transactivation of PER1. This gene is believed to be involved in the control of circadian rhythm and cell differentiation. Defects in this gene are associated with the short sleep phenotype. [provided by RefSeq, Feb 2014] This product is to be used for laboratory only. Not for diagnostic or therapeutic use. View online » ©2021 OriGene Technologies, Inc., 9620 Medical Center Drive, Ste 200, Rockville, MD 20850, US 1 / 2 SHARP1 (BHLHE41) Mouse Monoclonal Antibody [Clone ID: OTI3H4] – TA806354 Synonyms: BHLHB3; DEC2; hDEC2; SHARP1 Protein Families: Transcription Factors Protein Pathways: Circadian rhythm - mammal Product images: HEK293T cells were transfected with the pCMV6- ENTRY control (Left lane) or pCMV6-ENTRY BHLHE41 ([RC206882], Right lane) cDNA for 48 hrs and lysed.
    [Show full text]
  • Ncomms2254.Pdf
    ARTICLE Received 3 May 2012 | Accepted 5 Nov 2012 | Published 4 Dec 2012 DOI: 10.1038/ncomms2254 The RB family is required for the self-renewal and survival of human embryonic stem cells Jamie F. Conklin1,2,3, Julie Baker2,3 & Julien Sage1,2,3 The mechanisms ensuring the long-term self-renewal of human embryonic stem cells are still only partly understood, limiting their use in cellular therapies. Here we found that increased activity of the RB cell cycle inhibitor in human embryonic stem cells induces cell cycle arrest, differentiation and cell death. Conversely, inactivation of the entire RB family (RB, p107 and p130) in human embryonic stem cells triggers G2/M arrest and cell death through functional activation of the p53 pathway and the cell cycle inhibitor p21. Differences in E2F target gene activation upon loss of RB family function between human embryonic stem cells, mouse embryonic stem cells and human fibroblasts underscore key differences in the cell cycle regulatory networks of human embryonic stem cells. Finally, loss of RB family function pro- motes genomic instability in both human and mouse embryonic stem cells, uncoupling cell cycle defects from chromosomal instability. These experiments indicate that a homeostatic level of RB activity is essential for the self-renewal and the survival of human embryonic stem cells. 1 Department of Pediatrics, Stanford Medical School, Stanford, California 94305, USA. 2 Department of Genetics, Stanford Medical School, Stanford, California 94305, USA. 3 Institute for Stem Cell Biology and Regenerative Medicine, Stanford Medical School, Stanford, California 94305, USA. Correspondence and requests for materials should be addressed to J.S.
    [Show full text]
  • Author Manuscript Faculty of Biology and Medicine Publication
    Serveur Académique Lausannois SERVAL serval.unil.ch Author Manuscript Faculty of Biology and Medicine Publication This paper has been peer-reviewed but does not include the final publisher proof-corrections or journal pagination. Published in final edited form as: Title: Sexual dimorphism in cancer. Authors: Clocchiatti A, Cora E, Zhang Y, Dotto GP Journal: Nature reviews. Cancer Year: 2016 May Volume: 16 Issue: 5 Pages: 330-9 DOI: 10.1038/nrc.2016.30 In the absence of a copyright statement, users should assume that standard copyright protection applies, unless the article contains an explicit statement to the contrary. In case of doubt, contact the journal publisher to verify the copyright status of an article. Sexual dimorphism in cancer Andrea Clocchiatti1+, Elisa Cora2+, Yosra Zhang1,2 and G. Paolo Dotto1,2* 1Cutaneous Biology Research Center, Massachusetts General Hospital, Charlestown, MA 02129, USA; 2Department of Biochemistry, University of Lausanne, Epalinges, CH-1066, Switzerland + These authors contributed equally to the work * Corresponding author: G. Paolo Dotto email: [email protected] 1 Abstract The incidence of many cancer types is significantly higher in the male than female populations, with associated differences in survival. Occupational and/or behavioral factors are well known underlying determinants. However, cellular/molecular differences between the two sexes are also likely to be important. We are focusing here on the complex interplay that sexual hormones and sex chromosomes can have in intrinsic control of cancer initiating cell populations, tumor microenvironment and systemic determinants of cancer development like the immune system and metabolism. A better appreciation of these differences between the two sexes could be of substantial value for cancer prevention as well as treatment.
    [Show full text]
  • Transcription Factor P73 Regulates Th1 Differentiation
    ARTICLE https://doi.org/10.1038/s41467-020-15172-5 OPEN Transcription factor p73 regulates Th1 differentiation Min Ren1, Majid Kazemian 1,4, Ming Zheng2, JianPing He3, Peng Li1, Jangsuk Oh1, Wei Liao1, Jessica Li1, ✉ Jonathan Rajaseelan1, Brian L. Kelsall 3, Gary Peltz 2 & Warren J. Leonard1 Inter-individual differences in T helper (Th) cell responses affect susceptibility to infectious, allergic and autoimmune diseases. To identify factors contributing to these response differ- 1234567890():,; ences, here we analyze in vitro differentiated Th1 cells from 16 inbred mouse strains. Haplotype-based computational genetic analysis indicates that the p53 family protein, p73, affects Th1 differentiation. In cells differentiated under Th1 conditions in vitro, p73 negatively regulates IFNγ production. p73 binds within, or upstream of, and modulates the expression of Th1 differentiation-related genes such as Ifng and Il12rb2. Furthermore, in mouse experimental autoimmune encephalitis, p73-deficient mice have increased IFNγ production and less dis- ease severity, whereas in an adoptive transfer model of inflammatory bowel disease, transfer of p73-deficient naïve CD4+ T cells increases Th1 responses and augments disease severity. Our results thus identify p73 as a negative regulator of the Th1 immune response, suggesting that p73 dysregulation may contribute to susceptibility to autoimmune disease. 1 Laboratory of Molecular Immunology and the Immunology Center, National Heart, Lung, and Blood Institute, Bethesda, MD 20892-1674, USA. 2 Department of Anesthesia, Stanford University School of Medicine, Stanford, CA 94305, USA. 3 Laboratory of Molecular Immunology, National Institute of Allergy and Infectious Diseases, Bethesda, MD 20892, USA. 4Present address: Department of Biochemistry and Computer Science, Purdue University, West ✉ Lafayette, IN 37906, USA.
    [Show full text]
  • Neurons That Regulate Mouse Torpor
    Article Neurons that regulate mouse torpor https://doi.org/10.1038/s41586-020-2387-5 Sinisa Hrvatin1,6 ✉, Senmiao Sun1,2,6, Oren F. Wilcox1, Hanqi Yao1, Aurora J. Lavin-Peter1, Marcelo Cicconet3, Elena G. Assad1, Michaela E. Palmer1, Sage Aronson4, Received: 22 January 2020 Alexander S. Banks5, Eric C. Griffith1 & Michael E. Greenberg1 ✉ Accepted: 7 May 2020 Published online: xx xx xxxx The advent of endothermy, which is achieved through the continuous homeostatic Check for updates regulation of body temperature and metabolism1,2, is a defning feature of mammalian and avian evolution. However, when challenged by food deprivation or harsh environmental conditions, many mammalian species initiate adaptive energy-conserving survival strategies—including torpor and hibernation—during which their body temperature decreases far below its homeostatic set-point3–5. How homeothermic mammals initiate and regulate these hypothermic states remains largely unknown. Here we show that entry into mouse torpor, a fasting-induced state with a greatly decreased metabolic rate and a body temperature as low as 20 °C6, is regulated by neurons in the medial and lateral preoptic area of the hypothalamus. We show that restimulation of neurons that were activated during a previous bout of torpor is sufcient to initiate the key features of torpor, even in mice that are not calorically restricted. Among these neurons we identify a population of glutamatergic Adcyap1-positive cells, the activity of which accurately determines when mice naturally initiate and exit torpor, and the inhibition of which disrupts the natural process of torpor entry, maintenance and arousal. Taken together, our results reveal a specifc neuronal population in the mouse hypothalamus that serves as a core regulator of torpor.
    [Show full text]
  • Human Autologous Ipsc–Derived Dopaminergic Progenitors Restore Motor Function in Parkinson’S Disease Models
    Human autologous iPSC–derived dopaminergic progenitors restore motor function in Parkinson’s disease models Bin Song, … , Jeffrey S. Schweitzer, Kwang-Soo Kim J Clin Invest. 2020;130(2):904-920. https://doi.org/10.1172/JCI130767. Research Article Neuroscience Stem cells Graphical abstract Find the latest version: https://jci.me/130767/pdf RESEARCH ARTICLE The Journal of Clinical Investigation Human autologous iPSC–derived dopaminergic progenitors restore motor function in Parkinson’s disease models Bin Song,1,2 Young Cha,1,2 Sanghyeok Ko,1,2 Jeha Jeon,1,2 Nayeon Lee,1,2 Hyemyung Seo,1,2,3 Kyung-Joon Park,1 In-Hee Lee,4,5 Claudia Lopes,1,2 Melissa Feitosa,1,2 María José Luna,1,2 Jin Hyuk Jung,1,2 Jisun Kim,1,2,3 Dabin Hwang,1,2 Bruce M. Cohen,1 Martin H. Teicher,1 Pierre Leblanc,1,2 Bob S. Carter,6 Jeffrey H. Kordower,7 Vadim Y. Bolshakov,1 Sek Won Kong,4,5 Jeffrey S. Schweitzer,6 and Kwang-Soo Kim1,2 1Department of Psychiatry and 2Molecular Neurobiology Laboratory, McLean Hospital, Harvard Medical School, Belmont, Massachusetts, USA. 3Department of Molecular and Life Sciences, Hanyang University, Ansan, Korea. 4Department of Pediatrics, 5Computational Health Informatics Program, Boston Children’s Hospital, and 6Department of Neurosurgery, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA. 7Department of Neurological Sciences, Rush University Medical Center, Chicago, Illinois, USA. Parkinson’s disease (PD) is a neurodegenerative disorder associated with loss of striatal dopamine, secondary to degeneration of midbrain dopamine (mDA) neurons in the substantia nigra, rendering cell transplantation a promising therapeutic strategy.
    [Show full text]
  • Variations in Microrna-25 Expression Influence the Severity of Diabetic
    BASIC RESEARCH www.jasn.org Variations in MicroRNA-25 Expression Influence the Severity of Diabetic Kidney Disease † † † Yunshuang Liu,* Hongzhi Li,* Jieting Liu,* Pengfei Han, Xuefeng Li, He Bai,* Chunlei Zhang,* Xuelian Sun,* Yanjie Teng,* Yufei Zhang,* Xiaohuan Yuan,* Yanhui Chu,* and Binghai Zhao* *Heilongjiang Key Laboratory of Anti-Fibrosis Biotherapy, Medical Research Center, Heilongjiang, People’s Republic of China; and †Clinical Laboratory of Hong Qi Hospital, Mudanjiang Medical University, Heilongjiang, People’s Republic of China ABSTRACT Diabetic nephropathy is characterized by persistent albuminuria, progressive decline in GFR, and second- ary hypertension. MicroRNAs are dysregulated in diabetic nephropathy, but identification of the specific microRNAs involved remains incomplete. Here, we show that the peripheral blood from patients with diabetes and the kidneys of animals with type 1 or 2 diabetes have low levels of microRNA-25 (miR-25) compared with those of their nondiabetic counterparts. Furthermore, treatment with high glucose decreased the expression of miR-25 in cultured kidney cells. In db/db mice, systemic administration of an miR-25 agomir repressed glomerular fibrosis and reduced high BP. Notably, knockdown of miR-25 in normal mice by systemic administration of an miR-25 antagomir resulted in increased proteinuria, extracellular matrix accumulation, podocyte foot process effacement, and hypertension with renin-angiotensin system activation. However, excessive miR-25 did not cause kidney dysfunction in wild-type mice. RNA sequencing showed the alteration of miR-25 target genes in antagomir-treated mice, including the Ras-related gene CDC42. In vitro,cotrans- fection with the miR-25 antagomir repressed luciferase activity from a reporter construct containing the CDC42 39 untranslated region.
    [Show full text]
  • 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.
    [Show full text]
  • Regulation of Expression and Activity of the Bhlh-PAS Transcription
    Regulation of Expression and Activity of the bHLH-PAS Transcription Factor NPAS4 David Christopher Bersten B.Sc. (Biomedical Science), Honours (Biochemistry) A thesis submitted in fulfilment of the requirements for the degree of Doctor of Philosophy Discipline of Biochemistry School of Molecular and Biomedical Science University of Adelaide, Australia June 2014 1 Contents Abstract ................................................................................................................................................... 3 PhD Thesis Declaration ........................................................................................................................... 5 Acknowledgements ................................................................................................................................. 6 Publications ............................................................................................................................................. 8 Conference oral presentations ........................................................................................................... 9 Additional publications ....................................................................................................................... 9 Chapter 1: .............................................................................................................................................. 10 Introduction .....................................................................................................................................
    [Show full text]
  • Steroid-Dependent Regulation of the Oviduct: a Cross-Species Transcriptomal Analysis
    University of Kentucky UKnowledge Theses and Dissertations--Animal and Food Sciences Animal and Food Sciences 2015 Steroid-dependent regulation of the oviduct: A cross-species transcriptomal analysis Katheryn L. Cerny University of Kentucky, [email protected] Right click to open a feedback form in a new tab to let us know how this document benefits ou.y Recommended Citation Cerny, Katheryn L., "Steroid-dependent regulation of the oviduct: A cross-species transcriptomal analysis" (2015). Theses and Dissertations--Animal and Food Sciences. 49. https://uknowledge.uky.edu/animalsci_etds/49 This Doctoral Dissertation is brought to you for free and open access by the Animal and Food Sciences at UKnowledge. It has been accepted for inclusion in Theses and Dissertations--Animal and Food Sciences by an authorized administrator of UKnowledge. For more information, please contact [email protected]. STUDENT AGREEMENT: I represent that my thesis or dissertation and abstract are my original work. Proper attribution has been given to all outside sources. I understand that I am solely responsible for obtaining any needed copyright permissions. I have obtained needed written permission statement(s) from the owner(s) of each third-party copyrighted matter to be included in my work, allowing electronic distribution (if such use is not permitted by the fair use doctrine) which will be submitted to UKnowledge as Additional File. I hereby grant to The University of Kentucky and its agents the irrevocable, non-exclusive, and royalty-free license to archive and make accessible my work in whole or in part in all forms of media, now or hereafter known.
    [Show full text]