Grape-Seed Polyphenolic Extract Improves the Eye Phenotype in a Drosophila Model of Tauopathy

Drosophila models of tauopathies have been developed by transgenically overexpressing the disease-associated forms of tau. In this paper we report for the first time that a recently developed Grape-Seed Polyphenolic Extract (GSPE) improves the eye phenotype of a Drosophila eye model of R406W tau. GSPE-mediated improvements in this distinct in vivo neurodegeneration model for protein misfolding/aggregation suggest that GSPE may have therapeutic value in disorders involving aberrant protein aggregation

Identification of a Rare Coding Variant in Complement 3 Associated with Age-related Macular Degeneration

Macular degeneration is a common cause of blindness in the elderly. To identify rare coding variants associated with a large increase in risk of age-related macular degeneration (AMD), we sequenced 2,335 cases and 789 controls in 10 candidate loci (57 genes). To increase power, we augmented our control set with ancestry-matched exome sequenced controls. An analysis of coding variation in 2,268 AMD cases and 2,268 ancestry matched controls revealed two large-effect rare variants; previously described R1210C in the CFH gene (fcase = 0.51%, fcontrol = 0.02%, OR = 23.11), and newly identified K155Q in the C3 gene (fcase = 1.06%, fcontrol = 0.39%, OR = 2.68). The variants suggest decreased inhibition of C3 by Factor H, resulting in increased activation of the alternative complement pathway, as a key component of disease biology

Narrative, metaphor and the subjective understanding of identity transition

This is the author accepted manuscript. The final version is available from the publisher via the DOI in this record.This paper examines the relevance of employing an oral history method and narrative interview techniques for business historians. We explore the use of oral history interviews as a means of capturing the expression of subjective experience in narrative and metaphor. We do so by analysing interviews concerning the transition of East German identities following reunification with West Germany. Self-expression emerges as critical to the vital identity work required for social integration following transformation, metaphor providing a means of articulating deep-rooted patterns of thought. We demonstrate that employing an oral history methodology can benefit business historians by affording access to the human dimension of a research project, unlocking the subjective understanding of experience by low-power actors among the non-hegemonic classes. Hence, employing an oral history methodology provides a valuable means of countering narrative imperialism, exemplified here by the dominant West German success story grounded in Western-style individual freedom

Genetic variants associated with subjective well-being, depressive symptoms, and neuroticism identified through genome-wide analyses

Very few genetic variants have been associated with depression and neuroticism, likely because of limitations on sample size in previous studies. Subjective well-being, a phenotype that is genetically correlated with both of these traits, has not yet been studied with genome-wide data. We conducted genome-wide association studies of three phenotypes: subjective well-being (n = 298,420), depressive symptoms (n = 161,460), and neuroticism (n = 170,911). We identify 3 variants associated with subjective well-being, 2 variants associated with depressive symptoms, and 11 variants associated with neuroticism, including 2 inversion polymorphisms. The two loci associated with depressive symptoms replicate in an independent depression sample. Joint analyses that exploit the high genetic correlations between the phenotypes (|ρ^| ≈ 0.8) strengthen the overall credibility of the findings and allow us to identify additional variants. Across our phenotypes, loci regulating expression in central nervous system and adrenal or pancreas tissues are strongly enriched for association.</p

The effects of time restricted feeding on age-related changes in the mouse retina

Dietary modifications such as caloric restriction (CR) and intermittent fasting (IF) have gained popularity due to their proven health benefits in aged populations. In time restricted feeding (TRF), a form of intermittent fasting, the amount of time for food intake is regulated without restricting the caloric intake. TRF is beneficial for the central nervous system to support brain health in the context of aging. Therefore, we here ask whether TRF also exerts beneficial effects in the aged retina. We compared aged mice (24 months) on a TRF paradigm (access to food for six hours per day) for either 6 or 12 months against young control mice (8 months) and aged control mice on an ad libitum diet. We examined changes in the retina at the functional (electroretinography), structural (histology and fluorescein angiograms) and molecular (gene expression) level. TRF treatment showed amelioration of age-related reductions in both scotopic and photopic b-wave amplitudes suggesting benefits for retinal interneuron signaling. TRF did not affect age-related signs of retinal inflammation or microglial activation at either the molecular or histological level. Our data indicate that TRF helps preserve some aspects of retinal function that are decreased with aging, adding to our understanding of the health benefits that altered feeding patterns may confer

The Labor Market Consequences of Childhood Maladjustment*

Objective. This article uses data from the National Child Development Survey on a cohort of individuals born in Great Britain during the first week of March 1958 to investigate whether educational attainment and labor force behavior 33 years later are affected by childhood behavioral problems that are exhibited at both age 7 and age 16. Method. Regression methods are used to test hypotheses concerning these effects. Results. Our results indicate that maladjusted children suffer economically when they reach adulthood. Maladjusted children perform worse on aptitude tests and have lower educational attainment. Maladjusted children also are less likely to be employed at age 33 and to have lower wages when employed. Part of the reduced employment and wages is the result of lower education, but part is also due to other factors. Conclusion. Future research should investigate whether adult labor market outcomes vary with the type of behavioral problems exhibited at younger ages. Parents often worry when the behavior of their young children deviates from what appears to be the norm for their age. In part, this concern is motivated by a fear that a maladjusted child—that is, a child whose be

Towards an Understanding of the Dynamics of Work and Employment Relations during Austerity

This is a post-peer-review, pre-copyedit version of 'Towards an Understanding of the Dynamics of Work and Employment Relations during Austerity. Public Organiz Rev (2020). https://doi.org/10.1007/s11115-020-00488-z'This study considers how public sector organisations respond to the effects of austerity. While some organisations take advantage of austerity to increase the workload of employees with little or no engagement with employees, others encourage dialogue by increasing employee and union engagement. Drawing on a systematic analysis of 26 articles, the study finds that austerity policies have negative consequences for public sector employees and presents employee voice as a potential mitigator of the negative consequences. This study is one of the first to review the small but growing literature on the effects of austerity on work and employment relationship.Peer reviewe