Modeling gene-environment interaction in longitudinal data : risk for neuroticism due to interaction between maternal care and the Dopamine 4 Receptor gene (DRD4)

The purpose of this study was to investigate risk for neuroticism due to the joint action of low maternal care and compromised mesocorticolimbic ‘reward’ system function linked to a variable number tandem repeat (VNTR) in the dopamine 4 receptor gene (DRD4). Data were drawn from the Victorian Adolescent Health Cohort Study, a longitudinal study of the health and well-being of 2,000 young Australians followed from adolescence to young adulthood across 8 waves from 14- to 28-years. Genetic risk was defined by carriage of at least one copy of the 7-repeat allele or derivative alleles 5, 6, and 8 (labeled 7R+). Neuroticism was assessed in adolescence and young adulthood. We observed an approximately fourfold increase in the odds of reporting neurotic symptoms in carriers of the 7R+ disposition who reported low maternal care compared with non-carriers who reported high maternal care. The percentage of risk attributable to mechanisms in which both factors played a role was 35%. Findings are discussed in terms of implications for prevention.

Gene-environment interaction in problematic substance use : interaction between DRD4 and insecure attachments

To investigate the combined effect of an exon III variable number tandem repeat in the dopamine receptor gene (DRD4) and insecure attachment style on risk for tobacco, cannabis and alcohol use problems in young adulthood. It was hypothesized that (1) individuals with 5, 6, 7 or 8 repeats (labelled 7R+) would be at increased risk for problematic drug use, and (2) risk for drug use would be further increased in individuals with 7R+ repeats who also have a history of insecure parent–child attachment relations. Data were drawn from the Victorian Adolescent Health Cohort Study, an eight-wave longitudinal study of adolescent and young adult development. DRD4 genotypes were available for 839 participants. Risk attributable to the combined effects of 7R+ genotype and insecure attachments was evaluated within a sufficient causes framework under the assumptions of additive interaction using a two-by-four table format with a common reference group. 7R+ alleles were associated with higher tobacco, cannabis and alcohol use (binging). Insecure attachments were associated with higher tobacco and cannabis use but lower alcohol use. For tobacco, there was evidence of interaction for anxious but not avoidant attachments. For cannabis, there was evidence of interaction for both anxious and avoidant attachments, although the interaction for anxious attachments was more substantial. There is no evidence of interaction for binge drinking. Results are consistent with a generic reward deficit hypothesis of drug addiction for which the 7R+ disposition may play a role. Interaction between 7R+ alleles and attachment insecurity may intensify risk for problematic tobacco and cannabis use.

Linking the serotonin transporter gene, family environments, hippocampal volume and depression onset: a prospective imaging gene × environment analysis

A single imaging gene-environment (IGxE) framework that is able to simultaneously model genetic, neurobiological, and environmental influences on psychopathology outcomes is needed to improve understanding of how complex interrelationships between allelic variation, differences in neuroanatomy or neuroactivity, and environmental experience affect risk for psychiatric disorder. In a longitudinal study of adolescent development we demonstrate the utility of such an IGxE framework by testing whether variation in parental behavior at age 12 altered the strength of an imaging genetics pathway, involving an indirect association between allelic variation in the serotonin transporter gene to variation in hippocampal volume and consequent onset of major depressive disorder by age 18. Results were consistent with the presence of an indirect effect of the serotonin transporter S-allele on depression onset via smaller left and right hippocampal volumes that was significant only in family environments involving either higher levels of parental aggression or lower levels of positive parenting. The previously reported finding of S-allele carriers' increased risk of depression in adverse environments may, therefore, be partly because of the effects of these environments on a neurobiological pathway from the serotonin transporter gene to depression onset that proceeds through variation in hippocampal volume. 

Fat mass- and obesity-associated genotype, dietary intakes and anthropometric measures in European adults: the Food4Me study

The interplay between the fat mass- and obesity-associated (FTO) gene variants and diet has been implicated in the development of obesity. The aim of the present analysis was to investigate associations between FTO genotype, dietary intakes and anthropometrics among European adults. Participants in the Food4Me randomised controlled trial were genotyped for FTO genotype (rs9939609) and their dietary intakes, and diet quality scores (Healthy Eating Index and PREDIMED-based Mediterranean diet score) were estimated from FFQ. Relationships between FTO genotype, diet and anthropometrics (weight, waist circumference (WC) and BMI) were evaluated at baseline. European adults with the FTO risk genotype had greater WC (AA v. TT: +1·4 cm; P=0·003) and BMI (+0·9 kg/m2; P=0·001) than individuals with no risk alleles. Subjects with the lowest fried food consumption and two copies of the FTO risk variant had on average 1·4 kg/m2 greater BMI (Ptrend=0·028) and 3·1 cm greater WC (Ptrend=0·045) compared with individuals with no copies of the risk allele and with the lowest fried food consumption. However, there was no evidence of interactions between FTO genotype and dietary intakes on BMI and WC, and thus further research is required to confirm or refute these findings.

New approaches to gene discovery with animal models of obesity and diabetes

DNA-based approaches to the discovery of genes contributing to the development of type 2 diabetes have not been very successful despite substantial investments of time and money. The multiple gene-gene and gene-environment interactions that influence the development of type 2 diabetes mean that DNA approaches are not the ideal tool for defining the etiology of this complex disease. Gene expression-based technologies may prove to be a more rewarding strategy to identify diabetes candidate genes. There are a number of RNA-based technologies available to identify genes that are differentially expressed in various tissues in type 2 diabetes. These include differential display polymerase chain reaction (ddPCR), suppression subtractive hybridization (SSH), and cDNA microarrays. The power of new technologies to detect differential gene expression is ideally suited to studies utilizing appropriate animal models of human disease. We have shown that the gene expression approach, in combination with an excellent animal model such as the Israeli sand rat (Psammomys obesus), can provide novel genes and pathways that may be important in the disease process and provide novel therapeutic approaches. This paper will describe a new gene discovery, beacon, a novel gene linked with energy intake. As the functional characterization of novel genes discovered in our laboratory using this approach continues, it is anticipated that we will soon be able to compile a definitive list of genes that are important in the development of obesity and type 2 diabetes.

MUSTe method for quantifying virtual environment training system efficacy

In the current era increased attention and interest of utilizing advanced computer technologies for training and education at all managerial levels and functional areas is apparent. One of such technologies, virtual environment (VE), is perceived to be effective in enhancing human abilities to learn abstract concept and complex procedural tasks. Despite its adaptation for training and fast-paced technological advancements, ways in which to evaluate efficacy of such technology are unclear. We have approached this problem by developed a new evaluation method focus on cognitive, affective and skillbased learning dimensions, based on traditional usability evaluation methods but tailored to specifically suit for the quantification of 3D VE system. We first describe the construct of the new method and then report a study utilizing the method in the context of quantifying a VE efficacy in an object assembly task. At last, we discuss the implications of such a method.

Interpreting Fanger's comfort equation within the adaptive paradigm

This paper reviews the evolution of Fanger's heat balance equation in regard of adaptive opportunities. Heat balance and adaptive response are integrated into one model as two fundamental aspects of human-environment interaction that define thermal comfort perception, rather than being seen as two concepts of alternative comfort paradigms. The paper suggests to extent Fanger's model with a heat storage term in order to account for comfort perception under transient thermal conditions, and to review Fanger's modelling assumptions in order to allow for a greater variety of adaptive response options. In the presented model heat exchange is modulated through adaptation of physiological, environmental and behavioural parameters in the human-environment system defined through Fanger's heat exchange equations. A computational prototype is implemented to determine 'comfortable' values and ranges of the six comfort dimensions alternatively to Fanger's comfort indices. Thereby values of for example 'comfortable' clothing and metabolic rate are results rather than necessary input parameters, which are difficult to determine. This approach allows generating design advice for physical, organisational and social environments based on heat balance calculation in the six-dimensional opportunity space defined through Fanger's comfort equation. A starting point for the development of a dynamic adaptive comfort model is set.

The "strugglers" in selected computer based mathematics classrooms

In this paper, the experiences of lower achieving mathematics students in two secondary mathematics classrooms in which computers were regularly used are described. A year 8 and a year 9 mathematics class from one secondary school participated in the ethnographic study. The results show that in these two classrooms the learning relationships and power relationships did not, in general, support the learning and engagement of lower achievers in mathematics. Research into computer based teaching methods that engage low achieving students in computer based mathematics is needed.

Fuzzy simulation of pedestrian walking path considering local environmental stimuli

Pedestrian steering activity is a perception-based decision making process that involves interaction with the surrounding environment and insight into environmental stimuli. There are many stimuli within the environment that influence pedestrian wayfinding behaviour during walking activities. However, compelling factors such as individual physical and psychological characteristics and trip intention cause the behaviour become a very fuzzy concept. In this paper pedestrian steering behaviour is modelled using a fuzzy logic approach. The objective of this research is to simulate pedestrian walking paths in indoor public environments during normal and non-panic situations. The proposed algorithm introduces a fuzzy logic framework to predict the impact of perceived attractive and repulsive stimuli, within the pedestrian's field of view, on movement direction. Environmental stimuli are quantified using the social force method. The algorithm is implemented in a simulated area of an office corridor consist of a printer and exit door. Stochastic simulation using the proposed fuzzy algorithm generated realistic walking trajectories, contour map of dynamic change of environmental effects in each step of movement and high flow areas in the corridor.

The impact of self-efficacy and perceived system efficacy on effectiveness of virtual training systems

This study developed and tested a research model which examined the impact of user perceptions of self-efficacy (SE) and virtual environment (VE) efficacy on the effectiveness of VE training systems. The model distinguishes between the perceptions of one’s own capability to perform trained tasks effectively and the perceptions of system performance, regarding the established parameters from literature. Specifically, the model posits that user perceptions will have positive effects on task performance and memory. Seventy-six adults participated in a VE in a controlled experiment, designed to empirically test the model. Each participant performed a series of object assembly tasks. The task involved selecting, rotating, releasing, inserting and manipulating 3D objects. Initially, the results of factor analysis demonstrated dimensionality of two user perception measures and produced a set of empirical validated factors underlining the VE efficacy. The results of regression analysis revealed that SE had a significant positive effect on perceived VE efficacy. No significant effects were found of perceptions on performance and memory. Furthermore, the study provided insights into the relationships between the perception measures and performance measures for assessing the efficacy of VE training systems. The study also addressed how well users learn, perform, adapt to and perceive the VE training, which provides valuable insight into the system efficacy.
Research and practical implications are presented at the end of the paper.

Interaction of exercise and diet on GLUT-4 protein and gene expression in type I and type II rat skeletal muscle

We determined the interaction of exercise and diet on glucose transporter (GLUT-4) protein and mRNA expression in type I (soleus) and type II [extensor digitorum longus (EDL)] skeletal muscle. Forty-eight Sprague Dawley rats were randomly assigned to one of two dietary conditions: high-fat (FAT, n =24) or high-carbohydrate (CHO, n =24). Animals in each dietary condition were allocated to one of two groups: control (NT, n =8) or a group that performed 8 weeks of treadmill running (4 sessions week^–1 of 1000 m @ 28 m min^–1 , RUN, n =16). Eight trained rats were killed after their final exercise bout for determination of GLUT-4 protein and mRNA expression: the remainder were killed 48 h after their last session for measurement of muscle glycogen and triacylglycerol concentration. GLUT-4 protein expression in NT rats was similar in both muscles after 8 weeks of either diet. However, there was a main effect of training such that GLUT-4 protein was increased in the soleus of rats fed with either diet (P < 0.05) and in the EDL in animals fed with CHO (P < 0.05). There was a significant diet–training interaction on GLUT-4 mRNA, such that expression was increased in both the soleus (100% ↑P < 0.05) and EDL (142% ↑P < 0.01) in CHO-fed animals. Trained rats fed with FAT decreased mRNA expression in the EDL (↓ 45%, P < 0.05) but not the soleus (↓ 14%, NS). We conclude that exercise training in CHO-fed rats increased both GLUT-4 protein and mRNA expression in type I and type II skeletal muscle. Despite lower GLUT-4 mRNA in muscles from fat-fed animals, exercise-induced increases in GLUT-4 protein were largely preserved, suggesting that control of GLUT-4 protein and gene expression are modified independently by exercise and diet.