Interactions of lactoferricin-derived peptides with LPS and antimicrobial activity

Synthetic peptides derived from human and bovine lactoferricin, as well as tritrpticin sequences, were assayed for antimicrobial activity against wild-type Escherichia coli and LPS mutant strains. Antimicrobial activity was only obtained with peptides derived from the bovine lactoferricin sequence and peptides corresponding to chimeras of human and bovine sequences. None of the peptides corresponding to different regions of native human lactoferricin showed any antimicrobial activity. The results underline the importance of the content of tryptophan and arginine residues, and the relative location of these residues for antimicrobial activity. Results obtained for the same assays performed with LPS mutants suggest that lipid A is not the main binding site for lactoferricin which interacts first with the negative charges present in the inner core. Computer modelling of the most active peptides led to a model in which positively charged residues of the cationic peptide interact with negative charges carried by the LPS to disorganise the structure of the outer membrane and facilitate the approach of tryptophan residues to the lipid A in order to promote hydrophobic interactions.     

A statistical framework for the design of microarray experiments and effective detection of differential gene expression

MOTIVATION: Microarray experiments generate a high data volume. However, often due to financial or experimental considerations, e.g. lack of sample, there is little or no replication of the experiments or hybridizations. These factors combined with the intrinsic variability associated with the measurement of gene expression can result in an unsatisfactory detection rate of differential gene expression (DGE). Our motivation was to provide an easy to use measure of the success rate of DGE detection that could find routine use in the design of microarray experiments or in post-experiment assessment. RESULTS: In this study, we address the problem of both random errors and systematic biases in microarray experimentation. We propose a mathematical model for the measured data in microarray experiments and on the basis of this model present a t-based statistical procedure to determine DGE. We have derived a formula to determine the success rate of DGE detection that takes into account the number of microarrays, the number of genes, the magnitude of DGE, and the variance from biological and technical sources. The formula and look-up tables based on the formula, can be used to assist in the design of microarray experiments. We also propose an ad hoc method for estimating the fraction of non-differentially expressed genes within a set of genes being tested. This will help to increase the power of DGE detection. AVAILABILITY: The functions to calculate the success rate of DGE detection have been implemented as a Java application, which is accessible at http://www.le.ac.uk/mrctox/microarray_lab/Microarray_Softwares/Microarray_Softwares.htm     

Action of tremorgenic mycotoxins on GABAA receptor

The effects of four tremorgenic and one nontremorgenic mycotoxins were studied on gamma-aminobutyric acid (GABAA) receptor binding and function in rat brain and on binding of a voltage-operated Cl- channel in Torpedo electric organ. None of the mycotoxins had significant effect on [3H]muscimol or [3H]flunitrazepam binding to the GABAA receptor. However, only the four tremorgenic mycotoxins inhibited GABA-induced 36Cl- influx and [35S] t-butylbicyclophosphorothionate [( 35S]TBPS) binding in rat brain membranes, while the nontremorgenic verruculotoxin had no effect. Inhibition of [35S]TBPS binding by paspalinine was non-competitive. This suggests that tremorgenic mycotoxins inhibit GABAA receptor function by binding close to the receptor's Cl- channel. On the voltage-operated Cl- channel, only high concentrations of verruculogen and verruculotoxin caused significant inhibition of the channel's binding of [35S]TBPS. The data suggest that the tremorgenic action of these mycotoxins may be due in part to their inhibition of GABAA receptor function.     

Individual optimization: Mechanisms shaping the optimal reaction norm

In general, optimal reaction norms in heterogeneous populations can be obtained only by iterative numerical procedures (McNamara, 1991; Kawecki and Stearns, 1993). We consider two particular, but biologically plausible and analytically tractable cases of individual optimization to gain insight into the mechanisms which shape the optimal reaction norm of fecundity in relation to an environmental variable or an individual trait. In the first case, we assume that the quality of the environment (e.g. food abundance) or the quality of the individual (e.g. body size) is fixed during its entire life; it may also be a heritable individual trait. In the second case, individual quality is assumed to change randomly such that the probability distribution of quality in the next year is the same for the parent and for her offspring. For these two cases, we obtain analytical expressions for the shape of the optimal reaction norm, which are heuristically interpretable in terms of underlying selective mechanisms. It is shown that better quality may reduce the optimal fecundity. This outcome is particularly likely if better quality increases a fecundity-independent factor of parental survival in a long-lived species with fixed quality. This revised version was published online in July 2006 with corrections to the Cover Date.