Cocaine Directly Impairs Memory Extinction and Alters Brain DNA Methylation Dynamics in Honey Bees.

Drug addiction is a chronic relapsing behavioral disorder. The high relapse rate has often been attributed to the perseverance of drug-associated memories due to high incentive salience of stimuli learnt under the influence of drugs. Drug addiction has also been interpreted as a memory disorder since drug associated memories are unusually enduring and some drugs, such as cocaine, interfere with neuroepigenetic machinery known to be involved in memory processing. Here we used the honey bee (an established invertebrate model for epigenomics and behavioral studies) to examine whether or not cocaine affects memory processing independently of its effect on incentive salience. Using the proboscis extension reflex training paradigm we found that cocaine strongly impairs consolidation of extinction memory. Based on correlation between the observed effect of cocaine on learning and expression of epigenetic processes, we propose that cocaine interferes with memory processing independently of incentive salience by directly altering DNA methylation dynamics. Our findings emphasize the impact of cocaine on memory systems, with relevance for understanding how cocaine can have such an enduring impact on behavior.

Design, synthesis, and biological activity of pyridopyrimidine scaffolds as novel PI3K/mTOR dual inhibitors.

The design, synthesis, and screening of dual PI3K/mTOR inhibitors that gave nanomolar enzymatic and cellular activities on both targets with an acceptable kinase selectivity profile are described. A docking study was performed to understand the binding mode of the compounds and to explain the differences in biological activity. In addition, cellular effects of the best dual inhibitors were determined on six cancer cell lines and compared to those on a healthy diploid cell line for cellular cytotoxicity. Two compounds are highly potent on cancer cells in the submicromolar range without any toxicity on healthy cells. A more detailed analysis of the cellular effect of these PI3K/mTOR dual inhibitors demonstrated that they induce G1-phase cell cycle arrest in breast cancer cells and trigger apoptosis. These compounds show an interesting kinase profile as dual PI3K/mTOR tool compounds or as a chemical series for further optimization to progress into in vivo experiments.

Two new species of polystomes (Monogenea: Polystomatidae) from the anuran host Guibemantis liber.

Madapolystoma ramilijaonae n. sp. and Madapolystoma cryptica n. sp. (Monogenea, Polystomatidae) are described from the urinary bladder of disjunct populations of the Madagascar shrub frog Guibemantis liber. Although only minor morphological characters distinguish the new species from the single nominal species of the genus, i.e. Madapolystoma biritika, their strong and concordant differentiation in a mitochondrial and a nuclear gene supplemented by phylogenetic analyses indicates that M. ramilijaonae n. sp. and M. cryptica n. sp. should be regarded as two distinct species. Because anuran polystomes are known to be host-specific, the description of two cryptic species from a single host species points to a taxonomic complex situation in G. liber, a widespread frog that is characterized by the presence of several deep conspecific lineages and possibly by hybridization and admixture with other species of Guibemantis.

First monogenean flatworm from a microhylid frog host: Kankana, a new polystome genus from Madagascar.

Kankana manampoka n. gen., n. sp. (Monogenea, Polystomatidae), is described from the urinary bladder of the narrow-mouthed frog Platypelis pollicaris. This is the first record of a polystome from the Microhylidae and the third polystome genus from Madagascar, next to Metapolystoma and Madapolystoma. The extensive uterus and presence of hamuli resemble Metapolystoma but the vitellarium confined to the lateral fields in Kankana is different. Madapolystoma also has an extensive uterus but contain only up to 32 advanced developed larvae. Based on the extensive uterus filling the body proper and the vitellarium confined to two lateral fields posterior in the body this new polystome resembles Eupolystoma known from Africa and India. However, unlike Eupolystoma, the gonads are in the middle of the body, vaginae are lacking and a pair of hamuli is present. A molecular phylogenetic analysis of concatenated 18S and 28S ribosomal RNA gene sequences supplemented by genetic distances inferred from 28S and COI sequences showed that this new genus is more related to Madapolystoma, a genus only reported from Madagascar, than to Eupolystoma known from Africa and India and Metapolystoma known from Africa and Madagascar.

Evidence of parasite-mediated disruptive selection on genetic diversity in a wild fish population.

Identifying the processes maintaining genetic variability in wild populations is a major concern in conservation and evolutionary biology. Parasite-mediated selection may strongly affect genetic variability in wild populations. The inbreeding depression theory predicts that directional selection imposed by parasites should act against the most inbred hosts, thus favouring genetic diversity in wild populations. We have tested this prediction by evaluating the strength and shape of the relationship between the load of a harmful fin-feeder ectoparasite (Tracheliastes polycolpus) and the genome-wide genetic diversity (i.e. heterozygosity measured at a set of 15 microsatellites) of its fish host, the rostrum dace (Leuciscus leuciscus). Contrary to expectation, we found a nonlinear relationship between host genetic diversity and ectoparasite load, with hosts that were either homozygous or heterozygous harbouring significantly fewer parasites than hosts with an intermediate level of heterozygosity. This relationship suggests that parasites could increase the variance of global heterozygosity in this host population through disruptive selection on genetic diversity. Moreover, when genetic diversity was measured at each locus separately, we found two very strong positive associations between host genetic diversity and the ectoparasite load. This latter result has three main implications: (i) genome-wide effect cannot alone explain the nonlinear relationship between global heterozygosity and ectoparasite load, (ii) negative non-additive allelic interactions (i.e. underdominance) may be a mechanism for resisting ectoparasite infection, and (iii) ectoparasites may favour homozygosity at some loci in this host population.