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

Public viewpoints on new non-invasive prenatal genetic tests.

types: Journal ArticlePrenatal screening programmes have been critiqued for their routine implementation according to clinical rationale without public debate. A new approach, non-invasive prenatal diagnosis (NIPD), promises diagnosis of fetal genetic disorders from a sample of maternal blood without the miscarriage risk of current invasive prenatal tests (e.g. amniocentesis). Little research has investigated the attitudes of wider publics to NIPD. This study used Q-methodology, which combines factor analysis with qualitative comments, to identify four distinct "viewpoints" amongst 71 UK men and women: 1. NIPD as a new tool in the ongoing societal discrimination against the disabled; 2. NIPD as a positive clinical application offering peace of mind in pregnancy; 3. NIPD as a medical option justified for severe disorders only; and 4. NIPD as a valid expansion of personal choice. Concerns included the "trivialisation of testing" and the implications of commercial/direct-to-consumer tests. Q-methodology has considerable potential to identify viewpoints and frame public debate about new technologies.Economic and Social Research Counci

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

Is procrastination related to sleep quality? Testing an application of the procrastination-health model

Despite a growing body of research on the consequences of procrastination for health and well-being, there is little research focused on testing or explaining the potential links between procrastination and sleep quality. Using the procrastination-health model as our guiding conceptual lens, we addressed this gap by examining how and why trait procrastination may be linked to various dimensions of sleep quality across two student samples. In Study 1, procrastination was associated with feeling unrested, but not sleep disturbance frequency, in a sample of Greek undergraduate students (N = 141). In Study 2, bootstrapping analysis of the indirect effects of procrastination on an index of sleep quality through perceived stress in a sample of Canadian students (N = 339) was significant supporting an extended procrastination-health model view of how chronic self-regulation failure may compromise sleep quality. Given the potential for dynamic and reciprocal relations among procrastination, stress, and sleep quality suggested by the current and other research, the ways in which procrastination may contribute to and be influenced by poor sleep quality warrants further investigation

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

Less Adaptive or More Maladaptive? A Meta-analytic Investigation of Procrastination and Coping

Despite the theoretical and empirical accounts of trait procrastination as reflecting avoidance of aversive tasks as a means of mood repair, research documenting its links to coping is scarce and inconsistent. There is also little if any research to date examining whether coping strategies might explain the procrastination-stress relationship. The current research aimed to address these issues by integrating current research on procrastination and coping with our own data into a first meta-analysis of the associations of procrastination with adaptive and maladaptive coping and then testing the potential role of coping for understanding the procrastination-stress relationship. In Study 1, a literature search yielded five published papers and three theses, which were supplemented by seven unpublished data sets comprising 15 samples (N=4357). Meta-analyses revealed that procrastination was positively associated with maladaptive coping (average r=.31) and negatively associated with adaptive coping (average r=-.24). In Study 2, a meta-analysis of the indirect effects through coping across four samples revealed that the average indirect effects for maladaptive but not adaptive coping explained the link between procrastination and stress. These findings expand the nomological network of procrastination and highlight the role of maladaptive coping for understanding procrastinators' stress

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

General psychopathology links burden of recent life events and psychotic symptoms in a network approach

Recent life events have been implicated in the onset and progression of psychosis. However, psychological processes that account for the association are yet to be fully understood. Using a network approach, we aimed to identify pathways linking recent life events and symptoms observed in psychosis. Based on previous literature, we hypothesized that general symptoms would mediate between recent life events and psychotic symptoms. We analyzed baseline data of patients at clinical high risk for psychosis and with recent-onset psychosis (n = 547) from the Personalised Prognostic Tools for Early Psychosis Management (PRONIA) study. In a network analysis, we modeled links between the burden of recent life events and all individual symptoms of the Positive and Negative Syndrome Scale before and after controlling for childhood trauma. To investigate the longitudinal associations between burden of recent life events and symptoms, we analyzed multiwave panel data from seven timepoints up to month 18. Corroborating our hypothesis, burden of recent life events was connected to positive and negative symptoms through general psychopathology, specifically depression, guilt feelings, anxiety and tension, even after controlling for childhood trauma. Longitudinal modeling indicated that on average, burden of recent life events preceded general psychopathology in the individual. In line with the theory of an affective pathway to psychosis, recent life events may lead to psychotic symptoms via heightened emotional distress. Life events may be one driving force of unspecific, general psychopathology described as characteristic of early phases of the psychosis spectrum, offering promising avenues for interventions

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

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