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Jennifer Simpson

Publications and source records attributed to Jennifer Simpson.

5 recordsLinked to original sources

Altered glycosylated PrP proteins can have different neuronal trafficking in brain but do not acquire scrapie-like properties.

N-Linked glycans have been shown to have an important role in the cell biology of a variety of cell surface glycoproteins, including PrP protein. It has been suggested that glycosylation of PrP can influence the susceptibility to transmissible spongiform encephalopathy and determine the characteristics of the many different strains observed in this particular type of disease. To understand the role of carbohydrates in influencing the PrP maturation, stability, and cell biology, we have produced and analyzed gene-targeted murine models expressing differentially glycosylated PrP. Transgenic mice carrying the PrP substitution threonine for asparagine 180 (G1) or threonine for asparagine 196 (G2) or both mutations combined (G3), which eliminate the first, second, and both glycosylation sites, respectively, have been generated by double replacement gene targeting. An in vivo analysis of altered PrP has been carried out in transgenic mouse brains, and our data show that the lack of glycans does not influence PrP maturation and stability. The presence of one chain of sugar is sufficient for the trafficking to the cell membrane, whereas the unglycosylated PrP localization is mainly intracellular. However, this altered cellular localization of PrP does not lead to any overt phenotype in the G3 transgenic mice. Most importantly, we found that, in vivo, unglycosylated PrP does not acquire the characteristics of the aberrant pathogenic form (PrPSc), as was previously reported using in vitro models.

Aging↗

The alpha(v)beta6 integrin receptor for Foot-and-mouth disease virus is expressed constitutively on the epithelial cells targeted in cattle.

Field strains of Foot-and-mouth disease virus (FMDV) use a number of alpha(v)-integrins as receptors to initiate infection on cultured cells, and integrins are believed to be the receptors used to target epithelial cells in animals. In this study, immunofluorescence confocal microscopy and real-time RT-PCR were used to investigate expression of two of the integrin receptors of FMDV, alpha(v)beta6 and alpha(v)beta3, within various epithelia targeted by this virus in cattle. These studies show that alpha(v)beta6 is expressed constitutively on the surfaces of epithelial cells at sites where infectious lesions occur during a natural infection, but not at sites where lesions are not normally formed. Expression of alpha(v)beta6 protein at these sites showed a good correlation with the relative abundance of beta6 mRNA. In contrast, alpha(v)beta3 protein was only detected at low levels on the vasculature and not on the epithelial cells of any of the tissues investigated. Together, these data suggest that in cattle, alpha(v)beta6, rather than alpha(v)beta3, serves as the major receptor that determines the tropism of FMDV for the epithelia normally targeted by this virus.

Animals↗

Reception class predictors of literacy skills.

BACKGROUND: In the last decade, there has been a growing interest, both in the UK and abroad, in developing early screening tests for dyslexia that can be used with very young children. In addition to measures of literacy achievement, such screening tests typically aim to identify underlying difficulties, such as phonological deficits, that might hinder a child's educational progress. The Dyslexia Early Screening Test (DEST; Nicolson & Fawcett, 1996) is an example of such a test that combines attainment and diagnostic indicators. AIM: The study reported assessed the ability of the DEST to predict future literacy skills in contrast with the prediction afforded by school-based measures, such as letter knowledge. SAMPLE: Participants were 45 boys attending a reception class, with a mean age of 4.87 years at the start of the study and 6.63 years at the end. METHODS: Measures of literacy skills, phonological awareness, verbal memory, motor skill, and auditory processing were assessed using the DEST as the initial screening tool at Phase 1. Measures of letter knowledge, non-word reading, and rhyme judgment were taken at Phase 2. Phase 3 measures, 14 months after the start of the study, comprised single-word reading and spelling. At Phase 4, some 22 months after the beginning of the study, measures of reading and spelling ability were assessed again. RESULTS: Individual subtests of the DEST were more predictive of later literacy skills than the global screening test's score (the 'at risk quotient'). Better predictors were the DEST subtest of sound order and rapid automatized naming, together with the school attainment measure of letter knowledge. CONCLUSIONS: Although some DEST subtests did offer predictors of future literacy skills, school-based measures of letter knowledge may be equally valid as assessment measures. Additionally, the results question the usefulness of combining measures to form an 'at risk' index of future literacy difficulties, particularly in the age range assessed.

Auditory Perception↗