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Item does not contain fulltext, We investigated whether learning an artificial language at 17 months was predictive of children's natural language vocabulary and grammar skills at 54 months. Children at 17 months listened to an artificial language containing non-adjacent dependencies, and were then tested on their learning to segment and to generalise the structure of the language. At 54 months, children were then tested on a range of standardised natural language tasks that assessed receptive and expressive vocabulary and grammar. A structural equation model demonstrated that learning the artificial language generalisation at 17 months predicted language abilities - a composite of vocabulary and grammar skills - at 54 months, whereas artificial language segmentation at 17 months did not predict language abilities at this age. Artificial language learning tasks - especially those that probe grammar learning - provide a valuable tool for uncovering the mechanisms driving children's early language development, 13 p.

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We hypothesized that small molecule transcriptional perturbation could be harnessed to target a cellular dependency involving protein arginine methyltransferase 5 (PRMT5) in the context of methylthioadenosine phosphorylase (MTAP) deletion, seen frequently in malignant pleural mesothelioma (MPM). Here we show, that MTAP deletion is negatively prognostic in MPM. In vitro, the off-patent antibiotic Quinacrine efficiently suppressed PRMT5 transcription, causing chromatin remodelling with reduced global histone H4 symmetrical demethylation. Quinacrine phenocopied PRMT5 RNA interference and small molecule PRMT5 inhibition, reducing clonogenicity in an MTAP-dependent manner. This activity required a functional PRMT5 methyltransferase as MTAP negative cells were rescued by exogenous wild type PRMT5, but not a PRMT5E444Q methyltransferase-dead mutant. We identified c-jun as an essential PRMT5 transcription factor and a probable target for Quinacrine. Our results therefore suggest that small molecule-based transcriptional perturbation of PRMT5 can leverage a mutation-selective vulnerability, that is therapeutically tractable, and has relevance to 9p21 deleted cancers including MPM.

Reading for meaning is one of the most important activities in school and everyday life. The simple view of reading (SVR) has been used as a framework for studies of reading comprehension in individuals with Down syndrome (DS). These tend to show difficulties in reading comprehension despite better developed reading accuracy. Reading comprehension difficulties are influenced by poor oral language. These difficulties are common in individuals with DS and autism spectrum disorder (ASD), but they have never been compared directly. Moreover, the components of reading for comprehension have rarely been investigated in these populations: a better understanding of the nature of reading comprehension difficulties may inform both theory and practice. The aim of this study was to determine whether reading comprehension in the two populations is accounted for by the same component skills and to what extent the reading profile of the two atypical groups differs from that of typically developing children (TD). Fifteen individuals with DS (mean age = 22 years 4 months, SD = 5 years 2 months), 21 with ASD (mean age = 13 years 2 months, SD = 1 year 6 months), and 42 TD children (mean age = 8 years 1 month, SD = 7 months) participated and were assessed on measures of receptive vocabulary, text reading and listening comprehension, oral language comprehension, and reading accuracy. The results showed similar levels in word reading accuracy and in receptive vocabulary in all three groups. By contrast, individuals with DS and ASD showed poorer non-word reading and reading accuracy in context than TD children. Both atypical groups showed poorer listening and reading text comprehension compared to TD children. Reading for comprehension, investigated through a homograph reading accuracy task, showed a different pattern for individuals with DS with respect to the other two groups: they were less sensitive to meaning while reading. According to the SVR, the current results confirm that the t

Background and aims: Children with autism spectrum condition often have specific difficulties understanding that pictorial symbols refer to real-world objects in the environment. We investigated the influence of labelling on the symbolic understanding and dual representation of children with autism spectrum condition. Methods: Children with autism spectrum condition and typically developing children were shown four coloured photographs of objects that had different functions across four separate trials. The participants were given either a novel label alongside a description of the object’s function or a description of the object’s function without a label. Children were then given 30 seconds to interact with an array of stimuli (pictures and objects) in a mapping test and in a generalisation test for each trial. This exploration phase allowed for spontaneous word–picture–referent mapping through free-play, providing an implicit measure of symbolic understanding. Results: We found no significant difference in word–picture–referent mapping between groups and conditions. Both groups more often performed the described action on the target object in the exploration phase regardless of condition. Conclusions and implications: Our results suggest that a spontaneous measure of symbolic understanding (such as free-play) may reveal competencies in word–picture–referent mapping in autism spectrum condition.

The authors examined teachers’ (N = 19) use of different question types during small‐group comprehension instruction for 6–11‐year‐olds (N = 115). The authors tagged the corpus of 40 hours of guided reading sessions to enable computer‐based searches for syntactic forms of questions. Teachers frequently asked high‐challenge wh‐ word questions (e.g., “How does that fit in with what you just read?”), and this was more pronounced in schools located in regions of low socioeconomic status, a finding associated with recency of completion of teacher training. Students’ responses were more linguistically complex when teacher questions comprised a high frequency of high‐challenge questions, particularly wh‐ word adverb questions (predominantly why and how). These findings applied across the wide age and ability range of the sample, indicating that high‐challenge questions are effective in small‐group comprehension instruction for students in different age groups and at various levels of reading ability. The authors conclude that teachers benefit from being informed about the effect of various syntactic forms of questions, particularly the nuances of wh‐ word questions. The findings also highlight the advantages of using corpus search methods to examine the influence of teacher question‐asking strategies during classroom interactions.