Mushroom-derived preparations in the prevention of H2O2-induced oxidative damage to cellular DNA

Aqueous extracts of the sporophores of eight mushroom species were assessed for their ability to prevent H2O2-induced oxidative damage to cellular DNA using the single-cell gel electrophoresis (Comet) assay. The highest genoprotective effects were obtained with cold (20°C) and hot (100°C) water extracts of Agaricus bisporus and Ganoderma lucidum fruit bodies, respectively. No protective effects were observed with Mushroom Derived Preparations (MDPs) from Flammulina velutipes, Auricularia auricula, Hypsizygus marmoreus, Lentinula edodes, Pleurotus sajor-caju, and Volvariella volvacea. These findings indicate that some edible mushrooms represent a valuable source of biologically active compounds with potential for protecting cellular DNA from oxidative damage. © 2002 Wiley-Liss, Inc.

The Shell (Conus marmoreus), 2nd state

Rembrandt van Rijn; 3 13/16 in.x 5 5/32 in.; etching and drypoint on paper

Structures of mu O-conotoxins from Conus marmoreus - Inhibitors of tetrodotoxin (TTX)-sensitive and TTX-resistant sodium channels in mammalian sensory neurons

The muO-conotoxins are an intriguing class of conotoxins targeting various voltage-dependent sodium channels and molluscan calcium channels. In the current study, we have shown MrVIA and MrVIB to be the first known peptidic inhibitors of the transient tetrodotoxin-resistant (TTX-R) Na+ current in rat dorsal root ganglion neurons, in addition to inhibiting tetrodotoxin-sensitive Na+ currents. Human TTX-R sodium channels are a therapeutic target for indications such as pain, highlighting the importance of the muO-conotoxins as potential leads for drug development. Furthermore, we have used NMR spectroscopy to provide the first structural information on this class of conotoxins. MrVIA and MrVIB are hydrophobic peptides that aggregate in aqueous solution but were solubilized in 50% acetonitrile/water. The three-dimensional structure of MrVIB consists of a small beta-sheet and a cystine knot arrangement of the three-disulfide bonds. It contains four backbone loops between successive cysteine residues that are exposed to the solvent to varying degrees. The largest of these, loop 2, is the most disordered part of the molecule, most likely due to flexibility in solution. This disorder is the most striking difference between the structures of MrVIB and the known delta- and omega-conotoxins, which along with the muO-conotoxins are members of the O superfamily. Loop 2 of omega-conotoxins has previously been shown to contain residues critical for binding to voltage-gated calcium channels, and it is interesting to speculate that the flexibility observed in MrVIB may accommodate binding to both sodium and molluscan calcium channels.

Solution structure of χ-conopeptide MrIA, a modulator of the human norepinephrine transporter

The chi-conopeptides MrIA and MrIB are 13-residue peptides with two disulfide bonds that inhibit human and rat norepinephrine transporter systems and are of significant interest for the design of novel drugs involved in pain treatment. In the current study we have determined the solution structure of MrIA using NMR spectroscopy. The major element of secondary structure is a hairpin with the two strands connected by an inverse gamma-turn. The residues primarily involved in activity have previously been shown to be located in the turn region (Sharpe, I. A.; Palant, E.: Schroder, C. L; Kaye, D. M.; Adams, D. I.; Alewood, P. F.; Lewis, R. J. J Biol Client 2003, 278, 40317-40323), which appears to be more flexible than the beta-strands based on disorder in the ensemble of calculated structures. Analogues of MrIA with N-terminal truncations indicate that the N-terminal residues play a role in defining a stable conformation and the native disulfide connectivity. In particular, noncovalent interactions between Val3 and Hypl2 are likely to be involved in maintaining a stable conformation. The N-terminus also affects activity, as a single N-terminal deletion introduced additional pharmacology at rat vas deferens, while deleting the first two amino acids reduced chi-conopeptide potency. This article was originally published online as an accepted preprint. The Published Online date corresponds to the preprint version. You can request a copy of the preprint by entailing the Biopolymers editorial office at biopolymers@wiley.com (c) 2005 Wiley Periodicals, Inc.

Two new classes of conopeptides inhibit the alpha 1-adrenoceptor and noradrenaline transporter

Cone snails use venom containing a cocktail of peptides ('conopeptides') to capture their prey. Many of these peptides also target mammalian receptors, often with exquisite selectivity. Here we report the discovery of two new classes of conopeptides. One class targets alpha (1)-adrenoceptors (rho -TIA from the fish-hunting Conus tulipa), and the second class targets the neuronal noradrenaline transporter (chi -MrIA and chi -MrIB from the mollusk-hunting C. marmoreus). rho -TIA and chi -MrIA selectively modulate these important membrane-bound proteins. Both peptides act as reversible non-competitive inhibitors and provide alternative avenues for the identification of inhibitor drugs.

Revisão do gênero Antiteuchus Dallas (Heteroptera, Pentatomidae, Discocephalinae)

Revisão do gênero Antiteuchus Dallas (Heteroptera, Pentatomidae, Discocephalinae). O gênero Antiteuchus Dallas, 1851 com 46 espécies descritas é revisado; as espécies são redescritas com base na morfologia externa da genitália do macho e em algumas características da morfologia geral do corpo. Neodine Kirkaldy, 1909 é considerado sinônimo junior de Antiteuchus. As espécies foram subdivididas em seis grupos aqui propostos: A. amplus, A. supinatus, A. peruensis, A. tesselatus, A. marmoratus e A. mixtus. Oito novas espécies são descritas: A. amapensis sp. nov., A. beckerae sp. nov., A. doesburgi sp. nov., A. exiguus sp. nov., A. ledeburi sp. nov., A. marini sp. nov., A. melanicus sp. nov. and A. similis sp. nov. Nove espécies e uma subespécie são sinonimizadas. Antiteuchus varians Ruckes, 1964 é considerada sinônimo júnior de A. pallescens Stål, 1868; A. englemani Rolston, 1993 de A. amplus (Walker, 1867); A. tripterus limbativentris Ruckes, 1964 e A. minor Engleman, 1983 de A. tripterus (Fabricius, 1787); A. fuscus (Ruckes, 1959), A. piceus (Palisot de Beauvois, 1805), A. subgibbus Engleman, 1983, A. subimpunctatus Ruckes, 1964, A. unicolor (Westwood, 1837) e A. variolosus (Westwood, 1837) de A. mixtus (Fabricius, 1787). Antiteuchus tatei (Ruckes, 1958) é considerada species inquirenda. Empicoris marmoreus Spinola, 1837 é colocada em incertae sedis e tratada como species inquirenda. O macho de A. pictus, até agora desconhecido, é descrito. Chaves de identificação para os machos das espécies de Antiteuchus e para os grupos de espécies são apresentadas.

Revisão do gênero Antiteuchus Dallas (Heteroptera, Pentatomidae, Discocephalinae)

Revisão do gênero Antiteuchus Dallas (Heteroptera, Pentatomidae, Discocephalinae). O gênero Antiteuchus Dallas, 1851 com 46 espécies descritas é revisado; as espécies são redescritas com base na morfologia externa da genitália do macho e em algumas características da morfologia geral do corpo. Neodine Kirkaldy, 1909 é considerado sinônimo junior de Antiteuchus. As espécies foram subdivididas em seis grupos aqui propostos: A. amplus, A. supinatus, A. peruensis, A. tesselatus, A. marmoratus e A. mixtus. Oito novas espécies são descritas: A. amapensis sp. nov., A. beckerae sp. nov., A. doesburgi sp. nov., A. exiguus sp. nov., A. ledeburi sp. nov., A. marini sp. nov., A. melanicus sp. nov. and A. similis sp. nov. Nove espécies e uma subespécie são sinonimizadas. Antiteuchus varians Ruckes, 1964 é considerada sinônimo júnior de A. pallescens Stål, 1868; A. englemani Rolston, 1993 de A. amplus (Walker, 1867); A. tripterus limbativentris Ruckes, 1964 e A. minor Engleman, 1983 de A. tripterus (Fabricius, 1787); A. fuscus (Ruckes, 1959), A. piceus (Palisot de Beauvois, 1805), A. subgibbus Engleman, 1983, A. subimpunctatus Ruckes, 1964, A. unicolor (Westwood, 1837) e A. variolosus (Westwood, 1837) de A. mixtus (Fabricius, 1787). Antiteuchus tatei (Ruckes, 1958) é considerada species inquirenda. Empicoris marmoreus Spinola, 1837 é colocada em incertae sedis e tratada como species inquirenda. O macho de A. pictus, até agora desconhecido, é descrito. Chaves de identificação para os machos das espécies de Antiteuchus e para os grupos de espécies são apresentadas.

Benthos fauna in the North Sea from 2 surveys in 1986 and 1987

During two surveys in the North Sea, in summer 1986 and in winter 1987, larger epibenthos was collected with a 2 m beam trawl. The distributions of the species were checked for average linkage by means of the JACCARD-index cluster analysis. In summer two main clusters can be recognized. These are situated to the north and to the south of the Dogger Bank. In winter two main clusters may be recognized as well, but these clusters divide the North Sea into a western and an eastern part. We conclude, that these differences of epibenthos characteristics are correlated with seasonal changes in water body distributions.

Cyclic MrIA: A stable and potent cyclic conotoxin with a novel topological fold that targets the norepinephrine transporter

Conotoxins, disulfide-rich peptides from the venom of cone snails, have created much excitement over recent years due to their potency and specificity for ion channels and their therapeutic potential. One recently identified conotoxin, MrIA, a 13-residue member of the chi-conotoxin family, inhibits the human norepinephrine transporter (NET) and has potential applications in the treatment of pain. In the current study, we show that the, beta-hairpin structure of native MrIA is retained in a synthetic cyclic version, as is biological activity at the NET. Furthermore, the cyclic version has increased resistance to trypsin digestion relative to the native peptide, an intriguing result because the cleavage site for the trypsin is not close to the cyclization site. The use of peptides as drugs is generally hampered by susceptibility to proteolysis, and so, the increase in enzymatic stability against trypsin observed in the current study may be useful in improving the therapeutic potential of MrIA. Furthermore, the structure reported here for cyclic MrIA represents a new topology among a growing number of circular disulfide-rich peptides.

mu O-conotoxin MrVIB selectively blocks Na(v)1.8 sensory neuron specific sodium channels and chronic pain behavior without motor deficits

The tetroclotoxin-resistant voltage-gated sodium channel (VGSC) Na(v)1.8 is expressed predominantly by damage-sensing primary afferent nerves and is important for the development and maintenance of persistent pain states. Here we demonstrate that mu O-conotoxin MrVIB from Conus marmoreus displays substantial selectivity for Na(v)1.8 and inhibits pain behavior in models of persistent pain. In rat sensory neurons, submicromolar concentrations of MrVIB blocked tetroclotoxin-resistant current characteristic of Na(v)1.8 but not Na(v)1.9 or tetroclotoxin-sensitive VGSC currents. MrVIB blocked human Nav1.8 expressed in Xenopus oocytes with selectivity at least 10-fold greater than other VGSCs. In neuropathic and chronic inflammatory pain models, allodynia and hyperalgesia were both reduced by intrathecal infusion of MrVIB (0.03-3 nmol), whereas motor side effects occurred only at 30-fold higher doses. In contrast, the nonselective VGSC blocker lignocaine displayed no selectivity for allodynia and hyperalgesia versus motor side effects. The actions of MrVIB reveal that VGSC antagonists displaying selectivity toward Na(v)1.8 can alleviate chronic pain behavior with a greater therapeutic index than nonselective antagonists.