DOCSLIB.ORG

Chemistry and Medical Implications of Novel Amphibian Peptides

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Chemistry and Medical Implications of Novel Amphibian Peptides Chemistry and Medical lmplications of Novel Amph¡bian Peptides A thesis submitted for the Degree of Doctor of Philosophy by Paul Andrew Wabnitz B.Sc. (Hons) from the Department of Chemistry The University of Adelaide É.ï5 August, 1999 Preface CONTENTS Acknowledgements VI Statement of Originality vil List of Figures vil List of Tables xilt Abstract XV Ghapter l. lntroduction 1.1. Peptide PharmacologY 1.1a.General 1 1.1b. Structure and function of peptide mediators 2 4 1 .1c. Neuropeptides 1.1d. Hormonal pePtides 5 7 1 .1e. Peptide biosYnthesis 1.1f. Peptides as pharmaceuticals I 1.2. Amphibian Peptides 1.2a. Amphibians 10 1.2b. Why studY anurans? 10 1.2c. Anuran antibacterial peptides 16 I .2d. Anuran neuroPePtides 23 1.2e. The Litoria genus 24 1.3. Methodology 1.3a. Surface electrical stimulation 25 1.3b. Analysis bY HPLC 27 1.3c. Mass sPectrometry 28 1.3d. Vacuum Generators ZAB 2HF mass spectrometer 29 1.3e. Finnigan LCQ electrospray mass spectrometer 34 1.3f. Peptide sequencing 38 1.3g. C-terminal end group determination 40 1.3h. Preparation of synthetic peptides 40 41 1.4. References - Preface - Ghapter 2. lnvestigation of Bioactive Peptide Development in the Tadpole Gycle of Litoria splendida 2.1. lntroduction 2.1a. General 46 2.1b. Litoria splendida 50 2.1c. Development cycle of Litoria splendida 54 2.2. Results and Discussion 2.2a. General 56 2.2b. Structure determination 58 2.2c. lsolation of peptides from lawal Litoria splendida 58 2.2d. Conclusions 71 2.3. Experimental 2.3a. Collection and preparation of adult Litoria splendida secretions 73 2.3b. Collection and preparation of larval Litoria splendida samples 73 2.3c. HPLC seParation 74 74 2.3d. Methylation of PePtides 2.3e. Enzyme digestion using Lys-C 75 2.3f. Mass spectrometry analYsis 75 2.39. Antibacterial testing 76 2.3h. Preparation of synthetic peptides 76 2.3i. Automated Edman sequencing 76 2.4. References 77 Ghapter 3. Three-Year Peptide Profiling of Male and Female Litoria splendida 3.1. lntroduction 3.1a. General 79 3.2. Results and Discussion 3.2a. General BO 3.2b. Seasonal variation of the caerulein region 82 3.2c. Additional peptides in the adult male Litoria splendida secretions 86 3.2d. Biological activity determination 91 3.2e. Conclusions 92 3.3. Experimental 3.3a. Collection and preparation of male and female Litoria splendida secretions 93 3.3b. HPLC seParation 93 3.3c. Mass sPectrometry analYsis 94 3.3d. Additional information 94 3.4. References 95 Preface Ghapter 4. Litoria splendida behavioural studies 4.1. lntroduction 4.1a. Pheromones 96 4.1 b. Pheromone categories 97 4.1c. Alarm pheromones 98 4.1d. Sex pheromones 99 4.1e. The pheromone communication system 100 4.1f. Pheromones in amPhibians 101 4.2. Results and Discussion 4.2a. Behavioural studies procedure 103 4.2b. Behavioural studies of caerin 1 .10 with female and male Litoria splendida 104 4.2c. Behavioural studies of caerin 2.3 with female Litoria splendida 105 4.2d. Behavioural studies of caerin 2.3 with male Litoria splendida 110 4.2e. Behavioural studies of caerin 2.3 with female and male Litoria caerulea 111 4.2f. Conclusions 112 4.3. Experimental 4.3a. General 114 4.3b. Experimental Procedure 114 4.4. References 116 Ghapter 5. Peptides lrom Litoria citropa 5.1. lntroduction 5.1a. Litoria citropa 117 5.2. Results and Discussion 5.2a. General 119 5.2b. Citropin 1.1 122 5.2c. Citropin 2.1 130 5.2d. Citropin3.1.2 135 5.2e. Antibacterial activity determination 139 5.2f. The'carpet-like' mechanism 140 5.2g. Determination of structural conformation 142 5.2h. Synthetic modifications 144 5.2i. Conclusions 145 5.3. Experimental 5.3a. Collection and preparation of Litoria citropa secretions 147 5.3b. HPLC seParation 147 5.3c. Mass sPectrometry analYsis 147 5.3d. Additional information 148 5.4. References 149 - Preface - Ghapter 6. Gaerulein-Like Peptides from Litoria citropa 6.1. lntroduction 6.1a. General 150 6.2. Results and Discussion 6.2a. General 152 6.2b. HPLC analysis of fraction A 152 6.2c. HPLC analysis of fraction B 154 6.2d. Structural analysis of peptides from fraction A 155 ô.2e. Structural analysis of peptides from fraction B 160 6.2f. Conclusions 166 6.3. Experimental 6.3a. Collection and preparation oÍ Litoria citropa secretions 168 6.3b. HPLC separation 168 6.3c. Mass spectrometry analysis 169 6.3d. Additional information 169 6.4. References 170 Ghapter 7. nNOS lnhibition Activity and Preliminary Activity of the Gitropin I Peptides 7.1. lntroduction 7.1a. Nitric oxide 171 7.1b. Nitric oxide synthase 172 7.1c. lnducible nitric oxide synthase 173 7.1d. Endothelial nitric oxide synthase 174 7.1e. Neuronal nitric oxide synthase 175 7.1f. Calmodulin 176 7.19. Nitric oxide synthase mechanism 177 7.1h. Binding domains of nNOS 179 7.1 i. Medical implications 181 7.2. Results and Discussion 7.2a. nNOS and calcium channel activity testing 182 7.2b. Anticancer activity 185 7.2c. Conclusions 186 7.3. Experimental 7.3a. nNOS enzymic assay and Ntype calcium channel assay 188 7.3b. Anticancer assay 188 7.3c. Peptide synthesis 188 7.4. References 189 V - Preface - Ghapter 8. Peptides f¡om Litorìa electrica 8.1. lntroduction 8.1a. Litoria electrica 191 8.1b. Comparison oÍ Litoria electricawith Litoria rubella 192 8.2. Results and Discussion 8.2a. General 195 8.2b. Structure determination 196 8.2c. Biological activity determination 201 8.2d. A comparison of the peptide profiles of Litoria electrica and Litoria rubella 201 8.2e. Conclusions 203 8.3. Experimental 8.3a. Collection and preparation of Litoria electrica secretions 204 8.3b. HPLC separation 204 8.3c. Mass spectrometry analysis 204 8.3d. Additional information 205 8.4. References 206 Ghapter 9. Summary and Conclusions 207 Publications 210 V - Preface - Acknowledgements Firstly, I would like to thank my Ph.D. supervisor Professor John H. Bowie for his encouragement, advice, and constant enthusiasm towards my postgraduate studies. I am thankful to him for providing me with the opportunity to undertake such an exciting and rewarding field of research. I am also very grateful to Professor Bowie for making it possible for me to attend and participate in a number of intellectually stimulating conferences, which included two ANZMS conferences and the 'From Venoms to Drugs' conference. I would also like to thank the following people for their direct input into this research. Associate Professor Mike J. Tyler, from the Department of Environmental Biology, University of Adelaide, for his advice and for providing the amphibian secretions' Associate 'Wallace, Professor John C. from the Department of Biochemistry, University of Adelaide, for providing the automated Edman sequencing data. Dr. Lyndon E. Llewellyn and Jason R. Doyle, from the Australia Institute of Marine Science (Queensland), for their willingness in conducting the assay testing. Ben P. Smith, from the Department of Environmental Biology, University of Adelaide, for his help with the behavioural tests and provision of amphibian secretions. Thanks also to Kerry L. Hunter for kindly proofreading this thesis and for her continuous support and encouragement. I would also like to thank the academic, research and technical staff in the Department of Chemistry at the University of Adelaide for their help and advice. In particular I would like to acknowledge Tom Blumenthal, Dr. George Gream, Dr. Suresh Dua, Dr. Simon Steinborner, Dr. John Hevko, C.S. Brian Chia, Tom Rozek, Kate'Wegener and Stefan Creaser. Thanks also to my brothers, David, Daniel and Andrew, for their patience and assistance throughout my doctorate. Finally and most importantly, I would like to great\y acknowledge my parents for their amazingsupport, encouragement and their occasional gentle push throughout my education. VI - Preface - List of Figures Figure 1.1. Oxytocin. Figure 1.2 Structure of the peptide bond. (a) A schematic representation of the electron density around the peptide bond. tnL -C=O and -N-H bonds are parallel, accounting for the rigidity around the C-N. This is because the peptide bond exhibits partial double bond character due to the delocalisation of the ¡-electron orbitals over O-C-N, producing a resonance stabilisation. (b) Bond lengths and angles within the peptide bond. Bond lengths are in nanometers (nm). Figure 1.3. Mechanism of action of hormonal peptides on the target cell. H (free hydrophilic hormone), R (surface reõeptor), AC (adenylate cyclase), ATP (adenosine triphosphate), cAMP (cyclic adenosine monophosphate)' PDE (phosphodiesterase), lK (inactive protein kinase), K (active protein kinase), P (phosphate)' Figure 1.4. Production of a peptide mediator. The gene contains the coding regions (exons) interspersed with non-coding relions (introns). The coding regions of the gene (exons) are transcribed and spliced, which removes the introns and some of the exons, to give-rise to the messenger ribonucleic acid (mRNA). The mRNA segments are translated to produce the prepropeptide. Cleavage of the N-terminal signal peptide produces the propeptide. Figure 1.5. Two different species of poison dart frogs from the genus Phyl/obafes. Figure 1.6. The typical environment of an anuran. Figure '1.7. Representation of a granular gland found in anuran skin. Figure 1.8. Representations of an amphiphilic cr-helix. Figure 1.9. Edmundson helical wheel projection. Figure 1.10. Bacterial cell membrane model. Figure 1 .1 1 . Three-dimensional structure of maculatin 1 .1 . Figure 1.12.'Barrel-Stave' model. Figure 1.13. Distribution (indicated by the black reg¡on) of the genus Liforn throughout Australia. Figure 1.14. SES method. Figure 1 .1 5. Crude aqueous secretion taken from Litoria splendida. Figure 1 .1 6.
Load more

Recommended publications
  • National Resource Material Green and Black Poison Frog (Dendrobates Auratus)
    Indicative 10 Project National Resource Material Green and Black Poison frog (Dendrobates auratus) Michelle T. Christy and Win Kirkpatrick 2017 Department of Primary Industries and Regional Development 3 Baron-Hay Court, South Perth, WA 6151 An Invasive Animals CRC Project Contents Summary ............................................................................. 2 Key Messages ................................................................... 2 Classification ................................................................... 2 Common names ................................................................ 3 Biology and Ecology ................................................................ 3 Identification ................................................................... 3 Behaviours and Traits ......................................................... 4 Food and Foraging ............................................................. 4 Reproduction and Lifecycle ................................................. 5 Habitat ......................................................................... 5 Global Range ........................................................................ 5 Potential for Introduction ........................................................ 6 Potential for Eradication.......................................................... 7 Impacts ............................................................................... 7 Economic ........................................................................ 7 Environmental
    [Show full text]
  • 615.9Barref.Pdf
    INDEX Abortifacient, abortifacients bees, wasps, and ants ginkgo, 492 aconite, 737 epinephrine, 963 ginseng, 500 barbados nut, 829 blister beetles goldenseal blister beetles, 972 cantharidin, 974 berberine, 506 blue cohosh, 395 buckeye hawthorn, 512 camphor, 407, 408 ~-escin, 884 hypericum extract, 602-603 cantharides, 974 calamus inky cap and coprine toxicity cantharidin, 974 ~-asarone, 405 coprine, 295 colocynth, 443 camphor, 409-411 ethanol, 296 common oleander, 847, 850 cascara, 416-417 isoxazole-containing mushrooms dogbane, 849-850 catechols, 682 and pantherina syndrome, mistletoe, 794 castor bean 298-302 nutmeg, 67 ricin, 719, 721 jequirity bean and abrin, oduvan, 755 colchicine, 694-896, 698 730-731 pennyroyal, 563-565 clostridium perfringens, 115 jellyfish, 1088 pine thistle, 515 comfrey and other pyrrolizidine­ Jimsonweed and other belladonna rue, 579 containing plants alkaloids, 779, 781 slangkop, Burke's, red, Transvaal, pyrrolizidine alkaloids, 453 jin bu huan and 857 cyanogenic foods tetrahydropalmatine, 519 tansy, 614 amygdalin, 48 kaffir lily turpentine, 667 cyanogenic glycosides, 45 lycorine,711 yarrow, 624-625 prunasin, 48 kava, 528 yellow bird-of-paradise, 749 daffodils and other emetic bulbs Laetrile", 763 yellow oleander, 854 galanthamine, 704 lavender, 534 yew, 899 dogbane family and cardenolides licorice Abrin,729-731 common oleander, 849 glycyrrhetinic acid, 540 camphor yellow oleander, 855-856 limonene, 639 cinnamomin, 409 domoic acid, 214 rna huang ricin, 409, 723, 730 ephedra alkaloids, 547 ephedra alkaloids, 548 Absorption, xvii erythrosine, 29 ephedrine, 547, 549 aloe vera, 380 garlic mayapple amatoxin-containing mushrooms S-allyl cysteine, 473 podophyllotoxin, 789 amatoxin poisoning, 273-275, gastrointestinal viruses milk thistle 279 viral gastroenteritis, 205 silibinin, 555 aspartame, 24 ginger, 485 mistletoe, 793 Medical Toxicology ofNatural Substances, by Donald G.
    [Show full text]
  • A Review of Chemical Defense in Poison Frogs (Dendrobatidae): Ecology, Pharmacokinetics, and Autoresistance
    Chapter 21 A Review of Chemical Defense in Poison Frogs (Dendrobatidae): Ecology, Pharmacokinetics, and Autoresistance Juan C. Santos , Rebecca D. Tarvin , and Lauren A. O’Connell 21.1 Introduction Chemical defense has evolved multiple times in nearly every major group of life, from snakes and insects to bacteria and plants (Mebs 2002 ). However, among land vertebrates, chemical defenses are restricted to a few monophyletic groups (i.e., clades). Most of these are amphibians and snakes, but a few rare origins (e.g., Pitohui birds) have stimulated research on acquired chemical defenses (Dumbacher et al. 1992 ). Selective pressures that lead to defense are usually associated with an organ- ism’s limited ability to escape predation or conspicuous behaviors and phenotypes that increase detectability by predators (e.g., diurnality or mating calls) (Speed and Ruxton 2005 ). Defended organisms frequently evolve warning signals to advertise their defense, a phenomenon known as aposematism (Mappes et al. 2005 ). Warning signals such as conspicuous coloration unambiguously inform predators that there will be a substantial cost if they proceed with attack or consumption of the defended prey (Mappes et al. 2005 ). However, aposematism is likely more complex than the simple pairing of signal and defense, encompassing a series of traits (i.e., the apose- matic syndrome) that alter morphology, physiology, and behavior (Mappes and J. C. Santos (*) Department of Zoology, Biodiversity Research Centre , University of British Columbia , #4200-6270 University Blvd , Vancouver , BC , Canada , V6T 1Z4 e-mail: [email protected] R. D. Tarvin University of Texas at Austin , 2415 Speedway Stop C0990 , Austin , TX 78712 , USA e-mail: [email protected] L.
    [Show full text]
  • Regulation of Alkaloid Biosynthesis in Plants
    CONTRIBUTORS Numbers in parentheses indicate the pages on which the authors’ contributions begin. JAUME BASTIDA (87), Departament de Productes Naturals, Facultat de Farma` cia, Universitat de Barcelona, 08028 Barcelona, Spain YEUN-MUN CHOO (181), Department of Chemistry, University of Malaya, 50603 Kuala Lumpur, Malaysia PETER J. FACCHINI (1), Department of Biological Sciences, University of Calgary, Calgary, AB, Canada TOH-SEOK KAM (181), Department of Chemistry, University of Malaya, 50603 Kuala Lumpur, Malaysia RODOLFO LAVILLA (87), Parc Cientı´fic de Barcelona, Universitat de Barcelona, 08028 Barcelona, Spain DANIEL G. PANACCIONE (45), Division of Plant and Soil Sciences, West Virginia University, Morgantown, WV 26506-6108, USA CHRISTOPHER L. SCHARDL (45), Department of Plant Pathology, University of Kentucky, Lexington, KY 40546-0312, USA PAUL TUDZYNSKI (45), Institut fu¨r Botanik, Westfa¨lische Wilhelms Universita¨tMu¨nster, Mu¨nster D-48149, Germany FRANCESC VILADOMAT (87), Departament de Productes Naturals, Facultat de Farma` cia, Universitat de Barcelona, 08028 Barcelona, Spain vii PREFACE This volume of The Alkaloids: Chemistry and Biology is comprised of four very different chapters; a reflection of the diverse facets that comprise the study of alkaloids today. As awareness of the global need for natural products which can be made available as drugs on a sustainable basis increases, so it has become increas- ingly important that there is a full understanding of how key metabolic pathways can be optimized. At the same time, it remains important to find new biologically active alkaloids and to elucidate the mechanisms of action of those that do show potentially useful or novel biological effects. Facchini, in Chapter 1, reviews the significant studies that have been conducted with respect to how the formation of alkaloids in their various diverse sources are regulated at the molecular level.
    [Show full text]
  • Poison Dart Frogs
    POISON DART FROGS Anura Dendrobates tinctorius Family: Dendrobatidae Genus: multiple Range: Southern Central America and north and central South America Habitat: tropical rainforests Niche: Diurnal, terrestrial; breed in trees, carnivorous Wild diet: small invertebrates, particularly ants, which give them their poisonous properties in most cases Zoo diet: pinhead crickets, fruitflies Life Span: (Wild) 3-15 years (Captivity) up to 20 years Sexual dimorphism: Males slightly smaller Location in SF Zoo: South American Tropical Rainforest and Aviary APPEARANCE & PHYSICAL ADAPTATIONS: There are 40 species of Dendrobates poison dart frogs. All have bright coloration (aposematic coloration), which warns predators of their toxic skin secretions (alkaloids obtained from insects they eat). They are small frogs (most are no bigger than a paper clip). They have a good vision used to help capture prey. Their long, sticky tongue darts out and captures their prey once spoted. Each foot contains four toes which each have a flattened tip with a suction cup pad which is used for gripping and clinging to vegetation in its habitat. They lack webbing and are poor swimmers and are found near water but not in it. Weight: < 1 oz (< 28 g) Poison Dart Frogs have no webbing between the toes on their feet, so Length: 1 - 6 cm they are poor swimmers and are not often found in the water. STATUS & CONSERVATION: Many species are threatened by habitat loss and over-collection for the pet trade. COMMUNICATION AND OTHER BEHAVIOR The males are territorial, calling to advertise to females and to defend their area. Calls are species dependent and can be anything from a buzz to trilling whistles.
    [Show full text]
  • Yellow (Bumble Bee) Poison Dart Frog Dendrobates Leucomelas Family
    Yellow (Bumble Bee) Poison Dart Frog Dendrobates leucomelas Family: Dendrobatidae Locale: Brazil; Colombia; Guyana; Venezuela Habitat: Found in moist or wet forests in lowlands, found in leaf litter on forest floors or occasionally on trees at temperatures of 26 to 30C. Average Size: Range from 3.1 to 5 cm (1.2 to 1.97in) with average of 4 cm (1.57in) Average Lifespan: 10 to 15 years, but the oldest known lived to 20.5 years Activity: Diurnal Captive care: Rainforest terrarium: a breeding pair or trio can be housed in a 10 gallon well- planted aquarium with good drainage. Expanded clay pellets covered with sphagnum moss and planted with pothos and bromeliads works well. Water should be shallow as these frogs are not strong swimmers and can drown. A small hide, such as half a coconut shell or flowerpot will provide a breeding site. The tank should be covered with a hinged glass lid that has 1.5-2 inches of plastic along back in which ~6 small holes have been drilled (allows air exchange while maintaining high humidity, 95%). A small pump can be used to generate a stream, put pump in one corner (cover with clay pellets) and run aquarium tubing under rock to other corner where rocks are piled to generate a waterfall and rock stream. Temperature: Poison dart frogs prefer moderate temperatures. Daytime temperatures between 75F and 84F (23.5C to 29C). Lighting: Frogs need light to see their food, and full spectrum lighting is needed to maintain the plants. Diet: Insectivores: in captivity, the frogs are fed flightless fruit flies or pinhead crickets daily.
    [Show full text]
  • Poison Dart Frogs and South American Indians
    Copyrighted Material 118 F r o G s A N d t o A d s In medieval Europe, frogs and toads were synonymous with evil and witchcraft and toads are depicted as the familiars and alter-egos of witches. Almost all writings of the time portray the toad in a negative fashion (frogs are hardly mentioned) and Shakespeare refers to them as ‘ugly and venomous’. Even today, toads are not welcome in some places and are thought to cause warts, while superstitions concerning toads were commonplace in parts of England and North America until recently. Kenneth Grahame’s The Wind in the Willows, published in 1908, characterizes Toad as pompous and unreliable, but he redresses the balance by also describing him as intelligent and witty. In other children’s tales from Europe, frogs are princes in disguise waiting only for a maiden’s kiss. Poison dart frogs and South American Indians south American Indians of the Emberá Chocó group of frog was enough to kill at least 20,000 mice when tribes from the Pacific slopes of the Andes in Colombia injected under the skin. Extrapolating to humans this is use at least three species of poison dart frogs to tip their equivalent to six or seven average-sized people though blowgun darts: Phyllobates aurotaenia, P. bicolor and comparing toxicity between mice and humans is not P. terribilis. the poison consists of steroidal alkaloids in always completely accurate. the frogs’ skin secretions, of which the most powerful the Indians make their blowguns from a length of is produced by the golden poison dart frog, P.
    [Show full text]
  • 2017 National Veterinary Scholars Symposium 18Th Annual August 4
    2017 National Veterinary Scholars Symposium 18th Annual August – 4 5, 2017 Natcher Conference Center, Building 45 National Institutes of Health Bethesda, Maryland Center for Cancer Research National Cancer Institute with The Association of American Veterinary Medical Colleges https://www.cancer.gov/ Table of Contents 2017 National Veterinary Scholars Symposium Program Booklet Welcome .............................................................................................................................. 1 NIH Bethesda Campus Visitor Information and Maps .........................................................2 History of the National Institutes of Health ......................................................................... 4 Sponsors ............................................................................................................................... 5 Symposium Agenda .......................................................................................................6 Bios of Speakers ................................................................................................................. 12 Bios of Award Presenters and Recipients ........................................................................... 27 Training Opportunities at the NIH ...................................................................................... 34 Abstracts Listed Alphabetically .......................................................................................... 41 Symposium Participants by College of Veterinary Medicine
    [Show full text]
  • A Day in the Life of an Animal
    A Day in the Life of an Animal by the Centaur Class 3rd & 4th Grade - 2016-17 A day in the Life of an Animal By: 2016-17 Centaurs - 3rd & 4th Grade Table of Contents 3rd Grade (Frogs) • Amazon Horned Frog - Steck • Amazon Milk Frog - Isaac • Darwin’s frog - Coriandra • Eleutherodactylus Iberia -Lila • Mexican Burrowing Toad - Rose • Painted-Belly Leaf Frog - Jenna • Spring Peeper - Sofia • Strawberry Poison Dart Frog - Ethan • Water-Holding Frog - Malachi 4th Grade (Animal Defenses) • Bluespotted Ribbontail Ray - Hazel • Box Jellyfish - Raine • Common Dolphin - Dariah • Eurasian Roller - Tien Zin • Giant Cuttlefish - Rayden • Ground Pangolin - Gredel • Green Basilisk Lizard - Tiger Luc • Scorpion Mouse - Tomas • Secretary Bird - Shanti • Three-Banded Armadillo - Willow Preface: The Centaurs were asked the question, “What adaptations help animals survive?” Fourth graders were tasked with learning about animal defenses. To deepen their understanding of this topic, they researched different behavioral and physical adaptations using Christina Wilson’s “Animal Behavior, Animal Defenses” as a mentor text. Next, they choose an animal to research and become an expert on that species. Third graders learned about frogs and all the amazing adaptations that help them survive with help from their mentor text, DK’s “Everything You Need to Know about Frogs and Other Slippery Creatures.” Then they became experts on the frog species that they chose to research. Finally, after exploring the question, “How do writers inform and entertain their audience?” the Centaurs created non-fiction stories about their animals. We would like to give a special thanks to the 2nd graders at the Conservatory Lab Charter School in Boston, Massachusetts for providing inspiration for our stories! With the help and guidance of Christina González, students focused on creating colorful images of their selected animals to accompany their narrative text.
    [Show full text]
  • The Poison Dart Frog's Batrachotoxin Modulates Nav1.8
    FEBS 28940 FEBS Letters 577 (2004) 245–248 The poison Dart frog’s batrachotoxin modulates Nav1.8 Frank Bosmansa,1, Chantal Maertensa,1, Fons Verdonckb, Jan Tytgata,* aLaboratory of Toxicology, University of Leuven, E. Van Evenstraat 4, B-3000 Leuven, Belgium bInterdisciplinary Research Centre, University of Leuven Campus Kortrijk, B-8500 Kortrijk, Belgium Received 27 August 2004; revised 28 September 2004; accepted 5 October 2004 Available online 18 October 2004 Edited by Maurice Montal fast and slow inactivation processes of the channel are inhib- Abstract Batrachotoxin is a potent modulator of voltage-gated sodium channels, leading to irreversible depolarisation of nerves ited. Aside from these effects, the ion selectivity is reduced. and muscles, fibrillation, arrhythmias and eventually cardiac BTX-modified VGSCs display increased permeability for þ þ þ failure. Since its discovery, field researchers also reported NH4 ,K and Cs ions [10–17]. numbness after their skin came into contact with this toxin. In the literature, there is evidence that a specific VGSC plays Intrigued by this phenomenon, we determined the effect of an important role in nociception, namely Nav1.8 (Scn10A). batrachotoxin on the voltage-gated sodium channel Nav1.8, Nav1.8 is expressed in peripheral neurons such as the small which is considered to be a key player in nociception. As a result, diameter nociceptor neurons of dorsal root ganglia (DRG) we discovered that batrachotoxin profoundly modulates this that originate in afferent nociceptive fibres such as the C-fibres channel: the inactivation process is severely altered, the voltage- and Ad fibres [18–22]. Behavioural studies on Na 1.8 null dependence of activation is shifted towards more hyperpolarised v mutant mice have shown that Nav1.8 plays an important role potentials resulting in the opening of Nav1.8 at more negative membrane potentials and the ion selectivity is modified.
    [Show full text]
  • Military Potential of Biological Toxins
    journal of applied biomedicine 12 (2014) 63–77 Available online at www.sciencedirect.com ScienceDirect journal homepage: http://www.elsevier.com/locate/jab Review Article Military potential of biological toxins Xiujuan Zhang a, Kamil Kuča b,c,**, Vlastimil Dohnal c, Lucie Dohnalová d, Qinghua Wu e, Chu Wu a,* a College of Horticulture and Garden, Yangtze University, Jingzhou, Hubei 434023, People's Republic of China b Biomedical Research Center, University Hospital Hradec Kralove, Czech Republic c Department of Chemistry, Faculty of Science, University of Hradec Kralove, Hradec Kralove, Rokitanskeho 62, 500 03, Czech Republic d Department of Hygiene, Faculty of Military Health, University of Defence, Hradec Kralove, Czech Republic e National Reference Laboratory of Veterinary Drug Residues (HZAU), Huazhong Agricultural University, Wuhan, Hubei 430070, People's Republic of China article info abstract Article history: Toxins are produced by bacteria, plants and animals for defense or for predation. Most of the Received 27 November 2013 toxins specifically affect the mammalian nervous system by interfering with the transmission Received in revised form of nerve impulses, and such toxins have the potential for misuse by the military or terrorist 17 February 2014 organizations. This review discusses the origin, structure, toxicity and symptoms, transmis- Accepted 19 February 2014 sion, mechanism(s) of action, symptomatic treatment of the most important toxins and Available online 1 March 2014 venoms derived from fungi, plants, marine animals, and microorganisms, along with their potential for use in bioweapons and/or biocrime. Fungal trichothecenes and aflatoxins are Keywords: potent inhibitors of protein synthesis in most eukaryotes and have been used as biological Military toxins warfare agents.
    [Show full text]
  • Mueller-Schwarze D. Chemical Ecology of Vertebrates (CUP, 2006
    This page intentionally left blank Chemical Ecology of Vertebrates Chemical Ecology of Vertebrates is the first book to focus exclusively on the chem- ically mediated interactions between vertebrates, including fish, amphibians, reptiles, birds, and mammals, and other animals, and plants. Reviewing the lat- est research in three core areas: pheromones (where the interactions are between members of the same species), interspecific interactions involving allomones (where the sender benefits) and kairomones (where the receiver benefits) This book draws information into a coherent whole from widely varying sources in many different disciplines. Chapters on the environment, properties of odour signals, and the production and release of chemosignals set the stage for dis- cussion of more complex behavioral topics. While the main focus is ecological, dealing with behavior and interactions in the field, it also covers chemorecep- tion, orientation and navigation, the development of behavior, and the practical applications of chemosignals. Dietland Muller-Schwarze¨ is Professor of Environmental Biology at the State University of New York. Chemical Ecology of Vertebrates DIETLAND MULLER-SCHWARZE¨ State University of New York cambridge university press Cambridge, New York, Melbourne, Madrid, Cape Town, Singapore, São Paulo Cambridge University Press The Edinburgh Building, Cambridge cb2 2ru,UK Published in the United States of America by Cambridge University Press, New York www.cambridge.org Information on this title: www.cambridge.org/9780521363778 © Cambridge University Press 2006 This publication is in copyright. Subject to statutory exception and to the provision of relevant collective licensing agreements, no reproduction of any part may take place without the written permission of Cambridge University Press.
    [Show full text]