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Chung, W. Y.

Publications and source records attributed to Chung, W. Y..

2 recordsLinked to original sources

Integration of "what" and "when" predictions during action-effect processing

Voluntary actions generate predictions about their sensory consequences, but it remains unknown whether predictions arising from different dimensions of intentional action are processed independently or integrated into a unified expectation. We addressed this question by combining action choice ("what") and action timing ("when") within a single action-effect learning paradigm. Participants learned independent associations between each action dimension and a distinct auditory feature and performed self-paced actions while electroencephalography was recorded. This design allowed action-choice and action-timing predictions to be fulfilled or violated independently or simultaneously. Event-related potentials were analysed using Bayesian linear mixed-effects models. The P2 component showed a significant interaction between action-choice and action-timing prediction violations: neither violation alone reliably modulated P2 amplitude, whereas simultaneous violations produced a marked reduction, consistent with a conjunctive prediction-error response. The later P3 component exhibited a graded pattern, with action-timing violations increasing amplitude and action-choice violations contributing an additional increment when both predictions were violated. These findings suggest that predictions derived from different dimensions of voluntary action are integrated during early sensory processing, whereas later stages evaluate prediction violations more cumulatively. The present results extend previous work on action-effect prediction by showing that predictions associated with action choice and action timing interact during the processing of their sensory consequences.

neuroscience↗

The epithelial splicing regulator ESRP2 is epigenetically repressed by DNA hypermethylation in Wilms tumour and acts as a tumour suppressor

Wilms tumour (WT), a childhood kidney cancer with embryonal origins, has been extensively characterised for genetic and epigenetic alterations, but a proportion of WTs still lack identifiable abnormalities. To uncover DNA methylation changes critical for WT pathogenesis, we compared the epigenome of fetal kidney with two WT cell lines, using methyl-CpG immunoprecipitation. We filtered our results to remove common cancer-associated epigenetic changes, and to enrich for genes involved in early kidney development. This identified four candidate genes that were hypermethylated in WT cell lines compared to fetal kidney, of which ESRP2 (epithelial splicing regulatory protein 2), was the most promising gene for further study. ESRP2 was commonly repressed by DNA methylation in WT, and this was shown to occur early in WT development (in nephrogenic rests). ESRP2 expression could be reactivated by DNA methyltransferase inhibition in WT cell lines. When ESRP2 was overexpressed in WT cell lines, it acted as an inhibitor of cellular proliferation in vitro, and in vivo it suppressed tumour growth of orthotopic xenografts in nude mice. RNA-seq of the ESRP2-expressing WT cell lines identified several novel splicing targets, in addition to well-characterised targets of ESRP2. We propose a model in which the mesenchymal to epithelial transition that is essential for early kidney development, can be disrupted in to generate WT, either by genetic abnormalities such as WT1 mutations, or by epigenetic defects, such as ESRP2 methylation.

cancer biology↗