Sea anemone model has a single Toll-like receptor that can function in pathogen detection, NF-κB signal transduction, and development

In organisms from insects to vertebrates, Toll-like receptors (TLRs) are primary pathogen detectors that activate downstream pathways, specifically those that direct expression of innate immune effector genes. TLRs also have roles in development in many species. The sea anemone Nematostella vectensis is a useful cnidarian model to study the origins of TLR signaling because its genome encodes a single TLR and homologs of many downstream signaling components, including the NF-κB pathway. We have characterized the single N. vectensis TLR (Nv-TLR) and demonstrated that it can activate canonical NF-κB signaling in human cells. Furthermore, we show that the intracellular Toll/IL-1 receptor (TIR) domain of Nv-TLR can interact with the human TLR adapter proteins MAL and MYD88. We demonstrate that the coral pathogen Vibrio coralliilyticus causes a rapidly lethal disease in N. vectensis and that heat-inactivated V. coralliilyticus and bacterial flagellin can activate a reconstituted Nv-TLR–to–NF-κB pathway in human cells. By immunostaining of anemones, we show that Nv-TLR is expressed in a subset of cnidocytes and that many of these Nv-TLR–expressing cells also express Nv-NF-κB. Additionally, the nematosome, which is a Nematostella-specific multicellular structure, expresses Nv-TLR and many innate immune pathway homologs and can engulf V. coralliilyticus. Morpholino knockdown indicates that Nv-TLR also has an essential role during early embryonic development. Our characterization of this primitive TLR and identification of a bacterial pathogen for N. vectensis reveal ancient TLR functions and provide a model for studying the molecular basis of cnidarian disease and immunity.IOS-1354935 - National Science Foundation (NSF); GRFP - National Science Foundation (NSF); GRFP - National Science Foundation (NSF); 1262934 - National Science Foundation (NSF); 2014-BSP - Arnold and Mabel Beckman Foundatio

Development of a critical appraisal tool to assess the quality of cross-sectional studies (AXIS)

Objectives: The aim of this study was to develop a critical appraisal (CA) tool that addressed study design and reporting quality as well as the risk of bias in cross-sectional studies (CSSs). In addition, the aim was to produce a help document to guide the non-expert user through the tool. Design: An initial scoping review of the published literature and key epidemiological texts was undertaken prior to the formation of a Delphi panel to establish key components for a CA tool for CSSs. A consensus of 80% was required from the Delphi panel for any component to be included in the final tool. Results: An initial list of 39 components was identified through examination of existing resources. An international Delphi panel of 18 medical and veterinary experts was established. After 3 rounds of the Delphi process, the Appraisal tool for Cross-Sectional Studies (AXIS tool) was developed by consensus and consisted of 20 components. A detailed explanatory document was also developed with the tool, giving expanded explanation of each question and providing simple interpretations and examples of the epidemiological concepts being examined in each question to aid non-expert users. Conclusions: CA of the literature is a vital step in evidence synthesis and therefore evidence-based decision-making in a number of different disciplines. The AXIS tool is therefore unique and was developed in a way that it can be used across disciplines to aid the inclusion of CSSs in systematic reviews, guidelines and clinical decision-making

Distributed expertise: Qualitative study of a British network of multidisciplinary teams supporting parents of children with chronic kidney disease

© 2014 The Authors. Background: Long-term childhood conditions are often managed by hospital-based multidisciplinary teams (MDTs) of professionals with discipline specific expertise of a condition, in partnership with parents. However, little evidence exists on professional-parent interactions in this context. An exploration of professionals' accounts of the way they individually and collectively teach parents to manage their child's clinical care at home is, therefore, important for meeting parents' needs, informing policy and educating novice professionals. Using chronic kidney disease as an exemplar this paper reports on one aspect of a study of interactions between professionals and parents in a network of 12 children's kidney units in Britain. Methods: We conducted semi-structured, qualitative interviews with a convenience sample of 112 professionals (clinical-psychologists, dietitians, doctors, nurses, pharmacists, play-workers, therapists and social workers), exploring accounts of their parent-educative activity. We analysed data using framework and the concept of distributed expertise. Results: Four themes emerged that related to the way expertise was distributed within and across teams: (i) recognizing each other's' expertise, (ii) sharing expertise within the MDT, (iii) language interpretation, and (iv) acting as brokers. Two different professional identifications were also seen to co-exist within MDTs, with participants using the term 'we' both as the intra-professional 'we' (relating to the professional identity) when describing expertise within a disciplinary group (for example: 'As dietitians we aim to give tailored advice to optimize children's growth'), and the inter-professional 'we' (a 'team-identification'), when discussing expertise within the team (for example: 'We work as a team and make sure we're all happy with every aspect of their training before they go home'). Conclusions: This study highlights the dual identifications implicit in 'being professional' in this context (to the team and to one's profession) as well as the unique role that each member of a team contributes to children's care. Our methodology and results have the potential to be transferred to teams managing other conditions

Excessive daytime sleepiness and falls among older men and women: cross-sectional examination of a population-based sample

Background: Excessive daytime sleepiness (EDS) has been associated with an increased risk for falls among clinical samples of older adults. However, there is little detailed information among population-representative samples. The current study aimed to assess the relationship between EDS and falls among a cohort of population-based older adults. Methods: This study assessed 367 women aged 60-93years (median 72, interquartile range 65-79) and 451 men aged 60-92years (median 73, interquartile range 66-80) who participated in the Geelong Osteoporosis Study between the years 2001 and 2008. Falls during the prior year were documented via self-report, and for men, falls risk score was obtained using an Elderly Fall Screening Test (EFST). Sleepiness was assessed using the Epworth Sleepiness Scale (ESS), and scores of≥10 indicated EDS. Differences among those with and without EDS in regard to falls were tested using logistic regression models. Results: Among women, 50 (13.6 %) individuals reported EDS. Women with EDS were more likely to report a fall, and were more likely to report the fall occurring outside. EDS was similarly associated with an increased risk of a fall following adjustment for use of a walking aid, cases of nocturia and antidepressant medication use (adjusted OR∈=∈2.54, 95 % CI 1.24-5.21). Multivariate modelling revealed antidepressant use (current) as an effect modifier (p∈<∈.001 for the interaction term). After stratifying the data by antidepressant medication use, the association between EDS and falls was sustained following adjustment for nocturia among antidepressant non-users (adjusted OR∈=∈2.63, 95 % CI 1.31-5.30). Among men, 72 (16.0 %) individuals reported EDS. No differences were detected for men with and without EDS in regard to reported falls, and a trend towards significance was noted between EDS and a high falls risk as assessed by the EFST (p∈=∈0.06), however, age explained this relationship (age adjusted OR∈=∈2.20, 95 % CI 1.03-1.10). Conclusions: For women, EDS is independently associated with at least one fall during the previous year, and this is more likely to occur whilst located outside. Amelioration of EDS may assist in improving functional outcomes among these individuals by reducing the risk for falls

Evolutionary engineering improves tolerance for replacement jet fuels in Saccharomyces cerevisiae

Monoterpenes are liquid hydrocarbons with applications ranging from flavor and fragrance to replacement jet fuel. Their toxicity, however, presents a major challenge for microbial synthesis. Here we evolved limonene-tolerant Saccharomyces cerevisiae strains and sequenced six strains across the 200-generation evolutionary time course. Mutations were found in the tricalbin proteins Tcb2p and Tcb3p. Genomic reconstruction in the parent strain showed that truncation of a single protein (tTcb3p(1-989)), but not its complete deletion, was sufficient to recover the evolved phenotype improving limonene fitness 9-fold. tTcb3p(1-989) increased tolerance toward two other monoterpenes (beta-pinene and myrcene) 11- and 8-fold, respectively, and tolerance toward the biojet fuel blend AMJ-700t (10% cymene, 50% limonene, 40% farnesene) 4-fold. tTcb3p(1-989) is the first example of successful engineering of phase tolerance and creates opportunities for production of the highly toxic C-10 alkenes in yeast

Phobic Anxiety is Associated with Higher Serum Concentrations of Adipokines and Cytokines in Women with Diabetes

OBJECTIVE: Phobic anxiety has been associated with increased risk of cardiovascular disease (CVD), but the underlying mechanisms are poorly understood. We aimed to determine whether associations of phobic anxiety with several known markers of CVD might be contributors. RESEARCH DESIGN AND METHODS: We used a 16-point validated index (Crown-Crisp) measured in 1988 to categorize 984 women with type 2 diabetes from the Nurses' Health Study as having low, moderate, or high phobic anxiety. Groups were then compared for differences in adipokines (adiponectin and leptin), inflammatory markers (C-reactive protein and tumor necrosis factor [TNF]-α receptor II), and markers of endothelial function (sE-selectin, soluble intercellular adhesion molecule [sICAM]-1) measured on blood samples provided between 1989 and 1990. RESULTS: Higher levels of phobic anxiety were associated with higher BMI and lower education. Higher levels of phobic anxiety were also associated with higher leptin and soluble TNF-α receptor II in both crude analyses and after adjustment for potential confounders. sICAM and sE-selectin were higher in the highest tertile compared with the middle tertile, but there was no significant trend across tertiles. We found no association between phobic anxiety and adiponectin. CONCLUSIONS: High levels of phobic anxiety are associated with increased levels of leptin and inflammatory markers, which may in part explain the previously observed relationship between anxiety and other psychosocial disorders with CVD

Psychiatric disorders, psychotropic medication use and falls among women: an observational study

BACKGROUND: Psychotropic agents known to cause sedation are associated with an increased risk of falls, but the role of psychiatric illness as an independent risk factor for falls is not clear. Thus, this study aimed to investigate the association between psychiatric disorders, psychotropic medication use and falls risk. METHODS: This study examined data collected from 1062 women aged 20-93 yr (median 50 yr) participating in the Geelong Osteoporosis Study, a large, ongoing, population-based study. Depressive and anxiety disorders for the preceding 12-month period were ascertained by clinical interview. Current medication use and falls history were self-reported. Participants were classified as fallers if they had fallen to the ground at least twice during the same 12-month period. Anthropometry, demographic, medical and lifestyle factors were determined. Logistic regression was used to test the associations, after adjusting for potential confounders. RESULTS: Fifty-six women (5.3%) were classified as fallers. Those meeting criteria for depression within the past 12 months had a 2.4-fold increased odds of falling (unadjusted OR = 2.4, 95% CI 1.2-4.5). Adjustment for age and mobility strengthened the relationship (adjusted OR = 2.7, 95% CI 1.4-5.2) between depression and falling, with results remaining unchanged following further adjustment for psychotropic medication use (adjusted OR = 2.7, 95% CI 1.3-5.6). In contrast, past (prior to 12-month) depression were not associated with falls. No association was observed between anxiety and falls risk. Falling was associated with psychotropic medication use (unadjusted OR = 2.8, 95% CI 1.5-5.2), as well as antidepressant (unadjusted OR = 2.4, 95% CI 1.2-4.8) and benzodiazepine use (unadjusted OR = 3.4, 95% CI 1.6-7.3); associations remained unchanged following adjustment for potential confounders. CONCLUSION: The likelihood of falls was increased among those with depression within the past 12 months, independent of psychotropic medication use and other recognised confounders, suggesting an independent effect of depression on falls risk. Psychotropic drug use was also confirmed as an independent risk factor for falls, but anxiety disorders were not. Further research into the underlying mechanisms is warranted

Habitual physical activity and the risk for depressive and anxiety disorders among older men and women

Background: Regular physical activity is generally associated with psychological well-being, although there are relatively few prospective studies in older adults. We investigated habitual physical activity as a risk factor for de novo depressive and anxiety disorders in older men and women from the general population.Methods: In this nested case-control study, subjects aged 60 years or more were identified from randomly selected cohorts being followed prospectively in the Geelong Osteoporosis Study. Cases were individuals with incident depressive or anxiety disorders, diagnosed using the Structured Clinical Interview for DSM-IV-TR (SCID-I/NP); controls had no history of these disorders.Habitual physical activity,measured using a validated questionnaire, and other exposures were documented at baseline, approximately four years prior to psychiatric interviews. Those with depressive or anxiety disorders that pre-dated baseline were excluded.Results: Of 547 eligible subjects, 14 developed de novo depressive or anxiety disorders and were classified as cases; 533 controls remained free of disease. Physical activity was protective against the likelihood of depressive and anxiety disorders; OR = 0.55 (95% CI 0.32&ndash;0.94), p = 0.03; each standard deviation increase in the transformed physical activity score was associated with an approximate halving in the likelihood of developing depressive or anxiety disorders. Leisure-time physical activity contributed substantially to the overall physical activity score. Age, gender, smoking, alcohol consumption, weight and socioeconomic status did not substantially confound the association.Conclusion: This study provides evidence consistent with the notion that higher levels of habitual physical activity are protective against the subsequent risk of development of de novo depressive and anxiety disorders.<br /

Neoliberalisation and 'lad cultures' in higher education

This paper links HE neoliberalisation and ‘lad cultures’, drawing on interviews and focus groups with women students. We argue that retro-sexist ‘laddish’ forms of masculine competitiveness and misogyny have been reshaped by neoliberal rationalities to become modes of consumerist sexualised audit. We also suggest that neoliberal frameworks scaffold an individualistic and adversarial culture among young people that interacts with perceived threats to men’s privilege and intensifies attempts to put women in their place through misogyny and sexual harassment. Furthermore, ‘lad cultures’, sexism and sexual harassment in higher education may be invisibilised by institutions to preserve marketability in a neoliberal context. In response, we ask if we might foster dialogue and partnership between feminist and anti-marketisation politics