RNA interference: a new mechanism by which FMRP acts in the normal brain? What can Drosophila teach us?

Fragile X syndrome is the most common heritable form of mental retardation caused by loss-of-function mutations in the FMR1 gene. The FMR1 gene encodes an RNA-binding protein that associates with translating ribosomes and acts as a negative translational regulator. Recent work in Drosophila melanogaster has shown that the fly homolog of FMR1 (dFMR1) plays an important role in regulating neuronal morphology, which may underlie the observed deficits in behaviors of dFMR1 mutant flies. Biochemical analysis has revealed that dFMR1 forms a complex that includes ribosomal proteins and, surprisingly, Argonaute2 (AGO2), an essential component of the RNA-induced silencing complex (RISC) that mediates RNA interference (RNAi) in Drosophila. dFMR1 also associates with Dicer, another essential processing enzyme of the RNAi pathway. Moreover, both a micro-RNA (miRNA) and short interfering RNAs (siRNAs) can coimmunoprecipitate with dFMR1. Together these findings suggest that dFMR1 functions in an RNAi-related apparatus to regulate the expression of its target genes at the level of translation. These findings raise the possibility that Fragile X syndrome may be the result of a protein synthesis abnormality caused by a defect in an RNAi-related apparatus. Because the core mechanisms of complex behaviors such as learning and memory and circadian rhythms appear to be conserved, studies of Fragile X syndrome using Drosophila as a model provide an economy-of-scale for identifying biological processes that likely underlie the abnormal morphology of dendritic spines and behavioral disturbances observed in Fragile X patients.     

A scale-invariant treatment for recursive path models

A reparameterization is formulated that yields estimates of scale-invariant parameters in recursive path models with latent variables, and (asymptotically) correct standard errors, without the use of constrained optimization. The method is based on the logical structure of the reticular action model.     

Development of cross-linguistic variation in speech and gesture: motion events in English and Turkish

The way adults express manner and path components of a motion event varies across typologically different languages both in speech and cospeech gestures, showing that language specificity in event encoding influences gesture. The authors tracked when and how this multimodal cross-linguistic variation develops in children learning Turkish and English, 2 typologically distinct languages. They found that children learn to speak in language-specific ways from age 3 onward (i.e., English speakers used 1 clause and Turkish speakers used 2 clauses to express manner and path). In contrast, English- and Turkish-speaking children's gestures looked similar at ages 3 and 5 (i.e., separate gestures for manner and path), differing from each other only at age 9 and in adulthood (i.e., English speakers used 1 gesture, but Turkish speakers used separate gestures for manner and path). The authors argue that this pattern of the development of cospeech gestures reflects a gradual shift to language-specific representations during speaking and shows that looking at speech alone may not be sufficient to understand the full process of language acquisition.     

Language-specific and universal influences in children's syntactic packaging of Manner and Path: a comparison of English, Japanese, and Turkish

Different languages map semantic elements of spatial relations onto different lexical and syntactic units. These crosslinguistic differences raise important questions for language development in terms of how this variation is learned by children. We investigated how Turkish-, English-, and Japanese-speaking children (mean age 3;8) package the semantic elements of Manner and Path onto syntactic units when both the Manner and the Path of the moving Figure occur simultaneously and are salient in the event depicted. Both universal and language-specific patterns were evident in our data. Children used the semantic-syntactic mappings preferred by adult speakers of their own languages, and even expressed subtle syntactic differences that encode different relations between Manner and Path in the same way as their adult counterparts (i.e., Manner causing vs. incidental to Path). However, not all types of semantics-syntax mappings were easy for children to learn (e.g., expressing Manner and Path elements in two verbal clauses). In such cases, Turkish- and Japanese-speaking children frequently used syntactic patterns that were not typical in the target language but were similar to patterns used by English-speaking children, suggesting some universal influence. Thus, both language-specific and universal tendencies guide the development of complex spatial expressions.