Perturbed cholesterol and vesicular trafficking associated with dengue blocking in Wolbachia-infected Aedes aegypti cells

Wolbachia are intracellular maternally inherited bacteria that can spread through insect populations and block virus transmission by mosquitoes, providing an important approach to dengue control. To better understand the mechanisms of virus inhibition, we here perform proteomic quantification of the effects of Wolbachia in Aedes aegypti mosquito cells and midgut. Perturbations are observed in vesicular trafficking, lipid metabolism and in the endoplasmic reticulum that could impact viral entry and replication. Wolbachia-infected cells display a differential cholesterol profile, including elevated levels of esterified cholesterol, that is consistent with perturbed intracellular cholesterol trafficking. Cyclodextrins have been shown to reverse lipid accumulation defects in cells with disrupted cholesterol homeostasis. Treatment of Wolbachia-infected Ae. aegypti cells with 2-hydroxypropyl-β-cyclodextrin restores dengue replication in Wolbachia-carrying cells, suggesting dengue is inhibited in Wolbachia-infected cells by localised cholesterol accumulation. These results demonstrate parallels between the cellular Wolbachia viral inhibition phenotype and lipid storage genetic disorders

Exploring the psychological rewards of a familiar semirural landscape: connecting to local nature through a mindful approach

This study analyses a 53,000 word diary of a year engaging with nature through over 200 trips to a semi-rural landscape. Thematic analysis revealed two themes; the transition from observer to nature connectedness and the ways in which the natural environment was experienced once a connection was made. These themes are discussed in relation to theories that seek to explain the positive effect of nature and nature connectedness. The findings are important as they suggest that repeated engagement with local semi-rural countryside can lead to a mindful approach and psychological rewards that do not require travel into the wilderness. The work informs further research into outcomes and processes of nature based interventions such as: trip frequency, duration and diary keeping

The Social Construction of Conspiracy Beliefs: A Q-Methodology Study of How Ordinary People DefineThem and Judge Their Plausibility

Little is known about ordinary people’s understandings of conspiracy beliefs and how these understandings relate to the perspectives of researchers and scholars. Working within a social constructionist epistemological framework, we conducted a Q-methodology study aiming to identify a range of lay perspectives on two key topics: the defining features of conspiracy beliefs; and aspects considered important in judging their plausibility. Fifty-six people (32 men and 24 women), recruited via regional UK Facebook groups, sorted their agreement with a set of statements on each of the two topics. A principal component analysis, followed by varimax rotation, was performed on each data set. Five accounts about the defining features of conspiracy beliefs were identified: that they are false, illogical and harmful; that they are forms of political critique; that there are varied types; that they are entertaining but ineffectual; and that they are held by a self-reinforcing minority. Four accounts about their evaluation were identified: conventional realist criteria; the importance of personal judgement; skeptical realism; and the assessment of critical thinking. The findings are discussed in the context of the literature and limitations of the study are considered. Implications for research and educational and policy interventions are outlined

A Pluralistic Theory of Wordhood

What are words and how should we individuate them? There are two main answers on the philosophical market. For some, words are bundles of structural-functional features defining a unique performance profile. For others, words are non-eternal continuants individuated by their causal-historical ancestry. These conceptions offer competing views of the nature of words, and it seems natural to assume that at most one of them can capture the essence of wordhood. This paper makes a case for pluralism about wordhood: the view that there is a plurality of acceptable conceptions of the nature of words, none of which is uniquely entitled to inform us as to what wordhood consists in

The material properties of a bacterial-derived biomolecular condensate tune biological function in natural and synthetic systems

Intracellular phase separation is emerging as a universal principle for organizing biochemical reactions in time and space. It remains incompletely resolved how biological function is encoded in these assemblies and whether this depends on their material state. The conserved intrinsically disordered protein PopZ forms condensates at the poles of the bacterium Caulobacter crescentus, which in turn orchestrate cell-cycle regulating signaling cascades. Here we show that the material properties of these condensates are determined by a balance between attractive and repulsive forces mediated by a helical oligomerization domain and an expanded disordered region, respectively. A series of PopZ mutants disrupting this balance results in condensates that span the material properties spectrum, from liquid to solid. A narrow range of condensate material properties supports proper cell division, linking emergent properties to organismal fitness. We use these insights to repurpose PopZ as a modular platform for generating tunable synthetic condensates in human cells

A Q-methodological study of 'smoking identities'

publication-status: Publishedtypes: ArticleIn contrast to the psychological literature on adolescent smoking, little research has investigated the social identities of adult smokers. This study aimed to identify shared ‘smoking identities’ amongst a sample of 64 British smokers from different socio-economic groups using Q-methodology. Participants were asked to sort 70 items concerning smoking and smokers according to their agreement/disagreement with them. The 64 Q-sorts were then subjected to a by-person factor analysis yielding six factors, with the first four interpretable factors being presented here. Each factor is understood to represent a distinct ‘identity position’. The first two, the ‘addicted’ smoker, and the ‘in control’ smoker, oriented around a biomedical model of smoking as an addictive health risk. The final two, the ‘no big deal’ smoker and the ‘proud’ smoker reflected alternative understandings and values. The identity positions also differed in the extent to which smoking was considered a core part of self-identity. Unpacking the ‘smoking identities’ of current smokers offers the opportunity to devise targeted health promotion.Economic and Social Research Counci

Soft systems methodology: a context within a 50-year retrospective of OR/MS

Soft systems methodology (SSM) has been used in the practice of operations research and management science OR/MS) since the early 1970s. In the 1990s, it emerged as a viable academic discipline. Unfortunately, its proponents consider SSM and traditional systems thinking to be mutually exclusive. Despite the differences claimed by SSM proponents between the two, they have been complementary. An extensive sampling of the OR/MS literature over its entire lifetime demonstrates the richness with which the non-SSM literature has been addressing the very same issues as does SSM

Self-management of chronic low back pain: Four viewpoints from patients and healthcare providers

A move towards self-management is central to health strategy around chronic low back pain, but its concept and meaning for those involved are poorly understood. In the reported study, four distinct and shared viewpoints on self-management were identified among people with pain and healthcare providers using Q methodology. Each construes self-management in a distinctive manner and articulates a different vision of change. Identification of similarities and differences among the viewpoints holds potential for enhancing communication between patients and healthcare providers and for better understanding the complexities of self-management in practice

The Psychopathology and Neuroanatomical Markers of Depression in Early Psychosis

Depression frequently occurs in first-episode psychosis (FEP) and predicts longer-term negative outcomes. It is possible that this depression is seen primarily in a distinct subgroup, which if identified could allow targeted treatments. We hypothesize that patients with recent-onset psychosis (ROP) and comorbid depression would be identifiable by symptoms and neuroanatomical features similar to those seen in recent-onset depression (ROD). Data were extracted from the multisite PRONIA study: 154 ROP patients (FEP within 3 months of treatment onset), of whom 83 were depressed (ROP+D) and 71 who were not depressed (ROP-D), 146 ROD patients, and 265 healthy controls (HC). Analyses included a (1) principal component analysis that established the similar symptom structure of depression in ROD and ROP+D, (2) supervised machine learning (ML) classification with repeated nested cross-validation based on depressive symptoms separating ROD vs ROP+D, which achieved a balanced accuracy (BAC) of 51%, and (3) neuroanatomical ML-based classification, using regions of interest generated from ROD subjects, which identified BAC of 50% (no better than chance) for separation of ROP+D vs ROP-D. We conclude that depression at a symptom level is broadly similar with or without psychosis status in recent-onset disorders; however, this is not driven by a separable depressed subgroup in FEP. Depression may be intrinsic to early stages of psychotic disorder, and thus treating depression could produce widespread benefit