Identification of Human Myometrial Target Genes of the C-Jun NH2
Total Page:16
File Type:pdf, Size:1020Kb
Load more
Recommended publications
-
Design and Synthesis of Cyclic Analogs of the Kappa Opioid Receptor Antagonist Arodyn
Design and synthesis of cyclic analogs of the kappa opioid receptor antagonist arodyn By © 2018 Solomon Aguta Gisemba Submitted to the graduate degree program in Medicinal Chemistry and the Graduate Faculty of the University of Kansas in partial fulfillment of the requirements for the degree of Doctor of Philosophy. Chair: Dr. Blake Peterson Co-Chair: Dr. Jane Aldrich Dr. Michael Rafferty Dr. Teruna Siahaan Dr. Thomas Tolbert Date Defended: 18 April 2018 The dissertation committee for Solomon Aguta Gisemba certifies that this is the approved version of the following dissertation: Design and synthesis of cyclic analogs of the kappa opioid receptor antagonist arodyn Chair: Dr. Blake Peterson Co-Chair: Dr. Jane Aldrich Date Approved: 10 June 2018 ii Abstract Opioid receptors are important therapeutic targets for mood disorders and pain. Kappa opioid receptor (KOR) antagonists have recently shown potential for treating drug addiction and 1,2,3 4 8 depression. Arodyn (Ac[Phe ,Arg ,D-Ala ]Dyn A(1-11)-NH2), an acetylated dynorphin A (Dyn A) analog, has demonstrated potent and selective KOR antagonism, but can be rapidly metabolized by proteases. Cyclization of arodyn could enhance metabolic stability and potentially stabilize the bioactive conformation to give potent and selective analogs. Accordingly, novel cyclization strategies utilizing ring closing metathesis (RCM) were pursued. However, side reactions involving olefin isomerization of O-allyl groups limited the scope of the RCM reactions, and their use to explore structure-activity relationships of aromatic residues. Here we developed synthetic methodology in a model dipeptide study to facilitate RCM involving Tyr(All) residues. Optimized conditions that included microwave heating and the use of isomerization suppressants were applied to the synthesis of cyclic arodyn analogs. -
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. -
Université De La Méditerranée Faculte De Médecine De Marseille École Doctorale Des Sciences De La Vie Et De La Santé Centre De Recherche En Cancérologie De Marseille
UNIVERSITÉ DE LA MÉDITERRANÉE FACULTE DE MÉDECINE DE MARSEILLE ÉCOLE DOCTORALE DES SCIENCES DE LA VIE ET DE LA SANTÉ CENTRE DE RECHERCHE EN CANCÉROLOGIE DE MARSEILLE T H È S E Pour l’obtention du Diplôme de DOCTEUR de L’UNIVERSITÉ de la MÉDITERRANÉE SPÉCIALITÉ : Oncologie : Pharmacologie et Thérapeutique Présentée et soutenue publiquement par Mme Laetitia STUHL-GOURMAND Le 30 Mars 2010 ROLE DE NACA ET DE SES PARTENAIRES MOLÉCULAIRES DANS LA DIFFÉRENCIATION ÉRYTHROÏDE NORMALE ET PATHOLOGIQUE DES SYNDROMES MYÉLODYSPLASIQUES Directeur de Thèse : Dr Sophie GOMEZ Membres du Jury de Thèse : Pr Daniel Olive Président Pr Catherine Lacombe Rapporteur Dr Dominique Duménil Rapporteur Dr Christian Chabannon Examinateur 1 A mes deux hommes, mes deux amours : mon fils Anthony et mon mari Sébastien 2 REMERCIEMENTS Je remercie les membres du jury d’avoir accepté de juger ce travail: les Pr Catherine Lacombe, Dr Christian Chabannon, Dr Dominique Duménil et le Pr Daniel Olive de présider ce jury. Je remercie Françoise Birg de m’avoir accueillie au centre de Recherche en Cancérologie de Marseille UMR891. Je remercie ma directrice de thèse Dr Sophie Gomez a qui je dois beaucoup. Merci de m’avoir toujours soutenue tout au long de cette thèse, et de m’avoir accompagné avec patience dans l’aboutissement de ce travail à mon rythme de jeune maman. Je remercie le Dr Patrice Dubreuil de m’avoir accueilli dans son équipe, d’avoir toujours été à l’écoute, et de m’avoir soutenu pour la finalisation de mon projet. Je remercie Véronique Gelsi-Boyer, Virginie Trouplin, Daniel Birnbaum et Norvert Vey, sans qui le projet MDS n’aurait pas existé. -
Radial Glia Reveal Complex Regulation by the Neuropeptide Secretoneurin
Transcriptomic and proteomic characterizations of goldfish (Carassius auratus) radial glia reveal complex regulation by the neuropeptide secretoneurin Dillon Da Fonte Thesis submitted to the Faculty of Graduate and Postdoctoral Studies University of Ottawa in partial fulfillment of the requirements for the Master of Science degree in biology Department of Biology Faculty of Science University of Ottawa © Dillon Da Fonte, Ottawa, Canada, 2016 Acknowledgements Finishing this thesis has been both a challenging and rewarding experience. This accomplishment would not have been possible without the never-ending support of colleagues, friends, family. First, I would like to express my most sincere gratitude to my supervisor and mentor, Dr. Vance Trudeau. Thank you for the opportunities you have given me, this experience has truly solidified my passion for research. I appreciate our many conversations that were enjoyed over a beer – it was truly a memorable experience. I would also like to thank my M.Sc. advisory committee, Dr. Michael Jonz and Dr. Marc Ekker for your time and insightful comments. A special thank you to Dr. Chris Martynuik who taught me the bioinformatics needed to analyze both transcriptomic and proteomic data and for all your help during my time at the University of Florida. I would like to also acknowledge my funding support from University of Ottawa, NSERC, and the Michael Smith Foreign Study Award for supporting my research stay at the University of Florida. To all current and past members of TeamENDO, thank you for the sense of community you all instilled in the lab. Both inside and outside the lab, I have made memories with all of you that I will cherish forever. -
Clathrin-Dependent Mechanisms Modulate the Subcellular Distribution of Class C Vps/HOPS Tether Subunits in Polarized and Nonpolarized Cells Stephanie A
Clathrin-dependent mechanisms modulate the subcellular distribution of class C Vps/HOPS tether subunits in polarized and nonpolarized cells Stephanie A. Zlatic, Emory University Karine Tornieri, Emory University Steven L'Hernault, Emory University Victor Faundez, Emory University Journal Title: Molecular Biology of the Cell Volume: Volume 22, Number 10 Publisher: American Society for Cell Biology | 2011-05-15, Pages 1699-1715 Type of Work: Article | Final Publisher PDF Publisher DOI: 10.1091/mbc.E10-10-0799 Permanent URL: http://pid.emory.edu/ark:/25593/f71wm Final published version: http://www.molbiolcell.org/content/22/10/1699 Copyright information: © 2011 Zlatic et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License This is an Open Access work distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 3.0 Unported License (http://creativecommons.org/licenses/by-nc-sa/3.0/). Accessed September 26, 2021 8:16 AM EDT M BoC | ARTICLE Clathrin-dependent mechanisms modulate the subcellular distribution of class C Vps/HOPS tether subunits in polarized and nonpolarized cells Stephanie A. Zlatica,b, Karine Tornierib, Steven W. L’Hernaulta,c,d, and Victor Faundeza,b,d aGraduate Program in Biochemistry, Cell, and Developmental Biology, bDepartment of Cell Biology, cBiology Department, and dCenter for Neurodegenerative Diseases, Emory University, Atlanta, GA 30322 ABSTRACT Coats define the composition of carriers budding from organelles. In addition, Monitoring Editor coats interact with membrane tethers required for vesicular fusion. -
Naca Mouse Shrna Plasmid (Locus ID 17938) – TL501429 | Origene
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 TL501429 Naca Mouse shRNA Plasmid (Locus ID 17938) Product data: Product Type: shRNA Plasmids Product Name: Naca Mouse shRNA Plasmid (Locus ID 17938) Locus ID: 17938 Synonyms: AL022831; AL024382; Gm1878; mKIAA0363; skNAC Vector: pGFP-C-shLenti (TR30023) Format: Lentiviral plasmids Components: Naca - Mouse, 4 unique 29mer shRNA constructs in lentiviral GFP vector(Gene ID = 17938). 5µg purified plasmid DNA per construct Non-effective 29-mer scrambled shRNA cassette in pGFP-C-shLenti Vector, TR30021, included for free. RefSeq: BC083340, BC099375, NM_001113199, NM_001282976, NM_013608, BC029830 Summary: Prevents inappropriate targeting of non-secretory polypeptides to the endoplasmic reticulum (ER). Binds to nascent polypeptide chains as they emerge from the ribosome and blocks their interaction with the signal recognition particle (SRP), which normally targets nascent secretory peptides to the ER. Also reduces the inherent affinity of ribosomes for protein translocation sites in the ER membrane (M sites) (By similarity). Isoform 1 and isoform 2 appear to bind DNA and play roles in transcription. Isoform 1 may function as a specific coactivator for JUN, acting to stabilize the interaction of JUN homodimers with promoter elements. [UniProtKB/Swiss-Prot Function] shRNA Design: These shRNA constructs were designed against multiple splice variants at this gene locus. To be certain that your variant of interest is targeted, please contact [email protected]. If you need a special design or shRNA sequence, please utilize our custom shRNA service. -
Estrogen Receptor (ER) Expression and Function in the Pregnant Human Myometrium: Estradiol Via Era Activates ERK1/2 Signaling in Term Myometrium
227 Estrogen receptor (ER) expression and function in the pregnant human myometrium: estradiol via ERa activates ERK1/2 signaling in term myometrium Toni Welsh1,2, Matrika Johnson1, Lijuan Yi1, Huiqing Tan1, Roksana Rahman1, Amy Merlino1, Tamas Zakar2,3 and Sam Mesiano1 1Department of Reproductive Biology, Case Western Reserve University, 11100 Euclid Avenue, Cleveland, Ohio 44106, USA 2Mothers and Babies Research Centre, University of Newcastle, Newcastle, New South Wales 2308, Australia 3Department of Obstetrics and Gynaecology, John Hunter Hospital, Newcastle, New South Wales 2305, Australia (Correspondence should be addressed to S Mesiano; Email: [email protected]) Abstract Estrogens are thought to promote labor by increasing inhibition of 26S proteasome activity increased ERa protein the expression of pro-contraction genes in myometrial cells. abundance to detectable levels in term myometrial explants, The specific estrogen receptors ((ERs: ERa and ERb (also however, indicating rapid turnover of ERa protein by known as ESR1 and ESR2)) and G protein-coupled receptor proteasomal processing in the pregnant myometrium. E2 30 (GPR30; also known as G protein-coupled estrogen stimulated rapid extranuclear signaling in myometrial explants, receptor 1)) and signaling pathways that mediate these actions as evidenced by increased extracellularly regulated kinase are not clearly understood. In this study, we identified the ERs (ERK1/2) phosphorylation within 10 min. This effect was expressed in the pregnant human myometrium and determined inhibited by pre-treatment with an ER antagonist, ICI a key extranuclear signaling pathway through which estradiol 182 780, indicating the involvement of ERa. Inhibition of (E2) modulates expression of the gene encoding the oxytocin ERK signaling abrogated the ability of E2 to stimulate OXTR receptor (OXTR), a major pro-contraction protein. -
The Oxytocin/Vasopressin Receptor Family Has at Least Five Members in the Gnathostome Lineage, Including Two Distinct V2 Subtypes
The oxytocin/vasopressin receptor family has at least five members in the gnathostome lineage, including two distinct V2 subtypes General and Comparative Endocrinology 175(1): 135-143 doi:10.1016/j.ygcen.2011.10.011 Accepted October 20, 2011 E-pub October 28, 2012 Published January 1, 2012 Figshare doi:10.6084/m9.figshare.811860. Shared October 1, 2013 Daniel Ocampo Daza*, Michalina Lewicka¹, Dan Larhammar Department of Neuroscience, Science for Life Laboratory, Uppsala Universitet, Box 593, SE-751 24 Uppsala, Sweden * Corresponding author. E-mail address: [email protected] ¹ Current address: Department of Neuroscience, Karolinska Institutet, SE-171 77 Stockholm, Sweden Cite as D. Ocampo Daza, M. Lewicka and D. Larhammar. The oxytocin/vasopressin family has at least five members in the gnathostome lineage, including two distinct V2 subtypes. General and Comparative Endocrinology, 175 (1) (2012) 135-143. This document corresponds to the article as it appeared upon acceptance. You are free to download, print and distribute it for any purposes under a Creative Commons Attribution 3.0 Unported License (http://creativecommons.org/licenses/by/3.0/), provided the original work is cited as specified. Errata: The introduction incorrectly states that “the V2 receptor inhibits adenylyl cyclase, thereby reducing the production of cAMP” on page 3. In fact the V2-type vasopressin receptors stimulate adenylyl cyclase and increase the cytosolic cyclic AMP release, see for instance Schöneberg et al., Molecular aspects of vasopressin receptor function, Advances in experimental medicine and biology 449 (1998) 347–58. This mistake was reported in the proofreading phase of pre-publication, but the correction was not carried to the final version of the article. -
G Protein-Coupled Receptors: What a Difference a ‘Partner’ Makes
Int. J. Mol. Sci. 2014, 15, 1112-1142; doi:10.3390/ijms15011112 OPEN ACCESS International Journal of Molecular Sciences ISSN 1422-0067 www.mdpi.com/journal/ijms Review G Protein-Coupled Receptors: What a Difference a ‘Partner’ Makes Benoît T. Roux 1 and Graeme S. Cottrell 2,* 1 Department of Pharmacy and Pharmacology, University of Bath, Bath BA2 7AY, UK; E-Mail: [email protected] 2 Reading School of Pharmacy, University of Reading, Reading RG6 6UB, UK * Author to whom correspondence should be addressed; E-Mail: [email protected]; Tel.: +44-118-378-7027; Fax: +44-118-378-4703. Received: 4 December 2013; in revised form: 20 December 2013 / Accepted: 8 January 2014 / Published: 16 January 2014 Abstract: G protein-coupled receptors (GPCRs) are important cell signaling mediators, involved in essential physiological processes. GPCRs respond to a wide variety of ligands from light to large macromolecules, including hormones and small peptides. Unfortunately, mutations and dysregulation of GPCRs that induce a loss of function or alter expression can lead to disorders that are sometimes lethal. Therefore, the expression, trafficking, signaling and desensitization of GPCRs must be tightly regulated by different cellular systems to prevent disease. Although there is substantial knowledge regarding the mechanisms that regulate the desensitization and down-regulation of GPCRs, less is known about the mechanisms that regulate the trafficking and cell-surface expression of newly synthesized GPCRs. More recently, there is accumulating evidence that suggests certain GPCRs are able to interact with specific proteins that can completely change their fate and function. These interactions add on another level of regulation and flexibility between different tissue/cell-types. -
Supplementary Table S4. FGA Co-Expressed Gene List in LUAD
Supplementary Table S4. FGA co-expressed gene list in LUAD tumors Symbol R Locus Description FGG 0.919 4q28 fibrinogen gamma chain FGL1 0.635 8p22 fibrinogen-like 1 SLC7A2 0.536 8p22 solute carrier family 7 (cationic amino acid transporter, y+ system), member 2 DUSP4 0.521 8p12-p11 dual specificity phosphatase 4 HAL 0.51 12q22-q24.1histidine ammonia-lyase PDE4D 0.499 5q12 phosphodiesterase 4D, cAMP-specific FURIN 0.497 15q26.1 furin (paired basic amino acid cleaving enzyme) CPS1 0.49 2q35 carbamoyl-phosphate synthase 1, mitochondrial TESC 0.478 12q24.22 tescalcin INHA 0.465 2q35 inhibin, alpha S100P 0.461 4p16 S100 calcium binding protein P VPS37A 0.447 8p22 vacuolar protein sorting 37 homolog A (S. cerevisiae) SLC16A14 0.447 2q36.3 solute carrier family 16, member 14 PPARGC1A 0.443 4p15.1 peroxisome proliferator-activated receptor gamma, coactivator 1 alpha SIK1 0.435 21q22.3 salt-inducible kinase 1 IRS2 0.434 13q34 insulin receptor substrate 2 RND1 0.433 12q12 Rho family GTPase 1 HGD 0.433 3q13.33 homogentisate 1,2-dioxygenase PTP4A1 0.432 6q12 protein tyrosine phosphatase type IVA, member 1 C8orf4 0.428 8p11.2 chromosome 8 open reading frame 4 DDC 0.427 7p12.2 dopa decarboxylase (aromatic L-amino acid decarboxylase) TACC2 0.427 10q26 transforming, acidic coiled-coil containing protein 2 MUC13 0.422 3q21.2 mucin 13, cell surface associated C5 0.412 9q33-q34 complement component 5 NR4A2 0.412 2q22-q23 nuclear receptor subfamily 4, group A, member 2 EYS 0.411 6q12 eyes shut homolog (Drosophila) GPX2 0.406 14q24.1 glutathione peroxidase -
Identifying Potential Binding Partners of VPS16B and VPS33B in Mammalian Cells
Identifying Potential Binding Partners of VPS16B and VPS33B in Mammalian Cells by Shao Zun Chen A thesis submitted in conformity with the requirements for the degree of Master of Science Department of Biochemistry University of Toronto © Copyright by Shao Zun Chen 2013 Identifying Potential Binding Partners of VPS16B and VPS33B in Mammalian Cells Shao Zun Chen Master of Science Department of Biochemistry University of Toronto 2013 Abstract Platelets contain specialized granules that are required for platelet function in hemostasis. These granules are formed in the megakaryocyte precursor, and VPS33B and VPS16B are essential for this process as mutations in them cause arthrogryposis, renal dysfunction and cholestasis syndrome, where platelets lack α-granules. Here, it is shown that VPS33B and VPS16B exist as part of two complexes (480 kDa and 720 kDa). My project entailed the identification of the components of these complexes that could be required for platelet granule biogenesis. It was found that these complexes are distinct from the VPS33A HOPS complex as they are not associated with VPS11 or VPS18, but are formed through self- oligomerization. Yeast three hybrid and co-immunoprecipitation experiments suggest that VPS52, COG5 and ATP6AP2 may interact with VPS33B and VPS16B. In addition, VPS33B and VPS16B likely interact with Rab5 and/or Rab7, but not with Rab11A, based on both GST-pulldown assays and co-immunoprecipitation experiments. ii Acknowledgments I would like to express my deepest appreciation to my supervisor, Dr. Walter Kahr, for providing guidance and inspiration during my studies; to my supervisory committee Dr. Allen Volchuk and Dr. David Williams for their helpful inputs and guidance; to all members of the Kahr lab: Dr. -
Analysis of the Indacaterol-Regulated Transcriptome in Human Airway
Supplemental material to this article can be found at: http://jpet.aspetjournals.org/content/suppl/2018/04/13/jpet.118.249292.DC1 1521-0103/366/1/220–236$35.00 https://doi.org/10.1124/jpet.118.249292 THE JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS J Pharmacol Exp Ther 366:220–236, July 2018 Copyright ª 2018 by The American Society for Pharmacology and Experimental Therapeutics Analysis of the Indacaterol-Regulated Transcriptome in Human Airway Epithelial Cells Implicates Gene Expression Changes in the s Adverse and Therapeutic Effects of b2-Adrenoceptor Agonists Dong Yan, Omar Hamed, Taruna Joshi,1 Mahmoud M. Mostafa, Kyla C. Jamieson, Radhika Joshi, Robert Newton, and Mark A. Giembycz Departments of Physiology and Pharmacology (D.Y., O.H., T.J., K.C.J., R.J., M.A.G.) and Cell Biology and Anatomy (M.M.M., R.N.), Snyder Institute for Chronic Diseases, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada Received March 22, 2018; accepted April 11, 2018 Downloaded from ABSTRACT The contribution of gene expression changes to the adverse and activity, and positive regulation of neutrophil chemotaxis. The therapeutic effects of b2-adrenoceptor agonists in asthma was general enriched GO term extracellular space was also associ- investigated using human airway epithelial cells as a therapeu- ated with indacaterol-induced genes, and many of those, in- tically relevant target. Operational model-fitting established that cluding CRISPLD2, DMBT1, GAS1, and SOCS3, have putative jpet.aspetjournals.org the long-acting b2-adrenoceptor agonists (LABA) indacaterol, anti-inflammatory, antibacterial, and/or antiviral activity. Numer- salmeterol, formoterol, and picumeterol were full agonists on ous indacaterol-regulated genes were also induced or repressed BEAS-2B cells transfected with a cAMP-response element in BEAS-2B cells and human primary bronchial epithelial cells by reporter but differed in efficacy (indacaterol $ formoterol .