CpG island hypermethylation-associated silencing of non-coding RNAs transcribed from ultraconserved regions in human cancer

Although only 1.5% of the human genome appears to code for proteins, much effort in cancer research has been devoted to this minimal fraction of our DNA. However, the last few years have witnessed the realization that a large class of non-coding RNAs (ncRNAs), named microRNAs, contribute to cancer development and progression by acting as oncogenes or tumor suppressor genes. Recent studies have also shown that epigenetic silencing of microRNAs with tumor suppressor features by CpG island hypermethylation is a common hallmark of human tumors. Thus, we wondered whether there were other ncRNAs undergoing aberrant DNA methylation-associated silencing in transformed cells. We focused on the transcribed-ultraconserved regions (T-UCRs), a subset of DNA sequences that are absolutely conserved between orthologous regions of the human, rat and mouse genomes and that are located in both intra- and intergenic regions. We used a pharmacological and genomic approach to reveal the possible existence of an aberrant epigenetic silencing pattern of T-UCRs by treating cancer cells with a DNA-demethylating agent followed by hybridization to an expression microarray containing these sequences. We observed that DNA hypomethylation induces release of T-UCR silencing in cancer cells. Among the T-UCRs that were reactivated upon drug treatment, Uc.160+, Uc283+A and Uc.346+ were found to undergo specific CpG island hypermethylation-associated silencing in cancer cells compared with normal tissues. The analysis of a large set of primary human tumors (n=283) demonstrated that hypermethylation of the described T-UCR CpG islands was a common event among the various tumor types. Our finding that, in addition to microRNAs, another class of ncRNAs (T-UCRs) undergoes DNA methylation-associated inactivation in transformed cells supports a model in which epigenetic and genetic alterations in coding and non-coding sequences cooperate in human tumorigenesis

Entertainment starts with an E: the ecstasy market in Greece

The purpose of this article is to provide an account of the social organisation of the ecstasy market in Greece. Concern about ecstasy production, distribution and use in Greece has risen since ecstasy appeared in the country in the early to mid-1990s, and continues to be fuelled by media reports which reinforce the perception that there are huge profits for traders. Moreover, the Greek authorities have adopted a 'war on drug' rhetoric when it comes to ecstasy trafficking. Thus, the fact that such mentalities are commonplace, while the knowledge deficit about the particular market remains gaping, makes it an imperative to examine the structure and dynamics of the ecstasy market in the country. We aim here to provide an account of the 'extent' and nature of the ecstasy market in Greece as well as a presentation of the 'actors' involved. We also explicitly focus on the issue of price of ecstasy tablets in the country, which we regard as key to the understanding of the logic of this particular market. Our investigation of various aspects of the market concludes with a number of more systematic observations regarding the particular business

Prisoners in Their Habitat? Generalist Dispersal by Habitat Specialists: A Case Study in Southern Water Vole (Arvicola sapidus)

Habitat specialists inhabiting scarce and scattered habitat patches pose interesting questions related to dispersal such as how specialized terrestrial mammals do to colonize distant patches crossing hostile matrices. We assess dispersal patterns of the southern water vole (Arvicola sapidus), a habitat specialist whose habitat patches are distributed through less than 2% of the study area (overall 600 km2) and whose populations form a dynamic metapopulational network. We predict that individuals will require a high ability to move through the inhospitable matrix in order to avoid genetic and demographic isolations. Genotypes (N = 142) for 10 microsatellites and sequences of the whole mitochondrial Control Region (N = 47) from seven localities revealed a weak but significant genetic structure partially explained by geographic distance. None of the landscape models had a significant effect on genetic structure over that of the Euclidean distance alone and no evidence for efficient barriers to dispersal was found. Contemporary gene flow was not severely limited for A. sapidus as shown by high migration rates estimates (>10%) between non-neighbouring areas. Sex-biased dispersal tests did not support differences in dispersal rates, as shown by similar average axial parent-offspring distances, in close agreement with capture-mark-recapture estimates. As predicted, our results do not support any preferences of the species for specific landscape attributes on their dispersal pathways. Here, we combine field and molecular data to illustrate how a habitat specialist mammal might disperse like a habitat generalist, acquiring specific long-distance dispersal strategies as an adaptation to patchy, naturally fragmented, heterogeneous and unstable habitats

Human telomerase activity regulation

Telomerase has been recognized as a relevant factor distinguishing cancer cells from normal cells. Thus, it has become a very promising target for anticancer therapy. The cell proliferative potential can be limited by replication end problem, due to telomeres shortening, which is overcome in cancer cells by telomerase activity or by alternative telomeres lengthening (ALT) mechanism. However, this multisubunit enzymatic complex can be regulated at various levels, including expression control but also other factors contributing to the enzyme phosphorylation status, assembling or complex subunits transport. Thus, we show that the telomerase expression targeting cannot be the only possibility to shorten telomeres and induce cell apoptosis. It is important especially since the transcription expression is not always correlated with the enzyme activity which might result in transcription modulation failure or a possibility for the gene therapy to be overcome. This review summarizes the current state of knowledge of numerous telomerase regulation mechanisms that take place after telomerase subunits coding genes transcription. Thus we show the possible mechanisms of telomerase activity regulation which might become attractive anticancer therapy targets