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Silveira, M. M.

Publications and source records attributed to Silveira, M. M..

2 recordsLinked to original sources

Insight into differing decision-making strategies that underlie cognitively effort-based decision making using computational modeling in rats

RationaleThe rat Cognitive Effort Task (rCET), a rodent model of cognitive rather than physical effort, requires animals to choose between an easy or hard visuospatial discrimination, with a correct hard choice more highly rewarded. Like in humans, there is stable individual variation in choice behavior. In previous reports, animals were divided into two groups - workers and slackers - based on their mean preference for the harder option. Although these groups differed in their response to pharmacological challenges, the rationale for using this criterion for grouping was not robust. MethodsWe collated experimental data from multiple cohorts of male and female rats performing the rCET, and used a model-based framework combining drift diffusion modeling with cluster analysis to identify the decision-making processes underlying variation in choice behavior. ResultsWe verified that workers and slackers are statistically different groups, but also found distinct intra-group profiles. These subgroups exhibited dissociable performance during the attentional phase, linked to distinct decision-making profiles during choice. Reanalysis of previous pharmacology data using this model-based framework showed that serotonergic drug effects were explained by changes in decision boundaries and non-decision times, whilst scopolamines effects were driven by changes in decision starting points and rates of evidence accumulation. ConclusionsModeling revealed the decision-making processes that are associated with cognitive effort costs, and how these differ across individuals. Reanalysis of drug data provided insight into the mechanisms through which different neurotransmitter systems impact cognitively effortful attention and decision-making processes, with relevance to multiple psychiatric disorders.

neuroscience↗

Procaine and S-adenosyl-L-homocysteine (SAH) affect the expression of genes related to the epigenetic machinery and change the DNA methylation status of in vitro cultured bovine skin fibroblasts

Cloning using somatic cell nuclear transfer (SCNT) has many potential applications such as in transgenic and genomic-edited animal production. Abnormal epigenetic reprogramming of somatic cell nuclei is probably the major cause of the low efficiency associated with SCNT. Strategies to alter DNA reprogramming in donor cell nuclei may help improve the cloning efficiency. In the present study, we aimed to characterise the effects of procaine and S-adenosyl-L-homocysteine (SAH) as demethylating agents during the cell culture of bovine skin fibroblasts. We characterised the effects of procaine and SAH on the expression of genes related to the epigenetic machinery, including the DNMT1, DNMT3A, DNMT3B, TET1, TET2, TET3, and OCT4 genes, and on DNA methylation levels of bovine skin fibroblasts. We found that DNA methylation levels of satellite I were reduced by SAH (P=0.0495) and by the combination of SAH and procaine (P=0.0479) compared with that in the control group. Global DNA methylation levels were lower in cells that were cultivated with both compounds than in control cells [procaine (P=0.0116), SAH (P=0.0408), and both (P=0.0163)]. Regarding the transcriptional profile, there was a decrease in total DNMT transcript levels in cells cultivated with SAH and procaine. There was a higher level of TET3 transcripts in treated cells than in the controls. Our results showed that the use of procaine and SAH during bovine cell culture was able to alter the epigenetic profile of the cells. This approach may be a useful alternative strategy to improve the efficiency of reprogramming the somatic nuclei after fusion, which in turn will improve the SCNT efficiency.

genetics↗