Defining molecular sensors to assess long-term effects of pesticides on carcinogenesis.

The abundance of dioxins and dioxin-like pollutants has massively increased in the environment due to human activity. These chemicals are particularly persistent and accumulate in the food chain, which raises major concerns regarding long-term exposure to human health. Most dioxin-like pollutants activate the aryl hydrocarbon receptor (AhR) transcription factor, which regulates xenobiotic metabolism enzymes that belong to the cytochrome P450 1A family (that includes CYP1A1 and CYP1B1). Importantly, a crosstalk exists between estrogen receptor α (ERα) and AhR. More specifically, ERα represses the expression of the CYP1A1 gene, which encodes an enzyme that converts 17ß-estradiol into 2-hydroxyestradiol. However, (ERα) does not repress the CYP1B1 gene, which encodes an enzyme that converts 17ß-estradiol into 4-hydroxyestradiol, one of the most genotoxic estrogen metabolites. In this review, we discuss how chronic exposure to xenobiotic chemicals, such as pesticides, might affect the expression of genes regulated by the AhR-ERα crosstalk. Here, we focus on recent advances in the understanding of molecular mechanisms that mediate this crosstalk repression, and particularly on how ERα represses the AhR target gene CYP1A1, and could subsequently promote breast cancer. Finally, we propose that genes implicated in this crosstalk could constitute important biomarkers to assess long-term effects of pesticides on human health.

Personal familiarity of music and its cerebral effect on subsequent speech processing.

Despite the obvious personal relevance of some musical pieces, the cerebral mechanisms associated with listening to personally familiar music and its effects on subsequent brain functioning have not been specifically evaluated yet. We measured cerebral correlates with functional magnetic resonance imaging (fMRI) while composers listened to three types of musical excerpts varying in personal familiarity and self (familiar own/composition, familiar other/favorite or unfamiliar other/unknown music) followed by sequences of names of individuals also varying in personal familiarity and self (familiar own/own name, familiar other/close friend and unfamiliar other/unknown name). Listening to music with autobiographical contents (familiar own and/or other) recruited a fronto-parietal network including mainly the dorsolateral prefrontal cortex, the supramarginal/angular gyri and the precuneus. Additionally, while listening to familiar other music (favorite) was associated with the activation of reward and emotion networks (e.g. the striatum), familiar own music (compositions) engaged brain regions underpinning self-reference (e.g. the medial prefrontal cortex) and visuo-motor imagery. The present findings further suggested that familiar music with self-related reference (compositions) leads to an enhanced activation of the autobiographical network during subsequent familiar name processing (as compared to music without self-related reference); among these structures, the precuneus seems to play a central role in personally familiar processing.