Leptin: A Metabolic Signal for the Differentiation of Pituitary Cells

Pituitary cell function is impacted by metabolic states and therefore must receive signals that inform them about nutritional status or adiposity. A primary signal from adipocytes is leptin, which recent studies have shown regulates most pituitary cell types. Subsets of all pituitary cell types express leptin receptors and leptin has been shown to exert transcriptional control through classical JAK/STAT pathways. Recent studies show that leptin also signals through post-transcriptional pathways that involve the translational regulatory protein Musashi. Mechanistically, post-transcriptional control would permit rapid cellular regulation of critical pre-existing pituitary transcripts as energy states change. The chapter will review evidence for transcriptional and/or post-transcriptional regulation of leptin targets (including Gnrhr, activin, Fshb, Gh, Ghrhr, and Pou11f1) and the consequences of the loss of leptin signaling to gonadotrope and somatotrope functions

Crystalline inclusion of wheel-and-axle diol hosts featuring benzo[b]thiophene units as a lateral construction element

By applying the “wheel-and-axle” host concept and incorporating a previously developed heteroaromatic substitution strategy, a new type of diol host featuring two di(benzo[b]thien-2-yl)hydroxymethyl units attached to both ends of a central ethynylene (3) and 1,4-phenylene (4) moiety is reported. The syntheses of the host compounds are described, and solvent inclusion formation via crystallization has extensively been studied showing a remarkable inclusion capability of the compounds. X-ray diffraction analysis of relevant crystal structures have been performed and comparatively discussed. Vapor sorption behavior of the compounds as solid receptor films coated on a quartz crystal microbalance considering a variety of solvent vapors has been scrutinized, indicating potential application as mass sensitive materials

Experienced discrimination amongst European old citizens

This study analyses the experienced age discrimination of old European citizens and the factors related to this discrimination. Differences in experienced discrimination between old citizens of different European countries are explored. Data from the 2008 ESS survey are used. Old age is defined as being 62 years or older. The survey data come from 28 European countries and 14,364 old-age citizens. Their average age is 72 years. Factor analysis is used to construct the core variable ‘experienced discrimination’. The influence of the independent variables on experienced discrimination is analysed using linear regression analysis. About one-quarter of old European citizens sometimes or frequently experience discrimination because of their age. Gender, education, income and belonging to a minority are related to experienced age discrimination. Satisfaction with life and subjective health are strongly associated with experienced age discrimination, as is trust in other people and the seriousness of age discrimination in the country. Large, significant differences in experienced discrimination due to old age exist between European countries. A north-west versus south-east European gradient is found in experienced discrimination due to old age. The socio-cultural context is important in explaining experienced age discrimination in old European citizens. Old-age discrimination is experienced less frequently in countries with social security arrangements. Further research is needed to understand the variation in (old) age discrimination between European countries. Measures recommended include increasing public awareness about the value of ageing for communities and changing public attitudes towards the old in a positive way

Active ageing, pensions and retirement in the UK

The ageing population has led to increasing concerns about pensions and their future sustainability. Much of the dominant policy discourse around ageing and pension provision over the last decade has focussed on postponing retirement and prolonging employment. These measures are central to productive notions of ‘active ageing’. Initially the paper briefly sets out the pension developments in the UK. Then it introduces active ageing and active ageing policy, exploring its implications for UK pension provision. It demonstrates that a more comprehensive active ageing framework, which incorporates a life-course perspective, has the potential to assist the UK to respond to the challenges of an ageing population. In doing so it needs to highlight older people as an economic and social resource, and reduce barriers to older people’s participation in society

Multifaceted roles of GSK-3 and Wnt/β-catenin in hematopoiesis and leukemogenesis: opportunities for therapeutic intervention

Glycogen synthase kinase-3 (GSK-3) is well documented to participate in a complex array of critical cellular processes. It was initially identified in rat skeletal muscle as a serine/threonine kinase that phosphorylated and inactivated glycogen synthase. This versatile protein is involved in numerous signaling pathways that influence metabolism, embryogenesis, differentiation, migration, cell cycle progression and survival. Recently, GSK-3 has been implicated in leukemia stem cell pathophysiology and may be an appropriate target for its eradication. In this review, we will discuss the roles that GSK-3 plays in hematopoiesis and leukemogenesis as how this pivotal kinase can interact with multiple signaling pathways such as: Wnt/β-catenin, phosphoinositide 3-kinase (PI3K)/phosphatase and tensin homolog (PTEN)/Akt/mammalian target of rapamycin (mTOR), Ras/Raf/MEK/extracellular signal-regulated kinase (ERK), Notch and others. Moreover, we will discuss how targeting GSK-3 and these other pathways can improve leukemia therapy and may overcome therapeutic resistance. In summary, GSK-3 is a crucial regulatory kinase interacting with multiple pathways to control various physiological processes, as well as leukemia stem cells, leukemia progression and therapeutic resistance. GSK-3 and Wnt are clearly intriguing therapeutic targets

Understanding unequal ageing: towards a synthesis of intersectionality and life course analyses

Intersectionality has received an increasing amount of attention in health inequalities research in recent years. It suggests that treating social characteristics separately—mainly age, gender, ethnicity, and socio-economic position—does not match the reality that people simultaneously embody multiple characteristics and are therefore potentially subject to multiple forms of discrimination. Yet the intersectionality literature has paid very little attention to the nature of ageing or the life course, and gerontology has rarely incorporated insights from intersectionality. In this paper, we aim to illustrate how intersectionality might be synthesised with a life course perspective to deliver novel insights into unequal ageing, especially with respect to health. First we provide an overview of how intersectionality can be used in research on inequality, focusing on intersectional subgroups, discrimination, categorisation, and individual heterogeneity. We cover two key approaches—the use of interaction terms in conventional models and multilevel models which are particularly focussed on granular subgroup differences. In advancing a conceptual dialogue with the life course perspective, we discuss the concepts of roles, life stages, transitions, age/cohort, cumulative disadvantage/advantage, and trajectories. We conclude that the synergies between intersectionality and the life course hold exciting opportunities to bring new insights to unequal ageing and its attendant health inequalities