The Drosophila melanogaster host model

The deleterious and sometimes fatal outcomes of bacterial infectious diseases are the net result of the interactions between the pathogen and the host, and the genetically tractable fruit fly, Drosophila melanogaster, has emerged as a valuable tool for modeling the pathogen–host interactions of a wide variety of bacteria. These studies have revealed that there is a remarkable conservation of bacterial pathogenesis and host defence mechanisms between higher host organisms and Drosophila. This review presents an in-depth discussion of the Drosophila immune response, the Drosophila killing model, and the use of the model to examine bacterial–host interactions. The recent introduction of the Drosophila model into the oral microbiology field is discussed, specifically the use of the model to examine Porphyromonas gingivalis–host interactions, and finally the potential uses of this powerful model system to further elucidate oral bacterial-host interactions are addressed

Maternal fat intake during pregnancy and offspring metabolic health – a prospective study with 20 years of follow-up

Maternal fat intake during pregnancy in relation to offspring metabolic outcomes has been studied primarily in animal models, yet little is known about the association in humans. The aim of this study was to examine the association of total and subtype of fat consumption in pregnancy with anthropometric measures and biomarkers of adiposity and glucose metabolism in the offspring. Methods: A source population was 965 Danish pregnant women recruited in 1988e1989 with offspring follow-up at 20 years. Information on fat intake was collected in the 30th week of gestation, and we subdivided fat according to saturated (SFA), monounsaturated (MUFA), and polyunsaturated (PUFA) fat. Offspring body mass index (BMI) and waist circumference (WC) were recorded at follow-up (n ¼ 670678), and biomarkers were quantified in a subset (n ¼ 443) of participants. Multivariable linear and log-binomial regression were used to calculate effect estimates and 95% CI for a 1:1%energy substitution of carbohydrates for fat. Results: The mean (standard deviation) BMI was 22.1 (3.3) and 22.8 (2.9) kg/m2 in female and male offspring, respectively. The median (10th to 90th percentile) of maternal fat intake was 31% of energy [23,39]. We found no overall associations for maternal fat intake with female offspring anthropometry. However, for male offspring higher intake of MUFA during pregnancy was associated with higher insulin levels at 20 years (Q4 vs. Q1: %D: 37, 95% CI: 1, 86) accompanied by a non-significant 3.6 (95% CI: 1.1, 8.2) cm increase in WC. High maternal total fat intake (>¼35% energy) was also associated with higher BMI (0.9, 95% CI: 0.2, 1.6) and WC (4.0, 95% CI: 1.6, 2.3) among male offspring. Conclusions: A high fat diet during pregnancy may increase adiposity in adult male offspring. We surmise that maternal MUFA intake during this time included both MUFA and trans fat misclassified as MUFA, and that the associations observed may be more reflective of the latter exposure

VPS39-deficiency observed in type 2 diabetes impairs muscle stem cell differentiation via altered autophagy and epigenetics

Insulin resistance and lower muscle quality (strength divided by mass) are hallmarks of type 2 diabetes (T2D). Here, we explore whether alterations in muscle stem cells (myoblasts) from individuals with T2D contribute to these phenotypes. We identify VPS39 as an important regulator of myoblast differentiation and muscle glucose uptake, and VPS39 is downregulated in myoblasts and myotubes from individuals with T2D. We discover a pathway connecting VPS39-deficiency in human myoblasts to impaired autophagy, abnormal epigenetic reprogramming, dysregulation of myogenic regulators, and perturbed differentiation. VPS39 knockdown in human myoblasts has profound effects on autophagic flux, insulin signaling, epigenetic enzymes, DNA methylation and expression of myogenic regulators, and gene sets related to the cell cycle, muscle structure and apoptosis. These data mimic what is observed in myoblasts from individuals with T2D. Furthermore, the muscle of Vps39(+/-) mice display reduced glucose uptake and altered expression of genes regulating autophagy, epigenetic programming, and myogenesis. Overall, VPS39-deficiency contributes to impaired muscle differentiation and reduced glucose uptake. VPS39 thereby offers a therapeutic target for T2D. Insulin resistance and lower muscle strength in relation to mass are hallmarks of type 2 diabetes. Here, the authors report alterations in muscle stem cells from individuals with type 2 diabetes that may contribute to these phenotypes through VPS39 mediated effects on autophagy and epigenetics.Peer reviewe

Fish oil supplementation during pregnancy and allergic respiratory disease in the adult offspring

Background Maternal supplementation with long-chain n-3 polyunsaturated fatty acids can have immunologic effects on the developing fetus through several anti-inflammatory pathways. However, there is limited knowledge of the long-term programming effects. Objective In a randomized controlled trial from 1990 with 24 years of follow-up, our aim was to determine whether supplementation with 2.7 g of long-chain n-3 polyunsaturated fatty acids in pregnancy can reduce the risk of asthma in offspring and allergic respiratory disease. Methods The randomized controlled trial included 533 women who were randomly assigned to receive fish oil during the third trimester of pregnancy, olive oil, or no oil in the ratio 2:1:1. The offspring were followed in a mandatory national prescription register, with complete follow-up for prescriptions related to the treatment of asthma and allergic rhinitis as primary outcomes. Furthermore, the offspring were invited to complete a questionnaire (74% participated) and attend a clinical examination (47% participated) at age 18 to 19 years. Results In intention-to-treat analyses the probability of having had asthma medication prescribed was significantly reduced in the fish oil group compared with the olive oil group (hazard ratio, 0.54, 95% CI, 0.32-0.90; P = .02). The probability of having had allergic rhinitis medication prescribed was also reduced in the fish oil group compared with the olive oil group (hazard ratio, 0.70, 95% CI, 0.47-1.05; P = .09), but the difference was not statistically significant. Self-reported information collected at age 18 to 19 years supported these findings. No associations were detected with respect to lung function outcomes or allergic sensitization at 18 to 19 years of age. Conclusion Maternal supplementation with fish oil might have prophylactic potential for long-term prevention of asthma in offspring

Conceptual modelling for simulation Part I: definition and requirements

Conceptual modelling is probably the most important aspect of a simulation study. It is also the most difficult and least understood. Over 40 years of simulation research and practice have provided only limited information on how to go about designing a simulation conceptual model. This paper, the first of two, discusses the meaning of conceptual modelling and the requirements of a conceptual model. Founded on existing literature, a definition of a conceptual model is provided. Four requirements of a conceptual model are described: validity, credibility, utility and feasibility. The need to develop the simplest model possible is also discussed. Owing to a paucity of advice on how to design a conceptual model, the need for a conceptual modelling framework is proposed. Built on the foundations laid in this paper, a conceptual modelling framework is described in the paper that follows