Chemical warfare between leafcutter ant symbionts and a co-evolved pathogen

Acromyrmex leafcutter ants form a mutually beneficial symbiosis with the fungus Leucoagaricus gongylophorus and with Pseudonocardia bacteria. Both are vertically transmitted and actively maintained by the ants. The fungus garden is manured with freshly cut leaves and provides the sole food for the ant larvae, while Pseudonocardia cultures are reared on the ant-cuticle and make antifungal metabolites to help protect the cultivar against disease. If left unchecked, specialized parasitic Escovopsis fungi can overrun the fungus-garden and lead to colony collapse. We report that Escovopsis upregulates the production of two specialized metabolites when it infects the cultivar. These compounds inhibit Pseudonocardia and one, shearinine D, also reduces worker behavioral defences and is ultimately lethal when it accumulates in ant tissues. Our results are consistent with an active evolutionary arms race between Pseudonocardia and Escovopsis, which modifies both bacterial and behavioral defences such that colony collapse is unavoidable once Escovopsis infections escalate

Early Antiretroviral Therapy Reduces AIDS Progression/Death in Individuals with Acute Opportunistic Infections: A Multicenter Randomized Strategy Trial

Background: Optimal timing of ART initiation for individuals presenting with AIDS-related OIs has not been defined. Methods and Findings: A5164 was a randomized strategy trial of ‘‘early ART’’ - given within 14 days of starting acute OI treatment versus ‘‘deferred ART’’ - given after acute OI treatment is completed. Randomization was stratified by presenting OI and entry CD4 count. The primary week 48 endpoint was 3-level ordered categorical variable: 1. Death/AIDS progression; 2. No progression with incomplete viral suppression (ie HIV viral load (VL) [greater than or equal to] 50 copies/ml); 3. No progression with optimal viral suppression (ie HIV VL <50 copies/ml). Secondary endpoints included: AIDS progression/death; plasma HIV RNA and CD4 responses and safety parameters including IRIS. 282 subjects were evaluable; 141 per arm. Entry OIs included Pneumocytis jirovecii pneumonia 63%, cryptococcal meningitis 12%, and bacterial infections 12%. The early and deferred arms started ART a median of 12 and 45 days after start of OI treatment, respectively. The difference in the primary endpoint did not reach statistical significance: AIDS progression/death was seen in 20 (14%) vs. 34 (24%); whereas no progression but with incomplete viral suppression was seen in 54 (38%) vs. 44 (31%); and no progression with optimal viral suppression in 67 (48%) vs 63 (45%) in the early vs. deferred arm, respectively (p = 0.22). However, the early ART arm had fewer AIDS progression/deaths (OR = 0.51; 95% CI = 0.27–0.94) and a longer time to AIDS progression/death (stratified HR = 0.53; 95% CI = 0.30–0.92). The early ART had shorter time to achieving a CD4 count above 50 cells/mL (p<0.001) and no increase in adverse events. Conclusions: Early ART resulted in less AIDS progression/death with no increase in adverse events or loss of virologic response compared to deferred ART. These results support the early initiation of ART in patients presenting with acute AIDS-related OIs, absent major contraindications

Using affective judgement to increase physical activity in British adults.

Mobile phone apps have been shown to increase physical activity (PA), but existing apps fail to target the emotional aspects of PA, which influence whether individuals are active. We developed an app that encourages individuals to focus on the emotional aspects of PA. We aimed to assess the acceptability of this app, and conduct a preliminary evaluation of efficacy. The app was developed in collaboration with users through focus groups. Seven users tested the app over 4 months and provided feedback on acceptability, aesthetics and functionality in a follow-up focus group. Results were summarized descriptively. Before testing the app, participants completed a questionnaire assessing their current PA and psychological antecedents of PA. A second questionnaire was completed at the follow-up focus group. Change scores are reported for each participant and overall. The social and reminder aspects facilitated motivation to be active and many found it easy to integrate into their lives. Most suggested modifications. Small improvements in number of minutes spent walking per week were observed (overall mean change +25 min) and some psychological antecedents of PA (overall mean change for social support for PA +0.14, self-efficacy for PA +0.17, outcome expectations about PA +0.20; all five-point scales), but reductions were seen in other domains. The app was acceptable to users, although developments are required. Testing with a small number of individuals, offering preliminary evidence of efficacy of this app, provides justification for further evaluation on a larger scale

Objectively measured physical activity and sedentary time in youth: the International children's accelerometry database (ICAD).

BACKGROUND: Physical activity and sedentary behaviour in youth have been reported to vary by sex, age, weight status and country. However, supporting data are often self-reported and/or do not encompass a wide range of ages or geographical locations. This study aimed to describe objectively-measured physical activity and sedentary time patterns in youth. METHODS: The International Children's Accelerometry Database (ICAD) consists of ActiGraph accelerometer data from 20 studies in ten countries, processed using common data reduction procedures. Analyses were conducted on 27,637 participants (2.8-18.4 years) who provided at least three days of valid accelerometer data. Linear regression was used to examine associations between age, sex, weight status, country and physical activity outcomes. RESULTS: Boys were less sedentary and more active than girls at all ages. After 5 years of age there was an average cross-sectional decrease of 4.2% in total physical activity with each additional year of age, due mainly to lower levels of light-intensity physical activity and greater time spent sedentary. Physical activity did not differ by weight status in the youngest children, but from age seven onwards, overweight/obese participants were less active than their normal weight counterparts. Physical activity varied between samples from different countries, with a 15-20% difference between the highest and lowest countries at age 9-10 and a 26-28% difference at age 12-13. CONCLUSIONS: Physical activity differed between samples from different countries, but the associations between demographic characteristics and physical activity were consistently observed. Further research is needed to explore environmental and sociocultural explanations for these differences

International meta-analysis of PTSD genome-wide association studies identifies sex- and ancestry-specific genetic risk loci.

The risk of posttraumatic stress disorder (PTSD) following trauma is heritable, but robust common variants have yet to be identified. In a multi-ethnic cohort including over 30,000 PTSD cases and 170,000 controls we conduct a genome-wide association study of PTSD. We demonstrate SNP-based heritability estimates of 5-20%, varying by sex. Three genome-wide significant loci are identified, 2 in European and 1 in African-ancestry analyses. Analyses stratified by sex implicate 3 additional loci in men. Along with other novel genes and non-coding RNAs, a Parkinson's disease gene involved in dopamine regulation, PARK2, is associated with PTSD. Finally, we demonstrate that polygenic risk for PTSD is significantly predictive of re-experiencing symptoms in the Million Veteran Program dataset, although specific loci did not replicate. These results demonstrate the role of genetic variation in the biology of risk for PTSD and highlight the necessity of conducting sex-stratified analyses and expanding GWAS beyond European ancestry populations

Harmonising data on the correlates of physical activity and sedentary behaviour in young people: Methods and lessons learnt from the international Children's Accelerometry database (ICAD).

BACKGROUND: Large, heterogeneous datasets are required to enhance understanding of the multi-level influences on children's physical activity and sedentary behaviour. One route to achieving this is through the pooling and co-analysis of data from multiple studies. Where this approach is used, transparency of the methodology for data collation and harmonisation is essential to enable appropriate analysis and interpretation of the derived data. In this paper, we describe the acquisition, management and harmonisation of non-accelerometer data in a project to expand the International Children's Accelerometry Database (ICAD). METHOD: Following a consultation process, ICAD partners were requested to share accelerometer data and information on selected behavioural, social, environmental and health-related constructs. All data were collated into a single repository for cataloguing and harmonisation. Harmonised variables were derived iteratively, with input from the ICAD investigators and a panel of invited experts. Extensive documentation, describing the source data and harmonisation procedure, was prepared and made available through the ICAD website. RESULTS: Work to expand ICAD has increased the number of studies with longitudinal accelerometer data, and expanded the breadth of behavioural, social and environmental characteristics that can be used as exposure variables. A set of core harmonised variables, including parent education, ethnicity, school travel mode/duration and car ownership, were derived for use by the research community. Guidance documents and facilities to enable the creation of new harmonised variables were also devised and made available to ICAD users. An expanded ICAD database was made available in May 2017. CONCLUSION: The project to expand ICAD further demonstrates the feasibility of pooling data on physical activity, sedentary behaviour and potential determinants from multiple studies. Key to this process is the rigorous conduct and reporting of retrospective data harmonisation, which is essential to the appropriate analysis and interpretation of derived data. These documents, made available through the ICAD website, may also serve as a guide to others undertaking similar projects

Association between maternal education and objectively measured physical activity and sedentary time in adolescents

Investigating socioeconomic variation in physical activity (PA) and sedentary time is important as it may represent a pathway by which socioeconomic position (SEP) leads to ill health. Findings on the association between children's SEP and objectively assessed PA and/or sedentary time are mixed, and few studies have included international samples.Examine the associations between maternal education and adolescent's objectively assessed PA and sedentary time.This is an observational study of 12 770 adolescents (10-18 years) pooled from 10 studies from Europe, Australia, Brazil and the USA. Original PA data were collected between 1997 and 2009. The associations between maternal education and accelerometer variables were examined using robust multivariable regression, adjusted for a priori confounders (ie, body mass index, monitor wear time, season, age and sex) and regression coefficients combined across studies using random effects meta-analyses. Analyses were conducted in March 2014.Adolescents of university educated mothers spent more time sedentary (9.5 min/day, p=0.005) and less time in light activity (10 min/day, p<0.001) compared with adolescents of high school educated mothers. Pooled analysis across two studies from Brazil and Portugal (analysed separately because of the different coding of maternal education) showed that children of higher educated mothers (tertiary vs primary/secondary) spent less time in moderate to vigorous PA (MVPA) (6.6 min/day, p=0.001) and in light PA (39.2 min/day: p<0.001), and more time sedentary (45.9 min/day, p<0.001).Across a number of international samples, adolescents of mothers with lower education may not be at a disadvantage in terms of overall objectively measured PA

Sub region-specific modulation of synchronous neuronal burst firing after a kainic acid insult in organotypic hippocampal cultures

<p>Abstract</p> <p>Background</p> <p>Excitotoxicity occurs in a number of pathogenic states including stroke and epilepsy. The adaptations of neuronal circuits in response to such insults may be expected to play an underlying role in pathogenesis. Synchronous neuronal firing can be induced in isolated hippocampal slices and involves all regions of this structure, thereby providing a measure of circuit activity. The effect of an excitotoxic insult (kainic acid, KA) on Mg²⁺-free-induced synchronized neuronal firing was tested in organotypic hippocampal culture by measuring extracellular field activity in CA1 and CA3.</p> <p>Results</p> <p>Within 24 hrs of the insult regional specific changes in neuronal firing patterns were evident as: (i) a dramatic <it>reduction </it>in the ability of CA3 to generate firing; and (ii) a contrasting <it>increase </it>in the frequency and duration of synchronized neuronal firing events in CA1. Two distinct processes underlie the increased propensity of CA1 to generate synchronized burst firing; a lack of ability of the CA3 region to 'pace' CA1 resulting in an increased frequency of synchronized events; and a change in the 'intrinsic' properties limited to the CA1 region, which is responsible for increased event duration. Neuronal quantification using NeuN immunoflurescent staining and stereological confocal microscopy revealed no significant cell loss in hippocampal sub regions, suggesting that changes in the properties of neurons within this region were responsible for the KA-mediated excitability changes.</p> <p>Conclusion</p> <p>These results provide novel insight into adaptation of hippocampal circuits following excitotoxic injury. KA-mediated disruption of the interplay between CA3 and CA1 clearly increases the propensity to synchronized firing in CA1.</p

Harmonising data on the correlates of physical activity and sedentary behaviour in young people: Methods and lessons learnt from the International Children's Accelerometry database (ICAD)

Background: Large, heterogeneous datasets are required to enhance understanding of the multi-level influences on children's physical activity and sedentary behaviour. One route to achieving this is through the pooling and co-analysis of data from multiple studies. Where this approach is used, transparency of the methodology for data collation and harmonisation is essential to enable appropriate analysis and interpretation of the derived data. In this paper, we describe the acquisition, management and harmonisation of non-accelerometer data in a project to expand the International Children's Accelerometry Database (ICAD). Method: Following a consultation process, ICAD partners were requested to share accelerometer data and information on selected behavioural, social, environmental and health-related constructs. All data were collated into a single repository for cataloguing and harmonisation. Harmonised variables were derived iteratively, with input from the ICAD investigators and a panel of invited experts. Extensive documentation, describing the source data and harmonisation procedure, was prepared and made available through the ICAD website. Results: Work to expand ICAD has increased the number of studies with longitudinal accelerometer data, and expanded the breadth of behavioural, social and environmental characteristics that can be used as exposure variables. A set of core harmonised variables, including parent education, ethnicity, school travel mode/duration and car ownership, were derived for use by the research community. Guidance documents and facilities to enable the creation of new harmonised variables were also devised and made available to ICAD users. An expanded ICAD database was made available in May 2017. Conclusion: The project to expand ICAD further demonstrates the feasibility of pooling data on physical activity, sedentary behaviour and potential determinants from multiple studies. Key to this process is the rigorous conduct and reporting of retrospective data harmonisation, which is essential to the appropriate analysis and interpretation of derived data. These documents, made available through the ICAD website, may also serve as a guide to others undertaking similar projects