Iron Behaving Badly: Inappropriate Iron Chelation as a Major Contributor to the Aetiology of Vascular and Other Progressive Inflammatory and Degenerative Diseases

The production of peroxide and superoxide is an inevitable consequence of aerobic metabolism, and while these particular "reactive oxygen species" (ROSs) can exhibit a number of biological effects, they are not of themselves excessively reactive and thus they are not especially damaging at physiological concentrations. However, their reactions with poorly liganded iron species can lead to the catalytic production of the very reactive and dangerous hydroxyl radical, which is exceptionally damaging, and a major cause of chronic inflammation. We review the considerable and wide-ranging evidence for the involvement of this combination of (su)peroxide and poorly liganded iron in a large number of physiological and indeed pathological processes and inflammatory disorders, especially those involving the progressive degradation of cellular and organismal performance. These diseases share a great many similarities and thus might be considered to have a common cause (i.e. iron-catalysed free radical and especially hydroxyl radical generation). The studies reviewed include those focused on a series of cardiovascular, metabolic and neurological diseases, where iron can be found at the sites of plaques and lesions, as well as studies showing the significance of iron to aging and longevity. The effective chelation of iron by natural or synthetic ligands is thus of major physiological (and potentially therapeutic) importance. As systems properties, we need to recognise that physiological observables have multiple molecular causes, and studying them in isolation leads to inconsistent patterns of apparent causality when it is the simultaneous combination of multiple factors that is responsible. This explains, for instance, the decidedly mixed effects of antioxidants that have been observed, etc...Comment: 159 pages, including 9 Figs and 2184 reference

Comprehensive Transcriptional Analysis of Early-Stage Urothelial Carcinoma

Non-muscle-invasive bladder cancer (NMIBC) is a heterogeneous disease with widely different outcomes. We performed a comprehensive transcriptional analysis of 460 early-stage urothelial carcinomas and showed that NMIBC can be subgrouped into three major classes with basal-and luminal-like characteristics and different clinical outcomes. Large differences in biological processes such as the cell cycle, epithelial-mesenchymal transition, and differentiation were observed. Analysis of transcript variants revealed frequent mutations in genes encoding proteins involved in chromatin organization and cytoskeletal functions. Furthermore, mutations in well-known cancer driver genes (e.g., TP53 and ERBB2) were primarily found in high-risk tumors, together with APOBEC-related mutational signatures. The identification of subclasses in NMIBC may offer better prognostication and treatment selection based on subclass assignment

Long-distance parenting: The impact of parental separation and absence due to work commitments on families

Dittman, CK ORCiD: 0000-0003-0203-8785This chapter reviews the theory and research related to the impact of parental separation due to work commitments on family life, with a particular focus on two categories of parental work absences: (1) long-distance commuting; and (2) military service and deployment. There is significant diversity both between and within these categories of parental absence in terms of length and timing of separation, the context and reasons for separation, and the risks associated with the parent’s employment. However, they are characterized by challenges not generally experienced by other working families, including transitions in family routines and parenting roles and responsibilities, reliance on the functioning of the athome parent or family member, and ongoing disruptions to parent–child relationships. The impact of these transitions and disruptions is only beginning to be understood. This chapter reviews the research on the effects of parental absence due to work on parenting, family relationships, and child adjustment, and aims to identify factors that influence outcomes for families. Note that in the vast majority of the literature, the absent parent is the father, and the at-home parent is the mother; exceptions to this are noted throughout the review. The chapter also highlights areas for further research, and concludes with evidence based recommendations for policy and practice