Convergent genetic linkage and associations to language, speech and reading measures in families of probands with Specific Language Impairment

We analyzed genetic linkage and association of measures of language, speech and reading phenotypes to candidate regions in a single set of families ascertained for SLI. Sib-pair and family-based analyses were carried out for candidate gene loci for Reading Disability (RD) on chromosomes 1p36, 3p12-q13, 6p22, and 15q21, and the speech-language candidate region on 7q31 in a sample of 322 participants ascertained for Specific Language Impairment (SLI). Replication or suggestive replication of linkage was obtained in all of these regions, but the evidence suggests that the genetic influences may not be identical for the three domains. In particular, linkage analysis replicated the influence of genes on chromosome 6p for all three domains, but association analysis indicated that only one of the candidate genes for reading disability, KIAA0319, had a strong effect on language phenotypes. The findings are consistent with a multiple gene model of the comorbidity between language impairments and reading disability and have implications for neurocognitive developmental models and maturational processes

Pragmatic Inferences in High-Functioning Adults with Autism and Asperger Syndrome

Contains fulltext : 76784.pdf (publisher's version ) (Closed access)Although people with autism spectrum disorders (ASD) often have severe problems with pragmatic aspects of language, little is known about their pragmatic reasoning. We carried out a behavioral study on high-functioning adults with autistic disorder (n = 11) and Asperger syndrome (n = 17) and matched controls (n = 28) to investigate whether they are capable of deriving scalar implicatures, which are generally considered to be pragmatic inferences. Participants were presented with underinformative sentences like “Some sparrows are birds”. This sentence is logically true, but pragmatically inappropriate if the scalar implicature “Not all sparrows are birds” is derived. The present findings indicate that the combined ASD group was just as likely as controls to derive scalar implicatures, yet there was a difference between participants with autistic disorder and Asperger syndrome, suggesting a potential differentiation between these disorders in pragmatic reasoning. Moreover, our results suggest that verbal intelligence is a constraint for task performance in autistic disorder but not in Asperger syndrome.12 p

PRR5L degradation promotes mTORC2-mediated PKC-δ phosphorylation and cell migration downstream of Gα(12)

Mammalian target of rapamycin complex (MTORC) 2 phosphorylates AGC protein kinases including PKC and regulates cellular functions including cell migration. However, its regulation remains poorly understood. Here we show that LPA induces two phases of PKCδ hydrophobic motif (HM) phosphorylation. The late phase is mediated by Gα12, which specifically activates ARAF, leading to upregulation of the expression of an E3 ubiquitin ligase RFFL and subsequent ubiquitination and degradation of PRR5L. Destabilization of PRR5L, a suppressor of mTORC2-mediated HM phosphorylation of PKCδ, but not AKT, results in PKCδ HM phosphorylation and activation. This Gα12-mediated pathway is critically important for fibroblast migration and pulmonary fibrosis development. Thus, our study unravels a signaling pathway for mTORC2 regulation and fibroblast migration