Functional Connection Between Yeast Dynamin and Retromer at the Endosome

Intracellular trafficking from the late endosome to Golgi in cells is termed retrograde transport, essential for recycling of important macromolecules including cell membrane receptors. Retrograde transport is regulated by a family of proteins known as the Retromer” composed of 5 VPS proteins (Vps5, Vps17, Vps26, Vps29, and Vps35). Retromer acts as the coat proteins for vesicles emerging from late endosomes. Loss of Retromer function has been previously implicated in both Parkinson\u27s and Alzheimer\u27s disease. Vps1, a yeast dynamin-like protein, plays a role in intracellular trafficking. Vps1 has been shown to localize at the endocytic sites to promote pinching off of endocytic vesicles. The goal of this study was to further investigate the relationship between the Retromer and Vps1. My data show colocalization between Vps1 and the Retromer, and that Vps1 knockout cells show a decrease in Retromer targeting to endosomes, a phenotype reminiscent of human Alzheimer\u27s disease. In order to evaluate the functional relationship of the Retromer and Vps1, colocalization and interaction studies, both genetic and physical, were conducted. The data suggest that various Retromer proteins interact with Vps1 on both the genetic and physical levels. I explore this possible relationship, further expanding Vps1\u27s role as an intracellular trafficking mediator

Pooling and Correlated Neural Activity

Correlations between spike trains can strongly modulate neuronal activity and affect the ability of neurons to encode information. Neurons integrate inputs from thousands of afferents. Similarly, a number of experimental techniques are designed to record pooled cell activity. We review and generalize a number of previous results that show how correlations between cells in a population can be amplified and distorted in signals that reflect their collective activity. The structure of the underlying neuronal response can significantly impact correlations between such pooled signals. Therefore care needs to be taken when interpreting pooled recordings, or modeling networks of cells that receive inputs from large presynaptic populations. We also show that the frequently observed runaway synchrony in feedforward chains is primarily due to the pooling of correlated inputs

Patient-reported outcomes of periacetabular osteotomy from the prospective ANCHOR cohort study

BACKGROUND: Current literature describing the periacetabular osteotomy (PAO) is mostly limited to retrospective case series. Larger, prospective cohort studies are needed to provide better clinical evidence regarding this procedure. The goals of the current study were to (1) report minimum 2-year patient-reported outcomes (pain, hip function, activity, overall health, and quality of life), (2) investigate preoperative clinical and disease characteristics as predictors of clinical outcomes, and (3) report the rate of early failures and reoperations in patients undergoing contemporary PAO surgery. METHODS: A large, prospective, multicenter cohort of PAO procedures was established, and outcomes at a minimum of 2 years were analyzed. A total of 391 hips were included for analysis (79% of the patients were female, and the average patient age was 25.4 years). Patient-reported outcomes, conversion to total hip replacement, reoperations, and major complications were documented. Variables with a p value of ≤0.10 in the univariate linear regressions were included in the multivariate linear regression. The backward stepwise selection method was used to determine the final risk factors of clinical outcomes. RESULTS: Clinical outcome analysis demonstrated major clinically important improvements in pain, function, quality of life, overall health, and activity level. Increasing age and a body mass index status of overweight or obese were predictive of improved results for certain outcome metrics. Male sex and mild acetabular dysplasia were predictive of lesser improvements in certain outcome measures. Three (0.8%) of the hips underwent early conversion to total hip arthroplasty, 12 (3%) required reoperation, and 26 (7%) experienced a major complication. CONCLUSIONS: This large, prospective cohort study demonstrated the clinical success of contemporary PAO surgery for the treatment of symptomatic acetabular dysplasia. Patient and disease characteristics demonstrated predictive value that should be considered in surgical decision-making. LEVEL OF EVIDENCE: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence

A quantitative study of the attitudes of Japanese learners towards varieties of English speech : aspects of the sociolinguistics of English in Japan

Language attitude studies focussing specifically on native speaker perceptions of varieties of English speech have demonstrated consistently that standard varieties tend to be evaluated positively in terms of competence/ status whilst non-standard varieties are generally rated higher in terms of social attractiveness/ solidarity. However, the great majority of studies which have investigated non-native attitudes have tended to measure evaluations of ‘the English language’, conceptualised as a single entity, thus ignoring the substantial regional and social variation within the language. This is somewhat surprising considering the importance of attitudes towards language variation in the study of second language acquisition and in sociolinguistics. More specifically, there is a dearth of in-depth quantitative attitude research in Japan concentrating specifically on social evaluations of varieties of English, as the limited number of previous studies conducted amongst Japanese learners have either been qualitative in design or too small in scale. Moreover, the findings of these studies have been somewhat inconclusive. The present quantitative study, employing a range of innovative direct and indirect techniques of attitude measurement, investigated the perceptions of 558 Japanese university students of six varieties of English speech. The results obtained suggest that Japanese learners are able to differentiate between speech varieties within a single language of which they are not native speakers and hold different and often complex attitudes towards (a) standard/ non-standard and (b) native/ non-native varieties of English speech. For instance, the learners rated both the standard and non-standard varieties of inner circle speech more highly than varieties of expanding circle English in terms of prestige. In contrast, it was found that the learners expressed higher levels of solidarity with the Japanese speaker of heavily-accented English and intriguingly, with speakers of non-standard varieties of UK and US English than with speakers of standard varieties of inner circle English. Moreover, differences in the Japanese students’ gender, level of self-perceived competence in English, level of exposure to English and attitudes towards varieties of Japanese all had significant main effects on perceptions of varieties of English speech. However, the regional provenance of the informants was not found to be significant in determining their language attitudes. The results also imply that Japanese learners retain representations of varieties of English speech and draw upon this resource, whether consciously or unconsciously, in order to identify and evaluate (speakers of) these speech varieties. The findings are discussed in relation to the pedagogical and language planning implications for the choice of linguistic model in English language teaching both inside and outwith Japan and in terms of the methodological importance of the study for potential future attitudinal research in this area.EThOS - Electronic Theses Online ServiceGBUnited Kingdo