Concreteness and emotional valence of episodic future thinking (EFT) independently affect the dynamics of intertemporal decisions

During intertemporal decisions, the value of future rewards decreases as a function of the delay of its receipt (temporal discounting, TD). Since high discount rates have been associated with a series of problematic behaviours and clinical conditions, current research has focused on possible modulators of TD. Specifically, a reduction of individual discount rates has been shown during episodic future thinking (EFT), wherein time intervals are anchored to personal future events. However, it is not entirely clear whether this effect is mediated by a change in the representation of future events (i.e., from abstract to concrete) or by a positive-emotion modulation. Here, we investigated this issue by manipulating the valence of the EFT (i.e., using negative, neutral and positive episodic tags), and by collecting explicit and implicit measures of behaviour. The results showed a significant reduction of TD in all the three emotional conditions compared to the baseline, with differences among them, thus suggesting the existence of a cumulative effect of the concreteness and affective components of the EFT. The analyses of implicit measures additionally revealed that this effect was mediated by a simultaneous increase/decrease of attraction toward the delayed/immediate alternative. Finally, these effects appeared to be modulated by participants' baseline discounting preferences. These findings provide important insights on clinical applications in reward-related disorders

OXTR Gene DNA Methylation Levels Are Associated with Discounting Behavior with Untrustworthy Proposers

Individual differences in temporal and probabilistic discounting are associated with a wide range of life outcomes in literature. Traditional approaches have focused on impulsiveness and cognitive control skills, on goal-oriented personality traits as well as on the psychological perception of time. More recently, literature started to consider the role of social and contextual factors in discounting behavior. Between others, higher generalized trust in human beings and specific trust in people who will deliver the future/probabilistic rewards have been related to a stronger willingness to wait and to assume risk. Moreover, the tendency to trust others has been associated with the oxytocin receptor gene regulation that can be modified by life experiences. In this perspective, we hypothesized that differences in the tendency to wait and to take risks for a more desirable reward according to the proposer’s trustworthiness could be related to a different level of DNA methylation at the oxytocin receptor gene. Findings confirmed that participants are less willing to wait and to risk when the proposer is considered highly untrustworthy and revealed how higher oxytocin receptor gene DNA methylation is associated with a stronger effect due to the presence of an untrustworthy proposer. Limits and future directions are outlined

Transcriptional Shift Identifies a Set of Genes Driving Breast Cancer Chemoresistance

Background Distant recurrences after antineoplastic treatment remain a serious problem for breast cancer clinical management, which threats patients’ life. Systemic therapy is administered to eradicate cancer cells from the organism, both at the site of the primary tumor and at any other potential location. Despite this intervention, a significant proportion of breast cancer patients relapse even many years after their primary tumor has been successfully treated according to current clinical standards, evidencing the existence of a chemoresistant cell subpopulation originating from the primary tumor.Methods/Findings To identify key molecules and signaling pathways which drive breast cancer chemoresistance we performed gene expression analysis before and after anthracycline and taxane-based chemotherapy and compared the results between different histopathological response groups (good-, mid- and bad-response), established according to the Miller & Payne grading system. Two cohorts of 33 and 73 breast cancer patients receiving neoadjuvant chemotherapy were recruited for whole-genome expression analysis and validation assay, respectively. Identified genes were subjected to a bioinformatic analysis in order to ascertain the molecular function of the proteins they encode and the signaling in which they participate. High throughput technologies identified 65 gene sequences which were over-expressed in all groups (P ≤ 0·05 Bonferroni test). Notably we found that, after chemotherapy, a significant proportion of these genes were over-expressed in the good responders group, making their tumors indistinguishable from those of the bad responders in their expression profile (P ≤ 0.05 Benjamini-Hochgerg`s method).Conclusions These data identify a set of key molecular pathways selectively up-regulated in post-chemotherapy cancer cells, which may become appropriate targets for the development of future directed therapies against breast cancer.Thanks are due to the Consejería de Economia, Innovación y Ciencia (CEIC) from the Junta de Andalucía and Fondo Europeo de Desarrollo Regional (FEDER)/Fondo de Cohesión Europeo (FSE) to financial support through the Programa Operativo FEDER/FSE de Andalucía 2007-2013 and the research project CTS-5350. The authors also acknowledge financial support by the PN de I+D+i 2006-2009/ISCIII/Ministerio de Sanidad, Servicios Sociales e Igualdad (Spain) and Fondo Europeo de Desarrollo Regional (FEDER) from the European Union, through the research project PI06/90388

Epithelial-Mesenchymal Transition in Cancer: Parallels Between Normal Development and Tumor Progression

From the earliest stages of embryonic development, cells of epithelial and mesenchymal origin contribute to the structure and function of developing organs. However, these phenotypes are not always permanent, and instead, under the appropriate conditions, epithelial and mesenchymal cells convert between these two phenotypes. These processes, termed Epithelial-Mesenchymal Transition (EMT), or the reverse Mesenchymal-Epithelial Transition (MET), are required for complex body patterning and morphogenesis. In addition, epithelial plasticity and the acquisition of invasive properties without the full commitment to a mesenchymal phenotype are critical in development, particularly during branching morphogenesis in the mammary gland. Recent work in cancer has identified an analogous plasticity of cellular phenotypes whereby epithelial cancer cells acquire mesenchymal features that permit escape from the primary tumor. Because local invasion is thought to be a necessary first step in metastatic dissemination, EMT and epithelial plasticity are hypothesized to contribute to tumor progression. Similarities between developmental and oncogenic EMT have led to the identification of common contributing pathways, suggesting that the reactivation of developmental pathways in breast and other cancers contributes to tumor progression. For example, developmental EMT regulators including Snail/Slug, Twist, Six1, and Cripto, along with developmental signaling pathways including TGF-β and Wnt/β-catenin, are misexpressed in breast cancer and correlate with poor clinical outcomes. This review focuses on the parallels between epithelial plasticity/EMT in the mammary gland and other organs during development, and on a selection of developmental EMT regulators that are misexpressed specifically during breast cancer