Prolyl isomerase Pin1 and protein kinase HIPK2 cooperate to promote cortical neurogenesis by suppressing Groucho/TLE:Hes1-mediated inhibition of neuronal differentiation.

The Groucho/transducin-like Enhancer of split 1 (Gro/TLE1):Hes1 transcriptional repression complex acts in cerebral cortical neural progenitor cells to inhibit neuronal differentiation. The molecular mechanisms that regulate the anti-neurogenic function of the Gro/TLE1:Hes1 complex during cortical neurogenesis remain to be defined. Here we show that prolyl isomerase Pin1 (peptidyl-prolyl cis-trans isomerase NIMA-interacting 1) and homeodomain-interacting protein kinase 2 (HIPK2) are expressed in cortical neural progenitor cells and form a complex that interacts with the Gro/TLE1:Hes1 complex. This association depends on the enzymatic activities of both HIPK2 and Pin1, as well as on the association of Gro/TLE1 with Hes1, but is independent of the previously described Hes1-activated phosphorylation of Gro/TLE1. Interaction with the Pin1:HIPK2 complex results in Gro/TLE1 hyperphosphorylation and weakens both the transcriptional repression activity and the anti-neurogenic function of the Gro/TLE1:Hes1 complex. These results provide evidence that HIPK2 and Pin1 work together to promote cortical neurogenesis, at least in part, by suppressing Gro/TLE1:Hes1-mediated inhibition of neuronal differentiation.

Effects of signal probability on individual differences in vigilance.

Decrements in the proportion of signals detected over time on task and large individual differences in performance are typical findings in studies of vigilance. This study investigates the effects of signal probability on individual differences in vigilance performance. Participants monitored stimulus events on computer displays over 2-h periods at three signal probability levels (.01, .04, & .12). Results were analyzed between groups, within groups, and within subjects. Detection decrements were found to be inversely related to signal probability levels across groups. High signal probabilities generated consistent within-group and within-subject performance, whereas low probabilities generated both lower performance and larger within-subject variance. This relationship between signal probability and within-group and within-subject variance has not been previously demonstrated. Future investigations should focus on the sources of both between-subjects and within-subject variation in vigilance performance in order to identify optimal interventions. Actual or potential applications include designing work to minimize vigilance decrement and maximize human performance under conditions that require sustained attention.