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Characterization of the Ca2+-gated and voltage-dependent k+-channel slo-1 of nematodes and its interaction with emodepside

The cyclooctadepsipeptide emodepside and its parent compound PF1022A are broad-spectrum nematicidal drugs which are able to eliminate nematodes resistant to other anthelmintics. The mode of action of cyclooctadepsipeptides is only partially understood, but involves the latrophilin Lat-1 receptor and the voltage- and calcium-activated potassium channel Slo-1. Genetic evidence suggests that emodepside exerts its anthelmintic activity predominantly through Slo-1. Indeed, slo-1 deficient Caenorhabditis elegans strains are completely emodepside resistant. However, direct effects of emodepside on Slo-1 have not been reported and these channels have only been characterized for C. elegans and related Strongylida. Molecular and bioinformatic analyses identified full-length Slo-1 cDNAs of Ascaris suum, Parascaris equorum, Toxocara canis, Dirofilaria immitis, Brugia malayi, Onchocerca gutturosa and Strongyloides ratti. Two paralogs were identified in the trichocephalids Trichuris muris, Trichuris suis and Trichinella spiralis. Several splice variants encoding truncated channels were identified in Trichuris spp. Slo-1 channels of trichocephalids form a monophyletic group, showing that duplication occurred after the divergence of Enoplea and Chromadorea. To explore the function of a representative protein, C. elegans Slo-1a was expressed in Xenopus laevis oocytes and studied in electrophysiological (voltage-clamp) experiments. Incubation of oocytes with 1-10 µM emodepside caused significantly increased currents over a wide range of step potentials in the absence of experimentally increased intracellular Ca2+, suggesting that emodepside directly opens C. elegans Slo-1a. Emodepside wash-out did not reverse the effect and the Slo-1 inhibitor verruculogen was only effective when applied before, but not after, emodepside. The identification of several splice variants and paralogs in some parasitic nematodes suggests that there are substantial differences in channel properties among species. Most importantly, this study showed for the first time that emodepside directly opens a Slo-1 channel, significantly improving the understanding of the mode of action of this drug class

Nature and origins of unique high diversity reef faunas in the Bay of Tomini, Central Sulawesi: the ultimate "Centre of Diversity"?

The staghorn corals (Acropora spp.) of the Bay of Tomini in eastern Central Sulawesi may typify the maximal marine biodiversity associated with the idea of a "centre of diversity" in the central Indo-Pacific: other faunal groups have variable diversity, but unexpected species composition. Faunal assemblages from several phyla in this bay were assessed against phylogenetic and biogeographic data and biotic and environmental parameters in order to compare several hypotheses about the origins of the unusual species composition. It was found that the Togian Islands within the bay support a fauna with strong affinities to sites in the western equatorial Pacific, in all the studied groups except Stomatopoda. Both species composition and distribution of ecological functional groups is influenced by unusually calm and oligotrophic conditions in the islands and populations within the islands have various levels of genetic connectively to populations in other parts of Sulawesi, including complete isolation of some populations. It is proposed that these islands represent lagoonal refugia from Pleistocene lowstands, with affinities to similar refugia in the western Pacific. Additionally, the bay is possibly influenced by larval distributions from the Pacific through-flow current and there is little or no influence from the Indian Ocean

The falling chain of Hopkins, Tait, Steele and Cayley

A uniform, flexible and frictionless chain falling link by link from a heap by the edge of a table falls with an acceleration $g/3$ if the motion is nonconservative, but $g/2$ if the motion is conservative, $g$ being the acceleration due to gravity. Unable to construct such a falling chain, we use instead higher-dimensional versions of it. A home camcorder is used to measure the fall of a three-dimensional version called an $xyz$-slider. After frictional effects are corrected for, its vertical falling acceleration is found to be $a_x/g = 0.328 \pm 0.004$. This result agrees with the theoretical value of $a_x/g = 1/3$ for an ideal energy-conserving $xyz$-slider.Comment: 17 pages, 5 figure

A proteomic approach for the rapid, multi-informative and reliable identification of blood

Blood evidence is frequently encountered at the scene of violent crimes and can provide valuable intelligence in the forensic investigation of serious offences. Because many of the current enhancement methods used by crime scene investigators are presumptive, the visualisation of blood is not always reliable nor does it bear additional information. In the work presented here, two methods employing a shotgun bottom up proteomic approach for the detection of blood are reported; the developed protocols employ both an in solution digestion method and a recently proposed procedure involving immobilization of trypsin on hydrophobin Vmh2 coated MALDI sample plate. The methods are complementary as whilst one yields more identifiable proteins (as biomolecular signatures), the other is extremely rapid (5 minutes). Additionally, data demonstrate the opportunity to discriminate blood provenance even when two different blood sources are present in a mixture. This approach is also suitable for old bloodstains which had been previously chemically enhanced, as experiments conducted on a 9-year-old bloodstain deposited on a ceramic tile demonstrate

The highly rearranged mitochondrial genomes of the crabs Maja crispata and Maja squinado (Majidae) and gene order evolution in Brachyura

Abstract We sequenced the mitochondrial genomes of the spider crabs Maja crispata and Maja squinado (Majidae, Brachyura). Both genomes contain the whole set of 37 genes characteristic of Bilaterian genomes, encoded on both \u3b1- and \u3b2-strands. Both species exhibit the same gene order, which is unique among known animal genomes. In particular, all the genes located on the \u3b2-strand form a single block. This gene order was analysed together with the other nine gene orders known for the Brachyura. Our study confirms that the most widespread gene order (BraGO) represents the plesiomorphic condition for Brachyura and was established at the onset of this clade. All other gene orders are the result of transformational pathways originating from BraGO. The different gene orders exhibit variable levels of genes rearrangements, which involve only tRNAs or all types of genes. Local homoplastic arrangements were identified, while complete gene orders remain unique and represent signatures that can have a diagnostic value. Brachyura appear to be a hot-spot of gene order diversity within the phylum Arthropoda. Our analysis, allowed to track, for the first time, the fully evolutionary pathways producing the Brachyuran gene orders. This goal was achieved by coupling sophisticated bioinformatic tools with phylogenetic analysis