A transcriptional network associated with natural variation in Drosophila aggressive behavior

A genome-wide screen of inbred Drosophila lines together with transcriptional network modeling reveals insights into the genetic bases of heritable aggression

Mutations in many genes affect aggressive behavior in Drosophila melanogaster

BACKGROUND: Aggressive behavior in animals is important for survival and reproduction. Identifying the underlying genes and environmental contexts that affect aggressive behavior is important for understanding the evolutionary forces that maintain variation for aggressive behavior in natural populations, and to develop therapeutic interventions to modulate extreme levels of aggressive behavior in humans. While the role of neurotransmitters and a few other molecules in mediating and modulating levels of aggression is well established, it is likely that many additional genetic pathways remain undiscovered. Drosophila melanogaster has recently been established as an excellent model organism for studying the genetic basis of aggressive behavior. Here, we present the results of a screen of 170 Drosophila P-element insertional mutations for quantitative differences in aggressive behavior from their co-isogenic control line. RESULTS: We identified 59 mutations in 57 genes that affect aggressive behavior, none of which had been previously implicated to affect aggression. Thirty-two of these mutants exhibited increased aggression, while 27 lines were less aggressive than the control. Many of the genes affect the development and function of the nervous system, and are thus plausibly relevant to the execution of complex behaviors. Others affect basic cellular and metabolic processes, or are mutations in computationally predicted genes for which aggressive behavior is the first biological annotation. Most of the mutations had pleiotropic effects on other complex traits. We characterized nine of these mutations in greater detail by assessing transcript levels throughout development, morphological changes in the mushroom bodies, and restoration of control levels of aggression in revertant alleles. All of the P-element insertions affected the tagged genes, and had pleiotropic effects on brain morphology. CONCLUSION: This study reveals that many more genes than previously suspected affect aggressive behavior, and that these genes have widespread pleiotropic effects. Given the conservation of aggressive behavior among different animal species, these are novel candidate genes for future study in other animals, including humans

Opposing associations of depression with sexual behaviour: implications for epidemiological investigation among gay, bisexual and other men who have sex with men

OBJECTIVE: The aim of this report is to investigate the nature of the relationship between depression and condomless sex (CLS) among gay, bisexual and other men who have sex with men (GBMSM). METHODS: Data are from the Antiretrovirals, Sexual Transmission Risk and Attitude (ASTRA) study of people living with HIV and attending one of eight HIV outpatient clinics in England (2011-2012) and the Attitudes to and Understanding of Risk of Acquisition of HIV (AURAH) study of HIV-negative/unknown status individuals attending one of 20 genitourinary medicine clinics in England (2013-2014). This analysis included GBMSM only. For each study, the prevalence of depressive symptoms (Patient Health Questionnaire-9 score ≥10) was presented according to three categories of sex in the past 3 months (considering anal/vaginal sex with men/women and anal sex with men in separate definitions): (1) no sex, (2) condom-protected sex only and (3) CLS. Multinomial logistic regression with 'condom-protected sex only' as the reference group was used to adjust for age and (for ASTRA participants) time since HIV diagnosis. RESULTS: There were opposing associations of depression with recent sexual behaviour: the prevalence of depression was higher among those who reported no sex and those who reported CLS, compared with those who reported condom-protected sex only. Among the 2170 HIV-positive GBMSM in ASTRA, considering anal/vaginal sex with men/women, the prevalence of depressive symptoms was 32%, 20% and 28%, respectively, among men reporting no sex (n=783), condom-protected sex only (n=551) and CLS (n=836) (global p<0.001). Among the 1477 HIV-negative GBMSM in AURAH, the prevalence of depressive symptoms was 12%, 8% and 13%, respectively, for no sex (n=137), condom-protected sex only (n=487) and CLS (n=853) (global p=0.017). Patterns were similar after adjustment and when only considering anal sex between men. CONCLUSIONS: Depression may be linked both to lack of sexual activity and to sexual risk taking. When investigating associations between depression and CLS, it is important to separate out individuals reporting condom-protected sex only from those reporting no sex

Forefoot pathology in rheumatoid arthritis identified with ultrasound may not localise to areas of highest pressure: cohort observations at baseline and twelve months

BackgroundPlantar pressures are commonly used as clinical measures, especially to determine optimum foot orthotic design. In rheumatoid arthritis (RA) high plantar foot pressures have been linked to metatarsophalangeal (MTP) joint radiological erosion scores. However, the sensitivity of foot pressure measurement to soft tissue pathology within the foot is unknown. The aim of this study was to observe plantar foot pressures and forefoot soft tissue pathology in patients who have RA.Methods A total of 114 patients with established RA (1987 ACR criteria) and 50 healthy volunteers were assessed at baseline. All RA participants returned for reassessment at twelve months. Interface foot-shoe plantar pressures were recorded using an F-Scan® system. The presence of forefoot soft tissue pathology was assessed using a DIASUS musculoskeletal ultrasound (US) system. Chi-square analyses and independent t-tests were used to determine statistical differences between baseline and twelve months. Pearson’s correlation coefficient was used to determine interrelationships between soft tissue pathology and foot pressures.ResultsAt baseline, RA patients had a significantly higher peak foot pressures compared to healthy participants and peak pressures were located in the medial aspect of the forefoot in both groups. In contrast, RA participants had US detectable soft tissue pathology in the lateral aspect of the forefoot. Analysis of person specific data suggests that there are considerable variations over time with more than half the RA cohort having unstable presence of US detectable forefoot soft tissue pathology. Findings also indicated that, over time, changes in US detectable soft tissue pathology are out of phase with changes in foot-shoe interface pressures both temporally and spatially.Conclusions We found that US detectable forefoot soft tissue pathology may be unrelated to peak forefoot pressures and suggest that patients with RA may biomechanically adapt to soft tissue forefoot pathology. In addition, we have observed that, in patients with RA, interface foot-shoe pressures and the presence of US detectable forefoot pathology may vary substantially over time. This has implications for clinical strategies that aim to offload peak plantar pressures

Knowledge based improvement:simulation and artificial intelligence for identifying and improving human decision-making in an operations systems

The performance of most operations systems is significantly affected by the interaction of human decision-makers. A methodology, based on the use of visual interactive simulation (VIS) and artificial intelligence (AI), is described that aims to identify and improve human decision-making in operations systems. The methodology, known as 'knowledge-based improvement' (KBI), elicits knowledge from a decision-maker via a VIS and then uses AI methods to represent decision-making. By linking the VIS and AI representation, it is possible to predict the performance of the operations system under different decision-making strategies and to search for improved strategies. The KBI methodology is applied to the decision-making surrounding unplanned maintenance operations at a Ford Motor Company engine assembly plant

MultiMetEval: comparative and multi-objective analysis of genome-scale metabolic models

Comparative metabolic modelling is emerging as a novel field, supported by the development of reliable and standardized approaches for constructing genome-scale metabolic models in high throughput. New software solutions are needed to allow efficient comparative analysis of multiple models in the context of multiple cellular objectives. Here, we present the user-friendly software framework Multi-Metabolic Evaluator (MultiMetEval), built upon SurreyFBA, which allows the user to compose collections of metabolic models that together can be subjected to flux balance analysis. Additionally, MultiMetEval implements functionalities for multi-objective analysis by calculating the Pareto front between two cellular objectives. Using a previously generated dataset of 38 actinobacterial genome-scale metabolic models, we show how these approaches can lead to exciting novel insights. Firstly, after incorporating several pathways for the biosynthesis of natural products into each of these models, comparative flux balance analysis predicted that species like Streptomyces that harbour the highest diversity of secondary metabolite biosynthetic gene clusters in their genomes do not necessarily have the metabolic network topology most suitable for compound overproduction. Secondly, multi-objective analysis of biomass production and natural product biosynthesis in these actinobacteria shows that the well-studied occurrence of discrete metabolic switches during the change of cellular objectives is inherent to their metabolic network architecture. Comparative and multi-objective modelling can lead to insights that could not be obtained by normal flux balance analyses. MultiMetEval provides a powerful platform that makes these analyses straightforward for biologists. Sources and binaries of MultiMetEval are freely available from https://github.com/PiotrZakrzewski/MetEv​al/downloads

Metabolic analysis of the interaction between plants and herbivores

Insect herbivores by necessity have to deal with a large arsenal of plant defence metabolites. The levels of defence compounds may be increased by insect damage. These induced plant responses may also affect the metabolism and performance of successive insect herbivores. As the chemical nature of induced responses is largely unknown, global metabolomic analyses are a valuable tool to gain more insight into the metabolites possibly involved in such interactions. This study analyzed the interaction between feral cabbage (Brassica oleracea) and small cabbage white caterpillars (Pieris rapae) and how previous attacks to the plant affect the caterpillar metabolism. Because plants may be induced by shoot and root herbivory, we compared shoot and root induction by treating the plants on either plant part with jasmonic acid. Extracts of the plants and the caterpillars were chemically analysed using Ultra Performance Liquid Chromatography/Time of Flight Mass Spectrometry (UPLCT/MS). The study revealed that the levels of three structurally related coumaroylquinic acids were elevated in plants treated on the shoot. The levels of these compounds in plants and caterpillars were highly correlated: these compounds were defined as the ‘metabolic interface’. The role of these metabolites could only be discovered using simultaneous analysis of the plant and caterpillar metabolomes. We conclude that a metabolomics approach is useful in discovering unexpected bioactive compounds involved in ecological interactions between plants and their herbivores and higher trophic levels.

A cognitive behavioral based group intervention for children with a chronic illness and their parents: a multicentre randomized controlled trial

<p>Abstract</p> <p>Background</p> <p>Coping with a chronic illness (CI) challenges children's psychosocial functioning and wellbeing. Cognitive-behavioral intervention programs that focus on teaching the active use of coping strategies may prevent children with CI from developing psychosocial problems. Involvement of parents in the intervention program may enhance the use of learned coping strategies in daily life, especially on the long-term. The primary aim of the present study is to examine the effectiveness of a cognitive behavioral based group intervention (called 'Op Koers') <abbrgrp><abbr bid="B1">1</abbr></abbrgrp> for children with CI and of a parallel intervention for their parents. A secondary objective is to investigate why and for whom this intervention works, in order to understand the underlying mechanisms of the intervention effect.</p> <p>Methods/design</p> <p>This study is a multicentre randomized controlled trial. Participants are children (8 to 18 years of age) with a chronic illness, and their parents, recruited from seven participating hospitals in the Netherlands. Participants are randomly allocated to two intervention groups (the child intervention group and the child intervention combined with a parent program) and a wait-list control group. Primary outcomes are child psychosocial functioning, wellbeing and child disease related coping skills. Secondary outcomes are child quality of life, child general coping skills, child self-perception, parental stress, quality of parent-child interaction, and parental perceived vulnerability. Outcomes are evaluated at baseline, after 6 weeks of treatment, and at a 6 and 12-month follow-up period. The analyses will be performed on the basis of an intention-to-treat population.</p> <p>Discussion</p> <p>This study evaluates the effectiveness of a group intervention improving psychosocial functioning in children with CI and their parents. If proven effective, the intervention will be implemented in clinical practice. Strengths and limitations of the study design are discussed.</p> <p>Trial registration</p> <p>Current Controlled Trials <a href="http://www.controlled-trials.com/ISRCTN60919570">ISRCTN60919570</a></p