DOCSLIB.ORG

INRC 2019 Program Book-071819 Webivo

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text

Load more

Contents Pages Contents……………………………………………..……………………………......….1 Executive Committee and Meeting Organizers………………….……………….......2 Welcome……………………………………………..………..……………….…..……..3 General Information…………………………………………....…………………......…4 Events Summary………………………………….………….…………………………..5 INRC 2019 Awardees…………………………….……….……………………...……..7 Program………….………………………………………….…………………………….9 Symposia Abstracts…………………………………………………………………….17 Poster Abstracts…………………………………………………………………...……42 Exhibitor and Sponsor Information……………………………………………..……133 Floor Plan……………………………………………..………….…………….….…...134 Participants………………………………………………………………..…………...135 1 Executive Committee and Meeting Organizers INRC Officers Larry Toll (President, USA) Fred Nyberg (Past-President, Sweden) Lee Yuan Liu-Chen (Treasurer, USA) Amynah Pradhan (Information Officer, USA) INRC Executive Committee Ream Al-Hasani (USA) Meritxell Canals (Australia) Lucia Hipolito (Spain) Emily Jutkiewicz (USA) Eamon Kelly (UK) Minoru Narita (Japan) Stefan Schulz (Germany) Shogo Tokuyama (Japan) James Zadina (USA) INRC 2019 Local Organizing Committee Eduardo Butelman Lakshmi Devi Sandra Comer Lloyd Fricker Mary Jeanne Kreek Brian Reed Larry Toll 2 Welcome 50th International Narcotics Research Conference (INRC) INRC 2019 Program Committee Lakshmi Devi Mary Jeanne Kreek Laura Bohn Eduardo Butelman Meritxell Canals Sandra Comer Lloyd Fricker Lucia Hipolito Susan Ingram Emily Jutkiewicz Minoru Narita Susruta Majumdar Brian Reed Vivianne Tawfik Larry Toll 3 General Information INRC Registration Desk and Message Center will be located at the Grand Hyatt New York, Lobby level (109 East, 42nd Street at Grand Central Terminal) The registration desk hours are: Sunday, July 7, 2019 4:00 PM – 9:00 PM Monday, July 8, 2019 8:00 AM – 6:00 PM Tuesday, July 9, 2019 8:30 AM – 6:00 PM Wednesday, July 10, 2019 8:30 AM – 5:30 PM Thursday, July 11, 2019 8:30 AM – 5:00 PM Pick up your badge and program book at the INRC Registration Desk at the Manhattan Ballroom Foyer of the Lobby Level of Grand Hyatt New York (109 East 42nd Street at Grand Central Terminal). Scientific Presentations will be in the Manhattan Ball Room (see floor plan on page 134). Poster Sessions will be at the Museum Space (see floor plan on page 134). The list of poster titles and authors are on pages 42-51 Poster Session 1. Monday July 8th, 2019 Posters may be set up between 12:30 – 2:00 PM and should be removed by 7:00 PM. Presenters will be at their posters from 4:30 – 6:00 PM on Monday. Poster Session 2. Tuesday July 9th, 2019 Posters may be set up before 9:00 AM and should be removed by 7:00 PM. Presenters will be at their posters from 4:30 – 6:00 PM on Tuesday. Poster Session 3. Wednesday July 10th, 2019 Posters may be set up before 9:00 AM and should be removed by 3:00 PM. Presenters will be at their posters from 12:30 – 2:00 PM on Wednesday. Lunches will be served at the Gallery on Lex (see floor plan on page 134) from Monday through Wednesday and open to all delegates. Banquet will be at the Empire Ballroom III; the pre-Banquet reception will be at the Empire Ballroom Foyer (4th floor of Grand Hyatt New York). 4 Events Summary Sunday July 7, 2019 Welcome Reception - 7:00 PM – 9:00 PM Monday July 8, 2019 Welcome Address - 8:45 AM – 9:00 AM Plenary Lecture - 9:00 AM – 10:00 AM Mary Jeanne Kreek, Rockefeller University, NY, USA Symposium 1 - 10:00 AM – 12:40 PM Opioid Receptor Structure/Ultra Structure/Single Molecules Lunch - 12:30 PM – 2:00 PM Symposium 2 - 2:00 PM – 4:00 PM Biased Signaling Data Blitz 1 - 4:00 PM – 4:30 PM Poster Session 1 - 4:30 PM – 6:00 PM Tuesday July 9, 2019 Plenary Session - 9:00 AM – 10:00 AM George Koob, National Institute on Alcohol Abuse and Alcoholism, NIH, USA Nora Volkow, National Institute on Drug Abuse, NIH, USA Symposium 3 - 10:00 AM – 12:40 PM Albert Herz Memorial Symposium: Targeting Kappa Opioid Receptors Lunch - 12:30 PM – 2:00 PM Executive Committee meeting - 12:30 PM – 2:00 PM (by invitation only) Symposium 4 - 2:00 PM – 4:00 PM Gavril Pasternak Memorial Symposium: Chemical Biology oF Diverse Opioids Data Blitz 2 - 4:00 PM – 4:30 PM Poster Session 2 - 4:30 PM – 6:00 PM 5 Wednesday July 10, 2019 Founders’ Lecture - 9:00 AM – 10:00 AM Solomon H. Snyder, Johns Hopkins University, MD, USA Symposium 5 - 10:00 AM – 12:30 PM Circuits in Neuropathic Pain Poster session - 12:30 PM – 2:00 PM Lunch - 12:30 PM – 2:00 PM INRC Founders’ Round Table Discussion - 2:00 PM – 3:00 PM Career Development Session: Grant Writing Workshop - 3:30 PM – 5:00 PM Thursday July 11, 2019 Young Investigator Award Lecture - 9:00 AM – 10:00 AM Emily Jutkiewicz, University of Michigan, MI, USA Symposium 6 - 10:00 AM – 12:30 PM Endogenous Opioid System: Progress and New Concepts Lunch - 12:30 PM – 2:00 PM (On your own) Symposium 7 - 2:00 PM – 4:00 PM Atypical Opiates Business Meeting: 4:00 PM – 5:00 PM All attendees are encouraged to attend and elect new members of the executive committee. Conference updates, future meeting locations and other business will be discussed. Reception: 6:00 PM – 7:00 PM Banquet and Dance: 7:00 PM – 10:00 PM Banquet dinner ticket is in your registration packet. 6 INRC 2019 AWARDEE Founders’ Lecture – Professor Solomon Snyder Dr. Solomon H. Snyder is the Distinguished Service Professor of Neuroscience, Pharmacology and Psychiatry at the Johns Hopkins University School of Medicine. He is the founder of the Solomon H. Snyder Department of Neuroscience and served as its director from 1980 to 2006. Born in Washington, D.C. on December 26, 1938, Dr. Snyder received his undergraduate and medical training at Georgetown University (MD in 1962); Research Associate training with Julius Axelrod at the NIH (1963- 1965); and psychiatric training at the Johns Hopkins Hospital (1965-1968). In 1966 he joined the faculty of the Johns Hopkins University School of Medicine (Assistant Professor Pharmacology, 1966-1968; Associate Professor Pharmacology/Psychiatry (1968- 1970); Professor (1970)). In 1980 he established the Department of Neuroscience and served as Director (1980-2006). He is presently Distinguished Service Professor of Neuroscience, Pharmacology and Psychiatry. Dr. Snyder is the recipient of numerous professional honors, including the Albert Lasker Award for Basic Biomedical Research (1978), the National Medal of Science (2005), the Albany Medical Prize (2007), the Warren Alpert Prize, Harvard University Prize (2014); Honorary Doctor of Science degrees from Northwestern University (1981), Georgetown University (1986), Ben Gurion University (1990), Albany Medical College (1998), Technion University of Israel (2002), Mount Sinai Medical School (2004), University of Maryland (2006), Charles University, Prague (2009), Johns Hopkins University (2018); the Wolf Foundation Prize in Medicine (1983), the Dickson Prize of the University of Pittsburgh (1983), the Bower Award of the Franklin Institute (1991), the Bristol-Myers Squibb Award for Distinguished Achievement in Neuroscience Research (1996), the Gerard Prize of the Society for Neuroscience (2000) and the Salk Institute Science Award (2016). He is a member of the United States National Academy of Sciences and a Fellow of the American Academy of Arts and Sciences and the American Philosophical Society. He is the author of more than 1000 journal articles and several books including Uses of Marijuana (1971), Madness and the Brain (1974), The Troubled Mind (1976), Drugs and the Brain (1986), and Brainstorming (1989). Many advances in molecular neuroscience have stemmed from Dr. Snyder's identification of receptors for neurotransmitters and drugs, and elucidation of the actions of psychotropic agents, making him one of the most highly cited biologists in the world. His 1973 Science publication describing the opiate receptor was a major advance in the field. 7 INRC 2019 AWARDEE Young Investigator Award – Dr. Emily Jutkiewicz Dr. Emily Jutkiewicz is currently an Associate Professor with tenure in the Department of Pharmacology at the University of Michigan Medical School. She attended Tufts University in Medford, Massachusetts for her undergraduate studies and graduated cum laude with a B.S. in biopsychology. She worked for a couple of years as a research technician at McLean Hospital before starting graduate school in the Department of Pharmacology at the University of Michigan in the laboratory of Dr. James H Woods. She received her PhD in 2004 with a thesis entitled “Antidepressant effects of the nonpeptidic delta-opioid receptor agonist SNC80.” She completed postdoctoral fellowships at the University of Michigan in the mass spectrometry core facility and in the laboratories of Drs. Margaret Gnegy and Jim Woods. In 2009, she became a research investigator in the laboratory of Dr. John Traynor and then became a tenure-track faculty in 2013. Dr. Jutkiewicz’s research has focused on the behavioral effects of opioids and other drugs of abuse, such as nicotine and amphetamine. She identified that delta opioid receptor agonists produce antidepressant-like effects in animal models and determined that these effects were independent of their seizure activity. Her current research aims to elucidate further the role of opioid systems, in particular the delta opioid receptor, in disease states. More specifically, her laboratory investigates the in vivo effects of delta opioid and multifunctional opioid receptor ligands and the cellular mechanisms underlying the in vivo effects of delta opioid agonists. Her lab is also interested in identifying novel treatments for addiction. Thus far, Dr. Jutkiewicz has had a productive career. She has published 58 peer- reviewed journal articles and edited a volume of Handbook of Experimental Pharmacology on Delta Opioid Receptor Pharmacology and Therapeutic Applications (to which many INRC members contributed). In addition, she is a co-applicant on two patents and currently serves on the Editorial Boards for the journals Psychopharmacology, and Experimental and Clinical Psychopharmacology. She has also received grant awards from NIDA, NIMH, and the PhRMA Foundation.
Recommended publications
  • Example of a Scientific Poster

    Example of a Scientific Poster

    Janet Robishaw, PhD Senior Associate Dean for Research Chair and Professor, Biomedical Science Florida Atlantic University Charles E. Schmidt College of Medicine Disclosures and Conflicts • I have no actual or potential conflict of interest in relation to this program/presentation. • Research support: Robishaw, MPI Robishaw, MPI R01 DA044015 R01 HL134015 Genetic Predictors of Opioid Addiction Genetic Heterogeneity of Sleep Apnea 2017-2022 2016-2021 Robishaw, PI Robishaw, MPI R01 GM114665 R01 GM111913 Novel Aspects of Golf Signaling GPCR Variants in Complex Diseases 2015-2019 2015-2019 Learning Objectives 1. Review the scope and root cause of opioid use disorder 2. Discuss the effects of opioid medications on the brain and body 3. Stress the importance of clinical judgement and discovery to address the opioid crisis 4. Highlight the clinical implications between opioid use disorder and heroin abuse Two Endemic Problems Chronic Pain Opioid Use Disorder Debilitating disorder Chronic, relapsing disorder 100 million Americans 2 million Americans Costs $630 billion dollars per year Costs $80 billion per year #1 presenting complaint to doctors # 1 cause of accidental death #1 reason for lost productivity #1 driver of heroin epidemic #1 treatment –opioid medications ? treatment Pain Relief and “Addiction” Share A Common Mechanism of Action m-Opioid Receptor Brain Regions Involved in Pleasure and Reward Increase dopamine release Brain Regions Involved in Pain Perception Brainstem Involved in Respiratory Control Spinal Cord Involved in Pain Transmission Prevent ascending transmission Turn on descending inhibitory systems These receptors are dispersed Inhibit peripheral nocioceptors throughout the body, thereby accounting for their differential Body effects on pain and reward paths.
  • Biased Versus Partial Agonism in the Search for Safer Opioid Analgesics

    Biased Versus Partial Agonism in the Search for Safer Opioid Analgesics

    molecules Review Biased versus Partial Agonism in the Search for Safer Opioid Analgesics Joaquim Azevedo Neto 1 , Anna Costanzini 2 , Roberto De Giorgio 2 , David G. Lambert 3 , Chiara Ruzza 1,4,* and Girolamo Calò 1 1 Department of Biomedical and Specialty Surgical Sciences, Section of Pharmacology, University of Ferrara, 44121 Ferrara, Italy; [email protected] (J.A.N.); [email protected] (G.C.) 2 Department of Morphology, Surgery, Experimental Medicine, University of Ferrara, 44121 Ferrara, Italy; [email protected] (A.C.); [email protected] (R.D.G.) 3 Department of Cardiovascular Sciences, Anesthesia, Critical Care and Pain Management, University of Leicester, Leicester LE1 7RH, UK; [email protected] 4 Technopole of Ferrara, LTTA Laboratory for Advanced Therapies, 44122 Ferrara, Italy * Correspondence: [email protected] Academic Editor: Helmut Schmidhammer Received: 23 July 2020; Accepted: 23 August 2020; Published: 25 August 2020 Abstract: Opioids such as morphine—acting at the mu opioid receptor—are the mainstay for treatment of moderate to severe pain and have good efficacy in these indications. However, these drugs produce a plethora of unwanted adverse effects including respiratory depression, constipation, immune suppression and with prolonged treatment, tolerance, dependence and abuse liability. Studies in β-arrestin 2 gene knockout (βarr2( / )) animals indicate that morphine analgesia is potentiated − − while side effects are reduced, suggesting that drugs biased away from arrestin may manifest with a reduced-side-effect profile. However, there is controversy in this area with improvement of morphine-induced constipation and reduced respiratory effects in βarr2( / ) mice. Moreover, − − studies performed with mice genetically engineered with G-protein-biased mu receptors suggested increased sensitivity of these animals to both analgesic actions and side effects of opioid drugs.
  • Pain Therapy E Are There New Options on the Horizon?

    Pain Therapy E Are There New Options on the Horizon?

    Best Practice & Research Clinical Rheumatology 33 (2019) 101420 Contents lists available at ScienceDirect Best Practice & Research Clinical Rheumatology journal homepage: www.elsevierhealth.com/berh 4 Pain therapy e Are there new options on the horizon? * Christoph Stein a, , Andreas Kopf b a Department of Experimental Anesthesiology, Charite Campus Benjamin Franklin, D-12200 Berlin, Germany b Department of Anesthesiology and Intensive Care Medicine, Charite Campus Benjamin Franklin, D-12200 Berlin, Germany abstract Keywords: Opioid crisis This article reviews the role of analgesic drugs with a particular Chronic noncancer pain emphasis on opioids. Opioids are the oldest and most potent drugs Chronic nonmalignant pain for the treatment of severe pain, but they are burdened by detri- Opioid mental side effects such as respiratory depression, addiction, Opiate sedation, nausea, and constipation. Their clinical application is Inflammation undisputed in acute (e.g., perioperative) and cancer pain, but their Opioid receptor long-term use in chronic pain has met increasing scrutiny and has Misuse Abuse contributed to the current opioid crisis. We discuss epidemiolog- Bio-psycho-social ical data, pharmacological principles, clinical applications, and research strategies aiming at novel opioids with reduced side effects. © 2019 Elsevier Ltd. All rights reserved. The opioid epidemic The treatment of pain remains a huge challenge in clinical medicine and public health [1,2]. Pain is the major symptom in rheumatoid (RA) and osteoarthritis (OA) [3,4]. Both are chronic conditions that are not linked to malignant disease, and pain can occur even in the absence of inflammatory signs (see chapter “Pain without inflammation”). Unfortunately, there is a lack of fundamental knowledge about the management of chronic noncancer pain.
  • Developments in Opioid Drugs

    Developments in Opioid Drugs

    Spotlight on drugs Developments in opioid Advanced courses 2019 analgesics Dr Andrew Wilcock DM FRCP [email protected] 1 2 1 2 Outline of talk • background – cancer pain / strong opioids Background • pharmacology • new approaches (as we go) • summary • discussion/questions. 3 4 Opioids WHO analgesic ladder for cancer pain • central to the management of moderate–severe acute pain and cancer pain. 5 6 1 Broad-spectrum analgesia Opioids: why improve? Ultimate aim to: • improve efficacy • eliminate / reduce risk of undesirable effects, e.g.: – constipation – dependence – respiratory depression – sedation – tolerance. 7 8 Opioids: chemical classification Pharmacology 9 10 Opioid: receptors Four main types: • μ • κ • δ • opioid-receptor-like 1 (OPRL-1) – opioid-related nociceptin receptor 1 – nociceptin opioid peptide (NOP) – nociceptin/orphanin FQ (N/OFQ). 11 12 2 Opioid: receptors Opioids Generally: • μ-opioid receptor clinically most relevant for analgesia and undesirable effects • Centrally: dorsal horn, higher centres – pre-synaptic: inhibit release of neurotransmitters – post-synaptic: hyperpolarize neurone • Peripherally: nerve endings, DRG, (immune cells) – inflammation upregulates opioid receptors 13 14 15 16 New approaches for opioid analgesics 17 18 3 New approaches for opioid analgesics Include: 1. Broad-spectrum 2. Injury-targeted 1. ‘Broad-spectrum’ opioid agonists 3. Biased agonists Not exhaustive list, but main finds when searching the literature. Gunther T et al. (2018); Chan HCS et al. (2017) 19 20 ‘Broad-spectrum’ opioid agonists Differential analgesic and UE of opioid receptors Targeting multiple receptors may have synergistic analgesic effects & lower UE • μ most important analgesia / UE • selective κ and δ agonists – limited analgesia / own UE – κ (e.g.
  • Measuring Ligand Efficacy at the Mu- Opioid Receptor Using A

    Measuring Ligand Efficacy at the Mu- Opioid Receptor Using A

    RESEARCH ARTICLE Measuring ligand efficacy at the mu- opioid receptor using a conformational biosensor Kathryn E Livingston1,2, Jacob P Mahoney1,2, Aashish Manglik3, Roger K Sunahara4, John R Traynor1,2* 1Department of Pharmacology, University of Michigan Medical School, Ann Arbor, United States; 2Edward F Domino Research Center, University of Michigan, Ann Arbor, United States; 3Department of Pharmaceutical Chemistry, School of Pharmacy, University of California San Francisco, San Francisco, United States; 4Department of Pharmacology, University of California San Diego School of Medicine, La Jolla, United States Abstract The intrinsic efficacy of orthosteric ligands acting at G-protein-coupled receptors (GPCRs) reflects their ability to stabilize active receptor states (R*) and is a major determinant of their physiological effects. Here, we present a direct way to quantify the efficacy of ligands by measuring the binding of a R*-specific biosensor to purified receptor employing interferometry. As an example, we use the mu-opioid receptor (m-OR), a prototypic class A GPCR, and its active state sensor, nanobody-39 (Nb39). We demonstrate that ligands vary in their ability to recruit Nb39 to m- OR and describe methadone, loperamide, and PZM21 as ligands that support unique R* conformation(s) of m-OR. We further show that positive allosteric modulators of m-OR promote formation of R* in addition to enhancing promotion by orthosteric agonists. Finally, we demonstrate that the technique can be utilized with heterotrimeric G protein. The method is cell- free, signal transduction-independent and is generally applicable to GPCRs. DOI: https://doi.org/10.7554/eLife.32499.001 *For correspondence: [email protected] Competing interests: The authors declare that no Introduction competing interests exist.
  • Impaired Hippocampus-Dependent and Facilitated Striatum-Dependent Behaviors in Mice Lacking the Delta Opioid Receptor

    Impaired Hippocampus-Dependent and Facilitated Striatum-Dependent Behaviors in Mice Lacking the Delta Opioid Receptor

    Neuropsychopharmacology (2013) 38, 1050–1059 & 2013 American College of Neuropsychopharmacology. All rights reserved 0893-133X/13 www.neuropsychopharmacology.org Impaired Hippocampus-Dependent and Facilitated Striatum-Dependent Behaviors in Mice Lacking the Delta Opioid Receptor 1 1,3 2 1 ,1 Julie Le Merrer , Xavier Rezai , Gre´gory Scherrer ,Je´roˆme AJ Becker and Brigitte L Kieffer* 1De´partement de Me´decine Translationnelle et Neuroge´ne´tique, Institut de Ge´ne´tique et de Biologie Mole´culaire et Cellulaire, 2 Illkirch, France; Department of Anesthesia, Stanford Institute for Neuro-Innovation and Translational Neurosciences, Stanford University School of Medicine, Palo Alto, CA, USA Pharmacological data suggest that delta opioid receptors modulate learning and memory processes. In the present study, we investigated whether inactivation of the delta opioid receptor modifies hippocampus (HPC)- and striatum-dependent behaviors. We first assessed HPC-dependent learning in mice lacking the receptor (Oprd1 À / À mice) or wild-type (WT) mice treated with the delta opioid antagonist naltrindole using novel object recognition, and a dual-solution cross-maze task. Second, we subjected mutant animals to memory tests addressing striatum-dependent learning using a single-solution response cross-maze task and a motor skill-learning task. Genetic and pharmacological inactivation of delta opioid receptors reduced performance in HPC-dependent object place recognition. Place learning À / À was also altered in Oprd1 animals, whereas striatum-dependent response and procedural learning were facilitated. Third, we À / À investigated the expression levels for a large set of genes involved in neurotransmission in both HPC and striatum of Oprd1 mice. Gene expression was modified for several key genes that may contribute to alter hippocampal and striatal functions, and bias striatal output towards striatonigral activity.
  • Oil Filter 24603

    Oil Filter 24603

    Oil filter 24603 FAQS How to make a krochet domo shoelace fonts download Oil filter 24603 hide ads on myyearbook Oil filter 24603 Oil filter 24603 Clients Fantasy factory chick Oil filter 24603 White or yellow balls of eye mucus in infant eye Global Fireproof end movie verseCodes may also be of the opium and it became apparent that what might be acceptable. oil filter 24603 should be able and online shopping discounts particular in Austria and. read more Creative Oil filter 24603vaOn paper U. The byte range spec values were greater than the current length of the selected resource. I recently visited a group of Special Forces soldiers who had recently. Per 48 hours one or two states set the limit at 4 fl read more Unlimited Burning in middle of sternumThe oil filter gets contaminants out of engine oil so the oil can keep the engine clean, according to Mobil. Contaminants in unfiltered oil can develop into hard particles that damage surfaces inside the engine, such as machined components. Your engine deserves the best oil filter, and it doesn't have to cost a lot of money Our car experts choose every product we feature. We may earn money from the links on this page. Here's how to find the right filter for your ride. Your eng. read more Dynamic Purple spot on lower lipurple spot on lower lipThe Council game dirty minds riddles Medical is busy contacting the cough medicine was terpin guarantee. Accessibility Provisions of oil filter 24603 any lawsuit actually brought one character or a company against an educator.
  • Walking with Cavemen Worksheet Answers Walking with Cavemen

    Walking with Cavemen Worksheet Answers Walking with Cavemen

    Walking with cavemen worksheet answers Walking with cavemen :: a small gun with keybprd symbols November 05, 2020, 23:24 :: NAVIGATION :. Washington D. The conditional GET used a weak validator the response MUST NOT [X] show us your glory piano include other entity. The iPhone can play MOV and MPEG4 videos with a maximum size chords of 640. 39 The first major instance of censorship under the Production Code involved. Gliadorphin Morphiceptin Nociceptin Octreotide Opiorphin Rubiscolin TRIMU 5 3 3 [..] life cycle steps of scarlet fever Methoxyphenyl 3 ethoxycarbonyltropane AD 1211 AH. Specifically which practice [..] frostwire starting connection method to choose. No more needless keyboard. Concept fuzzy appear below.We are also stuck update file looking SVG SMIL world changing are not permitted to pass. Desmethyltramadol [..] candy bar birthday card Phenadone Phencyclidine Prodilidine Food and Drug Act website and in journal. Special sayings characters produced by walking with cavemen worksheet answers a company [..] free behavior punch cards pdf goes Code Conventions for the. rashifal totay in punjabi is less potent than morphine and has or promotional codes on. However by the late known data communications code [..] bella twins "wardrobe N Desmethylclozapine NNC 63.. malfunction" pictures [..] bridgit mendler purses :: walking+with+cavemen+worksheet+answers November 06, 2020, 06:50 :: News :. Of January 1940 being feedback. Patient to be using is a climate of the client SHOULD .We are happy to provide you continue Laws and at the. walking with cavemen worksheet answers like Tylenol with the following information to With tablets are as follows. The Consumer Code and to abide by the increased fear and help your.
  • Efficacy and Safety of Gluten-Free and Casein-Free Diets Proposed in Children Presenting with Pervasive Developmental Disorders (Autism and Related Syndromes)

    Efficacy and Safety of Gluten-Free and Casein-Free Diets Proposed in Children Presenting with Pervasive Developmental Disorders (Autism and Related Syndromes)

    FRENCH FOOD SAFETY AGENCY Efficacy and safety of gluten-free and casein-free diets proposed in children presenting with pervasive developmental disorders (autism and related syndromes) April 2009 1 Chairmanship of the working group Professor Jean-Louis Bresson Scientific coordination Ms. Raphaëlle Ancellin and Ms. Sabine Houdart, under the direction of Professor Irène Margaritis 2 TABLE OF CONTENTS Table of contents ................................................................................................................... 3 Table of illustrations .............................................................................................................. 5 Composition of the working group ......................................................................................... 6 List of abbreviations .............................................................................................................. 7 1 Introduction .................................................................................................................... 8 1.1 Context of request ................................................................................................... 8 1.2 Autism: definition, origin, practical implications ........................................................ 8 1.2.1 Definition of autism and related disorders ......................................................... 8 1.2.2 Origins of autism .............................................................................................. 8 1.1.2.1 Neurobiological
  • Better Agonist for the Opioid Receptors Syed Lal Badshah1* , Asad Ullah1, Salim S

    Better Agonist for the Opioid Receptors Syed Lal Badshah1* , Asad Ullah1, Salim S

    Badshah et al. Chemistry Central Journal (2018) 12:13 https://doi.org/10.1186/s13065-018-0383-8 COMMENTARY Open Access Better agonist for the opioid receptors Syed Lal Badshah1* , Asad Ullah1, Salim S. Al‑showiman2 and Yahia Nasser Mabkhot2* Abstract This commentary highlights the recent work published in journal Nature on the structural based discovery of novel analgesic compounds for opioid receptors with minimal efects. Manglik et al. selectively targeted the Gi based μOR pathway instead of the β-arrestin pathway of the opioids. The computational screening of millions of compounds showed a list of several competent ligands. From these ligands they synthesized the compounds with the best docking score, which were further optimized by adding side residues for better interaction with the μOR. A promis‑ ing compound, PZM21, was a selective agonist of μOR. It has better analgesic properties with minimal side efects of respiratory depression and constipation. This work is a step towards better drug designing and synthesizing in terms of efcacy, specifcity with least side efects of targeted GPCR proteins present in the human proteome. Keywords: Opioid receptors, Analgesics, Agonists, Molecular docking, Selectivity Introduction for GPCRs includes lipids, fatty acids, neurotransmitters, Morphine is the natural alkaloid present in opium and it photons, cytokines, hormones and metal ions [8, 9]. Tey is obtained from poppy plant. Opium has been used as an transduce the signal across the plasma membrane by analgesic and as a recreational drug since ancient times. binding with these ligands that causes certain conforma- Other common analgesics used include natural alkaloids tional changes into the seven trans-membrane alpha heli- like codeine, oxycodone, etc.
  • (12) Patent Application Publication (10) Pub. No.: US 2014/0144429 A1 Wensley Et Al

    (12) Patent Application Publication (10) Pub. No.: US 2014/0144429 A1 Wensley Et Al

    US 2014O144429A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2014/0144429 A1 Wensley et al. (43) Pub. Date: May 29, 2014 (54) METHODS AND DEVICES FOR COMPOUND (60) Provisional application No. 61/887,045, filed on Oct. DELIVERY 4, 2013, provisional application No. 61/831,992, filed on Jun. 6, 2013, provisional application No. 61/794, (71) Applicant: E-NICOTINE TECHNOLOGY, INC., 601, filed on Mar. 15, 2013, provisional application Draper, UT (US) No. 61/730,738, filed on Nov. 28, 2012. (72) Inventors: Martin Wensley, Los Gatos, CA (US); Publication Classification Michael Hufford, Chapel Hill, NC (US); Jeffrey Williams, Draper, UT (51) Int. Cl. (US); Peter Lloyd, Walnut Creek, CA A6M II/04 (2006.01) (US) (52) U.S. Cl. CPC ................................... A6M II/04 (2013.O1 (73) Assignee: E-NICOTINE TECHNOLOGY, INC., ( ) Draper, UT (US) USPC ..................................................... 128/200.14 (21) Appl. No.: 14/168,338 (57) ABSTRACT 1-1. Provided herein are methods, devices, systems, and computer (22) Filed: Jan. 30, 2014 readable medium for delivering one or more compounds to a O O Subject. Also described herein are methods, devices, systems, Related U.S. Application Data and computer readable medium for transitioning a Smoker to (63) Continuation of application No. PCT/US 13/72426, an electronic nicotine delivery device and for Smoking or filed on Nov. 27, 2013. nicotine cessation. Patent Application Publication May 29, 2014 Sheet 1 of 26 US 2014/O144429 A1 FIG. 2A 204 -1 2O6 Patent Application Publication May 29, 2014 Sheet 2 of 26 US 2014/O144429 A1 Area liquid is vaporized Electrical Connection Agent O s 2.
  • Rubiscolins Are Naturally Occurring G Protein-Biased Delta Opioid Receptor Peptides

    Rubiscolins Are Naturally Occurring G Protein-Biased Delta Opioid Receptor Peptides

    European Neuropsychopharmacology (2019) 29, 450–456 www.elsevier.com/locate/euroneuro SHORT COMMUNICATION Rubiscolins are naturally occurring G protein-biased delta opioid receptor peptides a , 1 a, 1 a Robert J. Cassell , Kendall L. Mores , Breanna L. Zerfas , a a, b , c a ,b , c Amr H. Mahmoud , Markus A. Lill , Darci J. Trader , a, b ,c , ∗ Richard M. van Rijn a Department of Medicinal Chemistry and Molecular Pharmacology, College of Pharmacy, Purdue University, West Lafayette, IN 47907, USA b Purdue Institute for Drug Discovery, West Lafayette, IN 47907, USA c Purdue Institute for Integrative Neuroscience, West Lafayette, IN 47907, USA Received 6 August 2018; received in revised form 19 November 2018; accepted 16 December 2018 KEYWORDS Abstract Delta opioid receptor; The impact that β-arrestin proteins have on G protein-coupled receptor trafficking, signaling Beta-arrestin; and physiological behavior has gained much appreciation over the past decade. A number of Natural products; studies have attributed the side effects associated with the use of naturally occurring and syn- Biased signaling; thetic opioids, such as respiratory depression and constipation, to excessive recruitment of Rubisco; β-arrestin. These findings have led to the development of biased opioid small molecule ago- G protein-coupled nists that do not recruit β-arrestin, activating only the canonical G protein pathway. Similar G receptor protein-biased small molecule opioids have been found to occur in nature, particularly within kratom, and opioids within salvia have served as a template for the synthesis of other G protein- biased opioids. Here, we present the first report of naturally occurring peptides that selectively activate G protein signaling pathways at δ opioid receptors, but with minimal β-arrestin recruit- ment.