Granulomatous jellyfish dermatitis

The induction of a granulomatous inflammation by jellyfish toxins is rare. More typically, acute toxic and urticarial reactions are seen. An 11-year-old boy developed a striated urticarial erythema on the left cheek after contact with a gelatinous mass while swimming in the sea in Croatia. After initial erosion, a striated induration developed in the area of contact. Histological examination revealed a granulomatous inflammation with some eosinophils. While topical steroid-based antiinflammatory and antibacterial therapy over several weeks was not effective, topical therapy with tacrolimus 0.1% for two two-week treatment periods led to healing of the skin changes with a slight scar. There was no clinical recurrence after 5 month of follow-up.     

A new membrane-attack complex/perforin (MACPF) domain lethal toxin from the nematocyst venom of the Okinawan sea anemone Actineria villosa.

The Okinawan sea anemone Actineria villosa causes severe cases of stinging. We isolated the 60 kDa A. villosa toxin (AvTX-60A) as the major toxin from the isolated nematocysts of this species. AvTX-60A showed fatal toxicity to mice with intraperitoneal injection at a minimum lethal dose of less than 250 microg/kg. The N-terminal amino acid sequence was determined and the corresponding cDNA encoding AvTX-60A was sequenced. The deduced amino acid sequence of AvTX-60A showed high similarity with PsTX-60A, which had been isolated as one of the major toxins from the venomous sea anemone Phyllodiscus semoni. These sea anemone toxins are new members of the family of proteins containing membrane-attack complex/perforin (MACPF) domains, best known in pore forming proteins such as perforin. These are the first examples of MACPF domain proteins as toxins for prey acquisition or repelling predators in nature.     

Aging and longevity in the simplest animals and the quest for immortality

Here we review the examples of great longevity and potential immortality in the earliest animal types and contrast and compare these to humans and other higher animals. We start by discussing aging in single-celled organisms such as yeast and ciliates, and the idea of the immortal cell clone. Then we describe how these cell clones could become organized into colonies of different cell types that lead to multicellular animal life. We survey aging and longevity in all of the basal metazoan groups including ctenophores (comb jellies), sponges, placozoans, cnidarians (hydras, jellyfish, corals and sea anemones) and myxozoans. Then we move to the simplest bilaterian animals (with a head, three body cell layers, and bilateral symmetry), the two phyla of flatworms. A key determinant of longevity and immortality in most of these simple animals is the large numbers of pluripotent stem cells that underlie the remarkable abilities of these animals to regenerate and rejuvenate themselves. Finally, we discuss briefly the evolution of the higher bilaterians and how longevity was reduced and immortality lost due to attainment of greater body complexity and cell cycle strategies that protect these complex organisms from developing tumors. We also briefly consider how the evolution of multiple aging-related mechanisms/pathways hinders our ability to understand and modify the aging process in higher organisms.     

BMPs and Chordin regulate patterning of the directive axis in a sea anemone

The TGF-β molecules Dpp/BMP2/4/7 and their antagonist Sog/Chd play a conserved role in establishing the dorso-ventral (DV) axis in bilaterians. Homologues of BMPs and the antagonist, Chordin, have been isolated from Cnidaria and show a striking asymmetric expression pattern with respect to the primary oral-aboral (OA) axis. We used Morpholino knockdowns of Nematostella dpp (bmp2/4), bmp5-8, chordin, and tolloid to investigate their function during early development of the sea anemone Nematostella vectensis. Molecular analysis of the BMP Morpholino phenotypes revealed an upregulated and radialized expression of bmps and chordin in ectoderm and endoderm indicating a negative feedback loop. Our data further suggest that BMP signaling is required for symmetry breaking of bmp and chordin expression during gastrulation. While bmps and chordin marker genes of the ectodermal OA axis extended aborally, other ectodermal markers of the OA axis were not significantly affected. By contrast, expression of other endodermal marker genes marking both the OA and the directive axis were abolished. Our data suggest that the logic of BMP2/4 signaling and the BMP antagonist, Chordin, differs significantly between Cnidaria and Bilateria, yet the double negative feedback loop detected in Nematostella bears systemic similarities with part of the regulatory network of the DV axis patterning system in amphibians.     

The regulation of cnidocyte discharge

Because cnidocytes are exceedingly complex cells which can only be used once, their discharge is highly regulated by way of a variety of chemosensory, mechanosensory and endogenous pathways. The integration of these various inputs ultimately results in exocytosis and then discharge of the cnidocyte's diagnostic organelle, the cnidocyst. Here we review what is known about the sensory pathways that regulate cnidocytes, the electrical events that manifest in cnidocytes following sensory stimulation and the ionic mechanisms that underlie discharge.     

Isolation and biological characterization of neurotoxic compounds from the sea anemone Lebrunia danae (Duchassaing and Michelotti, 1860)

This paper describes two neurotoxic proteins obtained from the Caribbean sea anemone Lebrunia danae. To assess the neurotoxic activity of the venom of L. danae, several bioassays were carried out, and to evaluate the effect of the toxin, Median Lethal Doses (LD₅₀) were determined in vivo using sea crabs (Ocypode quadrata) and Artemia salina nauplii with the crude extract of the proportion of 2.82 mg/m. The proteins with neurotoxic effects were isolated using low-pressure liquid chromatography. The fractions containing the neurotoxic activity were analyzed by SDS-PAGE and showed protein bands with an apparent molecular weight of 62.50 kDa (LdNt1) and 58 kDa (LdNt2). To demonstrate that these proteins were indeed responsible for the neurotoxic activity observed, we injected a small fraction of the purified protein into the third walking leg of a crab and observed the typical convulsions, paralysis and death provoked by neurotoxins. Hemolytic activity was also tested for 0.238 mg of crude extract; the hemolytic value was 39.5, 49.6 and 50.1% for cow, sheep and pig erythrocytes, respectively.     

Development of a rational nomenclature for naming peptide and protein toxins from sea anemones

Sea anemone toxins are predominantly peptide and proteins that act mainly on sodium and potassium channels, as well as in a variety of target cells causing lysis. Over recent years, the number of sea anemone peptide toxins as well as cytolytic pore-forming proteins and phospholipase A₂ sequences submitted to databases has been rapidly increasing due to the developments in DNA sequencing technology and proteomic approaches. However, the lack of a systematic nomenclature has resulted in multiple names being assigned to the same toxins, toxins from unrelated species being designated by the same name, and ambiguous name designations. Therefore, in this work we propose a systematic nomenclature in which we adopted specific criteria, based on order of discovery and phylogenetic analysis, in order to avoid redundant sea anemone toxin names. Implementation of the nomenclature proposed here not only allowed us to rename the already published 191 anemone toxins without ambiguities, but it can be used to unambiguously name newly discovered toxins whether or not they are related to previously published sea anemone sequences. In the new nomenclature each toxin name contains information about the toxin's biological activity, origin and relationship to known isoforms. Ongoing increases in the speed of DNA sequencing will raise significantly the number of sea anemone toxin sequences in the literature. This will represent a constant challenge in their clear identification and logical classification, which could be solved using the proposed nomenclature.     

Treatment of Atlantic cnidarian envenomations

Envenomation syndromes induced by Atlantic cnidaria have been tabulated and their therapy discussed. The pharmacokinetics of the venom has been emphasized. Pain occurs instantly and reaches a zenith rapidly in the surf. The nematocysts have already penetrated the dermis and disease proceeds before help can arrive. This fact plus the relative impermeability of human epidermis hampers the efficacy of topical agents. Oral analgesics, the agents of choice, are seldom offered and systemic administration of these drugs is usually not necessary. The use of hot or cold applications has not been settled. Measures to inactivate nematocysts within tentacles adherent to skin post-sting have been demonstrated in vitro, but the clinical significance of these actions has not been shown. Using an abrader (sand, crystalline papain) to counter-irritate nearby skin might provide relief. Antivenoms for Atlantic cnidaria are not available. The instances when verapamil might be employed are very rare. The reasons for the increasing case load of these injuries are discussed and the need to discover more effective therapeutic agents is emphasized.