Structural basis of ligand activation in a cyclic nucleotide regulated potassium channel

Here we describe the initial functional characterization of a cyclic nucleotide regulated ion channel from the bacterium Mesorhizobium loti and present two structures of its cyclic nucleotide binding domain, with and without cAMP. The domains are organized as dimers with the interface formed by the linker regions that connect the nucleotide binding pocket to the pore domain. Together, structural and functional data suggest the domains form two dimers on the cytoplasmic face of the channel. We propose a model for gating in which ligand binding alters the structural relationship within a dimer, directly affecting the position of the adjacent transmembrane helices.     

Paraquat resistance of transgenic tobacco plants over-expressing the Ochrobactrum anthropi pqrA gene

Transgenic tobacco plants over-expressing the Ochrobactrum anthropi pqrA gene, which encodes a membrane transporter mediating resistance to paraquat, were generated. Transgenic plants displayed higher resistance against paraquat than wild-type plants, as estimated by plant viability, ion leakage and chlorophyll loss, but no resistance against other active oxygen generators, such as H2O2 and menadione. Moreover, lower levels of paraquat accumulated in transgenic plants, compared to wild-type plants, indicating that the PqrA protein detoxifies paraquat either via increased efflux or decreased uptake of the herbicide, but not by removing active oxygen species. The results collectively demonstrate that the bacterial paraquat resistance gene, pqrA, can be functionally expressed in plant cells, and utilized for the development of paraquat-resistant crop plants.     

Nematodes from the squeaker fishes Synodontis nigromaculatus and S. vanderwaali from the Okavango River, Botswana, including three new species

Five nematode species were recorded from the stomach and rectum of the spotted squeaker Synodontis nigromaculatus Boulenger or the finetooth squeaker S. vanderwaali Skelton & White (Mochokidae, Siluriformes) from the Okavango River, Botswana: Falcaustra similis n. sp. (Kathlaniidae), Labeonema africanum n. sp. (Cosmocercidae), Synodontisia okavangoensis n. sp. (Pharyngodonidae), Procamallanus ( Procamallanus ) laeviconchus (Wedl, 1861) (Camallanidae) and Spinitectus sp. (Cystidicolidae) (only a single female). F. similis (type-host Synodontis nigromaculatus ) differs from the similar species F. straeleni Campana-Rouget, 1961 mainly by the number and disposition of the male caudal papillae and the structure of the mouth; L. africanum (type-host S. nigromaculatus ) differs from its congeners in having distinctly longer spicules (105-120 microm), a relatively shorter gubernaculum (30-36 microm) and in the number and arrangement of the male caudal papillae; Synodontisia okavangoensis (type-host Synodontis nigromaculatus ) is characterised principally by crescent-shaped cephalic papillae, length (87 microm) and shape of the spicule as well as large eggs (0.156-0.180x69-102 microm). Synodontisia moraveci Anderson & Lim, 1996 is transferred to a newly established genus, Royandersonia n. g., (as its type-species) as R. moraveci (Anderson & Lim, 1996) n. comb. Some taxonomic problems concerning Procamallanus ( P .) laeviconchus are discussed. All species were studied by scanning electron microscopy for the first time.     

Spectral analysis and fingerprinting for biomedia characterisation

Classical culture media, as well as domestic and/or industrial wastewater treated by biological processes, have a complex composition. The on-line and/or in situ determination of some substances is possible, but expensive, as sample collection and pre-treatment are often necessary with strict rules of sterility. More global methods can be used to detect rapidly "accidents" such as the appearance of an undesirable by-product in a fermentation broth or of a toxic substance in wastewater. These methods combine a "hard" part, for sensing, and a "soft" part, for data treatment. Among potential "hard" candidates, spectroscopy can be the basis for non-invasive and non-destructive measuring systems. Some of them have been already tested in situ: ultra-violet-visible, infra-red (mid or near), fluorescence (mono-dimensional, two-dimensional or synchronous), dielectric, while others, more sophisticated, such as mass spectrometry, coupled or not to pyrolysis, nuclear magnetic resonance and Raman spectroscopy, have been proposed. All these methods provide spectra, i.e. large sets of data, from which meaningful information should be rapidly extracted, either for analysis or fingerprinting. The recourse to data-mining techniques (the "soft" part) such as principal components analysis, projection on latent structures or artificial neural networks, is a necessary step for that task. A review of techniques, mostly based on spectroscopy, with examples taken in the bioengineering field in general is proposed.     

Design and synthesis of de novo cytotoxic alkaloids through mimicking taxoid skeleton

Based on a common pharmacophore model and the hypothesis that the baccatin core of taxoids is a scaffold securing the proper orientation of the side chains, a bicyclic alkaloid scaffold was designed as a baccatin surrogate. Using this scaffold, two novel macrocyclic and open-chain 'taxoid-mimicking' compounds were synthesized. Two of these 'taxoid-mimics', 2 and 3, were found to possess cytotoxicity with micromolar level IC50 values against human breast cancer cell lines.     

A mixture model-based strategy for selecting sets of genes in multiclass response microarray experiments

MOTIVATION: Multiclass response (MCR) experiments are those in which there are more than two classes to be compared. In these experiments, though the null hypothesis is simple, there are typically many patterns of gene expression changes across the different classes that led to complex alternatives. In this paper, we propose a new strategy for selecting genes in MCR that is based on a flexible mixture model for the marginal distribution of a modified F-statistic. Using this model, false positive and negative discovery rates can be estimated and combined to produce a rule for selecting a subset of genes. Moreover, the method proposed allows calculation of these rates for any predefined subset of genes. RESULTS: We illustrate the performance our approach using simulated datasets and a real breast cancer microarray dataset. In this latter study, we investigate predefined subset of genes and point out interesting differences between three distinct biological pathways. AVAILABILITY: http://www.bgx.org.uk/software.html