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

Q methodology and a Delphi poll: a useful approach to researching a narrative approach to therapy

Q methodology and a Delphi poll combined qualitative and quantitative methods to explore definitions of White and Epston's (1990) narrative approach to therapy among a group of UK practitioners. A Delphi poll was used to generate statements about narrative therapy. The piloting of statements by the Delphi panel identified agreement about theoretical ideas underpinning narrative therapy and certain key practices. A wider group of practitioners ranked the statements in a Q sort and made qualitative comments about their sorting. Quantitative methods (principal components analysis) were used to extract eight accounts of narrative therapy, five of which are qualitatively analysed in this paper. Agreement and differences were identified across a range of issues, including the social construction of narratives, privileging a political stance or narrative techniques and the relationship with other therapies, specifically systemic psychotherapy. Q methodology, combined with the Delphi poll, was a unique and innovative feature of this study

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

Doing fence sitting: a discursive analysis of clinical psychologists' constructions of mental health

A growing body of research indicates that the way health care professionals conceptualize mental health might have important clinical implications. We adopted a discursive psychology approach to explore clinical psychologists’ accounts of mental health and its effects. Semistructured interviews were conducted with 11 clinical psychologists in the East Midlands region of the United Kingdom. The participants constructed mental health through building up biological factors and psychosocial aspects as opposite ends of the same spectrum, and then positioned themselves as distant from these extremes to manage issues of stake and accountability. A discourse of moral concern for service users was used to negotiate the implications of having different views of mental health from service users, enabling clinicians to manage issues of accountability and demonstrate their ability to be helpful. This suggests that clinicians should be mindful of the effects of their use of language and make the contingent nature of their knowledge explicit

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

Contrasting responses to climate change at Himalayan treelines revealed by population demographics of two dominant species

Alpine treelines are expected to shift upward due to recent climate change. However, interpretation of changes in montane systems has been problematic because effects of climate change are frequently confounded with those of land use changes. The eastern Himalaya, particularly Langtang National Park, Central Nepal, has been relatively undisturbed for centuries and thus presents an opportunity for studying climate change impacts on alpine treeline uncontaminated by potential confounding factors. We studied two dominant species, Abies spectabilis (AS) and Rhododendron campanulatum (RC), above and below the treeline on two mountains. We constructed 13 transects, each spanning up to 400 m in elevation, in which we recorded height and state (dead or alive) of all trees, as well as slope, aspect, canopy density, and measures of anthropogenic and animal disturbance. All size classes of RC plants had lower mortality above treeline than below it, and young RC plants (<2 m tall) were at higher density above treeline than below. AS shows little evidence of a position change from the historic treeline, with a sudden extreme drop in density above treeline compared to below. Recruitment, as measured by size–class distribution, was greater above treeline than below for both species but AS is confined to ~25 m above treeline whereas RC is luxuriantly growing up to 200 m above treeline. Synthesis. Evidence suggests that the elevational limits of RC have shifted upward both because (a) young plants above treeline benefited from facilitation of recruitment by surrounding vegetation, allowing upward expansion of recruitment, and (b) temperature amelioration to mature plants increased adult survival. We predict that the current pure stand of RC growing above treeline will be colonized by AS that will, in turn, outshade and eventually relegate RC to be a minor component of the community, as is the current situation below the treeline