Profiling G Protein-Coupled Receptors of Fasciola Hepatica Identifies Orphan Rhodopsins Unique to Phylum Platyhelminthes
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Mir-338-3P Is Regulated by Estrogens Through GPER in Breast Cancer Cells and Cancer-Associated Fibroblasts (Cafs)
cells Article miR-338-3p Is Regulated by Estrogens through GPER in Breast Cancer Cells and Cancer-Associated Fibroblasts (CAFs) Adele Vivacqua 1,*, Anna Sebastiani 1, Anna Maria Miglietta 2, Damiano Cosimo Rigiracciolo 1, Francesca Cirillo 1, Giulia Raffaella Galli 1, Marianna Talia 1, Maria Francesca Santolla 1, Rosamaria Lappano 1, Francesca Giordano 1, Maria Luisa Panno 1 and Marcello Maggiolini 1,* 1 Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, 87036 Rende, Italy; [email protected] (A.S.); [email protected] (D.C.R.); [email protected] (F.C.); [email protected] (G.R.G.); [email protected] (M.T.); [email protected] (M.F.S.); [email protected] (R.L.); [email protected] (F.G.); [email protected] (M.L.P.) 2 Regional HospitalCosenza, 87100 Cosenza, Italy; [email protected] * Correspondence: [email protected] (A.V.); [email protected] (M.M.); Tel.: +39-0984-493-048 (A.V.); +39-0984-493-076 (M.M.) Received: 12 October 2018; Accepted: 7 November 2018; Published: 9 November 2018 Abstract: Estrogens acting through the classic estrogen receptors (ERs) and the G protein estrogen receptor (GPER) regulate the expression of diverse miRNAs, small sequences of non-coding RNA involved in several pathophysiological conditions, including breast cancer. In order to provide novel insights on miRNAs regulation by estrogens in breast tumor, we evaluated the expression of 754 miRNAs by TaqMan Array in ER-negative and GPER-positive SkBr3 breast cancer cells and cancer-associated fibroblasts (CAFs) upon 17β-estradiol (E2) treatment. Various miRNAs were regulated by E2 in a peculiar manner in SkBr3 cancer cells and CAFs, while miR-338-3p displayed a similar regulation in both cell types. -
The G Protein-Coupled Receptor Subset of the Dog Genome Is More Similar
BMC Genomics BioMed Central Research article Open Access The G protein-coupled receptor subset of the dog genome is more similar to that in humans than rodents Tatjana Haitina1, Robert Fredriksson1, Steven M Foord2, Helgi B Schiöth*1 and David E Gloriam*2 Address: 1Department of Neuroscience, Functional Pharmacology, Uppsala University, BMC, Box 593, 751 24, Uppsala, Sweden and 2GlaxoSmithKline Pharmaceuticals, New Frontiers Science Park, 3rd Avenue, Harlow CM19 5AW, UK Email: Tatjana Haitina - [email protected]; Robert Fredriksson - [email protected]; Steven M Foord - [email protected]; Helgi B Schiöth* - [email protected]; David E Gloriam* - [email protected] * Corresponding authors Published: 15 January 2009 Received: 20 August 2008 Accepted: 15 January 2009 BMC Genomics 2009, 10:24 doi:10.1186/1471-2164-10-24 This article is available from: http://www.biomedcentral.com/1471-2164/10/24 © 2009 Haitina 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: The dog is an important model organism and it is considered to be closer to humans than rodents regarding metabolism and responses to drugs. The close relationship between humans and dogs over many centuries has lead to the diversity of the canine species, important genetic discoveries and an appreciation of the effects of old age in another species. The superfamily of G protein-coupled receptors (GPCRs) is one of the largest gene families in most mammals and the most exploited in terms of drug discovery. -
Lgr5 Homologues Associate with Wnt Receptors and Mediate R-Spondin Signalling
ARTICLE doi:10.1038/nature10337 Lgr5 homologues associate with Wnt receptors and mediate R-spondin signalling Wim de Lau1*, Nick Barker1{*, Teck Y. Low2, Bon-Kyoung Koo1, Vivian S. W. Li1, Hans Teunissen1, Pekka Kujala3, Andrea Haegebarth1{, Peter J. Peters3, Marc van de Wetering1, Daniel E. Stange1, Johan E. van Es1, Daniele Guardavaccaro1, Richard B. M. Schasfoort4, Yasuaki Mohri5, Katsuhiko Nishimori5, Shabaz Mohammed2, Albert J. R. Heck2 & Hans Clevers1 The adult stem cell marker Lgr5 and its relative Lgr4 are often co-expressed in Wnt-driven proliferative compartments. We find that conditional deletion of both genes in the mouse gut impairs Wnt target gene expression and results in the rapid demise of intestinal crypts, thus phenocopying Wnt pathway inhibition. Mass spectrometry demonstrates that Lgr4 and Lgr5 associate with the Frizzled/Lrp Wnt receptor complex. Each of the four R-spondins, secreted Wnt pathway agonists, can bind to Lgr4, -5 and -6. In HEK293 cells, RSPO1 enhances canonical WNT signals initiated by WNT3A. Removal of LGR4 does not affect WNT3A signalling, but abrogates the RSPO1-mediated signal enhancement, a phenomenon rescued by re-expression of LGR4, -5 or -6. Genetic deletion of Lgr4/5 in mouse intestinal crypt cultures phenocopies withdrawal of Rspo1 and can be rescued by Wnt pathway activation. Lgr5 homologues are facultative Wnt receptor components that mediate Wnt signal enhancement by soluble R-spondin proteins. These results will guide future studies towards the application of R-spondins for regenerative purposes of tissues expressing Lgr5 homologues. The genes Lgr4, Lgr5 and Lgr6 encode orphan 7-transmembrane 4–5 post-induction onwards. -
The Role of the Serotonergic System and the Effects of Antidepressants During Brain Development Examined Using in Vivo Pet Imaging and in Vitro Receptor Binding
From THE DEPARTMENT OF CLINICAL NEUROSCIENCE Karolinska Institutet, Stockholm, Sweden THE ROLE OF THE SEROTONERGIC SYSTEM AND THE EFFECTS OF ANTIDEPRESSANTS DURING BRAIN DEVELOPMENT EXAMINED USING IN VIVO PET IMAGING AND IN VITRO RECEPTOR BINDING Stal Saurav Shrestha Stockholm 2014 Cover Illustration: Voxel-wise analysis of the whole monkey brain using the PET radioligand, [11C]DASB showing persistent serotonin transporter upregulation even after more than 1.5 years of fluoxetine discontinuation. All previously published papers were reproduced with permission from the publisher. Published by Karolinska Institutet. Printed by Universitetsservice-AB © Stal Saurav Shrestha, 2014 ISBN 978-91-7549-522-4 Serotonergic System and Antidepressants During Brain Development To my family Amaze yourself ! Stal Saurav Shrestha, 2014 The Department of Clinical Neuroscience The role of the serotonergic system and the effects of antidepressants during brain development examined using in vivo PET imaging and in vitro receptor binding AKADEMISK AVHANDLING som för avläggande av medicine doktorsexamen vid Karolinska Institutet offentligen försvaras i CMM föreläsningssalen L8:00, Karolinska Universitetssjukhuset, Solna THESIS FOR DOCTORAL DEGREE (PhD) Stal Saurav Shrestha Date: March 31, 2014 (Monday); Time: 10 AM Venue: Center for Molecular Medicine Lecture Hall Floor 1, Karolinska Hospital, Solna Principal Supervisor: Opponent: Robert B. Innis, MD, PhD Klaus-Peter Lesch, MD, PhD National Institutes of Health University of Würzburg Department of NIMH Department -
Smoothened Variants Explain the Majority of Drug Resistance in Basal Cell Carcinoma
Article Smoothened Variants Explain the Majority of Drug Resistance in Basal Cell Carcinoma Graphical Abstract Authors Scott X. Atwood, Kavita Y. Sarin, ..., Anthony E. Oro, Jean Y. Tang Correspondence [email protected] (A.E.O.), [email protected] (J.Y.T.) In Brief Atwood et al. identify key SMO mutations that confer resistance to SMO inhibitors in basal cell carcinomas (BCC) and show that these mutants respond to aPKC-i/l or GLI2 inhibitors, providing potential approaches for treating BCCs resistant to SMO inhibitors. Highlights Accession Numbers d Functional SMO mutations are detected in the majority of GSE58377 SMO inhibitor-resistant BCCs d Resistance occurs by suppressing drug responsiveness and SMO autoinhibition d SMO mutants explain both intrinsic and acquired tumor resistance d Inhibition of aPKC-i/l or GLI2 bypasses SMO variants to suppress Hedgehog signaling Atwood et al., 2015, Cancer Cell 27, 342–353 March 9, 2015 ª2015 Elsevier Inc. http://dx.doi.org/10.1016/j.ccell.2015.02.002 Cancer Cell Article Smoothened Variants Explain the Majority of Drug Resistance in Basal Cell Carcinoma Scott X. Atwood,1,2 Kavita Y. Sarin,1,2 Ramon J. Whitson,1 Jiang R. Li,1 Geurim Kim,1 Melika Rezaee,1 Mina S. Ally,1 Jinah Kim,1 Catherine Yao,1 Anne Lynn S. Chang,1,3 Anthony E. Oro,1,3,* and Jean Y. Tang1,3,* 1Program in Epithelial Biology and Department of Dermatology, Stanford University School of Medicine, Stanford, CA 94305, USA 2Co-first author 3Co-senior author *Correspondence: [email protected] (A.E.O.), [email protected] (J.Y.T.) http://dx.doi.org/10.1016/j.ccell.2015.02.002 SUMMARY Advanced basal cell carcinomas (BCCs) frequently acquire resistance to Smoothened (SMO) inhibitors through unknown mechanisms. -
System, Method and Software for Calculation of a Cannabis Drug Efficiency Index for the Reduction of Inflammation
International Journal of Molecular Sciences Article System, Method and Software for Calculation of a Cannabis Drug Efficiency Index for the Reduction of Inflammation Nicolas Borisov 1,† , Yaroslav Ilnytskyy 2,3,†, Boseon Byeon 2,3,4,†, Olga Kovalchuk 2,3 and Igor Kovalchuk 2,3,* 1 Moscow Institute of Physics and Technology, 9 Institutsky lane, Dolgoprudny, Moscow Region 141701, Russia; [email protected] 2 Department of Biological Sciences, University of Lethbridge, Lethbridge, AB T1K 3M4, Canada; [email protected] (Y.I.); [email protected] (B.B.); [email protected] (O.K.) 3 Pathway Rx., 16 Sandstone Rd. S., Lethbridge, AB T1K 7X8, Canada 4 Biomedical and Health Informatics, Computer Science Department, State University of New York, 2 S Clinton St, Syracuse, NY 13202, USA * Correspondence: [email protected] † First three authors contributed equally to this research. Abstract: There are many varieties of Cannabis sativa that differ from each other by composition of cannabinoids, terpenes and other molecules. The medicinal properties of these cultivars are often very different, with some being more efficient than others. This report describes the development of a method and software for the analysis of the efficiency of various cannabis extracts to detect the anti-inflammatory properties of the various cannabis extracts. The method uses high-throughput gene expression profiling data but can potentially use other omics data as well. According to the signaling pathway topology, the gene expression profiles are convoluted into the signaling pathway activities using a signaling pathway impact analysis (SPIA) method. The method was tested by inducing inflammation in human 3D epithelial tissues, including intestine, oral and skin, and then exposing these tissues to various extracts and then performing transcriptome analysis. -
Tamoxifen Resistance: Emerging Molecular Targets
International Journal of Molecular Sciences Review Tamoxifen Resistance: Emerging Molecular Targets Milena Rondón-Lagos 1,*,†, Victoria E. Villegas 2,3,*,†, Nelson Rangel 1,2,3, Magda Carolina Sánchez 2 and Peter G. Zaphiropoulos 4 1 Department of Medical Sciences, University of Turin, Turin 10126, Italy; [email protected] 2 Faculty of Natural Sciences and Mathematics, Universidad del Rosario, Bogotá 11001000, Colombia; [email protected] 3 Doctoral Program in Biomedical Sciences, Universidad del Rosario, Bogotá 11001000, Colombia 4 Department of Biosciences and Nutrition, Karolinska Institutet, Huddinge 14183, Sweden; [email protected] * Correspondence: [email protected] (M.R.-L.); [email protected] (V.E.V.); Tel.: +39-01-1633-4127 (ext. 4388) (M.R.-L.); +57-1-297-0200 (ext. 4029) (V.E.V.); Fax: +39-01-1663-5267 (M.R.-L.); +57-1-297-0200 (V.E.V.) † These authors contributed equally to this work. Academic Editor: William Chi-shing Cho Received: 5 July 2016; Accepted: 16 August 2016; Published: 19 August 2016 Abstract: 17β-Estradiol (E2) plays a pivotal role in the development and progression of breast cancer. As a result, blockade of the E2 signal through either tamoxifen (TAM) or aromatase inhibitors is an important therapeutic strategy to treat or prevent estrogen receptor (ER) positive breast cancer. However, resistance to TAM is the major obstacle in endocrine therapy. This resistance occurs either de novo or is acquired after an initial beneficial response. The underlying mechanisms for TAM resistance are probably multifactorial and remain largely unknown. Considering that breast cancer is a very heterogeneous disease and patients respond differently to treatment, the molecular analysis of TAM’s biological activity could provide the necessary framework to understand the complex effects of this drug in target cells. -
Exploring the Heteromeric Interface of the 5-HT2A-Mglu2 Receptor Complex
Virginia Commonwealth University VCU Scholars Compass Theses and Dissertations Graduate School 2020 Exploring the Heteromeric Interface of the 5-HT2A-mGlu2 Receptor Complex Mohamed Aarif Abdul Kareem Virginia Commonwealth University Follow this and additional works at: https://scholarscompass.vcu.edu/etd Part of the Nervous System Diseases Commons, Other Psychiatry and Psychology Commons, Physiological Processes Commons, and the Translational Medical Research Commons © The Author Downloaded from https://scholarscompass.vcu.edu/etd/6235 This Thesis is brought to you for free and open access by the Graduate School at VCU Scholars Compass. It has been accepted for inclusion in Theses and Dissertations by an authorized administrator of VCU Scholars Compass. For more information, please contact [email protected]. Exploring the Heteromeric Interface of the 5-HT2A-mGlu2 Receptor Complex A Thesis submitted in partial fulfillment of the requirements for the degree of Master of Science in Physiology and Biophysics at Virginia Commonwealth University By: Mohamed Aarif Abdul Kareem B.A. Neurobiology, Boston University, 2018 Mentor: Javier González-Maeso Associate Professor Department of Physiology and Biophysics Virginia Commonwealth University Richmond, Virginia April 30, 2020 Acknowledgments: Thank you to my peers for their continued support of my dreams and aspirations. Thank you to my mentors for pushing and supporting me every step of the way. Thank you to Virginia Commonwealth University for providing opportunities which foster my passion for science and allow it to continue to flourish. Indeed, I owe much gratitude to my parents, Abdul & Jasmine Kareem, who have guided me in becoming a strong, independent student, and encourage me to take calculated risks and face challenges head on. -
Emerging Role of Tumor Cell Plasticity in Modifying Therapeutic Response
Signal Transduction and Targeted Therapy www.nature.com/sigtrans REVIEW ARTICLE OPEN Emerging role of tumor cell plasticity in modifying therapeutic response Siyuan Qin1, Jingwen Jiang1,YiLu 2,3, Edouard C. Nice4, Canhua Huang1,5, Jian Zhang2,3 and Weifeng He6,7 Resistance to cancer therapy is a major barrier to cancer management. Conventional views have proposed that acquisition of resistance may result from genetic mutations. However, accumulating evidence implicates a key role of non-mutational resistance mechanisms underlying drug tolerance, the latter of which is the focus that will be discussed here. Such non-mutational processes are largely driven by tumor cell plasticity, which renders tumor cells insusceptible to the drug-targeted pathway, thereby facilitating the tumor cell survival and growth. The concept of tumor cell plasticity highlights the significance of re-activation of developmental programs that are closely correlated with epithelial–mesenchymal transition, acquisition properties of cancer stem cells, and trans- differentiation potential during drug exposure. From observations in various cancers, this concept provides an opportunity for investigating the nature of anticancer drug resistance. Over the years, our understanding of the emerging role of phenotype switching in modifying therapeutic response has considerably increased. This expanded knowledge of tumor cell plasticity contributes to developing novel therapeutic strategies or combination therapy regimens using available anticancer drugs, which are likely to -
Subcellular Localization of MC4R with ADCY3 at Neuronal Primary Cilia Underlies a Common Pathway for Genetic Predisposition to Obesity
HHS Public Access Author manuscript Author ManuscriptAuthor Manuscript Author Nat Genet Manuscript Author . Author manuscript; Manuscript Author available in PMC 2018 July 08. Published in final edited form as: Nat Genet. 2018 February ; 50(2): 180–185. doi:10.1038/s41588-017-0020-9. Subcellular localization of MC4R with ADCY3 at neuronal primary cilia underlies a common pathway for genetic predisposition to obesity Jacqueline E. Siljee1,*, Yi Wang1,*, Adelaide A. Bernard1, Baran A. Ersoy1, Sumei Zhang1, Aaron Marley2, Mark Von Zastrow2, Jeremy F. Reiter3, and Christian Vaisse1,** 1Department of Medicine and Diabetes Center, University of California, San Francisco, California, USA 2Department of Psychiatry and Cellular & Molecular Pharmacology, University of California, San Francisco, California, USA 3Department of Biochemistry and Biophysics, Cardiovascular Research Institute, University of California, San Francisco, California, USA MAIN TEXT Most monogenic cases of obesity in humans have been linked to mutations in genes of the leptin-melanocortin pathway. Specifically, mutations in the Melanocortin-4 Receptor (MC4R), account for 3–5% of all severe obesity cases in humans1–3. Recently, adenylate cyclase 3 (ADCY3) mutations have been implicated in obesity4,5. ADCY3 is expressed at the primary cilia of neurons6, organelles that function as hubs for select signaling pathways. Mutations that disrupt the functions of primary cilia cause ciliopathies, rare recessive pleiotropic diseases, of which obesity is a cardinal manifestation7. We demonstrate that MC4R co-localizes with ADCY3 at the primary cilium of a subset of hypothalamic neurons, that obesity-associated MC4R mutations can impair ciliary localization and that inhibition of adenylyl-cyclase signaling at the primary cilia of these neurons increases body weight. -
Review of the Molecular Genetics of Basal Cell Carcinoma; Inherited Susceptibility, Somatic Mutations, and Targeted Therapeutics
cancers Review Review of the Molecular Genetics of Basal Cell Carcinoma; Inherited Susceptibility, Somatic Mutations, and Targeted Therapeutics James M. Kilgour , Justin L. Jia and Kavita Y. Sarin * Department of Dermatology, Stanford University School of Medcine, Stanford, CA 94305, USA; [email protected] (J.M.K.); [email protected] (J.L.J.) * Correspondence: [email protected] Simple Summary: Basal cell carcinoma is the most common human cancer worldwide. The molec- ular basis of BCC involves an interplay of inherited genetic susceptibility and somatic mutations, commonly induced by exposure to UV radiation. In this review, we outline the currently known germline and somatic mutations implicated in the pathogenesis of BCC with particular attention paid toward affected molecular pathways. We also discuss polymorphisms and associated phenotypic traits in addition to active areas of BCC research. We finally provide a brief overview of existing non-surgical treatments and emerging targeted therapeutics for BCC such as Hedgehog pathway inhibitors, immune modulators, and histone deacetylase inhibitors. Abstract: Basal cell carcinoma (BCC) is a significant public health concern, with more than 3 million cases occurring each year in the United States, and with an increasing incidence. The molecular basis of BCC is complex, involving an interplay of inherited genetic susceptibility, including single Citation: Kilgour, J.M.; Jia, J.L.; Sarin, nucleotide polymorphisms and genetic syndromes, and sporadic somatic mutations, often induced K.Y. Review of the Molecular Genetics of Basal Cell Carcinoma; by carcinogenic exposure to UV radiation. This review outlines the currently known germline and Inherited Susceptibility, Somatic somatic mutations implicated in the pathogenesis of BCC, including the key molecular pathways Mutations, and Targeted affected by these mutations, which drive oncogenesis. -
Allosteric Modulation of Gabaergic and Glutamatergic Metabotropic Receptors — Thibaud Freyd a Dissertation for the Degree of Philosophiae Doctor – June 2018
Molecular Pharmacology and Toxicology Faculty of Health Sciences Allosteric modulation of GABAergic and glutamatergic metabotropic receptors — Thibaud Freyd A dissertation for the degree of Philosophiae Doctor – June 2018 Content Acknowledgments ...................................................................................................................... iii List of papers ................................................................................................................................. v Abbreviations ............................................................................................................................. vii Summary .......................................................................................................................................ix 1. Introduction ............................................................................................................................. 1 1.1. Glutamate and GABA neurotransmitters in the CNS ....................................................... 1 1.2. G-protein coupled receptors .................................................................................................... 4 1.2.1. G-protein coupled receptor families ................................................................................................................ 4 1.2.2. Activation of signalling pathways ..................................................................................................................... 5 1.2.3. General structural knowledge ...........................................................................................................................