31 August 1998 

• Posted the Final Program and Posters on cone shells and conotoxins delivered at the Inaugural Meeting "From Venoms to Drugs" on Heron Island, Queensland, Australia (August 16-21, 1998). The abstracts of these talks will appear later in the year in the Conference Proceedings to be published in Toxicon.

• Meeting Announcement: Workshop on Natural Toxins, September 27-October 1, 1998 at Dusit Thani Hotel, Bankok, Thailand. Contact: Dr. Anthony Tu, Fort Collins, Co. USA. Phone: 1-800-564-5213 or (970)-482-4632 or Fax: (970)-482-9169
  Selected papers include: "Studies on conotoxins of Conus betulinus" by Dr. Ji-Sheng Chen.

• Added information to the Contact List of folk interested in Cone Shells and Conotoxins - for Rik Deitsch, a member of the Research Team of Dr. Frank Mari, Department of Chemistry and Biochemistry at Florida Atlantic University in Boca Raton, Florida. Rik is a Researcher at Florida Atlantic University, Department of Biochemistry, working on contoxins. The research team consists of Dr. Frank Mari, Aldo Franco, Rik Deitsch, Alex Uribe, Herminsul Cano and Fred Pfleuger. They have a nascent web page at http://chemindy.sci.fau.edu/~mari/usscono.html

29 August 1998 

• Images of cones auctioned at Bret Raines' Molluscs Net Auction, August 1998: C.aurisiacus, C.barthelemyi, C.bengalensis, C.bullatus, C.crocatus, C.episcopus, C.geographus C.tulipa & C.obscorus, C.harlandi (Pair), C.hirasi, C.jaspideus forma pusillus (Set), C.jucundus (Parir), C.marmoreus (Pair), C.moluccensis merletti, C.natalis (mauve), C.natalis (orange), C.regius & C.regius citrinus, C.textle choimondaeieyi, C.textle suzannae, C.textile forma ??? (Set), C.zonatus. Next auction is on October 31, 1998.

27 August 1998 

• Elan Corporation, plc Completes Acquisition of Neurex Corporation

  Friday, August 14, 1998 12:44 PM
  DUBLIN, Ireland, Aug. 14 /PRNewswire/ -- Elan Corporation, plc (NYSE: ELN) ("Elan") today announced that it has completed its previously announced acquisition of Neurex Corporation (Nasdaq: NXCO) following approval by the stockholders of Neurex on August 11, 1998. Pursuant to the Agreement and Plan of Merger entered into on April 29, 1998, Neurex becomes a wholly-owned subsidiary of Elan and each Neurex stockholder will receive 0.51 of an Elan American Depositary Share ("ADS"), each ADS representing one Elan Ordinary Share, for each share of Neurex common stock. Neurex will be operated as a business unit of the Elan Pharmaceuticals division and Paul Goddard, Ph.D., the Chairman, Chief Executive Officer and President of Neurex immediately prior to the merger, will be appointed as President of such division. Neurex is a late-stage biopharmaceutical company developing products for pain management and the acute care market, principally in the area of cardiorenal and neurological disease. Neurex's strategy is to discover, develop and commercialize its products for acute care treatment in hospital settings, such as emergency rooms, intensive care units and pain clinics. Elan is a leading worldwide specialty pharmaceutical company, with its principal research and manufacturing facilities located in Ireland, the United States and Israel. Elan's shares trade on the New York, London and Dublin stock exchanges. SOURCE Elan Corporation, plc CONTACT: Mary Bingham, Director, Investor Relations of Elan Corporation, plc, 212-755-3218 Quote for referenced ticker symbols: NXCO, ELN © 1998, PR Newswire

  Direct your browser here to read about The Discovery and Development of SNX-111 and its clinical applications as Ziconotide, at the Neurex web site. Download a movie of Conus magus envenomating a guppy (2.2Mb), or for a faster download, obtain the animated gif (228K).

• The three articles linked here come from Worth magazine, USA, March 1997 (Part1 and Part 2) and March 1998 (98/03 Follow-Up). They provide a fascinating account of the history of the founding and development of Neurex Corp., the biotechnology company in Menlo Park, California, USA, who have pioneered the development of the cone shell toxin, omega conotoxin MVIIA from the venom of Conus magus, into a drug called ziconotide also known as SNX-111) through Stage III clinical trials for the treatment of intractible morphine-resistant pain.

12 August 

• Added Dr. Ronald L. Shimek , Montana,USA, to the "Contact List of folk interested in conotoxins". Ron has provided me with a number of references to the earlier work of Alan Kohn which I will endeavour to review in the context of these web pages. Ron writes that "My interest in Conus and conotoxins is as an analogue to the more numerous  and widespread, yet equally venomous gastropods that used to be classified in the Family Turridae.  The more advanced toxoglossate members of that family are now classified in the Family Conidae, in one of several subfamilies, but particularly the Oenopotinae, Borsoniinae, and Mangeliinae.   All of these are common and abundant predators in marine benthic communities throughout the world, yet are poorly known even though there are several thousand described species".

• The Preliminary Program for the scientific meeting on Heron Is., "From Venoms to Drugs" 16-21 August 1998, is now listed. Conotoxins are featured in the talks by Prof. Baldomero Olivera, Dr. George Miljanich, Prof. Michael McIntosh, John Gehrmann, Prof. Kazuki Sato, Dr. K. Nielsen, Dr. Christine Wright, Dr. P. Pallaghy, Mr. S. Warder, Dr. J. Cox, and Dr. Bruce Livett. In addition to these talks there will be other presentations on cone shells and contotoxins in video showings and posters. Looks like an interesting and active meeting. Both marine and terrestial toxins are featured.

• Emergency Medicine information about CONIDAE, detailing procedures for dealing with cone shell envenomation. Essential reading for cone shell collectors and field trip participants.[Authored by Suzanne Shepherd, Residency Director, Associate Professor of Emergency Medicine, Department of Emergency Medicine, Hospital of the University of Pennsylvania and James Martin, M.D., Emergency Medicine, Hospital of the University of Pennsylvania]

• George Sangiouloglou has recently updated his web site to include several specimens of "freak" Conus litteratus, "freak" Conus striatus and an albino Conus amadis. Also a very attractive Conus figulinus ? from Zamboanga Philippines with an unusual color and pattern [possibly Conus betulinus form (Zulu), see Manual of Living Conidae, page 352 #11], and a live Conus omaria under dead coral half in sand from Mactan Is. Cebu. Take a look - there are other cone shells of interest here too.

• from : Science Daily , a News Release (Posted 27/7/98)- "Marine Snail Toxin Targeted at African Toad Eggs Reveals Novel Impact on the Regulation of Serotonin", reporting on the recent article in Science by the UC San Francisco scientists Drs. David Julius and Laura England, together with Dr. Baldomero M. Olivera (University of Utah) and Drs A. Grey Craig and Jean Rivier from the Salk Institute. A 41-amino acid peptide, sigma-conotoxin GVIIIA, extracted from the venom of C.geographus, was found to inhibit the actions of serotonin on 5-HT3 receptors expressed in African toad eggs. Potential medical applications for drugs based on this conotoxins structure include treatment of nausea that accompanies chemotherapy, and pain and anxiety.For original article see :

England, L.J., Imperial, J., Jacobsen, R., Craig, A.G., Gulyas, J., Akhtar, M., Rivier, J., Julius, D. and Olivera, B.M. (1998) Inactivation of a Serotonin-Gated Ion Channel by a Polypeptide Toxin from Marine Snails. Science 281(5376) 575-578.

• Added reference to new paper on Conotoxin GI structure: Gehrmann J., Alewood, P.F. and Craik, D.J. (1998) "Structure determination of the three disulfide bond isomers of alpha-conotoxin GI: A model for the role of disulfide bonds in structural stability" J Mol Biol 278(2):401-415.

• Bret Raines has a huge auction going on at The Molluscs Net , until 11pm EST on Wednesday, 1 July 1998. He has about 150 shells on this auction and a lot of them are from Easter Is. There are 26 cones for auction - some very pretty. Here is a list: C.advertex (pair, Queensland, Australia) , C.aurisiacus (Mauritius), C.barthelemyi (Mauritius), C.bengalensis ( Phuket, Thailand), C.bocki (Thailand), C.brunneus (California, Mexico), C.gloriamaris (Cebu, Philippines), C.hirasei (Cebu, Philippines), C.lucidus (rare local, Cocos Islands, Costa Rica), C.memiae (pair, Cebu, Philippines), C.pascuaensis (pair, Easter Island), C.paulucciae (Reunion Is.), C. polyglotta (set of 4, Cebu, Philippines), C.poppei (pair, Cape Verde Islands), C.princeps (Baja Sur, Mexico), C.pulicarius (pair, Cebu, Philippines), C.sculletti (pair, Queensland), C.sindon (Mozambique), C.telatus (Philippines), C.thomae (Balutis, Philippines), C.tulipa (Noongoor Reef, Zanzibar), C.victoriae (set of 4, Western Australia ), C.vicdani (Bohol, Philippines), C.viola (Bolo Point, Okinawa), C.zapatoensis (pair, Mactan Is., Philippines ). So far the prices are low, so you might be able to get some super shells at a low price. Have fun - see if you can out-bid me !

• Added a Discussion List so you can participate in discussions about Cone Shells and Conotoxins. Join now by entering your email address above. With a discussion list, anyone on the list may send a message to the list. You send a message to Cone shells and conotoxins Discussion List by addressing your email to Cones_and_conotoxins@listbot.com . The system will check to make sure you are subscribed to the list.

NOTE: If you use an e-mail address other than the one you signed up with, then it will not allow you to send the message. However, you can go to the List Members area and enter additional "aliases" which will let the system accept any new email address you nominate.
Once you have joined, you can click on "View List Archive" (in small type below the box above) to view the previous messages OR click on the message:
View Cone Shells and Conotoxins Discussion List Archive 
SENDING A MESSAGE: When you send a message to Cones_and_conotoxins@listbot.com remember that it goes direct to list members' email addresses, unlike when you post a message to a bulletin board where members have to log in to the bulletin board in order to read the messages. So be careful to word your messages politely :)

• Guido Poppe's Cyberconchology web page now has over 145 images of cone shells and lists some 600 species.
• The homepage of the Dutch Malacological Society has been updated and is now largely bilingual (Dutch & English). You are invited to visit.
• Some recent scientific papers on conotoxins:
• Groebe, D.R., Gray, W.R. and Abramson, S.N. (1997) Determinants involved in the affinity of a-conotoxins GI and SI for the muscle subtype of nicotinic acetylcholine receptors. Biochemistry 36: 6469-6474.
• Jones, A., Bingham, J., Gehrmann, J., Bond, T., Loughnan, M., Atkins, A., Lewis, R.L. and Alewood, P.F. (1996) Isolation and characterization of conopeptides by HPLC/MS and MS/MS. Rapid Commun. Mass Spectrometry 10: 138-143.
• Lew, M.J., Flinn, J.P., Pallaghy, P.K., Murphy, R., Whorlow, S.L., Wright, C.E., Norton, R.S. and Angus, J.A. (1997) Structure-function relationships of omega-conotoxin GVIA. J.Biol.Chem. 272: 12014-12023.
• Loughnan,M., Bond, T., Atkins, A., Cuevas, J., Adams, D.J., Broxton, N.M., Down, J.G., Livett, B.G., Jones, A., Alewood, P.F. and Lewis, R.J. a-Conotoxin EpI, a Novel Sulfated Peptide from Conus episcopatus that Selectively Targets Neuronal Nicotinic Acetylcholine Receptors. Journal of Biological Chemistry 273: 15667-15674(1998) [Published June 19, 1998]
• Quiram, P.A. and Sine, S.M (1998a) Identification of residues in the neuronal a₇ acetylcholine receptor that confer selectivity for conotoxin ImI.J.Biol. Chem. 273: 11001-11006.
• Quiram, P.A. and Sine, S.M. (1998b) Structural elements in a-conotoxin essential for binding to neuronal a₇ receptors. J.Biol.Chem. 273: 11007-11011.
• Villarroya, M., De la Fuente, M., Lopez, M.G., Gandia, L. and Garcia, A.G. (1997) Distinct effects of omega-toxins and various groups of Ca²⁺-entry inhibitors on nicotinic acetylcholine receptors and Ca²⁺ channels of chromaffin cells. Eur. J. Pharm. 320: 249-257.

• Added report of studies on a conotoxin-G precursor from Conus geographus.

Bandyopadhyay, P.K., Colledge, C.J., Walker, C.S., Zhou, L.M., Hillyard, D.R. and Olivera, B.M. (1998) Conantokin-G precursor and its role in g-carboxylation by vitamin K-dependent carboxylase from a Conus snail. J. Biol. Chem. 273: (10) 5447-5450.

• The g-carboxylated 17-amino acid Conus peptide conantokin-G is initially translated as a prepropeptide of 100 amino acids. The precursor is similar to that previously reported for disufide-rich conotoxins. The mature peptide is found in a single copy at the C-terminal end of the precursor and is processed post-translationally producing : g-carboxylation of five glu residues, C-terminal amidation of asparagine-17 following excision of the C-terminal tripeptide, and a proteolytic event between Arg-1 and Gly1.
• The conantokin-G precursor has 59 amino acids in the intervening pro-region, the longest so far reported for any Conus venom peptide with a potential function of a g-carboxylation recognition sequence for the Conus venom duct g-glutamyl carboxylase in the -1 to -20 region.
• The g-carboxylation recognition sequence included in the -1 to -20 region of the conantokin-G prepropeptide appears to increase the affinity of the Conus carboxylase by approximately 2 orders of magnitude !!

9 June, 1998 

Added transcript of interview on June 7 1998 with Dr. Bruce Livett, on "Cone Shells and Conotoxins - Medical Applications" on station 3RRR(102.7 FM)Melbourne, Australia. Interviewer Tim Allen.

Added link to images of the following 8 Conus  from Brett Raines' site "The Molluscs Net" (one cone was collected from Easter Island, and the others from various places). If you would like some good quality, low priced shells point your browser at www.molluscs.net.  Bret Raines runs a shell auction on the web where the prices are low. Many of the cones are normally hard to obtain.. Have fun at the auction at URL http://www.molluscs.net/molluscan/mini_auction.htm.
• The auction began 5pm on 29th May 1998 and closes at 8pm PST on Wednesday, 3 June 1998): Among the Conus family up for auction is  Conus pascuaensis  (Easter Island). The Easter Island specimen was dead collected. Exact locality data is provided with the individual specimens.   For identification, Raines uses "The Marine Mollusks of Easter Island (Isla de Pascua) and Sala y Gomez" by Dr Harald Rehder as his reference.
• The other 7 cones include Conus brunneus (Gulf of California, Mexico), dusaveli (Cebu, Philippines), euetrios (Inhaca Island, Mozambique), gloriamaris (Cebu, Philippines), ione (Panglao, Bohol, Philippines), poppei (Cape Verde Islands),  and zonatus (Maldvides).
• At the Molluscs Net you will also find a neat List of Mollusc Links.
• The Molluscs Net is a network of shell dealers and collectors. It is the only site on the internet that offers free classifieds for collectors, on-line dealer's lists, shell auctions, a list of hundreds of collectors and clubs, a chat room and online forum and tons of links to other shell-related sites all from one location. The Molluscs Net also builds and hosts custom webpages for any shell club in the world - absolutely free of charge.  Enjoy :)  B.G.L.

• Listed four new patents on conotoxins issued between September 1997 and April 1998. Added to main list of conotoxin patents

• Added notice of publication about a-Conotoxin EpI, a Novel Sulfated Peptide from Conus episcopatus that Selectively Targets Neuronal Nicotinic Acetylcholine Receptors" - by Marion Loughnan,Trudy Bond, Anne Atkins, Javier Cuevas, David J. Adams, Natalie M. Broxton, John G. Down, Bruce G. Livett, Alun Jones, Paul F. Alewood and Richard J. Lewis. Journal of Biological Chemistry 273: 15667-15674(1998) [Published June 19, 1998]

• Added link to Mike Fainzilber's Molecular Neurobiology Group at the Dept. of Biological Chemistry, Weizmann Institute of Science, Rehovot, Israel. Some recent publications on conotoxins from Mike Fainzilber:
• Kits, K.S., Lodder, J.C., van der Schors, R., Li, K.W., Geraerts, W.P.M., & Fainzilber, M. , 1996: Novel w-conotoxins block dihydropyridine-insensitive high voltage-activated calcium channels in molluscan neurons. J. Neurochem. 67: 2155-2163.
• Fainzilber, M., Nakamura, T., Lodder, J.C., Zlotkin, E., Kits, K.S., & Burlingame, A.L., 1998: g-Conotoxin-PnVIIA, a gGlu-containing peptide agonist of neuronal pacemaker cation currents. Biochemistry 37, 1470-1477.

• Link to George Sangioulo's Seashells & Underwater World Home Page (see also entry for 2 April, below) containing the Live Seashells Gallery where the following two live specimens of Conus are shown: (1) Conus terebra can be seen under dead coral between big coral blocks in 5 m depth in Had Klong Muang Krabi, December 1997; and (2) Conus omaria under dead coral, half in sand, from Mactan Is., Cebu, April 1997.

Also, specimen shells of Conus terebra in various sizes and shapes. Conus ranonganus (Gem 92.6 mm $1,050, very nice pattern. Trawled 80-120 m depth - from west side of Phuket Is. Andaman Sea, 1997), and Conus schech (form of Castanofasiatus); F+/Gem 69.3 mm $300, very nice. Trawled 80-120 m depth, - from Phuket Is. Andaman Sea, 1997) and Conus vicweei (Gem 80.8 mm $1,450. Dark color with excellent pattern to the lips - the best ever seen - a jewel ! Trawled 80-120 m depth - from west side of Phuket Is. Andaman Sea, 1997).

• Link to Conchologists of America (COA) New Species of Conus.
• Link to Brian Hayes'ALGOA BAY SPECIMEN SHELLS.

Algoa Bay Specimen Shells specializes in shells from South Africa. Brian Hayes has an honours degree in Zoology and has carried out research on molluscs at University. Brian obtains many of his shells from local divers, collectors and deep-sea fishing vessels. Among Brian Hayes' collection of CONIDAE for sale are the following: Conus altispiratus,Conus infrenatus, Conus natalis, Conus pictus, Conus tinianus, and Conus visagenus (new addition).

• Added link to PBS OnLine Nature program featuring venomous creatures. Titled, VICTIMS OF VENOM, the program contains information about Venom From the Sea, including venomous cone shells, marine snakes, octopi and sea slugs. Terrestrial snakes (eg. rattlesnakes and cobra), scorpions, and other creatures such as shrews, spiders, insects, salamanders, and even some types of plants also use poisonous venoms.

PBS OnLine Nature : "Victims of Venom"
Discover the poisons that make animals, plants and even people victims of venom with this informative site. Meet venom expert Bill Haast as well as some creatures of the deep who use poison as a survival tactic, and learn why a dwindling rattlesnake population could be bad news for the drug industry.

A very useful Resources section contains both Online Resources with links to many interesting web sites, Print Resources - Books and Video.

Video
To purchase the video of VICTIMS OF VENOM, please contact WNET Video Distribution by calling (800) 336-1917, or by writing to WNET Video Distribution, P.O. Box 2284, South Burlington, VT 05407.

• Added link to image of rare orange form of Conus pictus Reeve, 1843. Source: Brian Hayes, ALGOA BAY SPECIMEN SHELLS - the  Largest Specimen Dealer in South Africa (specialist in S. African and world-wide shells) P.O.BOX 804, Port Elizabeth, 6000, South Africa.

 

• Added link to Conus pennaceus: Growth, fecundity and mortality of Conus Pennaceus in Hawaii, another in the sequence of excellent illustrated articles (this one about Conus pennaceus) resurrected by Wesley Thorssen from the original article by Frank E. Perron. Note: The complete reference section of the original paper is presented here, but the remainder of the original paper has been shortened and most statistical formulae have not been included. The complete article is available, however in Ecology 64 (1) (1983) pp. 53-62.

See also entry below for 2 March 1998 giving links to two other articles by Frank Perron "Laboratory Culture of Conus Textile" , and "Larval Growth and Metamorphosis of Conus".

• Link to George Sangiouloglou's Seashell Gallery. Here are some nice images of Conus amadis albino (F+ 81 mm 350 $  Trawled 60-80 mtrs depths. From  Ranong Andaman Sea, 1997), Conus amadis (Gem 72,6-87,7 mm 20 $ Trawled From  Ranong Andaman Sea  1997), Conus arbornatalis (F+/Gem 87 mm  300 $ Trawled 60-80 mtrs depths From  Phuket Isl. Andaman Sea  1997), Conus bengalensis  (F+/Gem 113 mm 250 $ Trawled 60-120 mtrs depths From west side of Phuket Isl. Andaman Sea 1997). Conus bengalensis Golden Form  (Gem 119,4 mm 300 $ Trawled 60-120 mtrs depths From west side of Phuket Isl. Andaman Sea 1997), Conus chusaki (F+/Gem 51-56 mm  30 $ & 40-49 mm 20 $ Dived 30 mtrs. Racha Isl. Phuket Andaman Sea1997), Conus dusaveli  (F+++  82 mm 150 $ Dark color variation only one growth flow not important still very beautiful. Balut Isl. Mindanao 1997), Conus phuketensis  (F+/Gem 70 mm 180 $ Dark color. Trawled 80-120 mtrs. From Ranong  to Phuket Isl. Andaman Sea 1997), Conus phuketensis (F+/Gem 69 mm 180 $ Light color.Trawled 80-120 mtrs. From Ranong  to Phuket Isl. Andaman Sea 1997), Conus ranonganus  (Gem 92,6 mm 1.050 $ Very nice Pattern. Trawled 80-120 mtrs depths. From  West side of Phuket Isl. Andaman Sea 97), Conus terebra in various sizes and shapes. Conus schech (form of Castanofasiatus)  F+/Gem 69,3 mm 300 $ Very nice. Trawled 80-120 mtrs depths, From  Phuket Isl. Andaman Sea  1997) and Conus vicweei  (Gem 80,8 mm 1.450 $ Dark color with excellent pattern till the lips the best never seen is a jewel.Trawled 80-120 mtrs depths From  West side of Phuket Isl. Andaman Sea 1997).

Provided link to an 87Kb animated gif of a cone shell attacking a small fish. Not for the feint hearted. Video source courtesy of Dr. George Miljanich of Neurex Corporation, Menlo Park, California. View animation here.

11 March, 1998 

The Web site http://www.erols.com/worldwide/Presentations.htm describes a video program "Focus On Conchology" a professionally produced television program (on VHS cassette) in magazine format dealing with the hobby and science of shell collecting. It takes you around the world to meet the people, go to the places, and see the trends in Conchology. The one hour program has four major segments interspersed with shorter segments. The feature segment takes you to Hawaii's remote country to see why its endemic land snail fauna is becoming endangered. The footage is breathtaking. The VHS video cassette is available for rental to Shell Clubs. An interview with Cone shell expert Bob DaMotta will give you a better understanding about the man who has spent many years studying and amassing one of the largest private Cone collections in the world. His thoughts and ideas on Cone shell taxonomy have been considered controversial. Click here to see a graphic from the Cone Shell section of the video. A number of beautiful Cone shells are shown during the interview.

• Added reference of potential interest to mechanism of action of conotoxins and other small peptides at the nicotinic receptor. Lin-Shiau, S-Y. (1998) Studies on curare-like action of the tripeptide carbobenzoxy-Gly-Gly-Arg-[beta]-naphthylamide in mouse diaphragm. Eur. J. Pharmacol. 343: 51-56.

Added links to two articles in the Hawaii Shell News (March 1998).

"Laboratory Culture of Conus Textile" by Frank E. Perron
A summary of information from a paper of this name in the Journal Exp. Mar. Biol. Ecol., 1980, Vol 42, pp 27 - 38  by Frank E. Perron ^* and personal communications. Summary by Wesley Thorsson^** with more photos and observations of this Conus
    ^* 26 Union St., Peterborough, NH 03458
  ^** thorsson@hits.net

"Larval Growth and Metamorphosis of Conus" by Frank E. Perron
A summary of a paper² by Frank E. Perron¹.
Summarized by Wesley Thorsson³ with additional observations.
  ¹  26 Union St., Peterborough, NH 03458
  ²  Larval Growth and Metamorphosis of Conus (Gastropoda: Toxoglossa) in Hawaii
       in Pacific Science (1981), Vol. 35, No. 1, pgs 25 to 38  By Frank E. Perron
  ³  thorsson@hits.net
 

Added link to United States Patent 5700778 Conotoxins I (INVENTORS: Olivera; Baldomero M., Salt Lake City, UT et al. ASSIGNEES: The Salk Institute for Biological Studies, La Jolla, CA., and University of Utah Research Foundation, Salt Lake City, UT. ISSUED Dec. 23, 1997; Filed June 2, 1995.)

• Added a Search capability to this site.

• Added link to three past Shell-O-Gram newsletter articles from the Jacksonville Shell Club containing a very interesting article on Mollusks and Man: A Medical Perspective, by Harry G. Lee, M.D.  (Adapted from The Junonia, newsletter of The Sanibel-Captiva Shell Club, June 1995 and published in the Shell-O-Gram, July-August, 1995). The first two installments deal with infections and intoxications (biotoxins) brought to man through the agency of mollusks. Part Three - gives a historical perspective on the discovery of  cones and the examination of their venom, together with preliminary data on the toxins that constitute the venom  This article  reports on envenomation from Conus aulicus, Conus textile and Conus striatus and is very readable.

• Added several sources of information to the First Aid  page dealing with management and treatment of cone shell envenomation . These are essential reading for anyone handling or collecting cone shells.
• Safety Procedures for dealing with envenomation by Conidae (Univ. Pennsylvania)
• The Diver's First Aid Reference to Potentially Hazardous Marine Life (Auburn University), this 4 page reference guide covers a wide range of potentially hazardous marine life including cone shells.
• Venomous Bites and Stings - Active First Aid Online v2.5
• Australian Venoms Database, (Molluscs: Cone snails, Blue-ringed Octopi, Sea Hares) . Maintained by Bryan Grieg Fry (Queensland) provides an on-line guide to Australian venomous animals, including cone shells. Lists the Poisons Information Centre (13 11 26 Australia wide). Available 24 hours a day..

• Added two references on Conus venoms and their toxins (one new, one old).
• Fainzilber, M., Nakamura, T., Lodder, J.C., Zlotkin, E., Kits, K.S. and Burlingame, A.L. (1998) g-Conotoxin-PnVIIA, A g-carboxygutamate-containing peptide agonist of neuronal pacemaker cation currents. Biochemistry (in press).
• Lev-Ram, V., Olivera, B.M., Levitan, I.B., Corpuz, G.P., Ramilo, C.A., Hillyard, D.R. and Cruz, L.J. (1991) Molluscan Conus venoms: A source of toxin probes for molluscan neurobiology. In: Molluscan Neurobiology. Edited by K.S. Kits, H.H. Boer and J. Joose.  Proceedings of the 3rd Symposium on Molluscan Neurobiology, Amsterdam, the Netherlands, Aug 20-24 1990, North-Holland, Amsterdam / Oxford / New York, 1991 [Abstract: The approximately 50 different species of molluscivorous Conus marine snails use their venoms to prey on other molluscs. Although the physiological characterization of these venoms has just been initiated, extensive biochemical work has revealed that the venoms are very complex, with many disulfide rich peptides present in a single venom. Preliminary evidence that these components are likely to affect receptors and ion channels in molluscan neurons is described here. The molluscivorous Conus are therefore a potentially rich source of specifically targeted ligands for the receptors and ion channels that are responsible for molluscan nervous system function. We anticipate that these will become standard tools in molluscan neurobiology]

• Link to Company Information for Neurex Pharmaceuticals, including Valuation, Analyst Reports, Recent SEC Filings, Quote Graph, News, Alliances, Clinicals and Contacts. (Neurex has 2 drugs in advanced Phase 3 trials (Corlopam and (SNX-111) and the results for both so far are very promising. Corlopam, is used to control blood pressure in patients undergoing major heart surgery and for severely hypertensive patients who can't take pills. Approximately 450,000 bypass operations and heart surgeries are performed in the USA each year requiring patient's blood pressure to be lowered. Another 120,000 patients suffer from severe hypertension. "Montgomery Securities analyst Scott Sacane sees Corlopam pulling in sales of $9 million in 1997, $18 million in 1998 and $36 million in 1999." SNX-111 (w-conotoxin MVIIA) is Neurex's revolutionary pain killing drug and when approved may replace morphine and the popular pain killer, codeine. The drug has two main applications : the treatment of severe intractable pain caused by cancer or AIDS or phantom limb syndrome, and the treatment of brain damage due to a lack of oxygen to the brain, a condition known as ischemia. A history of the discussions on this stock appears in AOL under "Company Message Boards".

• Cancer-pain remedy wins orphan-drug status. The Food and Drug Administration has granted orphan drug status to methylnaltrexone, a medication that blocks the side effects of morphine without interfering with pain relief…Many patients with chronic pain cannot tolerate the side effects of long-term use of opioid-based pain medications such as morphine. These side effects include nausea and severe constipation. As many as 40 percent of chronic pain patients chose to live with the pain rather than endure the side effects. But methylnaltrexone may make morphine more manageable. Recently published studies from Roizen, Foss and colleagues Chun-Su Yuan, PhD and Jonathan Moss, MD PhD from the University of Chicago, demonstrated that it can block the side effects of opioid-based pain relievers, preventing the constipation without altering its effects on pain….Phase II-III trials of methylnaltrexone, which will test how well the drug works and how it compares to alternative medications, will begin at the University of Chicago Hospitals Clinical Research Center and a hospice in Great Britain this year.

• Presentations on conotoxins at the Twenty Third Annual Lorne Conference on "Protein structure and Function", Lorne, Australia, 8-12 February 1998.
• Added reference to molecular action of SNX-111 in humans. Mcguire, D., Bowersox, S., Fellmann, J.D. and Luther, R.R . (1997) "Sympatholysis after neuron-specific, N-type, voltage-sensitive calcium channel blockade - first demonstration of N-channel function in humans". Journal of Cardiovascular Pharmacology. 30(3):400-403.
• Abstract: "SNX-111 [w-conotoxin MVIIA] is the first neuronal N-type, voltage-sensitive calcium channel (VSCC) blocker to enter clinical drug development. Areas of potential therapeutic utility include treatment of nociceptive and neuropathic pain and neuroprotection after ischemic brain injury. The data presented demonstrate that SNX-111 is biologically active in humans and indicate for the first time a neurophysiologic function of N-type VSCCs in humans".
• Reference on action of w-conotoxins on chromaffin cells. Gandia, L., Lara, B., Imperial, J.S., Villarroya, M., Albillos, A., Maroto, R., Garcia, A.G. and Olivera B.M. (1997) "Analogies and differences between omega-conotoxins MVIIC and MVIID - binding sites and functions in bovine chromaffin cells". Pflugers Archiv - European Journal of Physiology. 435(1):55-64, 1997

 

• Conference : From Venoms to Drugs, Heron Island, Great Barrier Reef, Australia, 16­21 August, 1998. Preliminary Program, Invited Speakers and Information. View the Logo (alpha conotoxin GI).

 
• Molecular Neurobiology: A Gallery of Animations: 3-D Studio graphic of ions entering the pentameric ligand-gated ion channel associated with the nicotinic acetylcholine receptor (as found at cholinergic synapses).

As seen on ABC, Peter Jennings. Animation of nicotine competition with acetylcholine at nicotinic cholinergic receptors showing opening of ion channels and current spread. (see also Neuroscience on the Internet).
Copyright 1997, Gayle Gross de Nunez and SAVANTES. Used with permission.
• To see full animation DOWNLOAD "nicotine.avi" FROM FTP SITE: 100 X 67 pixels, 1.258 MB,
or click here (and then click again on image after it has downloaded).
• Portions of these animations were featured on "An ABC News Town Meeting, 'Kids ... Parents ... Straight Talk on Drugs' with Peter Jennings" (ABC) Sunday March 30th, 1997. Videotapes of that show are available via ABC at 800-913-3434.
• "Animated Neuroscience" is a SAVANTES production
• Copyright 1996, Gayle Gross de Nunez and SAVANTES.
• ALL RIGHTS RESERVED
• Representation of cholinergic synapses. Ions enter channels in receptors activated by the binding of neurotransmitter molecules; electrical current begins to spread from the activated receptors.
• Interior of nerve terminal showing fusion of synaptic vesicles with terminal membrane and release of neurotransmitters into synaptic cleft (animation "fusion.avi", 850K). Representation of neuron with terminals. Cross section through nerve terminal with synaptic vesicles showing blockage of neurotransmitter uptake pumps by drug molecules - dopamine reuptake into synaptic terminal, and block of reuptake by cocaine (animation "newpump.avi" 1.01 Mb).
• The images are from a 20 min. animation on normal brain function produced by Savantes under a grant from the National Institute on Drug Abuse.

Animations may be downloaded from Animation Gallery I : Medical Animation, Synaptic Pharmacology.

• Ackerman, S. J. Reform of the Killer Snails. National Center for Research Resources (NCRR) Reporter XXI: 5- 7, 1997.
• Aceto, M. D.; Bowman, E. R.; Harris, L. S.; and May, E. L.: Dependence Studies of New Compounds in the Rhesus Monkey, Rat and Mouse (1997). In: L. S. Harris, ed. Problems of Drug Dependence 1997, NIDA Research Monograph, Washington, D.C., 1998, in press.
• Woods, J. H.; Traynor, J.; Butelman, E. R.; and Winger, G. D.: Evaluation of New Compounds for Opioid Activity (1997). In: L. S. Harris, ed. Problems of Drug Dependence 1997, NIDA Research Monograph, Washington, D.C., 1998, in press.

• Link to Eddie's Shell Catalogue listing some 650 species of CONIDAE (cone shells) with location and habitat given. Those listed with an asterisk (*) preceding the name (eg. *Conus marmoreus and *Conus magus) are accompanied by an image. There are over 197 different images of cone shells in this catalogue. Also take a look at Eddie's list of shell books.
• The shell connection: A Quality Specimen Shell Supplier. Extensive database of quality shells including cone shells (be patient, takes a while to load 86K database).
• Cyberdiver : with on line images to allow you to preview each dive location.Includes an image of a live tented cone shell.
• TV program and video on Conus envenomation: This ITV science program is Part 4 in a Nature Watch Digest series designed for schools. It contains video footage of cone shell envenomation.
• Print of Linnaeus giving a cone shell its pattern !: One of the most common questions asked of a shell collector is "Are those shells painted ?". It was this question that gave Ed Blackwell the idea for this print. The shells in the print were chosen by the Indianapolis Shell Club to depict the most common classes - and naturally the cone shell is prominently featured. The print (in Black & White, or Color) is available for purchase from the Indianapolis Shell Club.
• Kathleen Mccabe's nightmare about collecting live cones. This amusing and scary piece appeared on CONCH-L on Tue, 6 Jan 1998, in response to emails to Kathleen Mccabe from mail list members giving her advice on how to handle dangerous cones in advance of her collecting trip to Fiji later this year. -- Still want to work on cone shells ?
• Cone shell armbands from Nan Madol. The rulers of Nan Madol on the island of Pohnpei were identified by their shell armbands made of tridacna and conus shell. The armbands, carved in several styles, have been found in association with the remains of chiefs on the islets Nan Madol within tombs (date 600 BP) and as surface finds. This fascinating article by Christopher J. Scheller, Department of Anthropology, University of Oregon, describes the classification, analysis and construction of these shell armbands in which the largest part of the conus shell is cut away and then the inside spirals are removed (see Figure 1) leaving a natural band to be worn on the arm or strung as bead.
• Link to publications from "Of Sea and Shore" which publishes "Of Sea and Shore Magazine", "Catalog of Dealer's Prices of Shells (Marine, Land & Freshwater)", "A Sheller's Directory of Clubs, Books, Periodicals & Dealers", "The Directory of Conchologists / Malacologists", "A Checklist of Mollusks on Postage Stamps", "Dictionary to English/French Shell Terms", and other shell-related publications. These publications include information on cone shells.
• Link to Cone Shells at Einstein's Emporium. Here are some nice images of the Geographic Cone (Conus geographus), Textile Cone (Conus textile), Lettered Cone (Conus litteratus), Marbled Cone (Conus marmoreus) and the Virgin Cone (Conus virgo).
• Links to current research on Conus peptides (conotoxins). Studies by Drs. Baldomero Olivera (Utah), Jean E. Rivier, J.M. Mc Intosh (Utah), Steven M. Sine (Mayo), Vladimir J. Basus (UCSF), Thomas L. James (UCSF) and others. Summaries of work completed and work in progress on conotoxins from Conus magus, striatus, obscurus, tulipa, purpurascens, radiatus, californicus, textile, geographus, imperialis and pacificus.The conotoxins being studied include w-conotoxins GVIA, MVIIA, MVIIC and SVIB;and alpha conotoxins MI and ImI. The research program initiated by Dr. Olivera supports three major projects, each divided into three subprojects.The program supports three scientific coores: (1) a Conus venom resource core, which includes a molecular biology component, (2) a peptide sequencing and synthesis core and (3) an electrophysiology core. The focus of each project is : Project I - omega-conotoxins and Ca++ channels; Project II - Cholinergic Conus peptides and nicotinic acetylcholine receptors and Project III - Conantokins and NMDA receptors. Studies include use of mass spectrometry to determine post translational modifications including acylation, glycosylation, phosphorylation, sulfation and amidation. Sequence and structure analysis of synthetic peptides (Rivier) makes use of solid-phase peptide synthesis, HPLC, capillary zone electrophoresis, Edman degradation, amino acid analysis, mass spectrometry (LC/MS) (Rivier / Fainzilber), enzymatic and chemical hydrolysis and partial reduction techniques. A variety of conotoxins isolated from conus snails from the Gulf of Acquaba are being studied by Michael Fainzilber by mass spectrometric methods.Dynamic structural studies of w-conotoxins (Basus / James) and psi-conotoxin, a novel non-competitive inhibitor of the nicotinic acetylcholine receptor (Shon) makes use of both solid phase and solution NMR. The study by Basus and James makes use of the program MARDIGRAS to obtain accurate distance constraints, and PARSE (Probability Assessment via Relaxation rates of a Structural Ensemble), respectively, to refine individual conformers contributing to the observable NMR parameters giving rise to multiple conformers of w-conotoxins in solution. In other studies (Mc Intosh / Sine) site-directed mutagenesis, an oocyte expression system and expression in mammalian cells as well as a battery of functional measurements including radiolabeling and receptor binding techniques, single channel recording and protein biochemistry will be used to determine the subtype specificity of novel ligands (conotoxins) to cloned nicotinic receptors (nAChRs) expressed in oocytes. Conotoxins will help researchers determine the functional role and significance of neuronal nAChRs in health and in several neuromuscular and neuropsychiatric disorders including congenital myasthenic syndromes (CMS), Tourette's syndrome, Alzheimer's disease, schizophrenia, tardive dyskinesia, and Parkinson's disease.

• It has come to my attention through information provided on CONCH-L mail list by Wes Thorsson (Hawaiin Shell Club), that some time ago Frank Perron raised almost all the Hawaiian Conus from eggs. Wes is compiling this material as a web document. In the meantime, here are the original references to these fascinating studies:
• "Growth, Fecundity, and Mortality of Conus Pennaceus in Hawaii" by Frank E. Perron. Ecology, 64(1), 1983, pp 53-62 Copywrite 1983 by the Ecological Society of America.
• "Laboratory Culture of the Larvae of Conus Textile Linne (Gastropoda: Toxoglossa)" by Frank E. Perron. J. exp. mar. Biol. Ecol., 1980, Vol 42, pp. 27-28 Copywrite Elsevier/North-Holland Biomedical Press.
• "Larval Growth and Metamorphosis of Conus (Gastropoda: Toxoglossa) in Hawaii" by Frank E. Peron. Pacific Science (1981), vol.35 no. 1. Copywrite 1981 by The University Press of Hawaii.

17 January, 1998 

• Added reference to "Venom Peptides as Human Pharmaceuticals" by George Miljanich, Science and Medicine, September-October 1997, pp. 6-15.

• Added link to images of the following cones (for auction at Molluscs Net at URL http://www.molluscs.net/molluscan/mini_auction.htm until 8 PM Friday 15 January, 1998): Conus cedonulli (South of St. Vincent), centurio (Guajiara Peninsula, Columbia), crotchii (Cape Verde Islands), delessertii (Ft. Myers Beach, Florida), dusaveli (Balut Is., Mindanao, Philippines), episcopus (Sempora, Sabah, Borneo), gloriamaris (Cebu, Philippines), gubernator (Mozambique), ione (Philippines), kinoshitae (Philippines), natalis (Northern Transkei area of S. Africa), poppei (Cape Verde Islands), pulicarius (Kota Kinabalu, Sabah, Borneo), victoriae (Broome, Australia), zapatoensis (Mactan Is., Philippines), and zonatus (Maldvides).
• Mollusca: The Southern Synthesis is now published (Jan. 1998) and is the most comprehensive and authoritative treatment yet of Australia's marine, freshwater and terrestrial molluscs. It is a significant international reference, with contributions from 70 authors, and in which some 7700 papers in the primary literature are cited. Most molluscan families described in the book are also found in the Northern Hemisphere, making this title an essential reference for malacologists worldwide.

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