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Hypoxia induces histone clipping and H3K4me3 loss in neutrophil progenitors resulting in long-term impairment of neutrophil immunity
No full textThe long-term impact of systemic hypoxia resulting from acute respiratory distress syndrome (ARDS) on the function of short-lived innate immune cells is unclear. We show that patients 3-6 months after recovering from ARDS have persistently impaired circulating neutrophil effector functions and an increased susceptibility to secondary infections. These defects are linked to a widespread loss of the activating histone mark H3K4me3 in genes that are crucial for neutrophil activities. By studying healthy volunteers exposed to altitude-induced hypoxemia, we demonstrate that oxygen deprivation alone causes this long-term neutrophil reprogramming. Mechanistically, mouse models of systemic hypoxia reveal that persistent loss of H3K4me3 originates in proNeu and preNeu progenitors within the bone marrow and is linked to N-terminal histone 3 clipping, which removes the lysine residue for methylation. Thus, we present new evidence that systemic hypoxia initiates a sustained maladaptive reprogramming of neutrophil immunity by triggering histone 3 clipping and H3K4me3 loss in neutrophil progenitors.</p
Persistent maternal age effects on male offspring fitness traits in a wild mammal population
No full textEffects of parental age on juvenile survival are well documented, but whether parental age has long-term consequences for the fitness of surviving offspring remains poorly understood. This is particularly the case for polygynous mammals, where differential impacts on sons versus daughters are predicted. Here, we investigate the effects of maternal and paternal age on offspring first-year survival, longevity, lifetime reproduction, and annual reproduction in a wild Soay sheep population. We find that younger and older mothers produced offspring that were less likely to survive their first year than middle-aged mothers, and this effect was independent of offspring sex. However, among offspring that survived their first year, adult lifespan and lifetime reproductive success were only influenced by maternal age in sons and not in daughters. Increased adult reproductive success in sons of middle-aged mothers, compared to young and old mothers, was not driven by maternal age effects on offspring reproductive ageing patterns, but potentially by consistent effects on offspring average annual reproductive performance. There was weak evidence of a paternal age effect on offspring longevity but no effect on other offspring traits. Our study shows long-lasting, sex-dependent maternal age effects on offspring fitness traits in the wild, adding to the growing body of literature that highlights the potential importance of intergenerational effects in natural populations
Art-based interventions for health and wellbeing in rural, remote and island communities:A literature review of current research
No full textBackgroundApproximately half of the global population resides in remote regions, yet healthcare resources remain disproportionately concentrated in urban areas. Social and geographical isolation exacerbate health disparities, resulting in limited access to services for rural, remote and island communities. This paper explores how arts-based health interventions respond to these inequalities.MethodsWe conducted a literature review of research studies published over the past two decades.ResultsArts-based health interventions have emerged as a promising approach to addressing disparities and enhancing overall health and wellbeing. The arts support healthcare literacy, individual agency, self-expression and a strengthened sense of community presence and identity. Creative practices rooted in local and Indigenous traditions foster sustainable and meaningful relationships between people and place, enabling a sense of connected belonging and intergenerational historicity. Active community participation, trustful relationships between stakeholders and communities, and an appreciation of cultural differences are seen to increase the effectiveness of these interventions.ConclusionThe findings of this review aim to inform policymakers, practitioners and researchers about the potential and challenges of arts-based health interventions in remote and marginalised communities
R-loops acted on by RNase H1 influence DNA replication timing and genome stability in Leishmania
No full textGenomes in eukaryotes normally undergo DNA replication in a choreographed temporal order, resulting in early and late replicating chromosome compartments. Leishmania, a human protozoan parasite, displays an unconventional DNA replication program in which the timing of DNA replication completion is chromosome size-dependent: larger chromosomes complete replication later then smaller ones. Here we show that both R-loops and RNase H1, a ribonuclease that resolves RNA-DNA hybrids, accumulate in Leishmania major chromosomes in a pattern that reflects their replication timing. Furthermore, we demonstrate that such differential organisation of R-loops, RNase H1 and DNA replication timing across the parasite’s chromosomes correlates with size-dependent differences in chromatin accessibility, G quadruplex distribution and sequence content. Using conditional gene excision, we show that loss of RNase H1 leads to transient growth perturbation and permanently abrogates the differences in DNA replication timing across chromosomes, as well as altering levels of aneuploidy and increasing chromosome instability in a size-dependent manner. This work provides a link between R-loop homeostasis and DNA replication timing in a eukaryotic parasite and demonstrates that orchestration of DNA replication dictates levels of genome plasticity in Leishmania
Intensive community and home-based treatments for eating disorders:A scoping review
Get PDFBackgroundIntensive community treatment (ICT) and home-based treatment (HBT) have emerged as valuable alternatives to institution-based intensive treatments (inpatient or day patient) for severe mental illnesses. Although potential benefits of ICT and HBT for eating disorders (EDs) have been proposed, this area of research remains largely unexplored.MethodA scoping review was conducted to map the available literature. Four databases (PubMed, PsycInfo, MEDLINE, Web of Science), grey literature, and trial registries were searched. Sources were included if they presented treatments offering more than two planned therapeutic contacts per week for at least part of the program, excluding physical monitoring contacts, for patients diagnosed with any ED across all ages.ResultsForty-six sources met the inclusion criteria (ICT: n = 31; HBT: n = 15), with most studies from Europe (n = 23) and the USA (n = 18). Among these, 28 reported quantitative data, six reported qualitative data, and three employed a mixed-methods approach. The remainder were either protocol papers or service descriptions only. The majority focused on anorexia nervosa (AN) or mixed EDs, with varying study designs and predominantly low to moderate evidence quality. There were no randomized controlled trials. HBTs primarily targeted children and adolescents with AN, emphasizing family-based approaches, while ICTs exhibited greater variability in age groups and diagnoses, frequently combining cognitive behavioral and dialectical behavioral therapies, often alongside family-based components for children and adolescents. Despite high variability in design, quality, and measurements, studies frequently reported improvements in clinical outcomes. Programs were often described as feasible and acceptable, noting patient satisfaction, strong adherence, and cost-effectiveness due to reduced hospital admissions.ConclusionsEven though there was variability in implementation and methodologies, ICTs and HBTs appear to be promising alternatives to traditional institution-based intensive treatments. Future research requires higher-quality large-scale randomized trials with improved reporting of treatment characteristics and outcomes to enable robust investigations of effectiveness
Reading and empathy:Qualitative insights into adolescents' experiences with fiction books
Get PDFFiction books offer opportunities for readers to gain insight into fictional characters' perspectives, lives, and experiences, and in doing so, have the potential to support their empathy. This article provides novel insights from semi-structured interviews with 37 (27 female, 10 male, aged 12–14 years) regular readers of fiction from two high schools in Scotland. A data-driven inductive thematic analysis approach illustrated the cognitive and affective ways in which adolescents empathise with fictional characters; how feelings of empathy can transfer beyond fiction to real-life others; how feelings of empathy can personally enrich readers and support their social relationships; and how book content and writing style can facilitate readers' empathy. However, while many adolescent readers shared examples of how reading had supported their empathy, others did not, suggesting that adolescent readers' may read for different purposes. Implications for teachers, librarians and others interested in supporting adolescents' literacy practices, experiences and empathy are discussed, in addition to future research directions.</p
Emerging issues and new frontiers in federalism, regionalism and territorial governance:The role of Regional & Federal Studies in shaping future research agendas
Get PDFThis essay marks the transition to a new editorial team at Regional & Federal Studies and offers a broad review of emerging themes and future directions in the study of federalism, regionalism, and territorial governance. Building on the journal’s legacy, it identifies key areas of conceptual and empirical development, highlights ongoing shifts in the global research landscape, and calls for greater geographical and epistemological diversity beyond Western-centric paradigms. The article also outlines the journal’s editorial priorities, including a commitment to methodological pluralism, diversity and inclusion, and stronger engagement with policymakers and wider publics. By mapping emerging issues and setting out new research frontiers, it positions Regional & Federal Studies as a leading platform for innovative, comparative, and globally relevant scholarship in territorial politics.</p
Batman returns! Leadership by crisis and the moral entrepreneurship of Donald J Trump:A dramaturgical perspective
Get PDFIn this paper I distinguish between ‘leadership through crisis’, using leadership to analyse, make sense of and respond to crisis, and ‘leadership by crisis’, using the construction and construal of crisis as the basis for the exercise of leadership. Using the framing of the multidisciplinary ‘moral entrepreneur’ literature, I examine the role of President Donald J Trump as a moral entrepreneur who leads by crisis in construing and constructing crises (moral panics) and persuading society to develop or enforce rules consistent with his own ardently held beliefs. I argue that Trump’s leadership by crisis draws on and is legitimated by three contextual factors: the ideology of entrepreneurialism; the structure (social media platforms) and content (hype and bullshit) of the messaging around moral panics; and the image of the superhero, specifically Batman, in popular culture which provided cultural legitimation for Trump’s presidency. The paper concludes with the argument that leadership is a performance and draws on Turner’s discussion of dramaturgy to identify directions for further research on the leadership implications of moral entrepreneurship as a social drama.</p
Confronting primordial black holes with LIGO-Virgo-KAGRA and the Einstein Telescope
Get PDFThe detection of gravitational waves from binary black hole coalescences by the LIGO-Virgo-KAGRA Collaboration has raised fundamental questions about the genesis of these events. In this chapter, we explore the possibility that primordial black holes, proposed candidates for dark matter, may serve as the progenitors of the binary black holes observed by LIGO-Virgo-KAGRA. Employing a Bayesian analysis, we constrain the primordial black hole model using the LIGO-Virgo-KAGRA third gravitational wave transient catalog, revealing that stellar-mass primordial black holes cannot dominate cold dark matter. Considering a mixed population of astrophysical black holes and primordial black holes, we determine that approximately 1/4 of the detectable events in the third gravitational wave transient catalog can be attributed to primordial black hole binaries. We also forecast detectable event rate distributions for primordial black hole and astrophysical black hole binaries by the third-generation ground-based gravitational wave detectors, such as the Einstein Telescope, offering a potential avenue to distinguish primordial black holes from astrophysical black holes based on their distinct redshift evolutions
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