Transgenic mouse models of neurodegenerative disease caused by CAG/polyglutamine expansions

CAG/polyglutamine expansion is the mutational mechanism that causes a number of late-onset neurodegenerative diseases. Expanded CAG repeats are unstable: they vary in size between tissues and change in size upon transmission from parent to offspring. These mutations are thought to impart a dominant gain of function to the proteins in which they are located. Recent reports describing the first mouse models of these diseases promise to shed light on the molecular mechanisms underlying CAG-repeat instability, the pathways by which polyglutamine expansion causes cell death and the factors that determine the specificity of the neurodegeneration.     

Narrative discourse in children with early focal brain injury

Children with early brain damage, unlike adult stroke victims, often go on to develop nearly normal language. However, the route and extent of their linguistic development are still unclear, as is the relationship between lesion site and patterns of delay and recovery. Here we address these questions by examining narratives from children with early brain damage. Thirty children (ages 3:7-10:10) with pre- or perinatal unilateral focal brain damage and their matched controls participated in a storytelling task. Analyses focused on linguistic proficiency and narrative competence. Overall, children with brain damage scored significantly lower than their age-matched controls on both linguistic (morphological and syntactic) indices and those targeting broader narrative qualities. Rather than indicating that children with brain damage fully catch up, these data suggest that deficits in linguistic abilities reassert themselves as children face new linguistic challenges. Interestingly, after age 5, site of lesion does not appear to be a significant factor and the delays we have witnessed do not map onto the lesion profiles observed in adults with analogous brain injuries.     

Transgenic mice in the study of polyglutamine repeat expansion diseases

We investigated the genetic heterogeneity of 2354 individuals from the 9 provinces of Sicily. The genetic markers we used were HP, GC, TF, PI, and AK1 plus other previously tested polymorphisms, for a total of 24 independent markers. Distinct multivariate statistics were applied to verify the claimed genetic distinctiveness between extant eastern and western Sicilian populations. Our hypothesis stated that any diversity found between the two subpopulations would represent the signature of early colonization of the island by Greek and Phoenician peoples. Correspondence analysis showed that there was no clear geographic clustering within Sicily. The genetic distance matrix used for identifying the main genetic barriers revealed no east-west differences within the island's population, at least at the provincial level. FST estimates proved that the population subdivision did not affect the pattern of gene frequency variation; this implies that Sicily is effectively one panmictic unit. The bulk of our results confirm the absence of genetic differentiation between eastern and western Sicilians, and thus we reject the hypothesis of the subdivision of an ancient population in two areas.     

Striking changes in anxiety in Huntington's disease transgenic mice

Huntington's disease transgenic mice were tested in the elevated plus-maze test of anxiety at 6, 8, 10 and 12 weeks of age. At all ages, they showed significant and striking increases in the percentages of open arm entries and time spent on the open arms, compared with their normal littermates, indicating reduced anxiety. These increases were not secondary to a non-specific stimulant effect, since the transgenic mice made fewer closed arm entries, significantly so from 10 weeks of age. The mice were also tested in the holeboard, which provides measures of locomotor activity and directed exploration. From 8 weeks of age, the Huntington's mice were significantly less active than their normal littermates and made fewer exploratory head-dips. The increased open arm activity in the elevated plus-maze cannot therefore be secondary to increased exploration in the transgenic mice. In order to determine whether the reduced anxiety was due to differences in benzodiazepine receptor function, the mice were challenged with the benzodiazepine receptor antagonist, flumazenil. The results indicated that some of the reduced anxiety could be attributed to the presence of an endogenous anxiolytic ligand.     

Mother–infant interaction and the development of individual differences in children's cognitive competence.

Assessed the antecedents of individual differences in children's cognitive/language competence at age 24 mo using multivariate methods at ages 6, 13, and 24 mo in 121 Ss. Assessments included detailed observations of mother–children interaction, standardized tests of child cognitive development (including the Home Observation for Measurement of the Environment and the Bayley Mental Scale of Infant Development), and examiner and maternal ratings of child sociability. There were meaningful patterns of continuity in the child and especially mother behavior factors across ages, and mother–child warm, verbal interactions at each age were associated with a composite index of child competence at 24 mo. A path analysis showed that altogether, 40% of the variance in competence outcome was explained by the 4 variables in the model (interaction at 3 ages and SES). The analysis also showed that the original bivariate correlation between interaction at 6 mo and later competence could be explained by continuity in interaction qualities at 6 and 24 mo rather than as a direct effect. However, the 13-mo interaction showed both a direct path to competence and an indirect one via age 24-mo interaction. SES had a modest significant correlation with competence, but in the path analysis this was dissipated in nonsignificant paths to the interaction variables. Partial correlations suggested that child developmental competence and sociability at earlier ages did not mediate the relationships between mother–infant interaction and later child competence. (34 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

X-ray photoemission studies of cesium antimonide photoemitters

X-ray photoemission spectra (XPS) of cesium antimonide photosurfaces prepared in ultrahigh vacuum on Pyrex, Suprasil quartz and stainless steel substrates were measured. A comparison of the XPS data for xenon gas, which is isoelectronic with Cs⁺, and cesium in good cesium antimonide photoemitters indicates that cesium exists predominantly in the form Cs⁺, in direct conflict with present theories concerning this surface. Measurements also indicated a slight excess of antimony above that given by the formula Cs₃Sb. Band bending is only inferred from the shifts of the cesium core levels as a function of photosensitivity.     

Supporting interactive presentation for distributed multimedia applications

In this paper we present IMP, a platform to support the authoring and run-time management of interactive multimedia applications in distributed environments. The multi-level platform model encourages slot-in extensibility to cater for the evolving environment. We illustrate with our prototype platform built above the Cambridge multimedia environment. The authoring model emphasises reusability, tailorability and use of environment features in a uniform way. We have shown the validity of our approach by constructing a variety of application types.     

Social information-processing patterns partially mediate the effect of early physical abuse on later conduct problems.

The authors tested the hypothesis that early physical abuse is associated with later externalizing behavior outcomes and that this relation is mediated by the intervening development of biased social information-processing patterns. They assessed 584 randomly selected boys and girls from European American and African American backgrounds for the lifetime experience of physical abuse through clinical interviews with mothers prior to the child's matriculation in kindergarten. Early abuse increased the risk of teacher-rated externalizing outcomes in Grades 3 and 4 by fourfold, and this effect could not be accounted for by confounded ecological or child factors. Abuse was associated with later processing patterns (encoding errors, hostile attributional biases, accessing of aggressive responses, and positive evaluations of aggression), which, in turn, predicted later externalizing outcomes. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Personality€nvironment constellations and alcohol use: A process-oriented study of intraindividual change during adolescence.

Tested the salience of documented risk and protective factors in contributing to intra-individual changes in alcohol use behaviors and negative consequences of use during adolescence within an interactionist and process-oriented perspective. 870 Ss from a longitudinal study of normal adolescent development completed self-report questionnaires. Ss were 12 or 15 yrs old at the 1st test and were retested twice at 3-yr intervals (92% longitudinal retest rate). Person–environment constellations comprising high impulsivity, disinhibition, and deviant peer group associations, and to a lesser extent, low parental control, most strongly influenced high-risk developmental trajectories of use intensity and problems. (PsycINFO Database Record (c) 2010 APA, all rights reserved)