DOCSLIB.ORG

An Atomic Scale Measurement from the Voltage Sensor in Herg Channels Using Lanthanide-Based Resonance Energy Transfer

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
An Atomic Scale Measurement from the Voltage Sensor in Herg Channels Using Lanthanide-Based Resonance Energy Transfer An Atomic Scale Measurement from the Voltage Sensor in hERG Channels Using Lanthanide-Based Resonance Energy Transfer by Danielle Jeong B.Sc., Simon Fraser University, 2014 Thesis Submitted in Partial Fulfillment of the Requirements for the Degree of Master of Science in the Department of Biomedical Physiology and Kinesiology Faculty of Science Danielle Jeong 2016 SIMON FRASER UNIVERSITY Summer 2016 Approval Name: Danielle Jeong Degree: Master of Science Title: An Atomic Scale Measurement from the Voltage Sensor in hERG Channels Using Lanthanide-Based Resonance Energy Transfer Examining Committee: Chair: Dr. William Cupples Professor Dr. Thomas Claydon Senior Supervisor Associate Professor Dr. Peter Ruben Supervisor Professor Dr. Glen Tibbits Supervisor Professor Dr. Jenifer Thewalt External Examiner Professor Department of Physics Date Defended/Approved: June 16, 2016 ii Ethics Statement iii Abstract The cardiac human ether-a-go-go related gene (hERG) channel is a voltage- gated potassium (Kv) channel that plays a fundamental role in cardiac repolarization. The importance of the hERG channel derives from its unusually slow activation (opening) and deactivation (closing) processes. Like other Kv channels, structural reconfigurations of the hERG voltage sensor upon membrane depolarization and repolarization underlie channel activation and deactivation, respectively. However, specific rearrangements of the voltage sensor that may dictate the unique slow activation and deactivation in hERG channels remain unclear. Lanthanide-based resonance transfer (LRET) is a spectroscopic technique that has previously demonstrated an ability to provide quantitative description of voltage sensor dynamics in an archetypal Kv channel. In this report, we outline a rationalized approach to applying LRET to examine hERG channel voltage sensor dynamics that may be of physiological significance. As a result, we report the first distance measurement from voltage sensors across the hERG channel pore. Keywords: hERG channels; lanthanide-based resonance energy transfer; voltage- gated potassium channels; voltage sensor iv Acknowledgements This project would not have been possible without the selfless assistance of many individuals. As such, I would like to first show my appreciation for those who have notably contributed to its progress. With respect to the donor chelate synthesis, Dr. Rikard Blunck from University of Montreal and Dr. Mattieu Starck, a post-doctorate fellow in Dr. Blunck’s lab, are to be recognized for their generosity in sharing the recipe they have developed. For graciously accommodating me to use their lab space and equipment for synthesizing the chelate, I would like to thank Dr. David Vocadlo from SFU Chemistry department and the members of his lab. Deep gratitude is specifically directed toward Hong Yee Tan, a PhD candidate from Dr. Vocadlo’s lab, and Hongwen Chen, a mass spectrometry specialist at SFU, for all the advice and patience they have provided throughout the synthesis troubleshooting phase. When it comes to addressing technical aspects of the LRET setup, the talent of Pawel Kowalski, an electronic technologist at SFU, is to be admired and appreciated. He has demonstrated utmost ingenuity through various tasks, which includes installing the interlock system, designing and building the delay generator, re-engineering the PMT gating mechanism, and extending the lifespan of the laser used in this project. On matters concerning the optics, I was also fortunate to have an inexhaustible access to the expertise of Dr. Eric Lin, a post-doctorate fellow in Dr. Glen Tibbits’ lab. I cannot be more thankful for his involvement in the alignment of LRET system apparatuses, as well as continued guidance in the maintenance of optical components. As well, I gratefully acknowledge the work of the former post-doctorate fellow in Dr. Tom Claydon’s lab, Dr. Stanislav Sokolov, in initiating the LRET project and establishing a foundation for me. It is upon his shoulders I stand. There are others who have offered more than a helping hand. Alison Li, a PhD candidate in Dr. Tibbits’ lab, is such an example. She not only has proactively arranged multiple sessions for me to use the MBB department spectrofluorometer and taught me how to operate the equipment, but has done so with persistent enthusiasm. The v kindness of Shyam Panchapakesan, a PhD candidate in Dr. Unrau’s lab, should also be noted in making the lab’s Nanodrop 2000 available for me to obtain the absorbance spectra recordings. Furthermore, I owe a heartfelt word of thanks to Ji Qi, a lab technician in Dr. Tom Claydon’s lab, for all her work in molecular biology. Her indefatigable ability to meet the demands to make all the constructs and cRNA used in this project is worthy of the highest praise. Every step forward taken through this project could not have been achieved without the gifts of trust and encouragement from my supervisor, Dr. Tom Claydon. I cannot thank him enough for instilling within me a love and passion for scientific research when I was an undergraduate student, and for making my decision to pursue graduate studies to be un-regrettable. To have Dr. Claydon as a role model in science and leadership has been the greatest source of inspiration for me to become a better science student and person. I know that he will continue to have such an effect on me in the years ahead. On the same note, I would like to show my whole-hearted appreciation for the members of my supervisory committee, Dr. Peter Ruben and Dr. Glen Tibbits, for their fatherly support since my undergraduate years. It is unbelievable how privileged I have been to receive their wise advice (though I seldom took them), and to have mentors who would accept me just as I am- neurotic and obstinate. I am also overwhelmed with gratefulness when I think of members of the Molecular Cardiac Physiology Group. From those who have religiously checked on my happiness quotient to those who have always lent an ear, I could not have asked for better lab mates. Most importantly, a special recognition should be given to my family for the relentless support they have provided behind the scene. I would like to specifically thank my dad for passing on his notorious stubbornness, for the same stubbornness in me was crucial in dealing with roadblocks encountered during the research process. I am also indebted to my mom for praying for me throughout the entire journey. The pillars of prayers that she had built were what had kept me standing strong. I will never be able to adequately express how grateful I am for my sister, Janelle, for injecting bursts of silliness back into my life whenever I was caught up in my work. Lastly, I would like to express my respect for my brother, Samuel, whose considerate nature often reminded me to look around and realize the people I have been blessed with during the duration of this project. vi Table of Contents Approval .......................................................................................................................... ii Ethics Statement ............................................................................................................ iii Abstract .......................................................................................................................... iv Acknowledgements ......................................................................................................... v Table of Contents .......................................................................................................... vii List of Tables ................................................................................................................... x List of Figures................................................................................................................. xi List of Acronyms and Symbols ...................................................................................... xii Chapter 1. Introduction ............................................................................................... 1 1.1. Voltage sensing in voltage-gated ion channels ....................................................... 1 1.1.1. Structural components of voltage-gated ion channels associated with voltage sensing .................................................................................. 2 1.1.2. The principle behind the voltage sensor .................................................... 3 1.1.3. Models of voltage sensor movement ......................................................... 5 1.2. Techniques used to reveal voltage sensor movement ............................................ 6 1.2.1. Description of voltage sensor dynamics from electrophysiological approaches ................................................................................................ 8 1.2.2. Structural insight on the voltage sensor ..................................................... 9 1.2.3. Fluorescence spectroscopy reveals conformational changes of the voltage sensor ......................................................................................... 10 1.3. Lanthanide-based resonance energy transfer (LRET) .......................................... 12 1.3.1. Principle of LRET ..................................................................................... 12 1.3.2. Advantages of LRET ............................................................................... 14 1.3.3. Properties of the lanthanide and donor complex .....................................
Load more

Recommended publications
  • Development of a Quantitative PCR Assay for the Detection And
    bioRxiv preprint doi: https://doi.org/10.1101/544247; this version posted February 8, 2019. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC-ND 4.0 International license. Development of a quantitative PCR assay for the detection and enumeration of a potentially ciguatoxin-producing dinoflagellate, Gambierdiscus lapillus (Gonyaulacales, Dinophyceae). Key words:Ciguatera fish poisoning, Gambierdiscus lapillus, Quantitative PCR assay, Great Barrier Reef Kretzschmar, A.L.1,2, Verma, A.1, Kohli, G.S.1,3, Murray, S.A.1 1Climate Change Cluster (C3), University of Technology Sydney, Ultimo, 2007 NSW, Australia 2ithree institute (i3), University of Technology Sydney, Ultimo, 2007 NSW, Australia, [email protected] 3Alfred Wegener-Institut Helmholtz-Zentrum fr Polar- und Meeresforschung, Am Handelshafen 12, 27570, Bremerhaven, Germany Abstract Ciguatera fish poisoning is an illness contracted through the ingestion of seafood containing ciguatoxins. It is prevalent in tropical regions worldwide, including in Australia. Ciguatoxins are produced by some species of Gambierdiscus. Therefore, screening of Gambierdiscus species identification through quantitative PCR (qPCR), along with the determination of species toxicity, can be useful in monitoring potential ciguatera risk in these regions. In Australia, the identity, distribution and abundance of ciguatoxin producing Gambierdiscus spp. is largely unknown. In this study we developed a rapid qPCR assay to quantify the presence and abundance of Gambierdiscus lapillus, a likely ciguatoxic species. We assessed the specificity and efficiency of the qPCR assay. The assay was tested on 25 environmental samples from the Heron Island reef in the southern Great Barrier Reef, a ciguatera endemic region, in triplicate to determine the presence and patchiness of these species across samples from Chnoospora sp., Padina sp.
    [Show full text]
  • Treatment Protocol Copyright © 2018 Kostoff Et Al
    Prevention and reversal of Alzheimer's disease: treatment protocol Copyright © 2018 Kostoff et al PREVENTION AND REVERSAL OF ALZHEIMER'S DISEASE: TREATMENT PROTOCOL by Ronald N. Kostoffa, Alan L. Porterb, Henry. A. Buchtelc (a) Research Affiliate, School of Public Policy, Georgia Institute of Technology, USA (b) Professor Emeritus, School of Public Policy, Georgia Institute of Technology, USA (c) Associate Professor, Department of Psychiatry, University of Michigan, USA KEYWORDS Alzheimer's Disease; Dementia; Text Mining; Literature-Based Discovery; Information Technology; Treatments Prevention and reversal of Alzheimer's disease: treatment protocol Copyright © 2018 Kostoff et al CITATION TO MONOGRAPH Kostoff RN, Porter AL, Buchtel HA. Prevention and reversal of Alzheimer's disease: treatment protocol. Georgia Institute of Technology. 2018. PDF. https://smartech.gatech.edu/handle/1853/59311 COPYRIGHT AND CREATIVE COMMONS LICENSE COPYRIGHT Copyright © 2018 by Ronald N. Kostoff, Alan L. Porter, Henry A. Buchtel Printed in the United States of America; First Printing, 2018 CREATIVE COMMONS LICENSE This work can be copied and redistributed in any medium or format provided that credit is given to the original author. For more details on the CC BY license, see: http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License<http://creativecommons.org/licenses/by/4.0/>. DISCLAIMERS The views in this monograph are solely those of the authors, and do not represent the views of the Georgia Institute of Technology or the University of Michigan. This monograph is not intended as a substitute for the medical advice of physicians. The reader should regularly consult a physician in matters relating to his/her health and particularly with respect to any symptoms that may require diagnosis or medical attention.
    [Show full text]
  • 1 Gambierol 1 2 3 4 Makoto Sasaki, Eva Cagide, and 5 M
    34570 FM i-xviii.qxd 2/9/07 9:16 AM Page i PHYCOTOXINS Chemistry and Biochemistry 34570 FM i-xviii.qxd 2/9/07 9:16 AM Page iii PHYCOTOXINS Chemistry and Biochemistry Luis M. Botana Editor 34570 FM i-xviii.qxd 2/9/07 9:16 AM Page iv 1 2 3 Dr. Luis M. Botana is professor of Pharmacology, University of Santiago de Compostela, Spain. His group is a 4 world leader in the development of new methods to monitor the presence of phycotoxins, having developed 5 methods to date for saxitoxins, yessotoxin, pectenotoxin, ciguatoxins, brevetoxins, okadaic acid and dinophy- 6 sistoxins. Dr. Botana is the editor of Seafood and Freshwater Toxins: Pharmacology, Physiology and Detection, 7 to date the only comprehensive reference book entirely devoted to marine toxins. 8 ©2007 Blackwell Publishing 9 All rights reserved 10 1 Blackwell Publishing Professional 2 2121 State Avenue, Ames, Iowa 50014, USA 3 4 Orders: 1-800-862-6657 5 Office: 1-515-292-0140 6 Fax: 1-515-292-3348 7 Web site: www.blackwellprofessional.com 8 Blackwell Publishing Ltd 9 9600 Garsington Road, Oxford OX4 2DQ, UK 20 Tel.: +44 (0)1865 776868 1 2 Blackwell Publishing Asia 3 550 Swanston Street, Carlton, Victoria 3053, Australia 4 Tel.: +61 (0)3 8359 1011 5 6 Authorization to photocopy items for internal or personal use, or the internal or personal use of specific clients, 7 is granted by Blackwell Publishing, provided that the base fee is paid directly to the Copyright Clearance Cen- 8 ter, 222 Rosewood Drive, Danvers, MA 01923.
    [Show full text]
  • A A–803467, 98 Absorption, Distribution, Metabolism, Elimination
    Index A Anxiety disorders, 55 A–803467, 98 APD. See Action potential duration Absorption, distribution, metabolism, Arrhythmias, 45, 46 elimination and toxicity Aryl sulfonamido indanes, 126–128, 130 (ADMET), 193 ATP-sensitive potassium channels (KATP Absorption, distribution, metabolism, channels), 61 excretion, and toxicity Atrial effective refractory period (AERP), 122, (ADMET), 68 124–126, 128, 129, 132, 138 Acetylcholine binding protein (AChBP), Autoimmune diseases, 254 61, 62, 64 AZD7009, 101 Acetylcholine receptor (AChR), 57, 64 Azimilide, 139 Action potential duration (APD), 120, 122, 123, 128, 132 B Action potentials, 243, 256, 259 Basis set, 69–70 ADME/T, 299, 304 b-Barrel membrane proteins AERP. See Atrial effective refractory period genome-wide annotation, 13 Agitoxin (AgTX), 60 machine-learning techniques Agonists, 59–61, 64 residue pair preference, 11 Alinidine, 40–42 TMBs, 10 ALS. See Amyotrophic lateral sclerosis pipeline, genomic sequences, 14 Alzheimer, 55, 61 statistical method, 9–10 AMBER, 61, 65 Bending hinge, 64 2-Amino–2-imidazolidinone, 123, 125 Benzanilide, 256–257 Ammi visnaga, 254 Benzimidazolone, 256–257 b-Amyloid peptide (Ab), 62–63, 65 Benzocaine, 140 Amyotrophic lateral sclerosis (ALS), 90, 94, Benzodiazepines, 245 101 Benzopyrane, 127–128 Anionic channel blockers Benzopyrans, 61, 246–251, 261 mechanism of action of, 329–330 Benzothiadiazine 1,1-dioxide, 252–254 Antagonists, 59, 60 Benzothiadiazines, 253 Antiarrhythmic, 65–66, 68, 99, 101 Benzothiazepine, 70 Antiarrhythmic agents Benzothiazine derivatives, 251–252 class I, 245 Benzotriazole, 256–257 class II, 245 Bestrophins, 321, 322, 330, 331 class III, 245 Big potassium channels (BK channels), Antidepressant, 65–67 256, 257 Antiepileptic, 46 Bupivacaine, 56, 58, 59, 64, 69, 140 S.P.
    [Show full text]
  • Marine Natural Products and Their Potential Application in the Future
    AJSTD Vol. 22 Issue 4 pp. 297-311 (2005) MARINE NATURAL PRODUCTS AND THEIR POTENTIAL APPLICATION IN THE FUTURE Chau Van Minh*, Phan Van Kiem, and Nguyen Hai Dang Institute of Natural Products Chemistry, Vietnamese Academy of Science and Technology 18 Hoang Quoc Viet Road, Cau Giay, Hanoi, Vietnam Received 04 November 2005 1. INTRODUCTION Oceans are the diverse resource, which cover more than 70% of the earth’s surface. No doubt, with 34 of 36 phyla of life represented, oceans are the greatest biodiversity in the world [1]. They are the extraordinary natural source of microorganism, algae, sponge, coelenterate, bryozoan, mollusk, and echinoderm… Especially, on coral reef, where shelter more than 1000 species per m2. Surprisingly, there is only a small number of researches in this field. Therefore increasing research on marine natural source may provide good results for exploiting and developing valuable natural products which benefit for human. Marine environment is a rich source of biological and chemical diversity. The diversity has been unique source of chemical compounds of potential for pharmaceuticals, cosmetics, dietary supplements, and agrochemicals. Ecological pressure, including competitions for food and space, the fouling of predator and surface, has led to the evolution of secondary metabolites with various biological activities. Many organisms are soft bodies and/or unmoved, hardly survive with the threat from around environment. Hence they have evolved the ability to synthesize toxic compounds or obtain them from microorganism to defense against predator or to paralyze their prey. The questions such as, why do fish not eat particular algae? Why do two sponges grow and expand until they reach but not grow over each other? may be explained by these reasons.
    [Show full text]
  • Influence of Lipid-Soluble Gating Modifier Toxins on Sodium Influx in Neocortical Neurons
    0022-3565/08/3262-604–613$20.00 THE JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS Vol. 326, No. 2 Copyright © 2008 by The American Society for Pharmacology and Experimental Therapeutics 138230/3358916 JPET 326:604–613, 2008 Printed in U.S.A. Influence of Lipid-Soluble Gating Modifier Toxins on Sodium Influx in Neocortical Neurons Zhengyu Cao, Joju George, William H. Gerwick, Daniel G. Baden, Jon D. Rainier, and Thomas F. Murray Creighton University, School of Medicine, Department of Pharmacology, Omaha, Nebraska (Z.C., J.G., T.F.M.); Center for Marine Biotechnology and Biomedicine, Scripps Institution of Oceanography, University of California at San Diego, La Jolla, California (W.H.G.); University of North Carolina, Center for Marine Science Research, Wilmington, North Carolina (D.G.B.); and Department of Chemistry, University of Utah, Salt Lake City, Utah (J.D.R.) Received February 20, 2008; accepted April 25, 2008 Downloaded from ABSTRACT The electrical signals of neurons are fundamentally dependent tridine and aconitine, and the pyrethroid deltamethrin were ϩ on voltage-gated sodium channels (VGSCs), which are respon- somewhat lower with maximal [Na ]i increments of less than 40 sible for the rising phase of the action potential. An array of mM. The rank order of efficacy of sodium channel gating mod- jpet.aspetjournals.org naturally occurring and synthetic neurotoxins have been iden- ifiers was brevetoxin (PbTx)-1 Ͼ PbTx-desoxydioxolane Ͼ tified that modify the gating properties of VGSCs. Using murine batrachotoxin Ͼ antillatoxin Ͼ PbTx-2 ϭ PbTx-3 Ͼ PbTx- neocortical neurons in primary culture, we have compared the 3␣-naphthoate Ͼ veratridine Ͼ deltamethrin Ͼ aconitine Ͼ ability of VGSC gating modifiers to evoke Naϩ influx.
    [Show full text]
  • Concurrent Sessions Abstracts
    20th World Congress of the International Society on Toxinology "Toxinology in the 21st century: Public health impact from basic, translational and clinical sciences" CONCURRENT SESSION ABSTRACTS 08 – 13 September, 2019 Buenos Aires, Argentina INDEX Page Concurrent Session I 1A. Public Health and Toxinology 2 1B. New Developments in Basic Toxinology I. 7 Concurrent Session II 2A. New Developments in Antivenoms 14 2B. New Developments in Basic Toxinology II. 20 Concurrent Session III 3A. Emerging Technologies in Toxinology 28 3B. Organ Systems and Toxins I 35 Concurrent Session IV 4A. Non-antibody and Adjuvant – Based Therapeutics 41 4B. Organ Systems and Toxins II 47 Concurrent Session V 5A. North American Society on Toxinology 55 Concurrent Session VI 6A. North American Society on Toxinology 60 Concurrent Session VII 7A. Clinical I 66 Concurrent Session VIII 8A. New Biology and Evolution of Venomous Organisms I 77 8B. Clinical II. Emerging Clinical Topics: Safety and Effectiveness of Current Antivenoms; Clinical Presentations of Intoxication and Management; 83 Epidemiology. Concurrent Session IX 9A. New Biology and Evolution of Venomous Organisms II 89 9B. SBTX: Innovation in Clinical and Basic Research in Toxinology 96 1 Concurrent Session I 1A. Public Health and Toxinology. Chairs: José M. Gutiérrez/Fan Hui Wen 1. Abdulrazaq Habib (Bayero University, Nigeria): Burden of Snakebite and Antivenom Supply Challenges in Africa. [email protected] 2. Mohammad Afzal Mahmood: A framework for shifting the paradigm and developing coalitions to address neglected public health problems: Lessons from the Myanmar Snakebite Project. [email protected] 3. Fan Hui Wen: (Instituto Butantan, Brazil): Public health policies to better manage the burden of scorpion sting envenoming.
    [Show full text]
  • Innovative Mode of Action Based in Vitro Assays for Detection of Marine Neurotoxins
    Innovative mode of action based in vitro assays for detection of marine neurotoxins Jonathan Nicolas Thesis committee Thesis advisor Prof. Dr I.M.C.M. Rietjens Professor of Toxicology Wageningen UR Thesis co-supervisors Dr P.J.M. Hendriksen Project leader, BU Toxicology and Bioassays RIKILT - Institute of Food Safety, Wageningen UR Dr T.F.H. Bovee Expertise group leader Bioassays & Biosensors, BU Toxicology and Bioassays RIKILT - Institute of Food Safety, Wageningen UR Other members Prof. Dr D. Parent-Massin, University of Western Brittany, Brest, France Dr P. Hess, French Research Institute for Exploitation of the Sea (IFREMER), Nantes, France Prof. Dr A.J. Murk, Wageningen UR Prof. Dr A. Piersma, National Institute for Public Health and the Environment (RIVM), Bilthoven This research was conducted under the auspices of the Graduate School VLAG (Avanced studies in Food Technology, Agrobiotechnology, Nutrition and Health Sciences). Innovative mode of action based in vitro assays for detection of marine neurotoxins Jonathan Nicolas Thesis submitted in fulfilment of the requirements for the degree of doctor at Wageningen University by the authority of the Rector Magnificus Prof. dr. ir. A.P.J. Mol, in the presence of the Thesis Committee appointed by the Academic Board to be defended in public on Wednesday 07 October 2015 at 11 a.m. in the Aula. Jonathan Nicolas Innovative mode of action based in vitro assays for detection of marine neurotoxins, 214 pages, PhD thesis, Wageningen UR, Wageningen, NL (2015) With references, with summary in
    [Show full text]
  • Ciguatera Mini Review: 21St Century Environmental Challenges and the Interdisciplinary Research Efforts Rising to Meet Them
    International Journal of Environmental Research and Public Health Review Ciguatera Mini Review: 21st Century Environmental Challenges and the Interdisciplinary Research Efforts Rising to Meet Them Christopher R. Loeffler 1,2,* , Luciana Tartaglione 2,3, Miriam Friedemann 4, Astrid Spielmeyer 1, Oliver Kappenstein 1 and Dorina Bodi 1 1 National Reference Laboratory of Marine Biotoxins, Department Safety in the Food Chain, German Federal Institute for Risk Assessment, Max-Dohrn-Str. 8-10, 10589 Berlin, Germany; [email protected] (A.S.); [email protected] (O.K.); [email protected] (D.B.) 2 Department of Pharmacy, School of Medicine and Surgery, University of Napoli Federico II, Via D. Montesano 49, 80131 Napoli, Italy; [email protected] 3 CoNISMa—National Inter-University Consortium for Marine Sciences, Piazzale Flaminio 9, 00196 Rome, Italy 4 Department Exposure, German Federal Institute for Risk Assessment, Max-Dohrn-Str. 8-10, 10589 Berlin, Germany; [email protected] * Correspondence: Christopher.Loeffl[email protected] Abstract: Globally, the livelihoods of over a billion people are affected by changes to marine ecosys- tems, both structurally and systematically. Resources and ecosystem services, provided by the Citation: Loeffler, C.R.; Tartaglione, marine environment, contribute nutrition, income, and health benefits for communities. One threat L.; Friedemann, M.; Spielmeyer, A.; to these securities is ciguatera poisoning; worldwide, the most commonly reported non-bacterial Kappenstein, O.; Bodi, D. Ciguatera seafood-related illness. Ciguatera is caused by the consumption of (primarily) finfish contaminated Mini Review: 21st Century with ciguatoxins, potent neurotoxins produced by benthic single-cell microalgae. When consumed, Environmental Challenges and the ciguatoxins are biotransformed and can bioaccumulate throughout the food-web via complex path- Interdisciplinary Research Efforts ways.
    [Show full text]
  • Lessons Learned
    Prevention and Reversal of Chronic Disease Copyright © 2019 RN Kostoff PREVENTION AND REVERSAL OF CHRONIC DISEASE: LESSONS LEARNED By Ronald N. Kostoff, Ph.D., School of Public Policy, Georgia Institute of Technology 13500 Tallyrand Way, Gainesville, VA, 20155 [email protected] KEYWORDS Chronic disease prevention; chronic disease reversal; chronic kidney disease; Alzheimer’s Disease; peripheral neuropathy; peripheral arterial disease; contributing factors; treatments; biomarkers; literature-based discovery; text mining ABSTRACT For a decade, our research group has been developing protocols to prevent and reverse chronic diseases. The present monograph outlines the lessons we have learned from both conducting the studies and identifying common patterns in the results. The main product of our studies is a five-step treatment protocol to reverse any chronic disease, based on the following systemic medical principle: at the present time, removal of cause is a necessary, but not necessarily sufficient, condition for restorative treatment to be effective. Implementation of the five-step treatment protocol is as follows: FIVE-STEP TREATMENT PROTOCOL TO REVERSE ANY CHRONIC DISEASE Step 1: Obtain a detailed medical and habit/exposure history from the patient. Step 2: Administer written and clinical performance and behavioral tests to assess the severity of symptoms and performance measures. Step 3: Administer laboratory tests (blood, urine, imaging, etc) Step 4: Eliminate ongoing contributing factors to the chronic disease Step 5: Implement treatments for the chronic disease This individually-tailored chronic disease treatment protocol can be implemented with the data available in the biomedical literature now. It is general and applicable to any chronic disease that has an associated substantial research literature (with the possible exceptions of individuals with strong genetic predispositions to the disease in question or who have suffered irreversible damage from the disease).
    [Show full text]
  • Neuroprotective Natural Products Neuroprotective Natural Products
    Neuroprotective Natural Products Neuroprotective Natural Products Clinical Aspects and Mode of Action Edited by Goutam Brahmachari Editor All books published by Wiley-VCH are carefully produced. Nevertheless, authors, Dr. Goutam Brahmachari editors, and publisher do not warrant the Visva-Bharati (a Central University) information contained in these books, including Department of Chemistry, Laboratory this book, to be free of errors. Readers are of Natural Products and Organic Synthesis, advised to keep in mind that statements, data, Santiniketan illustrations, procedural details or other items West Bengal 731 235 may inadvertently be inaccurate. India Cover Library of Congress Card No.: applied for Neurons: © fotolia_ktsdesign British Library Cataloguing-in-Publication Data A catalogue record for this book is available from the British Library. Bibliographic information published by the Deutsche Nationalbibliothek The Deutsche Nationalbibliothek lists this publication in the Deutsche Nationalbibliografie; detailed bibliographic data are available on the Internet at http:// dnb.d-nb.de. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Boschstr. 12, 69469 Weinheim, Germany All rights reserved (including those of translation into other languages). No part of this book may be reproduced in any form – by photoprinting, microfilm, or any other means – nor transmitted or translated into a machine language without written permission from the publishers. Registered names, trademarks, etc. used in this book, even when not specifically marked as such, are
    [Show full text]
  • Inhibition of Kv Channels by Gambierol Through an Interaction with the Voltage-Sensing Domain
    This item is the archived peer-reviewed author-version of: Voltage-sensor conformation shapes the intra-membrane drug binding site that determines gambierol affinity in Kv channels Reference: Kopljar Ivan, Grottesi Alessandro, de Block Tessa, Rainier Jon D., Tytgat Jan, Labro Alain, Snyders Dirk.- Voltage-sensor conformation shapes the intra-membrane drug binding site that determines gambierol affinity in Kv channels Neuropharmacology - ISSN 0028-3908 - 107(2016), p. 160-167 Full text (Publisher's DOI): http://dx.doi.org/doi:10.1016/J.NEUROPHARM.2016.03.010 To cite this reference: http://hdl.handle.net/10067/1330540151162165141 Institutional repository IRUA *Title page Voltage-sensor conformation shapes the intra-membrane drug binding site that determines gambierol affinity in Kv channels. Authors: Ivan Kopljar1Ψ, Alessandro Grottesi2, Tessa de Block1, Jon D. Rainier3, Jan Tytgat4, Alain J. Labro1, Dirk J. Snyders1* Affiliations: 1Laboratory for Molecular Biophysics, Physiology and Pharmacology, University of Antwerp, 2610 Antwerp, Belgium 2CINECA – Sede di Roma – Via dei Tizii 6, 00185 – Rome, Italy 3Department of Chemistry, University of Utah, Salt Lake City, UT 84112-0850, USA 4Toxicology and Pharmacology, University of Leuven Campus Gasthuisberg, 3000 Leuven, Belgium ΨCurrent affilation: Global Safety Pharmacology, PD&S, Discovery Sciences, Janssen Research and Development, Beerse, Belgium *Corresponding Author: Dirk J. Snyders, M.D., Ph.D. Laboratory for Molecular Biophysics, Physiology and Pharmacology Department of Biomedical Sciences University of Antwerp Universiteitsplein 1, T5.35 2610 Antwerp, Belgium Phone: +32-(3)-820-2335 Fax: +32-(3)-820-2326 Email: [email protected] *Abstract Abstract Marine ladder-shaped polyether toxins are implicated in neurological symptoms of fish-borne food poisonings.
    [Show full text]