Defective Lamin A-Rb Signaling in Hutchinson-Gilford Progeria Syndrome and Reversal by Farnesyltransferase Inhibition

Hutchinson-Gilford Progeria Syndrome (HGPS) is a rare premature aging disorder caused by a de novo heterozygous point mutation G608G (GGC>GGT) within exon 11 of LMNA gene encoding A-type nuclear lamins. This mutation elicits an internal deletion of 50 amino acids in the carboxyl-terminus of prelamin A. The truncated protein, progerin, retains a farnesylated cysteine at its carboxyl terminus, a modification involved in HGPS pathogenesis. Inhibition of protein farnesylation has been shown to improve abnormal nuclear morphology and phenotype in cellular and animal models of HGPS. We analyzed global gene expression changes in fibroblasts from human subjects with HGPS and found that a lamin A-Rb signaling network is a major defective regulatory axis. Treatment of fibroblasts with a protein farnesyltransferase inhibitor reversed the gene expression defects. Our study identifies Rb as a key factor in HGPS pathogenesis and suggests that its modulation could ameliorate premature aging and possibly complications of physiological aging

What’s a (Childless) Man Without a Woman? The Differential Importance of Couple Dynamics for the Wellbeing of Childless Men and Women in the Netherlands

Using rich couple data from the Netherlands Kinship Panel Study, we investigated to what extent there were gender differences in couple dynamics within childless couples (N = 163). Though the childless partners reported similar relationship satisfaction, we found gender differences in the link between relationship conflict and relationship satisfaction - the childless men were more strongly affected by the negative aspects of the partnership. This gender difference was not evident for the association between partner support and relationship satisfaction - the positive aspects of the partnership were equally important for the male and the female childless partners. Furthermore, the association between relationship satisfaction and health was stronger for the childless men than for the childless women and this difference was particularly evident when the levels of relationship satisfaction were low. These results indicate that when they are in unsatisfying romantic relationships, childless men are at a greater risk than childless women of physical and mental ill health

Keeping It Real: Making Space for Play in Early Education Policy and Practice

This chapter considers how the pedagogical framing of preschool activity as a preparation for a school, may be in conflict with an international consensus advocating allowing children greater control of some of their activities in preschool. The first sometimes promotes an early start to more formal learning, while the second proposes that personal responsibility and self-control and can lead to longer lasting benefits resulting from preschool experiences. A case study of changing policy and practice in Kazakhstan is used to illustrate the tensions between these two models of learning. Qualitative, semi-structured interviews with practitioners in the preschool environment were used to explore how national standards documents interact with underlying beliefs about the nature of learning in the formation of practice. The findings suggest that, as in other countries, the intention to increase child-led pedagogy may be inhibited by existing classroom-based expectations of children’s participation. The chapter considers how participatory research in play environments might help to increase awareness of the value of child-led play by focusing increased attention on how play supports learning