CLEC5A-mediated enhancement of the inflammatory response in myeloid cells contributes to influenza virus pathogenicity in vivo

Human infections with influenza viruses exhibit mild to severe clinical outcomes as a result of complex virus-host interactions. Induction of inflammatory mediators via pattern recognition receptors may dictate subsequent host responses for pathogen clearance and tissue damage. We identified that human C-type lectin domain family 5 member A (CLEC5A) interacts with the hemagglutinin protein of influenza viruses expressed on lentiviral pseudoparticles through lectin screening. Silencing CLEC5A gene expression, blocking influenza-CLEC5A interactions with anti-CLEC5A antibodies, or dampening CLEC5A-mediated signaling using a spleen tyrosine kinase inhibitor consistently reduced the levels of proinflammatory cytokines produced by human macrophages without affecting the replication of influenza A viruses of different subtypes. Infection of bone marrow-derived macrophages from CLEC5A-deficient mice showed reduced levels of tumor necrosis factor alpha (TNF-α) and IP-10 but elevated alpha interferon (IFN-α) compared to those of wild-type mice. The heightened type I IFN response in the macrophages of CLEC5A-deficient mice was associated with upregulated TLR3 mRNA after treatment with double-stranded RNA. Upon lethal challenges with a recombinant H5N1 virus, CLEC5A-deficient mice showed reduced levels of proinflammatory cytokines, decreased immune cell infiltration in the lungs, and improved survival compared to the wild-type mice, despite comparable viral loads noted throughout the course of infection. The survival difference was more prominent at a lower dose of inoculum. Our results suggest that CLEC5A-mediated enhancement of the inflammatory response in myeloid cells contributes to influenza pathogenicity in vivo and may be considered a therapeutic target in combination with effective antivirals. Well-orchestrated host responses together with effective viral clearance are critical for optimal clinical outcome after influenza infections.published_or_final_versio

Prevalence and Determinants of Obesity among Primary School Children in Dar es Salaam, Tanzania.

Childhood obesity has increased dramatically and has become a public health concern worldwide. Childhood obesity is likely to persist through adulthood and may lead to early onset of NCDs. However, there is paucity of data on obesity among primary school children in Tanzania. This study assessed the prevalence and determinants of obesity among primary school children in Dar es Salaam. A cross sectional study was conducted among school age children in randomly selected schools in Dar es Salaam. Anthropometric and blood pressure measurements were taken using standard procedures. Body Mass Index (BMI) was calculated as weight in kilograms divided by the square of height in meters (kg/m2). Child obesity was defined as BMI at or above 95th percentile for age and sex. Socio-demographic characteristics of children were determined using a structured questionnaire. Logistic regression was used to determine association between independent variables with obesity among primary school children in Dar es Salaam. A total of 446 children were included in the analysis. The mean age of the participants was 11.1±2.0 years and 53.1% were girls. The mean BMI, SBP and DBP were 16.6±4.0 kg/m2, 103.9±10.3mmHg and 65.6±8.2mmHg respectively. The overall prevalence of child obesity was 5.2% and was higher among girls (6.3%) compared to boys (3.8%). Obese children had significantly higher mean values for age (p=0.042), systolic and diastolic blood pressures (all p<0.001). Most obese children were from households with fewer children (p=0.019) and residing in urban areas (p=0.002). Controlling for other variables, age above 10 years (AOR=3.3, 95% CI=1.5-7.2), female sex (AOR=2.6, 95% CI=1.4-4.9), urban residence (AOR=2.5, 95% CI=1.2-5.3) and having money to spend at school (AOR=2.6, 95% CI=1.4-4.8) were significantly associated with child obesity. The prevalence of childhood obesity in this population was found to be low. However, children from urban schools and girls were proportionately more obese compared to their counterparts. Primary preventive measures for childhood obesity should start early in childhood and address socioeconomic factors of parents contributing to childhood obesity

An Action-Based Approach to Presence: Foundations and Methods

This chapter presents an action-based approach to presence. It starts by briefly describing the theoretical and empirical foundations of this approach, formalized into three key notions of place/space, action and mediation. In the light of these notions, some common assumptions about presence are then questioned: assuming a neat distinction between virtual and real environments, taking for granted the contours of the mediated environment and considering presence as a purely personal state. Some possible research topics opened up by adopting action as a unit of analysis are illustrated. Finally, a case study on driving as a form of mediated presence is discussed, to provocatively illustrate the flexibility of this approach as a unified framework for presence in digital and physical environment

Associations of sedentary behaviour, physical activity, blood pressure and anthropometric measures with cardiorespiratory fitness in children with cerebral palsy

Background - Children with cerebral palsy (CP) have poor cardiorespiratory fitness in comparison to their peers with typical development, which may be due to low levels of physical activity. Poor cardiorespiratory fitness may contribute to increased cardiometabolic risk. Purpose - The aim of this study was to determine the association between sedentary behaviour, physical activity and cardiorespiratory fitness in children with CP. An objective was to determine the association between cardiorespiratory fitness, anthropometric measures and blood pressure in children with CP. Methods- This study included 55 ambulatory children with CP [mean (SD) age 11.3 (0.2) yr, range 6-17 yr; Gross Motor Function Classification System (GMFCS) levels I and II]. Anthropometric measures (BMI, waist circumference and waist-height ratio) and blood pressure were taken. Cardiorespiratory fitness was measured using a 10 m shuttle run test. Children were classified as low, middle and high fitness according to level achieved on the test using reference curves. Physical activity was measured by accelerometry over 7 days. In addition to total activity, time in sedentary behaviour and light, moderate, vigorous, and sustained moderate-to-vigorous activity (≥10 min bouts) were calculated. Results - Multiple regression analyses revealed that vigorous activity (β = 0.339, p<0.01), sustained moderate-to-vigorous activity (β = 0.250, p<0.05) and total activity (β = 0.238, p<0.05) were associated with level achieved on the shuttle run test after adjustment for age, sex and GMFCS level. Children with high fitness spent more time in vigorous activity than children with middle fitness (p<0.05). Shuttle run test level was negatively associated with BMI (r2 = -0.451, p<0.01), waist circumference (r2 = -0.560, p<0.001), waist-height ratio (r2 = -0.560, p<0.001) and systolic blood pressure (r2 = -0.306, p<0.05) after adjustment for age, sex and GMFCS level. Conclusions - Participation in physical activity, particularly at a vigorous intensity, is associated with high cardiorespiratory fitness in children with CP. Low cardiorespiratory fitness is associated with increased cardiometabolic risk

ERP evidence suggests executive dysfunction in ecstasy polydrug users

Background: Deficits in executive functions such as access to semantic/long-term memory have been shown in ecstasy users in previous research. Equally, there have been many reports of equivocal findings in this area. The current study sought to further investigate behavioural and electro-physiological measures of this executive function in ecstasy users. Method: Twenty ecstasy–polydrug users, 20 non-ecstasy–polydrug users and 20 drug-naïve controls were recruited. Participants completed background questionnaires about their drug use, sleep quality, fluid intelligence and mood state. Each individual also completed a semantic retrieval task whilst 64 channel Electroencephalography (EEG) measures were recorded. Results: Analysis of Variance (ANOVA) revealed no between-group differences in behavioural performance on the task. Mixed ANOVA on event-related potential (ERP) components P2, N2 and P3 revealed significant between-group differences in the N2 component. Subsequent exploratory univariate ANOVAs on the N2 component revealed marginally significant between-group differences, generally showing greater negativity at occipito-parietal electrodes in ecstasy users compared to drug-naïve controls. Despite absence of behavioural differences, differences in N2 magnitude are evidence of abnormal executive functioning in ecstasy–polydrug users

Probing host pathogen cross-talk by transcriptional profiling of both Mycobacterium tuberculosis and infected human dendritic cells and macrophages

This study provides the proof of principle that probing the host and the microbe transcriptomes simultaneously is a valuable means to accessing unique information on host pathogen interactions. Our results also underline the extraordinary plasticity of host cell and pathogen responses to infection, and provide a solid framework to further understand the complex mechanisms involved in immunity to M. tuberculosis and in mycobacterial adaptation to different intracellular environments

Learning by hiring: the effects of scientists’ inbound mobility on research performance in academia

This study investigates the effects of scientists’ inbound mobility on the research performance of incumbent scientists in an academic setting. The theoretical framework integrates insights from learning theory and social comparison theory to suggest two main mechanisms behind these effects, localized learning and social comparison. The authors propose several hypotheses about the conditions that might intensify or weaken such effects. Specifically, the arrival of new scientific personnel is likely to exert stronger positive effects on the performance of incumbent scientists with shorter (cf. longer) organizational tenure; in addition, academic departments with less diversified expertise and with higher levels of internal collaborations likely reap greater benefits from learning by hiring. The empirical findings, based on a longitudinal analysis of a sample of 94 U.S. academic chemical engineering departments, provide empirical support for these contentions

Global analyses of TetR family transcriptional regulators in mycobacteria indicates conservation across species and diversity in regulated functions

BACKGROUND: Mycobacteria inhabit diverse niches and display high metabolic versatility. They can colonise both humans and animals and are also able to survive in the environment. In order to succeed, response to environmental cues via transcriptional regulation is required. In this study we focused on the TetR family of transcriptional regulators (TFTRs) in mycobacteria. RESULTS: We used InterPro to classify the entire complement of transcriptional regulators in 10 mycobacterial species and these analyses showed that TFTRs are the most abundant family of regulators in all species. We identified those TFTRs that are conserved across all species analysed and those that are unique to the pathogens included in the analysis. We examined genomic contexts of 663 of the conserved TFTRs and observed that the majority of TFTRs are separated by 200 bp or less from divergently oriented genes. Analyses of divergent genes indicated that the TFTRs control diverse biochemical functions not limited to efflux pumps. TFTRs typically bind to palindromic motifs and we identified 11 highly significant novel motifs in the upstream regions of divergently oriented TFTRs. The C-terminal ligand binding domain from the TFTR complement in M. tuberculosis showed great diversity in amino acid sequence but with an overall architecture common to other TFTRs. CONCLUSION: This study suggests that mycobacteria depend on TFTRs for the transcriptional control of a number of metabolic functions yet the physiological role of the majority of these regulators remain unknown. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12864-015-1696-9) contains supplementary material, which is available to authorized users

Production of π0 and η mesons in Cu+Au collisions at sNN =200 GeV

Production of π0 and η mesons has been measured at midrapidity in Cu+Au collisions at sNN=200GeV. Measurements were performed in π0(η)→γγ decay channel in the 1(2)-20GeV/c transverse momentum range. A strong suppression is observed for π0 and η meson production at high transverse momentum in central Cu+Au collisions relative to the p+p results scaled by the number of nucleon-nucleon collisions. In central collisions the suppression is similar to Au+Au with comparable nuclear overlap. The η/π0 ratio measured as a function of transverse momentum is consistent with mT-scaling parametrization down to pT=2GeV/c, its asymptotic value is constant and consistent with Au+Au and p+p and does not show any significant dependence on collision centrality. Similar results were obtained in hadron-hadron, hadron-nucleus, and nucleus-nucleus collisions as well as in e+e- collisions in a range of collision energies sNN=3-1800 GeV. This suggests that the quark-gluon-plasma medium produced in Cu+Cu collisions either does not affect the jet fragmentation into light mesons or it affects the π0 and η the same way

‘Do i care?’ young adults' recalled experiences of early adolescent overweight and obesity: a qualitative study

&lt;p&gt;Objective: Individual behaviour change to reduce obesity requires awareness of, and concern about, weight. This paper therefore describes how young adults, known to have been overweight or obese during early adolescence, recalled early adolescent weight-related awareness and concerns. Associations between recalled concerns and weight-, health- and peer-related survey responses collected during adolescence are also examined.&lt;/p&gt; &lt;p&gt;Design: Qualitative semi-structured interviews with young adults; data compared with responses to self-report questionnaires obtained in adolescence.&lt;/p&gt; &lt;p&gt;Participants: A total of 35 participants, purposively sub-sampled at age 24 from a longitudinal study of a school year cohort, previously surveyed at ages 11, 13 and 15. Physical measures during previous surveys allowed identification of participants with a body mass index (BMI) indicative of overweight or obesity (based on British 1990 growth reference) during early adolescence. Overall, 26 had been obese, of whom 11 had BMI99.6th centile, whereas 9 had been overweight (BMI=95th–97.9th centile).&lt;/p&gt; &lt;p&gt;Measures: Qualitative interview responses describing teenage life, with prompts for school-, social- and health-related concerns. Early adolescent self-report questionnaire data on weight-worries, self-esteem, friends and victimisation (closed questions).&lt;/p&gt; &lt;p&gt;Results: Most, but not all recalled having been aware of their overweight. None referred to themselves as having been obese. None recalled weight-related health worries. Recollection of early adolescent obesity varied from major concerns impacting on much of an individual's life to almost no concern, with little relation to actual severity of overweight. Recalled concerns were not clearly patterned by gender, but young adult males recalling concerns had previously reported more worries about weight, lower self-esteem, fewer friends and more victimisation in early adolescence; no such pattern was seen among females. Conclusion: The popular image of the unhappy overweight teenager was not borne out. Many obese adolescents, although well aware of their overweight recalled neither major dissatisfaction nor concern. Weight-reduction behaviours are unlikely in such circumstances.&lt;/p&gt