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 facilitative role for corticosterone in the acquisition of a spatial task under moderate stress

Emotionally charged experiences alter memory storage via the activation of hormonal systems. Previously, we have shown that compared with rats trained for a massed spatial learning task in the water maze in warm water (25°C), animals that were trained in cold water (19°C) performed better and showed higher levels of the stress hormone corticosterone. Here, we examined whether manipulating the levels of corticosterone can determine the strength of spatial information acquisition and retention. Rats were injected with metyrapone (25, 50, and 75 mg/kg, i.p.) or with corticosterone (10 and 25 mg/kg, i.p.) and trained in a massed spatial task in either cold (19°C) or warm (25°C) water. We found that whereas animals injected with vehicle performed well in the spatial task in cold water (moderate stress), rats injected with the intermediate metyrapone dose showed impairment in performance. Moreover, whereas animals injected with vehicle on average did not perform well in warm water (mild stress), rats injected with the lower corticosterone dose showed improvement in performance in warm water. These two mirror experiments of corticosterone blockade and enhancement strongly suggest that corticosterone is instrumental in the acquisition and retention of the spatial learning task.     

Visual estimation of spatial requirements for locomotion in novice wheelchair users

Locomotion using a wheelchair requires a wider space than does walking. Two experiments were conducted to test the ability of nonhandicapped adults to estimate the spatial requirements for wheelchair use. Participants judged from a distance whether doorlike apertures of various widths were passable or not passable. Experiment 1 showed that participants underestimated the spatial requirements for wheelchair use but overestimated the spatial requirements for walking. Experiment 2 showed that their underestimation improved but was not completely eliminated after 8 days of practice passing through apertures. Analyses of wheelchair performance in the practice condition showed that the underestimation may have arisen from misperception of the positions of the hands when the participants were grasping the wheelchair hand-rims. The theoretical and practical implications of these findings are discussed.     

Effectiveness Research: Transporting Interpersonal Psychotherapy for Depressed Adolescents (IPT-A) From the Lab to School-Based Health Clinics

This paper describes the process of modifying and transporting an evidence-based treatment, Interpersonal Psychotherapy for Depressed Adolescents (IPT-A), from a university setting to school-based health clinics. It addresses conceptual issues involved in the shift from efficacy to effectiveness research as well as operational issues specific to the transport of IPT-A into school-based health clinics. Consideration is given to the rationale for an IPT-A effectiveness study, methodological concerns, and the timing of the move from the lab to the community. The authors identify challenges and barriers to initiating effectiveness and transportability research and provide suggestions for overcoming these barriers. Recommendations for conducting research in school-based practice settings are provided.     

Individuation among bedouin versus urban arab adolescents: ethnic and gender differences

Three scales assessing individuation (Objective Measure of Ego-Identity Status [OMEIS], Separation-Individuation Test of Adolescence [SITA], and Multigenerational Interconnectedness Scale [MIS]) were administered to 40 female and 38 male Bedouin Arab adolescents and to 39 female and 38 male urban Arab adolescents in Grade 12. It was hypothesized that Bedouin Arab adolescents and female adolescents would manifest less individuation than urban Arab adolescents and male adolescents, respectively. Results from the OMEIS revealed that the identity foreclosed mean of the Bedouin adolescents was higher than that of the urban adolescents. As for the SITA, significant differences were found between Bedouin and urban Arabs in terms of dependency denial, separation anxiety, teacher enmeshment, peer enmeshment, and rejection expectancy. Significant gender differences were found in regard to dependency denial, and a borderline difference was found for separation anxiety. Significant effects of ethnicity and gender were found on the financial interconnectedness subscale of the MIS. The results support the present hypotheses concerning ethnicity differences and indicate that urbanization seems to narrow the differences in individuation between male and female adolescents.     

Illusory conjunctions in the time domain and the resulting time-course of the attentional blink

Illusory conjunctions in the time domain are errors made in binding stimulus features presented In the same spatial position in Rapid Serial Visual Presentation (RSVP) conditions. Botella, Barriopedro, and Suero (2001) devised a model to explain how the distribution of responses originating from stimuli around the target in the series is generated. They proposed two routes consisting of two sequential attempts to make a response. The second attempt (sophisticated guessing) is only employed if the first one (focal attention) fails in producing an integrated perception. This general outline enables specific predictions to be made and tested related to the efficiency of focal attention in generating responses in the first attempt. Participants had to report the single letter in an RSVP stream of letters that was presented in a previously specified color (first target, T1) and then report whether an X (second target, T2) was or was not presented. Performance on T2 showed the typical U-shaped function across the T1-T2 lag that reflects the attentional blink phenomenon. However, as was predicted by Botella, Barriopedro, and Suero's model, the time-course of the interference was shorter for trials with a correct response to T1 than for trials with a T1 error. Furthermore, longer time-courses of interference associated with pre-target and post-target errors to the first target were indistinguishable.     

Accurate referential communication and its relation with private and social speech in a naturalistic context

Research into human communication has been grouped under two traditions: referential and sociolinguistic. The study of a communication behavior simultaneously from both paradigms appears to be absent. Basically, this paper analyzes the use of private and social speech, through both a referential task (Word Pairs) and a naturalistic dyadic setting (Lego-set) administered to a sample of 64 children from grades 3 and 5. All children, of 8 and 10 years of age, used speech that was not adapted to the decoder, and thus ineffective for interpersonal communication, in both referential and sociolinguistic communication. Pairs of high-skill referential encoders used significantly more task-relevant social speech, that is, cognitively more complex, than did low-skill dyads in the naturalistic context. High-skill referential encoder dyads showed a trend to produce more inaudible private speech than did low-skill ones during spontaneous communication. Gender did not affect the results.     

Switching between spatial stimulus-response mappings: a developmental study of cognitive flexibility

Four different age groups (8-9-year-olds, 11-12-year-olds, 13-15-year-olds and young adults) performed a spatial rule-switch task in which the sorting rule had to be detected on the basis of feedback or on the basis of switch cues. Performance errors were examined on the basis of a recently introduced method of error scoring for the Wisconsin Card Sorting Task (WCST; Barcelo & Knight, 2002). This method allowed us to differentiate between errors due to failure-to-maintain-set (distraction errors) and errors due to failure-to-switch-set (perseverative errors). The anticipated age differences in performance errors were most pronounced for perseverative errors between 8-9 years and 11-12 years, but for distraction errors adult levels were not reached until 13-15 years. These findings were interpreted to support the notion that set switching and set maintenance follow distinct developmental trajectories.