39 research outputs found
Receptor-Mediated Endocytosis of α-Galactosidase A in Human Podocytes in Fabry Disease
Injury to the glomerular podocyte is a key mechanism in human glomerular disease and podocyte repair is an important therapeutic target. In Fabry disease, podocyte injury is caused by the intracellular accumulation of globotriaosylceramide. This study identifies in the human podocyte three endocytic receptors, mannose 6-phosphate/insulin-like growth II receptor, megalin, and sortilin and demonstrates their drug delivery capabilities for enzyme replacement therapy. Sortilin, a novel α-galactosidase A binding protein, reveals a predominant intracellular expression but also surface expression in the podocyte. The present study provides the rationale for the renal effect of treatment with α-galactosidase A and identifies potential pathways for future non-carbohydrate based drug delivery to the kidney podocyte and other potential affected organs
Male-biased sex allocation in ageing parents; a longitudinal study in a long-lived seabird
Optimal sex allocation is frequency-dependent, but senescence may cause behaviour at old age to be suboptimal. We investigated whether sex allocation changes with parental age, using 16 years of data comprising more than 2500 molecularly sexed offspring of more than 600 known-age parents in common terns (Sterna hirundo), slightly sexually size-dimorphic seabirds. We decomposed parental age effects into within-individual change and sex allocation-associated selective (dis)appearance. Individual parents did not differ consistently in sex allocation, but offspring sex ratios at fledging changed from female- to male-biased as parents aged. Sex ratios at hatching were not related to parental age, suggesting sons to outperform daughters after hatching in broods of old parents. Our results call for the integration of sex allocation theory with theory on ageing and demography, as a change in sex allocation with age per se will cause the age structure of a population to affect the frequency-dependent benefits and the age-specific strength of selection on sex allocation
Recent Evidence on Factors Influencing the Female Labor Force Participation Rate
Female labor force, Participation rate, State-level data,
The role of regulatory and temporal context in the construction of diversity discourses: The case of the UK, France and Germany, European Journal of Industrial Relations
Despite growing interest in how the concept of diversity management is reinterpreted as it crosses national boundaries, there has been little study of this process in Europe. To bridge this knowledge gap, this article explores the construction of diversity discourses in the context of the UK, France and Germany. We use the discursive politics approach to investigate the ways in which the meaning of diversity is shrunk, bent and stretched. We demonstrate that the concept of diversity has no universal fixed meaning but is contextual, contested and temporal. Temporarily fixed definitions and frames of diversity are path-dependent and shaped by the regulatory context. Thus unique national histories and the context of regulation are key determinants of the ways in which the concept is redefined as it crosses national and regional borders