Conformational and orientation studies of artificial ion channels incorporated into lipid bilayers

The conformational and orientation studies in lipid bilayers of 21 amino acid peptides bearing six crown ethers are reported. The compounds were designed to form artificial ion channels by stacking the crown rings, and were shown to be functional in bilayer membranes. We used Fourier transform infrared spectroscopy and CD spectropolarimetry to study the conformation of the peptides in solution and in lipid bilayers. These studies revealed that hexacrown peptides retain their alpha-helical conformation when incorporated in a lipid bilayer environment. Attenuated total reflectance spectroscopy was used to investigate the orientation of the peptides in a lipid bilayer. Results demonstrated that the peptides are not oriented at a fixed angle in membrane, but rather are in incorporation equilibrium between an active state parallel to the lipid chain and an inactive state adsorbed at the surface of the bilayer. From these results, we propose a model for the channel activity and the gating mechanism of these hexacrown peptides in bilayer membranes.     

Geographical origin of an introduced pest species, Delia radicum (Diptera: anthomyiidae), determined by RAPD analysis and egg micromorphology

The origin of introduction of the cabbage root fly, Delia radicum Linnaeus to the north-eastern coast of North America in the 19th century has been assumed to be from Europe. From that point of introduction, D. radicum gradually spread westward to occupy available ecological niches. DNA fingerprinting and egg micromorphology were used to determine the most likely geographical origin of the North American populations of this species. Forty-five informative RAPD loci obtained from ten primers and three criteria for egg micromorphology were studied. These characters indicated a common origin for the North American populations and a high similarity between populations from North America and north-western Europe. The results suggest a single entrance point of D. radicum into North America, probably via the north-eastern coast (New York area) from north-western Europe. The implications of this study in assisting selection of natural enemies of this important agricultural pest are discussed.     

Machine Learning Assisted Design of Highly Active Peptides for Drug Discovery

The discovery of peptides possessing high biological activity is very challenging due to the enormous diversity for which only a minority have the desired properties. To lower cost and reduce the time to obtain promising peptides, machine learning approaches can greatly assist in the process and even partly replace expensive laboratory experiments by learning a predictor with existing data or with a smaller amount of data generation. Unfortunately, once the model is learned, selecting peptides having the greatest predicted bioactivity often requires a prohibitive amount of computational time. For this combinatorial problem, heuristics and stochastic optimization methods are not guaranteed to find adequate solutions. We focused on recent advances in kernel methods and machine learning to learn a predictive model with proven success. For this type of model, we propose an efficient algorithm based on graph theory, that is guaranteed to find the peptides for which the model predicts maximal bioactivity. We also present a second algorithm capable of sorting the peptides of maximal bioactivity. Extensive analyses demonstrate how these algorithms can be part of an iterative combinatorial chemistry procedure to speed up the discovery and the validation of peptide leads. Moreover, the proposed approach does not require the use of known ligands for the target protein since it can leverage recent multi-target machine learning predictors where ligands for similar targets can serve as initial training data. Finally, we validated the proposed approach in vitro with the discovery of new cationic antimicrobial peptides. Source code freely available at http://graal.ift.ulaval.ca/peptide-design/.     

Host-parasite relations and seasonal occurrence of Paragordius tricuspidatus and Spinochordodes tellinii (Nematomorpha) in Southern France

Paragordius tricuspidatus (Dufour, 1828) and Spinochordodes tellinii (Camerano, 1888) are two sympatric species of horsehair worms in southern France. Paragordius tricuspidatus was found in only one host species, Nemobius sylvestris (Bosc, 1792), while Spinochordodes tellinii was found in nine different hosts belonging to Orthoptera Caelifera. Size of nematomorphs varied strongly, but is additionally influenced by host size (in Spinochordodes tellinii) or number of parasites per host (in Paragordius tricuspidatus). Both species have a clear seasonality with Paragordius tricuspidatus occurring from June to early August and Spinochordodes tellinii occurring in August and September.     

A Novel Clinically Relevant Animal Model for Studying Galectin-3 and Its Ligands During Colon Carcinogenesis

Galectin-3 (Gal-3) is a multifunctional protein that plays different roles in cancer biology. To better understand the role of Gal-3 and its ligands during colon carcinogenesis, we studied its expression in tumors induced in rats treated with 1,2-dimethylhydrazine (DMH) and in human tissues. Normal colon from untreated rats showed no staining using two specific monoclonal antibodies. In contrast, morphologically normal colon from DMH-treated rats and dysplastic aberrant crypt foci were strongly stained, indicating that increased Gal-3 expression is an early event during the neoplastic transformation in colon cells. Gal-3 was weakly expressed in adenocarcinomas. Overall, the Gal-3 expression pattern observed in the DMH rat model closely resembles that displayed by human colon stained with the same antibodies. We also found that Gal-3 phosphorylation diminishes in serines while increasing in tyrosines during rat colon carcinogenesis. Finally, we showed that Gal-3–ligands expression is strikingly similar in rat and human malignant colon and in non-malignant tissues. In conclusion, the DMH-induced rat colon cancer model displays expression patterns of Gal-3 and its ligands very similar to those observed in human samples. This animal model should contribute to clarifying the role of Gal-3 in colon carcinogenesis and also to finding effective preventive cancer agents based on Gal-3 targeting. (J Histochem Cytochem 58:553–565, 2010)