Chronic Dietary Exposure to a Low-Dose Mixture of Genistein and Vinclozolin Modifies the Reproductive Axis, Testis Transcriptome, and Fertility

Background: The reproductive consequences and mechanisms of action of chronic exposure to low-dose endocrine disruptors are poorly understood.[br/] Objective: We assessed the effects of a continuous, low-dose exposure to a phytoestrogen (genistein) and/or an antiandrogenic food contaminant (vinclozolin) on the male reproductive tract and fertility.[br/] Methods: Male rats were exposed by gavage to genistein and vinclozolin from conception to adulthood, alone or in combination, at low doses (1 mg/kg/day) or higher doses (10 and 30 mg/kg/day). We studied a number of standard reproductive toxicology end points and also assessed testicular mRNA expression profiles using long-oligonucleotide microarrays.[br/] Results: The low-dose mixture and high-dose vinclozolin produced the most significant alterations in adults: decreased sperm counts, reduced sperm motion parameters, decreased litter sizes, and increased post implantation loss. Testicular mRNA expression profiles for these exposure conditions were strongly correlated. Functional clustering indicated that many of the genes induced belong to the “neuroactive ligand-receptor interactions” family encompassing several hormonally related actors (e.g., follicle-stimulating hormone and its receptor). All exposure conditions decreased the levels of mRNAs involved in ribosome function, indicating probable decreased protein production.[br/] Conclusions: Our study shows that chronic exposure to a mixture of a dose of a phytoestrogen equivalent to that in the human diet and a low dose—albeit not environmental—of a common anti-androgenic food contaminant may seriously affect the male reproductive tract and fertility

DNA repair pathways as targets for cancer therapy.

DNA repair pathways can enable tumour cells to survive DNA damage that is induced by chemotherapeutic treatments; therefore, inhibitors of specific DNA repair pathways might prove efficacious when used in combination with DNA-damaging chemotherapeutic drugs. In addition, alterations in DNA repair pathways that arise during tumour development can make some cancer cells reliant on a reduced set of DNA repair pathways for survival. There is evidence that drugs that inhibit one of these pathways in such tumours could prove useful as single-agent therapies, with the potential advantage that this approach could be selective for tumour cells and have fewer side effects

Characterizing Belief Bias in Syllogistic Reasoning: A Hierarchical Bayesian Meta-Analysis of ROC Data

The belief-bias effect is one of the most-studied biases in reasoning. A recent study of the phenomenon using the signal detection theory (SDT) model called into question all theoretical accounts of belief bias by demonstrating that belief-based differences in the ability to discriminate between valid and invalid syllogisms may be an artifact stemming from the use of inappropriate linear measurement models such as analysis of variance (Dube et al., Psychological Review, 117(3), 831–863, 2010). The discrepancy between Dube et al.’s, Psychological Review, 117(3), 831–863 (2010) results and the previous three decades of work, together with former’s methodological criticisms suggests the need to revisit earlier results, this time collecting confidence-rating responses. Using a hierarchical Bayesian meta-analysis, we reanalyzed a corpus of 22 confidence-rating studies (N = 993). The results indicated that extensive replications using confidence-rating data are unnecessary as the observed receiver operating characteristic functions are not systematically asymmetric. These results were subsequently corroborated by a novel experimental design based on SDT’s generalized area theorem. Although the meta-analysis confirms that believability does not influence discriminability unconditionally, it also confirmed previous results that factors such as individual differences mediate the effect. The main point is that data from previous and future studies can be safely analyzed using appropriate hierarchical methods that do not require confidence ratings. More generally, our results set a new standard for analyzing data and evaluating theories in reasoning. Important methodological and theoretical considerations for future work on belief bias and related domains are discussed