The 13Th International Symposium on Primatology and Wildlife Science
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Strategies to Increase ß-Cell Mass Expansion
This electronic thesis or dissertation has been downloaded from the King’s Research Portal at https://kclpure.kcl.ac.uk/portal/ Strategies to increase -cell mass expansion Drynda, Robert Lech Awarding institution: King's College London The copyright of this thesis rests with the author and no quotation from it or information derived from it may be published without proper acknowledgement. END USER LICENCE AGREEMENT Unless another licence is stated on the immediately following page this work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International licence. https://creativecommons.org/licenses/by-nc-nd/4.0/ You are free to copy, distribute and transmit the work Under the following conditions: Attribution: You must attribute the work in the manner specified by the author (but not in any way that suggests that they endorse you or your use of the work). Non Commercial: You may not use this work for commercial purposes. No Derivative Works - You may not alter, transform, or build upon this work. Any of these conditions can be waived if you receive permission from the author. Your fair dealings and other rights are in no way affected by the above. Take down policy If you believe that this document breaches copyright please contact [email protected] providing details, and we will remove access to the work immediately and investigate your claim. Download date: 02. Oct. 2021 Strategies to increase β-cell mass expansion A thesis submitted by Robert Drynda For the degree of Doctor of Philosophy from King’s College London Diabetes Research Group Division of Diabetes & Nutritional Sciences Faculty of Life Sciences & Medicine King’s College London 2017 Table of contents Table of contents ................................................................................................. -
Peptide, Peptidomimetic and Small Molecule Based Ligands Targeting Melanocortin Receptor System
PEPTIDE, PEPTIDOMIMETIC AND SMALL MOLECULE BASED LIGANDS TARGETING MELANOCORTIN RECEPTOR SYSTEM By ALEKSANDAR TODOROVIC A DISSERTATION PRESENTED TO THE GRADUATE SCHOOL OF THE UNIVERSITY OF FLORIDA IN PARTIAL FULFILLMENT OF THE REQUIREMENTS FOR THE DEGREE OF DOCTOR OF PHILOSOPHY UNIVERSITY OF FLORIDA 2006 Copyright 2006 by Aleksandar Todorovic This document is dedicated to my family for everlasting support and selfless encouragement. ACKNOWLEDGMENTS I would like to thank and sincerely express my appreciation to all members, former and past, of Haskell-Luevano research group. First of all, I would like to express my greatest satisfaction by working with my mentor, Dr. Carrie Haskell-Luevano, whose guidance, expertise and dedication to research helped me reaching the point where I will continue the science path. Secondly, I would like to thank Dr. Ryan Holder who has taught me the principles of solid phase synthesis and initial strategies for the compounds design. I would like to thank Mr. Jim Rocca for the help and all necessary theoretical background required to perform proton 1-D NMR. In addition, I would like to thank Dr. Zalfa Abdel-Malek from the University of Cincinnati for the collaboration on the tyrosinase study project. Also, I would like to thank the American Heart Association for the Predoctoral fellowship that supported my research from 2004-2006. The special dedication and thankfulness go to my fellow graduate students within the lab and the department. iv TABLE OF CONTENTS page ACKNOWLEDGMENTS ................................................................................................ -
Information for Instructor
Using a Single-Nucleotide Polymorphism to Predict Bitter-Tasting Ability 21 INFORMATION FOR INSTRUCTOR CONCEPTS AND METHODS This laboratory can help students understand several important concepts of modern biology: • The relationship between genotype and phenotype. • The use of single-nucleotide polymorphisms (SNPs) in predicting drug response (pharmacogenetics). • A number of SNPs are inherited together as a haplotype. • The movement between in vitro experimentation and in silico computation. The laboratory uses several methods for modern biological research: • DNA extraction and purification. • Polymerase chain reaction (PCR). • DNA restriction. • Gel electrophoresis. • Bioinformatics. LAB SAFETY The National Association of Biology Teachers recognizes the importance of laboratory activities using human body samples and has developed safety guidelines to minimize the risk of transmitting serious disease. ("The Use of Human Body Fluids and Tissue Products in Biology," News & Views, June 1996.) These are summarized below: • Collect samples only from students under your direct supervision. • Do not use samples brought from home or obtained from an unknown source. • Do not collect samples from students who are obviously ill or are known to have a serious communicable disease. • Have students wear proper safety apparel: latex or plastic gloves, safety glasses or goggles, and lab coat or apron. • Supernatants and samples may be disposed of in public sewers (down lab drains). • Have students wash their hands at the end of the lab period. • Do not store samples in a refrigerator or freezer used for food. The risk of spreading an infectious agent by this lab method is much less likely than from natural atomizing processes, such as coughing or sneezing. -
Analgesics and the Effects of Pharmacogenomics Disclosures: None
Cohen, Mindy, MD Analgesics and the Effects of Pharmacogenetics Analgesics and the Effects of Pharmacogenomics Disclosures: none Mindy Cohen, MD Learning Objectives 1. Review genetic variations that influence analgesic pharmacotherapy in children. 2. Identify the most common Before there was the need for polymorphisms in drug-metabolizing enzymes that influence analgesics. analgesia, there was… 3. Describe strategies for modifying analgesic regimens based on pharmacogenomics. PAIN Multifactorial Influences Genetic influence on Personality pain sensitivity Secondary Socio-economic gain status Pain Genetic influence on Genetics Environment analgesic medications Prior stress or trauma Cohen, Mindy, MD Analgesics and the Effects of Pharmacogenetics Genetic Influences on Pain Genetic Influences on Pain - Cases of Absent Pain - Twin Studies • Some rare cases explained by genetics • 2007- Thermal & chemical noxious stimuli • Loss-of-function mutations . 98 pairs of twins . α-subunit of voltage-gated sodium channel . 22-55% of variability was genetic . Other components that regulate functioning • 2008- Thermal noxious stimuli and homeostasis of nervous system . 96 twins . Cold-pressor pain • 7% of variability was genetic . Heat pain • 3% of variability was genetic Smith M et al. Clinical Genetics 2012 Norbury T et al. Brain 2007 Lotsch J et al. Trends in Pharm Sci 2010 Nielsen C et al. Pain 2008 Genetic Influences on Pain - Twin Studies • 2012- Thermal noxious stimuli, μ-agonists Analgesics and Genetics: . 112 pairs of twins . Pain tolerance and opioid analgesia Pharmacokinetics and . 24-60% of the response was influenced by Pharmacodynamics genetic makeup Angst M et al. Pain 2012 Genetic variation affects Genetic variation affects Pharmacokinetics Pharmacokinetics Cohen, Mindy, MD Analgesics and the Effects of Pharmacogenetics Pharmacokinetics Pharmacokinetics - Phase I Enzymes - Phase I Enzymes • Cytochrome P450 superfamily • Alter the chemical structure of drugs . -
Functionality and Genetics of Melanocortin and Purinergic Receptors
University of Latvia Faculty of Biology Vita Ignatoviča Doctoral Thesis Functionality and genetics of melanocortin and purinergic receptors Promotion to the degree of Doctor of Biology Molecular Biology Supervisor: Dr. Biol. Jānis Kloviņš Riga, 2012 1 The doctoral thesis was carried out in University of Latvia, Faculty of Biology, Department of Molecular biology and Latvian Biomedical Reseach and Study centre. From 2007 to 2012 The research was supported by Latvian Council of Science (LZPSP10.0010.10.04), Latvian Research Program (4VPP-2010-2/2.1) and ESF funding (1DP/1.1.1.2.0/09/APIA/VIAA/150 and 1DP/1.1.2.1.2/09/IPIA/VIAA/004). The thesis contains the introduction, 9 chapters, 38 subchapters and reference list. Form of the thesis: collection of articles in biology with subdiscipline in molecular biology Supervisor: Dr. biol. Jānis Kloviņš Reviewers: 1) Dr. biol., Prof. Astrīda Krūmiņa, Latvian Biomedical Reseach and Study centre 2) Dr. biol., Prof. Ruta Muceniece, University of Latvia, Department of Medicine, Pharmacy program 3) PhD Med, Assoc.Prof.David Gloriam, University of Copenhagen, Department of Drug Design and Pharmacology The thesis will be defended at the public section of the Doctoral Commitee of Biology, University of Latvia, in the conference hall of Latvian Biomedical Research and Study centre on July 6th, 2012, at 11.00. The thesis is available at the Library of the University of Latvia, Kalpaka blvd. 4. This thesis is accepted of the commencement of the degree of Doctor of Biology on April 19th, 2012, by the Doctoral Commitee of Biology, University of Latvia. -
Bitter Taste Perception in Neanderthals Through the Analysis of The
View metadata, citation and similar papers Downloadedat core.ac.uk from http://rsbl.royalsocietypublishing.org/ on March 22, 2016 brought to you by CORE provided by Repositorio Institucional de la Universidad de Oviedo Biol. Lett. (2009) 5, 809–811 The most extensively studied taste variation in doi:10.1098/rsbl.2009.0532 humans is sensitivity to a bitter substance called phe- Published online 12 August 2009 nylthiocarbamide (PTC). Although approximately 75 Evolutionary biology per cent of the world population perceives this sub- stance as intensely bitter, it is virtually tasteless for the remaining 25 per cent of the population (Kim & Bitter taste perception in Drayna 2004). This is owing to a dominant ‘taster’ allele that shows a similar frequency to the recessive Neanderthals through the ‘non-taster’ allele. PTC itself is not found in any vegetable, but chemically similar substances that analysis of the TAS2R38 produce an identical response to PTC are present in gene many plant foods (including Brussels sprouts, cabbage, broccoli and others). It was discovered Carles Lalueza-Fox1,*, Elena Gigli1, (Kim et al. 2003) that most of the variation in PTC Marco de la Rasilla2, Javier Fortea2 sensitivity is related to polymorphisms at the and Antonio Rosas3 TAS2R38 gene, a single 1002 bp coding exon that encodes a 333-amino-acid, G-protein-coupled recep- 1Institut de Biologia Evolutiva, CSIC-UPF, Dr. Aiguader 88, 08003 Barcelona, Spain tor. The TAS2R38 gene has three amino-acid changes 2A´ rea de Prehistoria, Departamento de Historia, Universidad de Oviedo, in high frequencies that determine only five main hap- Teniente Alfonso Martı´nez s/n, 33011 Oviedo, Spain lotypes. -
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. -
G Protein-Coupled Receptors
S.P.H. Alexander et al. The Concise Guide to PHARMACOLOGY 2015/16: G protein-coupled receptors. British Journal of Pharmacology (2015) 172, 5744–5869 THE CONCISE GUIDE TO PHARMACOLOGY 2015/16: G protein-coupled receptors Stephen PH Alexander1, Anthony P Davenport2, Eamonn Kelly3, Neil Marrion3, John A Peters4, Helen E Benson5, Elena Faccenda5, Adam J Pawson5, Joanna L Sharman5, Christopher Southan5, Jamie A Davies5 and CGTP Collaborators 1School of Biomedical Sciences, University of Nottingham Medical School, Nottingham, NG7 2UH, UK, 2Clinical Pharmacology Unit, University of Cambridge, Cambridge, CB2 0QQ, UK, 3School of Physiology and Pharmacology, University of Bristol, Bristol, BS8 1TD, UK, 4Neuroscience Division, Medical Education Institute, Ninewells Hospital and Medical School, University of Dundee, Dundee, DD1 9SY, UK, 5Centre for Integrative Physiology, University of Edinburgh, Edinburgh, EH8 9XD, UK Abstract The Concise Guide to PHARMACOLOGY 2015/16 provides concise overviews of the key properties of over 1750 human drug targets with their pharmacology, plus links to an open access knowledgebase of drug targets and their ligands (www.guidetopharmacology.org), which provides more detailed views of target and ligand properties. The full contents can be found at http://onlinelibrary.wiley.com/doi/ 10.1111/bph.13348/full. G protein-coupled receptors are one of the eight major pharmacological targets into which the Guide is divided, with the others being: ligand-gated ion channels, voltage-gated ion channels, other ion channels, nuclear hormone receptors, catalytic receptors, enzymes and transporters. These are presented with nomenclature guidance and summary information on the best available pharmacological tools, alongside key references and suggestions for further reading. -
G Protein‐Coupled Receptors
S.P.H. Alexander et al. The Concise Guide to PHARMACOLOGY 2019/20: G protein-coupled receptors. British Journal of Pharmacology (2019) 176, S21–S141 THE CONCISE GUIDE TO PHARMACOLOGY 2019/20: G protein-coupled receptors Stephen PH Alexander1 , Arthur Christopoulos2 , Anthony P Davenport3 , Eamonn Kelly4, Alistair Mathie5 , John A Peters6 , Emma L Veale5 ,JaneFArmstrong7 , Elena Faccenda7 ,SimonDHarding7 ,AdamJPawson7 , Joanna L Sharman7 , Christopher Southan7 , Jamie A Davies7 and CGTP Collaborators 1School of Life Sciences, University of Nottingham Medical School, Nottingham, NG7 2UH, UK 2Monash Institute of Pharmaceutical Sciences and Department of Pharmacology, Monash University, Parkville, Victoria 3052, Australia 3Clinical Pharmacology Unit, University of Cambridge, Cambridge, CB2 0QQ, UK 4School of Physiology, Pharmacology and Neuroscience, University of Bristol, Bristol, BS8 1TD, UK 5Medway School of Pharmacy, The Universities of Greenwich and Kent at Medway, Anson Building, Central Avenue, Chatham Maritime, Chatham, Kent, ME4 4TB, UK 6Neuroscience Division, Medical Education Institute, Ninewells Hospital and Medical School, University of Dundee, Dundee, DD1 9SY, UK 7Centre for Discovery Brain Sciences, University of Edinburgh, Edinburgh, EH8 9XD, UK Abstract The Concise Guide to PHARMACOLOGY 2019/20 is the fourth in this series of biennial publications. The Concise Guide provides concise overviews of the key properties of nearly 1800 human drug targets with an emphasis on selective pharmacology (where available), plus links to the open access knowledgebase source of drug targets and their ligands (www.guidetopharmacology.org), which provides more detailed views of target and ligand properties. Although the Concise Guide represents approximately 400 pages, the material presented is substantially reduced compared to information and links presented on the website. -
Treatment of Chronic Alcoholism: an Integrated Approach Hemangi Rajput* Integrative Health Care Practitioner, Essence Natural Health Clinic, Canada
Integrati & ve e M iv t e a d n i c r i e n t l e A Alternative & Integrative Medicine Rajput, Altern Integ Med 2014, 3:2 ISSN: 2327-5162 DOI: 10.4172/2327-5162.1000152 Review Article Open Access Treatment of Chronic Alcoholism: An Integrated Approach Hemangi Rajput* Integrative Health care Practitioner, Essence Natural Health Clinic, Canada Abstract Alternative medicine coupled with conventional and psychosocial therapies has been shown to be greatly effective in treating chronic alcoholism with positive treatment outcomes. Herbs like Kudzu, Tangerine Peel, Gentian and Bupleurum have been used efficaciously to treat chronic alcoholism and reduce liver toxicity. This article reviews the herbs Kudzu, Tangerine Peel, Gentian and Bupleurum with respect to their actions on the enzymes alcohol and acetaldehyde dehydrogenase. We further explore the genetic and pathophysiological basis of alcoholism while unraveling genetic polymorphisms in the genes involved in metabolic and effector action pathways that have an important bearing on why some individuals are addicted to alcohol, have severe withdrawal response and increased tendency to relapse. In this article we mainly discuss the role of alternative medicine, specifically in context with the above mentioned herbs for their role in inhibiting production of acetaldehyde dehydrogenase, suppressing craving, regulating blood glucose balance and reducing hepatotoxicity in chronic alcoholics. Keywords: Acetaldehyde dehydrogenase; Alternative medicine; Alternative treatment with herbs has shown to be effective in Bupleurum; Chronic alcoholism; Gentian; Integrated medicine; ameliorating the side-effects of withdrawal, restore optimal homeostasis Kudzu; Tangerine Peel and decrease psychological dependence in chronic alcoholics. Background Pathophysiology of Chronic Alcoholism Alcoholism has been described as early as 1700 BC in “The book To treat alcoholism, we need to understand how ethanol is of Anni” where Egyptians described excessive intoxication in humans. -
The Potential Druggability of Chemosensory G Protein-Coupled Receptors
International Journal of Molecular Sciences Review Beyond the Flavour: The Potential Druggability of Chemosensory G Protein-Coupled Receptors Antonella Di Pizio * , Maik Behrens and Dietmar Krautwurst Leibniz-Institute for Food Systems Biology at the Technical University of Munich, Freising, 85354, Germany; [email protected] (M.B.); [email protected] (D.K.) * Correspondence: [email protected]; Tel.: +49-8161-71-2904; Fax: +49-8161-71-2970 Received: 13 February 2019; Accepted: 12 March 2019; Published: 20 March 2019 Abstract: G protein-coupled receptors (GPCRs) belong to the largest class of drug targets. Approximately half of the members of the human GPCR superfamily are chemosensory receptors, including odorant receptors (ORs), trace amine-associated receptors (TAARs), bitter taste receptors (TAS2Rs), sweet and umami taste receptors (TAS1Rs). Interestingly, these chemosensory GPCRs (csGPCRs) are expressed in several tissues of the body where they are supposed to play a role in biological functions other than chemosensation. Despite their abundance and physiological/pathological relevance, the druggability of csGPCRs has been suggested but not fully characterized. Here, we aim to explore the potential of targeting csGPCRs to treat diseases by reviewing the current knowledge of csGPCRs expressed throughout the body and by analysing the chemical space and the drug-likeness of flavour molecules. Keywords: smell; taste; flavour molecules; drugs; chemosensory receptors; ecnomotopic expression 1. Introduction Thirty-five percent of approved drugs act by modulating G protein-coupled receptors (GPCRs) [1,2]. GPCRs, also named 7-transmembrane (7TM) receptors, based on their canonical structure, are the largest family of membrane receptors in the human genome. -
Melanocortin-4 Receptor: a Novel Signalling Pathway Involved in Body Weight Regulation
International Journal of Obesity (1999) 23, Suppl 1, 54±58 ß 1999 Stockton Press All rights reserved 0307±0565/99 $12.00 http://www.stockton-press.co.uk/ijo Melanocortin-4 receptor: A novel signalling pathway involved in body weight regulation SL Fisher1, KA Yagaloff1 and P Burn1* 1Department of Metabolic Diseases, Hoffmann LaRoche, Nutley, NJ 07110, USA For many years, genetically obese mouse strains have provided models for human obesity. The Avy=-agouti mouse, one of the oldest obese mouse models, is characterized by maturity-onset obesity and diabetes as a result of ectopic expression of the secreted protein hormone, agouti protein. Agouti protein is normally expressed in hair follicles to regulate pigmentation through antagonism of the melanocortin-1 receptor, but in-vitro studies have demonstrated that the hormone also has potent antagonist activity for the melanocortin-4 receptor (MC4-R). Subsequent develop- ment of the MC4-R knockout mouse model demonstrated that MC4-R plays a role in weight homeostasis as these mice recapitulated the metabolic defects of the agouti mouse. Further evidence for this hypothesis was obtained from pharmacological studies utilizing peptides with MC4-R agonist activity, that inhibitied food intake (when administered intracerebrally). Additional studies with peptide antagonists have now implicated the MC4-R in the leptin signalling pathway. Finally, evidence that the MC4-R may play a role in human obesity has been obtained from the identi®cation of a dis-functional variant of the receptor in genetically obese subjects. Keywords: obesity; diabetes; agouti; melanocortin; POMC; leptin; ob Introduction There has been an explosion in obesity research and with this has come an understanding of the molecular mechanisms that underly the disease.