DOCSLIB.ORG

Molecular Characterization of the Injected Venom of Conus Ermineus

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Molecular Characterization of the Injected Venom of Conus Ermineus Molecular Characterization of the Injected Venom of Conus ermineus by Jose A. Rivera-Ortiz A Dissertation Submitted to the Faculty of the Charles E. Schmidt College of Science in Partial Fulfillment of the Requirements for the Degree of Doctor of Philosophy Florida Atlantic University Boca Raton, FL December 2011 © Copyright by Jose A Rivera-Ortiz 2011 Acknowledgements I would like to extend my gratitude to my advisor, Dr. Frank Mari for his guidance and time. Special thanks to Dr. Mari’s research group for their collaboration and the quality time they spent to make this work possible. Thanks also are due to Michael Bushman, Sanaz Dovell, Herminsul Cano, Carolina Moller, Hussam Abassi, Simon Bully, Orette Williams, Mari Heghinian, Danny Rojas, Adriana Pak, Craig Forbes and Frans Badenhorst . My special thanks go to Dr. Christian Melaun for his collaboration and to Dr. Seth Elsheimer and Dr. Otto Phanstiel for their support and words of encouragement. Finally, I especially would like to thank God for allowing me to come this far. iv Abstract Author: Jose A. Rivera-Ortiz Title: Molecular Characterization of the Injected Venom of Conus ermineus Institution: Florida Atlantic University Dissertation Advisor: Dr. Frank Mari Degree: Doctor of Philosophy Year: 2011 Cone snails are predatory marine animals that rely on their venom components to immobilize and capture their prey. According to the type of prey preference, cone snails can be divided into three groups: vermivorous, molluscivorous and piscivorous. Conus ermineus had been identified as the only piscivorous snail of the Atlantic Ocean. Cone snail venom is a complex and rich sources of natural toxins. The majority of the components of the venom are peptidic in nature, and they act over different ionic channels and membrane receptors. Initial studies using mixture of venom collected from dissected venom ducts concluded that the venom from the same species do not exhibit unusual peptide polymorphism [Olivera, Hillyard, et al., 1995] and that the only major difference between individuals of the same species are different concentrations of the venom components [Vianna, et al., 2005]. For this study, peptides in the injected venom were collected from individual snails and characterized using analytical RP-HPLC for a maximum of three years. The v different fractions collected were processed through capillary HPLC coupled with Q-TOF ESI-MS, and compared with analytical RP-HPLC fractions processed with MALDI-TOF MS. This study demonstrates that there is an animal-to-animal variation in the peptide components of the injected venom. The injected venom remains relatively constant over time for specific specimens in captivity. Finally, there are some peptides that had been found in all specimens both by MALDI-TOF MS and by ESI-MS. In this study, these peptides are called “molecular fingerprint” peptides. Based on matches of their derived masses to those predicted by published cDNA sequences, nine novel peptides were putatively identified. This study establishes that variations due to enzymatic posttranslational modification are omitted when we consider only information extrapolated from cDNA. The results of this study support the idea of the existence of a novel regulatory mechanism to expressed specific venom peptides for injection into the prey. vi Dedication This work is dedicated to all my extended family, but especially to my wife Marta, my son Cacimar and my mother Ricarda Ortiz. vii Molecular Characterization of the Injected Venom of Conus ermineus List of Figures...................................................................................................................xii List of Tables .................................................................................................................... xv List of Abbreviations and Symbols..................................................................................xvi Chapter 1: Introduction....................................................................................................... 1 1.1 General Physiological and Anatomical Characteristics of Cone Snails ................. 1 1.2 Cone Snail’s Habitat ............................................................................................... 8 1.3 Cone Snail Classification...................................................................................... 10 1.4 Cone Venom Composition and Classification...................................................... 12 1.4.1 Conopressins................................................................................................ 15 1.4.2 Contryphans ................................................................................................. 16 1.4.3 Conantokins ................................................................................................. 24 1.4.4 Contulakins .................................................................................................. 26 1.4.5 Conorfamides............................................................................................... 26 1.4.6 The α-conotoxins ......................................................................................... 28 1.4.7 The αA-conotoxin ........................................................................................ 33 1.4.8 The κA-conotoxins....................................................................................... 34 1.4.9 The ψ-conotoxins......................................................................................... 34 1.4.10 The σ-conotoxins ....................................................................................... 34 1.4.11 The χ-conotoxins........................................................................................ 35 viii 1.4.12 The μ-conotoxins ....................................................................................... 35 1.4.13 The μO-conotoxins .................................................................................... 36 1.4.14 The δ-conotoxins........................................................................................ 36 1.4.15 The κ-conotoxins ....................................................................................... 36 1.4.16 The κM-conotoxins.................................................................................... 37 1.4.17 The VcTx-conotoxins ................................................................................ 37 1.4.18 The ω-conotoxins....................................................................................... 37 1.5 Cone Snail Venom Efficiency .............................................................................. 37 Chapter 2: Comparative Analysis of Injected Venom vs. Dissected Venom in Conus ermineus................................................................................................................. 41 2.1 Background and Strategy...................................................................................... 41 2.2 Materials and Methods.......................................................................................... 43 2.2.1 Specimen Collection ................................................................................... 43 2.2.2 Injected Venom Extraction and Feeding...................................................... 45 2.2.3 NanoNMR Spectroscopy ............................................................................. 45 2.2.4 MALDI-TOF MS Analysis of the Injected Venom and Venom Fractions................................................................................................................ 47 2.2.5 Analytical RP-HPLC of Injected Venom .................................................... 47 2.2.6 Nanoflow LC–ESI-MS Analysis of the Injected Venom and Analytical RP-HPLC Fractions .............................................................................................. 48 2.2.7 Peptide Sequencing...................................................................................... 49 2.3 Results............................................................................................................. 49 2.3.1 Conus ermineus Behavior in Aquaria.......................................................... 49 ix 2.3.2 Injected Venom Characterization by NMR ................................................. 50 2.3.3. Injected Venom Characterization by MALDI-TOF MS ............................ 53 2.3.4 RP-HPLC Profiles of Injected Venom and MALDI-TOF MS of RP-HPLC of Fractions.......................................................................................... 55 2.3.5 NanoLC–ESI-MS of Injected Venom and RP-HPLC Venom Fractions..... 56 2.3.6 Biomarkers and Molecular Fingerprinting................................................... 57 2.4 Discussion....................................................................................................... 62 Chapter 3: Discovery of Peptide Components in the Pooled Injected Venom of Conus ermineus................................................................................................................. 69 3.1 Introduction..................................................................................................... 69 3.2 Materials and Methods.................................................................................... 72 3.2.1 mRNA-Extraction........................................................................................ 73 3.2.2 cDNA Synthesis..........................................................................................
Load more

Recommended publications
  • The Cone Collector N°23
    THE CONE COLLECTOR #23 October 2013 THE Note from CONE the Editor COLLECTOR Dear friends, Editor The Cone scene is moving fast, with new papers being pub- António Monteiro lished on a regular basis, many of them containing descrip- tions of new species or studies of complex groups of species that Layout have baffled us for many years. A couple of books are also in André Poremski the making and they should prove of great interest to anyone Contributors interested in Cones. David P. Berschauer Pierre Escoubas Our bulletin aims at keeping everybody informed of the latest William J. Fenzan developments in the area, keeping a record of newly published R. Michael Filmer taxa and presenting our readers a wide range of articles with Michel Jolivet much and often exciting information. As always, I thank our Bernardino Monteiro many friends who contribute with texts, photos, information, Leo G. Ros comments, etc., helping us to make each new number so inter- Benito José Muñoz Sánchez David Touitou esting and valuable. Allan Vargas Jordy Wendriks The 3rd International Cone Meeting is also on the move. Do Alessandro Zanzi remember to mark it in your diaries for September 2014 (defi- nite date still to be announced) and to plan your trip to Ma- drid. This new event will undoubtedly be a huge success, just like the two former meetings in Stuttgart and La Rochelle. You will enjoy it and of course your presence is indispensable! For now, enjoy the new issue of TCC and be sure to let us have your opinions, views, comments, criticism… and even praise, if you feel so inclined.
    [Show full text]
  • International Code of Zoological Nomenclature
    International Commission on Zoological Nomenclature INTERNATIONAL CODE OF ZOOLOGICAL NOMENCLATURE Fourth Edition adopted by the International Union of Biological Sciences The provisions of this Code supersede those of the previous editions with effect from 1 January 2000 ISBN 0 85301 006 4 The author of this Code is the International Commission on Zoological Nomenclature Editorial Committee W.D.L. Ride, Chairman H.G. Cogger C. Dupuis O. Kraus A. Minelli F. C. Thompson P.K. Tubbs All rights reserved. No part of this publication may be reproduced, stored in a retrieval system, or transmitted in any form or by any means (electronic, mechanical, photocopying or otherwise), without the prior written consent of the publisher and copyright holder. Published by The International Trust for Zoological Nomenclature 1999 c/o The Natural History Museum - Cromwell Road - London SW7 5BD - UK © International Trust for Zoological Nomenclature 1999 Explanatory Note This Code has been adopted by the International Commission on Zoological Nomenclature and has been ratified by the Executive Committee of the International Union of Biological Sciences (IUBS) acting on behalf of the Union's General Assembly. The Commission may authorize official texts in any language, and all such texts are equivalent in force and meaning (Article 87). The Code proper comprises the Preamble, 90 Articles (grouped in 18 Chapters) and the Glossary. Each Article consists of one or more mandatory provisions, which are sometimes accompanied by Recommendations and/or illustrative Examples. In interpreting the Code the meaning of a word or expression is to be taken as that given in the Glossary (see Article 89).
    [Show full text]
  • Pharmacological Modulation of Processes Contributing to Spinal Hyperexcitability: Electrophysiological Studies in the Rat
    Pharmacological modulation of processes contributing to spinal hyperexcitability: electrophysiological studies in the rat. By Katherine J Carpenter A thesis submitted to the University of London for the degree of Doctor of Philosophy Department of Pharmacology University College London Gower Street London WC1E6BT ProQuest Number: U642184 All rights reserved INFORMATION TO ALL USERS The quality of this reproduction is dependent upon the quality of the copy submitted. In the unlikely event that the author did not send a complete manuscript and there are missing pages, these will be noted. Also, if material had to be removed, a note will indicate the deletion. uest. ProQuest U642184 Published by ProQuest LLC(2015). Copyright of the Dissertation is held by the Author. All rights reserved. This work is protected against unauthorized copying under Title 17, United States Code. Microform Edition © ProQuest LLC. ProQuest LLC 789 East Eisenhower Parkway P.O. Box 1346 Ann Arbor, Ml 48106-1346 Abstract Two of the most effective analgesic strategies in man are (i) blockade of the NMDA receptor for glutamate, which plays a major role in nociceptive transmission and (ii) augmentation of inhibitory systems, exemplified by the use of ketamine and the opioids respectively. Both are, however, are associated with side effects. Potential novel analgesic targets are investigated here using in vivo electrophysiology in the anaesthetised rat with pharmacological manipulation of spinal neuronal transmission. Three different approaches were used to target NMDA receptors: (i) glycine site antagonists (Mrz 2/571 and Mrz 2/579), (ii) antagonists selective for receptors containing the NR2B subunit (ifenprodil and ACEA-1244), (iii) elevating the levels of N-acetyl-aspartyl- glutamate (NAAG), an endogenous peptide, by inhibition of its degradative enzyme.
    [Show full text]
  • The Hawaiian Species of Conus (Mollusca: Gastropoda)1
    The Hawaiian Species of Conus (Mollusca: Gastropoda) 1 ALAN J. KOHN2 IN THECOURSE OF a comparative ecological currents are factors which could plausibly study of gastropod mollus ks of the genus effect the isolation necessary for geographic Conus in Hawaii (Ko hn, 1959), some 2,400 speciation . specimens of 25 species were examined. Un­ Of the 33 species of Conus considered in certainty ofthe correct names to be applied to this paper to be valid constituents of the some of these species prompted the taxo­ Hawaiian fauna, about 20 occur in shallow nomic study reported here. Many workers water on marine benches and coral reefs and have contributed to the systematics of the in bays. Of these, only one species, C. ab­ genus Conus; nevertheless, both nomencla­ breviatusReeve, is considered to be endemic to torial and biological questions have persisted the Hawaiian archipelago . Less is known of concerning the correct names of a number of the species more characteristic of deeper water species that occur in the Hawaiian archi­ habitats. Some, known at present only from pelago, here considered to extend from Kure dredging? about the Hawaiian Islands, may (Ocean) Island (28.25° N. , 178.26° W.) to the in the future prove to occur elsewhere as island of Hawaii (20.00° N. , 155.30° W.). well, when adequate sampling methods are extended to other parts of the Indo-West FAUNAL AFFINITY Pacific region. As is characteristic of the marine fauna of ECOLOGY the Hawaiian Islands, the affinities of Conus are with the Indo-Pacific center of distribu­ Since the ecology of Conus has been dis­ tion .
    [Show full text]
  • THE LISTING of PHILIPPINE MARINE MOLLUSKS Guido T
    August 2017 Guido T. Poppe A LISTING OF PHILIPPINE MARINE MOLLUSKS - V1.00 THE LISTING OF PHILIPPINE MARINE MOLLUSKS Guido T. Poppe INTRODUCTION The publication of Philippine Marine Mollusks, Volumes 1 to 4 has been a revelation to the conchological community. Apart from being the delight of collectors, the PMM started a new way of layout and publishing - followed today by many authors. Internet technology has allowed more than 50 experts worldwide to work on the collection that forms the base of the 4 PMM books. This expertise, together with modern means of identification has allowed a quality in determinations which is unique in books covering a geographical area. Our Volume 1 was published only 9 years ago: in 2008. Since that time “a lot” has changed. Finally, after almost two decades, the digital world has been embraced by the scientific community, and a new generation of young scientists appeared, well acquainted with text processors, internet communication and digital photographic skills. Museums all over the planet start putting the holotypes online – a still ongoing process – which saves taxonomists from huge confusion and “guessing” about how animals look like. Initiatives as Biodiversity Heritage Library made accessible huge libraries to many thousands of biologists who, without that, were not able to publish properly. The process of all these technological revolutions is ongoing and improves taxonomy and nomenclature in a way which is unprecedented. All this caused an acceleration in the nomenclatural field: both in quantity and in quality of expertise and fieldwork. The above changes are not without huge problematics. Many studies are carried out on the wide diversity of these problems and even books are written on the subject.
    [Show full text]
  • Bioactive Marine Drugs and Marine Biomaterials for Brain Diseases
    Mar. Drugs 2014, 12, 2539-2589; doi:10.3390/md12052539 OPEN ACCESS marine drugs ISSN 1660–3397 www.mdpi.com/journal/marinedrugs Review Bioactive Marine Drugs and Marine Biomaterials for Brain Diseases Clara Grosso 1, Patrícia Valentão 1, Federico Ferreres 2 and Paula B. Andrade 1,* 1 REQUIMTE/Laboratory of Pharmacognosy, Department of Chemistry, Faculty of Pharmacy, University of Porto, Rua de Jorge Viterbo Ferreira, no. 228, 4050-313 Porto, Portugal; E-Mails: [email protected] (C.G.); [email protected] (P.V.) 2 Research Group on Quality, Safety and Bioactivity of Plant Foods, Department of Food Science and Technology, CEBAS (CSIC), P.O. Box 164, Campus University Espinardo, Murcia 30100, Spain; E-Mail: [email protected] * Author to whom correspondence should be addressed; E-Mail: [email protected]; Tel.: +351-22042-8654; Fax: +351-22609-3390. Received: 30 January 2014; in revised form: 10 April 2014 / Accepted: 16 April 2014 / Published: 2 May 2014 Abstract: Marine invertebrates produce a plethora of bioactive compounds, which serve as inspiration for marine biotechnology, particularly in drug discovery programs and biomaterials development. This review aims to summarize the potential of drugs derived from marine invertebrates in the field of neuroscience. Therefore, some examples of neuroprotective drugs and neurotoxins will be discussed. Their role in neuroscience research and development of new therapies targeting the central nervous system will be addressed, with particular focus on neuroinflammation and neurodegeneration. In addition, the neuronal growth promoted by marine drugs, as well as the recent advances in neural tissue engineering, will be highlighted. Keywords: aragonite; conotoxins; neurodegeneration; neuroinflammation; Aβ peptide; tau hyperphosphorylation; protein kinases; receptors; voltage-dependent ion channels; cyclooxygenases Mar.
    [Show full text]
  • Ion Channels
    UC Davis UC Davis Previously Published Works Title THE CONCISE GUIDE TO PHARMACOLOGY 2019/20: Ion channels. Permalink https://escholarship.org/uc/item/1442g5hg Journal British journal of pharmacology, 176 Suppl 1(S1) ISSN 0007-1188 Authors Alexander, Stephen PH Mathie, Alistair Peters, John A et al. Publication Date 2019-12-01 DOI 10.1111/bph.14749 License https://creativecommons.org/licenses/by/4.0/ 4.0 Peer reviewed eScholarship.org Powered by the California Digital Library University of California S.P.H. Alexander et al. The Concise Guide to PHARMACOLOGY 2019/20: Ion channels. British Journal of Pharmacology (2019) 176, S142–S228 THE CONCISE GUIDE TO PHARMACOLOGY 2019/20: Ion channels Stephen PH Alexander1 , Alistair Mathie2 ,JohnAPeters3 , Emma L Veale2 , Jörg Striessnig4 , Eamonn Kelly5, Jane F Armstrong6 , Elena Faccenda6 ,SimonDHarding6 ,AdamJPawson6 , Joanna L Sharman6 , Christopher Southan6 , Jamie A Davies6 and CGTP Collaborators 1School of Life Sciences, University of Nottingham Medical School, Nottingham, NG7 2UH, UK 2Medway School of Pharmacy, The Universities of Greenwich and Kent at Medway, Anson Building, Central Avenue, Chatham Maritime, Chatham, Kent, ME4 4TB, UK 3Neuroscience Division, Medical Education Institute, Ninewells Hospital and Medical School, University of Dundee, Dundee, DD1 9SY, UK 4Pharmacology and Toxicology, Institute of Pharmacy, University of Innsbruck, A-6020 Innsbruck, Austria 5School of Physiology, Pharmacology and Neuroscience, University of Bristol, Bristol, BS8 1TD, UK 6Centre for Discovery Brain Science, University of Edinburgh, Edinburgh, EH8 9XD, UK Abstract The Concise Guide to PHARMACOLOGY 2019/20 is the fourth in this series of biennial publications. The Concise Guide provides concise overviews of the key properties of nearly 1800 human drug targets with an emphasis on selective pharmacology (where available), plus links to the open access knowledgebase source of drug targets and their ligands (www.guidetopharmacology.org), which provides more detailed views of target and ligand properties.
    [Show full text]
  • (12) Patent Application Publication (10) Pub
    US 2003O181495A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2003/0181495 A1 Lai et al. (43) Pub. Date: Sep. 25, 2003 (54) THERAPEUTIC METHODS EMPLOYING Division of application No. 09/565,665, filed on May DSULFIDE DERVATIVES OF 5, 2000, now Pat. No. 6,589,991. DTHIOCARBAMATES AND Division of application No. 09/103,639, filed on Jun. COMPOSITIONS USEFUL THEREFOR 23, 1998, now Pat. No. 6,093,743. (75) Inventors: Ching-San Lai, Carlsbad, CA (US); Publication Classification Vassil P. Vassilev, San Diego, CA (US) (51) Int. Cl." ..................... A61K 31/426; A61K 31/325; Correspondence Address: A61K 31/55; A61K 31/4545; FOLEY & LARDNER A61K 31/4025 P.O. BOX 80278 (52) U.S. Cl. .................... 514/369; 514/476; 514/217.03; SAN DIEGO, CA 92138-0278 (US) 514/316; 514/422 (57) ABSTRACT Assignee: Medinox, Inc. (73) The present invention provides novel combinations of (21) Appl. No.: 10/394,794 dithiocarbamate disulfide dimers with other active agents. In one method, the disulfide derivative of a dithiocarbamate is (22) Filed: Mar. 21, 2003 coadministered with a thiazolidinedione for the treatment of diabetes. In another embodiment, In another embodiment, invention combinations further comprise additional active Related U.S. Application Data agents Such as, for example, metformin, insulin, Sulfony lureas, and the like. In another embodiment, the present (60) Continuation-in-part of application No. 10/044,096, invention relates to compositions and formulations useful in filed on Jan. 11, 2002, now Pat. No. 6,596,770. Such therapeutic methods. Patent Application Publication Sep. 25, 2003 Sheet 1 of 6 US 2003/0181495 A1 90 Wavelength 340 - Fig.
    [Show full text]
  • Proteins, Peptides, and Amino Acids
    Proteins, Peptides, and Amino Acids Chandra Mohan, Ph.D. Calbiochem-Novabiochem Corp., San Diego, CA The Chemical Nature of Amino Acids Peptides and polypeptides are polymers of α-amino acids. There are 20 α-amino acids that make-up all proteins of biological interest. The α-amino acids in peptides and proteins α consist of a carboxylic acid (-COOH) and an amino (-NH2) functional group attached to the same tetrahedral carbon atom. This carbon is known as the -carbon. The type of R- group attached to this carbon distinguishes one amino acid from another. Several other amino acids, also found in the body, may not be associated with peptides or proteins. These non-protein-associated amino acids perform specialized functions. Some of the α-amino acids found in proteins are also involved in other functions in the body. For example, tyrosine is involved in the formation of thyroid hormones, and glutamate and aspartate act as neurotransmitters at fast junctions. R Amino acids exist in either D- or L- enantiomorphs or stereoisomers. The D- and L-refer to the absolute confirmation of optically active compounds. With the exception of glycine, all other amino acids are mirror images that can not be superimposed. Most of the amino acids found in nature are of the L-type. Hence, eukaryotic proteins are always composed of L-amino acids although D-amino acids are found in bacterial cell walls and in some peptide antibiotics. All biological reactions occur in an aqueous phase. Hence, it is important to know how the R-group of any given amino acid dictates the structure-function relationships of peptides and proteins in solution.
    [Show full text]
  • Radular Morphology of Conus (Gastropoda: Caenogastropoda: Conidae) from India
    Molluscan Research 27(3): 111–122 ISSN 1323-5818 http://www.mapress.com/mr/ Magnolia Press Radular morphology of Conus (Gastropoda: Caenogastropoda: Conidae) from India J. BENJAMIN FRANKLIN, 1, 3 S. ANTONY FERNANDO, 1 B. A. CHALKE, 2 K. S. KRISHNAN. 2, 3* 1.Centre of Advanced Study in Marine Biology, Annamalai University, Parangipettai-608 502, Cuddalore, Tamilnadu, India. 2.Tata Institute of Fundamental Research, Homi Bhabha Road, Colaba, Mumbai-400 005, India. 3.National Centre for Biological Sciences, TIFR, Old Bellary Road, Bangalore-560 065, India.* Corresponding author E-mail: (K. S. Krishnan): [email protected]. Abstract Radular morphologies of 22 species of the genus Conus from Indian coastal waters were analyzed by optical and scanning elec- tron microscopy. Although the majority of species in the present study are vermivorous, all three feeding modes known to occur in the genus are represented. Specific radular-tooth structures consistently define feeding modes. Species showing simi- lar feeding modes also show fine differences in radular structures. We propose that these structures will be of value in species identification in cases of ambiguity in other characteristics. Examination of eight discrete radular-tooth components has allowed us to classify the studied species of Conus into three groups. We see much greater inter-specific differences amongst vermivorous than amongst molluscivorous and piscivorous species. We have used these differences to provide a formula for species identification. The radular teeth of Conus araneosus, C. augur, C. bayani, C. biliosus, C. hyaena, C. lentiginosus, C. loroisii, and C. malacanus are illustrated for the first time. In a few cases our study has also enabled the correction of some erroneous descriptions in the literature.
    [Show full text]
  • Florida Keys Species List
    FKNMS Species List A B C D E F G H I J K L M N O P Q R S T 1 Marine and Terrestrial Species of the Florida Keys 2 Phylum Subphylum Class Subclass Order Suborder Infraorder Superfamily Family Scientific Name Common Name Notes 3 1 Porifera (Sponges) Demospongia Dictyoceratida Spongiidae Euryspongia rosea species from G.P. Schmahl, BNP survey 4 2 Fasciospongia cerebriformis species from G.P. Schmahl, BNP survey 5 3 Hippospongia gossypina Velvet sponge 6 4 Hippospongia lachne Sheepswool sponge 7 5 Oligoceras violacea Tortugas survey, Wheaton list 8 6 Spongia barbara Yellow sponge 9 7 Spongia graminea Glove sponge 10 8 Spongia obscura Grass sponge 11 9 Spongia sterea Wire sponge 12 10 Irciniidae Ircinia campana Vase sponge 13 11 Ircinia felix Stinker sponge 14 12 Ircinia cf. Ramosa species from G.P. Schmahl, BNP survey 15 13 Ircinia strobilina Black-ball sponge 16 14 Smenospongia aurea species from G.P. Schmahl, BNP survey, Tortugas survey, Wheaton list 17 15 Thorecta horridus recorded from Keys by Wiedenmayer 18 16 Dendroceratida Dysideidae Dysidea etheria species from G.P. Schmahl, BNP survey; Tortugas survey, Wheaton list 19 17 Dysidea fragilis species from G.P. Schmahl, BNP survey; Tortugas survey, Wheaton list 20 18 Dysidea janiae species from G.P. Schmahl, BNP survey; Tortugas survey, Wheaton list 21 19 Dysidea variabilis species from G.P. Schmahl, BNP survey 22 20 Verongida Druinellidae Pseudoceratina crassa Branching tube sponge 23 21 Aplysinidae Aplysina archeri species from G.P. Schmahl, BNP survey 24 22 Aplysina cauliformis Row pore rope sponge 25 23 Aplysina fistularis Yellow tube sponge 26 24 Aplysina lacunosa 27 25 Verongula rigida Pitted sponge 28 26 Darwinellidae Aplysilla sulfurea species from G.P.
    [Show full text]
  • Ep 2932971 A1
    (19) TZZ ¥ __T (11) EP 2 932 971 A1 (12) EUROPEAN PATENT APPLICATION (43) Date of publication: (51) Int Cl.: 21.10.2015 Bulletin 2015/43 A61K 31/54 (2006.01) A61K 31/445 (2006.01) A61K 9/08 (2006.01) A61K 9/51 (2006.01) (2006.01) (21) Application number: 15000954.6 A61L 31/00 (22) Date of filing: 06.03.2006 (84) Designated Contracting States: • MCCORMACK, Stephen, Joseph AT BE BG CH CY CZ DE DK EE ES FI FR GB GR Claremont, CA 91711 (US) HU IE IS IT LI LT LU LV MC NL PL PT RO SE SI • SCHLOSS, John, Vinton SK TR Valencia, CA 91350 (US) • NAGY, Anna Imola (30) Priority: 04.03.2005 US 658207 P Saugus, CA 91350 (US) • PANANEN, Jacob, E. (62) Document number(s) of the earlier application(s) in 306 Los Angeles, CA 90042 (US) accordance with Art. 76 EPC: 06736872.0 / 1 861 104 (74) Representative: Ali, Suleman et al Avidity IP Limited (71) Applicant: Otonomy, Inc. Broers Building, Hauser Forum San Diego, CA 92121 (US) 21 JJ Thomson Avenue Cambridge CB3 0FA (GB) (72) Inventors: • LOBL, Thomas, Jay Remarks: Valencia, This application was filed on 09-04-2015 as a CA 91355-1995 (US) divisional application to the application mentioned under INID code 62. (54) KETAMINE FORMULATIONS (57) Formulations of ketamine for administration to the inner or middle ear. EP 2 932 971 A1 Printed by Jouve, 75001 PARIS (FR) EP 2 932 971 A1 Description [0001] This application claims the benefit of Serial No. 60/658,207 filed March 4, 2005.
    [Show full text]