Executive functions and adaptive behaviour in individuals with Down syndrome.

BACKGROUND: Previous research has explored executive functions (EFs) and adaptive behaviour in children and adolescents with Down syndrome (DS), but there is a paucity of research on the relationship between the two in this population. This study aims to shed light on the profile of EFs and adaptive behaviour in DS, exploring the differences by age and investigating the relationship between these two domains. METHOD: Parents/caregivers of 100 individuals with DS from 3 to 16 years old participated in the study. The sample was divided into preschoolers (3-6.11 years old) and school-age children (7-16 years old). Parents/caregivers completed either the Preschool Version of the Behaviour Rating Inventory of Executive Function (for children 2-6.11 years old) or the Second Edition of the same Inventory (for individuals 7 + years old). Adaptive behaviour was assessed with the Vineland Adaptive Behaviour Scale - Interview, Second Edition. RESULTS: Findings suggest that individuals with DS have overall difficulties, but also patterns of strength and weakness in their EFs and adaptive behaviour. The preschool-age and school-age children's EF profiles differed slightly. While both age groups showed Emotional Control as a relative strength and Working Memory as a weakness, the school-age group revealed further weaknesses in Shift and Plan/Organise. As concerns adaptive behaviour, the profiles were similar in the two age groups, with Socialisation as a strength, and Communication and Daily Living Skills as weaknesses, but with a tendency for preschoolers to obtain intermediate scores for the latter. When the relationship between EFs and adaptive behaviour was explored, Working Memory predicted Communication in the younger group, while in the older group the predictors varied, depending on the adaptive domains: Working Memory was a predictor of Communication, Inhibit of Daily Living Skills, and Inhibit and Shift of Socialisation. CONCLUSION: As well as elucidating the EF profiles and adaptive behaviour in individuals with DS by age, this study points to the role of EFs in adaptive functioning, providing important information for targeted interventions.

Inhibition of protein phosphorylation modulates expression of the Jak family protein tyrosine kinases.

Treatment of murine Friend cells with a dose of the protein kinase inhibitor staurosporine, which is able to block the response of the cells to interferons, appears to inhibit phosphorylation of Jak proteins and, interestingly, to specifically reduce tyk2 and Jak1 expression and to increase Jak2 both in the presence and in the absence of interferons. Therefore, a potential role for phosphorylation events in the regulation of expression of the Jak family members is suggested.

Staurosporine inhibits interferon alpha-induced gene expression in Friend erythroleukemia cells through a PKC independent pathway.

Interferons (IFNs) are able to induce an increased transcription of several genes, which can occur within minutes of the binding of IFNs to their receptors. The specific induced transcription is mediated by the interaction of specific transcription factors with regulatory DNA sequences that lie upstream the promoters of IFN induced genes. Phosphorylation of IFN-specific transcription factors is required for activation of transcription. We have studied the antiviral effect and the induction of gene expression by IFN-alpha in Friend Leukemia cells (FLC) in the presence of a series of inhibitors of known kinases. Protein kinase C (PKC)-specific inhibitors, i.e. calphostin C and bisindolylmaleimide, failed to influence the IFN-induced gene expression and the antiviral state. Likewise, little or no effect was found using inhibitors such as H7 or K252a. Chronic exposure of FLC to phorbol ester, that causes down regulation of PKC (the effectiveness of TPA treatment was proven by PKC enzymatic assay), has no effect on IFN-alpha action. In addition, treatment of FLC with staurosporine prevented the induction of IFN-stimulated genes and the establishment of the antiviral state only when this drug was used at high dosage (500 nM). This result indicates that, also in FLC, activation of PKC is not involved in the transcriptional response of the cells to IFN-alpha treatment. The non receptor tyrosine kinases of the JAK family that take part in the IFNs-specific transduction pathways could be the target of the staurosporine specific inhibition of the IFN-alpha action.