ABSTRACT
Children with Specific Language Impairment (SLI) have demonstrated general spelling and writing difficulties. We investigated the sensitivity of children with SLI to the consistent spelling of root morphemes, a feature to which young typically developing children demonstrate sensitivity. We asked children with SLI and two groups of typically developing children (n = 17 in each group) to spell the same letter-sound sequence (e.g., win) as a root, and as a component of inflected, derived, and control words (e.g., win, wins, winner, wink). Children with SLI and spelling-age-matched children (mean age of 9 and 7 years, respectively) were more accurate and more consistent in spelling the initial sections of the inflected and derived words than of the control words, a pattern that suggests sensitivity to the representation of roots in spelling. The absence of a group-level interaction suggests comparable sensitivity in the two groups. Our results suggest that elementary-school-aged children with SLI are sensitive to the consistent spelling of roots, at least to the extent predicted by their general spelling abilities.
Subject(s)
Language Development , Language Disorders/physiopathology , Reading , Writing , Child , Female , Humans , Language Tests , Male , Predictive Value of TestsABSTRACT
BACKGROUND: MDM4, also called MDMX or HDMX in humans, is an important negative regulator of the p53 tumor suppressor. MDM4 is overexpressed in about 17% of all cancers and more frequently in some types, such as colon cancer or retinoblastoma. MDM4 is known to be post-translationally regulated by MDM2-mediated ubiquitination to decrease its protein levels in response to genotoxic stress, resulting in accumulation and activation of p53. At the transcriptional level, MDM4 gene regulation has been less clearly understood. We have reported that DNA damage triggers loss of MDM4 mRNA and a concurrent increase in p53 activity. These experiments attempt to determine a mechanism for down-regulation of MDM4 mRNA. METHODOLOGY/PRINCIPAL FINDINGS: Here we report that MDM4 mRNA is a target of hsa-mir-34a (miR-34a). MDM4 mRNA contains a lengthy 3' untranslated region; however, we find that it is a miR-34a site within the open reading frame (ORF) of exon 11 that is responsible for the repression. Overexpression of miR-34a, but not a mutant miR-34a, is sufficient to decrease MDM4 mRNA levels to an extent identical to those of known miR-34a target genes. Likewise, MDM4 protein levels are decreased by miR-34a overexpression. Inhibition of endogenous miR-34a increased expression of miR-34a target genes and MDM4. A portion of MDM4 exon 11 containing this 8mer-A1 miR-34a site fused to a luciferase reporter gene is sufficient to confer responsiveness, being inhibited by additional expression of exogenous mir-34a and activated by inhibition of miR-34a. CONCLUSIONS/SIGNIFICANCE: These data establish a mechanism for the observed DNA damage-induced negative regulation of MDM4 and potentially provide a novel means to manipulate MDM4 expression without introducing DNA damage.
Subject(s)
Gene Expression Regulation/physiology , MicroRNAs/metabolism , Nuclear Proteins/biosynthesis , Open Reading Frames , Proto-Oncogene Proteins/biosynthesis , RNA, Messenger/metabolism , Ubiquitination/physiology , Cell Cycle Proteins , Cell Line, Tumor , DNA Damage/physiology , Humans , MicroRNAs/genetics , Nuclear Proteins/genetics , Proto-Oncogene Proteins/genetics , RNA, Messenger/genetics , Tumor Suppressor Protein p53/biosynthesis , Tumor Suppressor Protein p53/geneticsABSTRACT
This study investigated whether semantic information presented along with novel printed nonwords facilitates orthographic learning and examined predictors of individual differences in this important literacy skill. A sample of 35 fourth graders was tested on a variety of language and literacy tests, and participants were then exposed to 10 target nonwords, 5 of which were presented with semantic information. Children were tested 1 and 4days later on their ability to correctly recognize and spell the target nonwords. Results revealed a significant main effect on the recognition task, where items presented with semantic information were identified correctly more often than were words presented in isolation. No significant effect of training condition was found for the spelling posttests. Furthermore, multiple regression analyses revealed that both phonological and semantic factors were significant predictors of orthographic learning. The findings support the view that orthographic learning, as measured through visual recognition, involves the integration of phonological, orthographic, and semantic representations.