The retreat from locative overgeneralisation errors : a novel verb grammaticality judgment study

Whilst some locative verbs alternate between the ground- and figure-locative constructions (e.g. Lisa sprayed the flowers with water/Lisa sprayed water onto the flowers), others are restricted to one construction or the other (e.g. *Lisa filled water into the cup/*Lisa poured the cup with water). The present study investigated two proposals for how learners (aged 5–6, 9–10 and adults) acquire this restriction, using a novel-verb-learning grammaticality-judgment paradigm. In support of the semantic verb class hypothesis, participants in all age groups used the semantic properties of novel verbs to determine the locative constructions (ground/figure/both) in which they could and could not appear. In support of the frequency hypothesis, participants’ tolerance of overgeneralisation errors decreased with each increasing level of verb frequency (novel/low/high). These results underline the need to develop an integrated account of the roles of semantics and frequency in the retreat from argument structure overgeneralisation

Conversational correlates of children's acquisition of mental verbs and a theory of mind

The purpose of this study was to conduct a detailed examination of the ways mothers use mental verbs in conversations with three- and four-year-old children, and to link these usages to the children's developing understanding of mental verbs and a theory of mind. Sixty three- and four-year-olds, either attending preschool (PS) or not (NPS) were given tasks assessing mental verb distinctions and false belief. Their mothers' mental verb use was coded for (a) frequency, (b) type of utterance, (c) type of subordinate clause, (d) the person of the subject of the verb, and (e) the certainty of think. Within the three-year-olds, the NPS children performed significantly better on the mental verb comprehension task; moreover, compared to the PS mothers, the NPS mothers were found to use: (1) less statements and more questions, (2) less first person utterances and more second person utterances, and (3) think in its `very certain' form less often. In regression analyses, children's mental verb and false belief performance were positively predicted by maternal mental verb 1) questions, and 2) single clause utterances; the children's performance was negatively predicted by statements. These findings indicate how maternal input has the potential to promote or hinder children's understanding of the mind.Yeshttps://us.sagepub.com/en-us/nam/manuscript-submission-guideline

Genome-wide functional perturbation of human microsatellite repeats using engineered zinc finger transcription factors.

Repeat elements can be dysregulated at a genome-wide scale in human diseases. For example, in Ewing sarcoma, hundreds of inert GGAA repeats can be converted into active enhancers when bound by EWS-FLI1. Here we show that fusions between EWS and GGAA-repeat-targeted engineered zinc finger arrays (ZFAs) can function at least as efficiently as EWS-FLI1 for converting hundreds of GGAA repeats into active enhancers in a Ewing sarcoma precursor cell model. Furthermore, a fusion of a KRAB domain to a ZFA can silence GGAA microsatellite enhancers genome wide in Ewing sarcoma cells, thereby reducing expression of EWS-FLI1-activated genes. Remarkably, this KRAB-ZFA fusion showed selective toxicity against Ewing sarcoma cells compared with non-Ewing cancer cells, consistent with its Ewing sarcoma-specific impact on the transcriptome. These findings demonstrate the value of ZFAs for functional annotation of repeats and illustrate how aberrant microsatellite activities might be regulated for potential therapeutic applications

Avoiding dative overgeneralisation errors: semantics, statistics or both?

Item does not contain fulltextHow do children eventually come to avoid the production of overgeneralisation errors, in particular, those involving the dative (e.g., *I said her "no")? The present study addressed this question by obtaining from adults and children (5-6, 9-10 years) judgements of well-formed and over-general datives with 301 different verbs (44 for children). A significant effect of pre-emption - whereby the use of a verb in the prepositional-object (PO)-dative construction constitutes evidence that double-object (DO)-dative uses are not permitted - was observed for every age group. A significant effect of entrenchment - whereby the use of a verb in any construction constitutes evidence that unattested dative uses are not permitted - was also observed for every age group, with both predictors also accounting for developmental change between ages 5-6 and 9-10 years. Adults demonstrated knowledge of a morphophonological constraint that prohibits Latinate verbs from appearing in the DO-dative construction (e.g., *I suggested her the trip). Verbs' semantic properties (supplied by independent adult raters) explained additional variance for all groups and developmentally, with the relative influence of narrow- vs broad-range semantic properties increasing with age. We conclude by outlining an account of the formation and restriction of argument-structure generalisations designed to accommodate these findings.26 p

The chromatin landscape of primary synovial sarcoma organoids is linked to specific epigenetic mechanisms and dependencies.

Synovial sarcoma (SyS) is an aggressive mesenchymal malignancy invariably associated with the chromosomal translocation t(X:18; p11:q11), which results in the in-frame fusion of the BAF complex gene SS18 to one of three SSX genes. Fusion of SS18 to SSX generates an aberrant transcriptional regulator, which, in permissive cells, drives tumor development by initiating major chromatin remodeling events that disrupt the balance between BAF-mediated gene activation and polycomb-dependent repression. Here, we developed SyS organoids and performed genome-wide epigenomic profiling of these models and mesenchymal precursors to define SyS-specific chromatin remodeling mechanisms and dependencies. We show that SS18-SSX induces broad BAF domains at its binding sites, which oppose polycomb repressor complex (PRC) 2 activity, while facilitating recruitment of a non-canonical (nc)PRC1 variant. Along with the uncoupling of polycomb complexes, we observed H3K27me3 eviction, H2AK119ub deposition and the establishment of de novo active regulatory elements that drive SyS identity. These alterations are completely reversible upon SS18-SSX depletion and are associated with vulnerability to USP7 loss, a core member of ncPRC1.1. Using the power of primary tumor organoids, our work helps define the mechanisms of epigenetic dysregulation on which SyS cells are dependent

EWSR1-ATF1 dependent 3D connectivity regulates oncogenic and differentiation programs in Clear Cell Sarcoma.

Oncogenic fusion proteins generated by chromosomal translocations play major roles in cancer. Among them, fusions between EWSR1 and transcription factors generate oncogenes with powerful chromatin regulatory activities, capable of establishing complex gene expression programs in permissive precursor cells. Here we define the epigenetic and 3D connectivity landscape of Clear Cell Sarcoma, an aggressive cancer driven by the EWSR1-ATF1 fusion gene. We find that EWSR1-ATF1 displays a distinct DNA binding pattern that requires the EWSR1 domain and promotes ATF1 retargeting to new distal sites, leading to chromatin activation and the establishment of a 3D network that controls oncogenic and differentiation signatures observed in primary CCS tumors. Conversely, EWSR1-ATF1 depletion results in a marked reconfiguration of 3D connectivity, including the emergence of regulatory circuits that promote neural crest-related developmental programs. Taken together, our study elucidates the epigenetic mechanisms utilized by EWSR1-ATF1 to establish regulatory networks in CCS, and points to precursor cells in the neural crest lineage as candidate cells of origin for these tumors

Attentional learning helps language acquisition take shape for atypically developing children, not just children with Autism Spectrum Disorders

The shape bias-generalising labels to same shaped objects-has been linked to attentional learning or referential intent. We explore these origins in children with typical development (TD), autism spectrum disorders (ASD) and other developmental disorders (DD). In two conditions, a novel object was presented and either named or described. Children selected another from a shape, colour or texture match. TD children choose the shape match in both conditions, children with DD and 'high-verbal mental age' (VMA) children with ASD (language age > 4.6) did so in the name condition and 'low-VMA' children with ASD never showed the heuristic. Thus, the shape bias arises from attentional learning in atypically developing children and is delayed in ASD

Do two and three year old children use an incremental first-NP-as-agent bias to process active transitive and passive sentences? : A permutation analysis

We used eye-tracking to investigate if and when children show an incremental bias to assume that the first noun phrase in a sentence is the agent (first-NP-as-agent bias) while processing the meaning of English active and passive transitive sentences. We also investi-gated whether children can override this bias to successfully distinguish active from passive sentences, after processing the remainder of the sentence frame. For this second question we used eye-tracking (Study 1) and forced-choice pointing (Study 2). For both studies, we used a paradigm in which participants simultaneously saw two novel actions with reversed agent-patient relations while listening to active and passive sentences. We compared English-speaking 25-month-olds and 41-month-olds in between-subjects sentence struc-ture conditions (Active Transitive Condition vs. Passive Condition). A permutation analysis found that both age groups showed a bias to incrementally map the first noun in a sentence onto an agent role. Regarding the second question, 25-month-olds showed some evidence of distinguishing the two structures in the eye-tracking study. However, the 25-month-olds did not distinguish active from passive sentences in the forced choice pointing task. In contrast, the 41-month-old children did reanalyse their initial first-NP-as-agent bias to the extent that they clearly distinguished between active and passive sentences both in the eye-tracking data and in the pointing task. The results are discussed in relation to the development of syntactic (re)parsing