Epigenetic mechanisms mediating vulnerability and resilience to psychiatric disorders

The impact that stressful encounters have upon long-lasting behavioural phenotypes is varied. Whereas a significant proportion of the population will develop "stress-related" conditions such as post-traumatic stress disorder or depression in later life, the majority are considered "resilient" and are able to cope with stress and avoid such psychopathologies. The reason for this heterogeneity is undoubtedly multi-factorial, involving a complex interplay between genetic and environmental factors. Both genes and environment are of critical importance when it comes to developmental processes, and it appears that subtle differences in either of these may be responsible for altering developmental trajectories that confer vulnerability or resilience. At the molecular level, developmental processes are regulated by epigenetic mechanisms, with recent clinical and pre-clinical data obtained by ourselves and others suggesting that epigenetic differences in various regions of the brain are associated with a range of psychiatric disorders, including many that are stress-related. Here we provide an overview of how these epigenetic differences, and hence susceptibility to psychiatric disorders, might arise through exposure to stress-related factors during critical periods of development.

Nanomorphology influence on the light conversion mechanisms in highly efficient diketopyrrolopyrrole based organic solar cells

In this work, diketopyrrolopyrrole-based polymer bulk heterojunction solar cells with inverted and regular architecture have been investigated. The influence of the polymer:fullerene ratio on the photoactive film nanomorphology has been studied in detail. Transmission Electron Microscopy and Atomic Force Microscopy reveal that the resulting film morphology strongly depends on the fullerene ratio. This fact determines the photocurrent generation and governs the transport of free charge carriers. Slight variations on the PCBM ratio respect to the polymer show great differences on the electrical behavior of the solar cell. Once the polymer:fullerene ratio is accurately adjusted, power conversion efficiencies of 4.7% and 4.9% are obtained for inverted and regular architectures respectively. Furthermore, by correlating the optical and morphological characterization of the polymer:fullerene films and the electrical behavior of solar cells, an ad hoc interpretation is proposed to explain the photovoltaic performance as a function of this polymer:blend composition.

Integrated analysis of epigenomic and genomic changes by DNA methylation dependent mechanisms provides potential novel biomarkers for prostate cancer

Epigenetic silencing mediated by CpG methylation is a common feature of many cancers. Characterizing aberrant DNA methylation changes associated with tumor progression may identify potential prognostic markers for prostate cancer (PCa). We treated two PCa cell lines, 22Rv1 and DU-145 with the demethylating agent 5-Aza 2’–deoxycitidine (DAC) and global methylation status was analyzed by performing methylation-sensitive restriction enzyme based differential methylation hybridization strategy followed by genome-wide CpG methylation array profiling. In addition, we examined gene expression changes using a custom microarray. Gene Set Enrichment Analysis (GSEA) identified the most significantly dysregulated pathways. In addition, we assessed methylation status of candidate genes that showed reduced CpG methylation and increased gene expression after DAC treatment, in Gleason score (GS) 8 vs. GS6 patients using three independent cohorts of patients; the publically available The Cancer Genome Atlas (TCGA) dataset, and two separate patient cohorts. Our analysis, by integrating methylation and gene expression in PCa cell lines, combined with patient tumor data, identified novel potential biomarkers for PCa patients. These markers may help elucidate the pathogenesis of PCa and represent potential prognostic markers for PCa patients.

The dynamics of expertise acquisition in sport : the role of affective learning design

Objectives The aim of this position paper is to discuss the role of affect in designing learning experiences to enhance expertise acquisition in sport. The design of learning environments and athlete development programmes are predicated on the successful sampling and simulation of competitive performance conditions during practice. This premise is captured by the concept of representative learning design, founded on an ecological dynamics approach to developing skill in sport, and based on the individual-environment relationship. In this paper we discuss how the effective development of expertise in sport could be enhanced by the consideration of affective constraints in the representative design of learning experiences. Conclusions Based on previous theoretical modelling and practical examples we delineate two key principles of Affective Learning Design: (i) the design of emotion-laden learning experiences that effectively simulate the constraints of performance environments in sport; (ii) recognising individualised emotional and coordination tendencies that are associated with different periods of learning. Considering the role of affect in learning environments has clear implications for how sport psychologists, athletes and coaches might collaborate to enhance the acquisition of expertise in sport.

Facial motion engages predictive visual mechanisms

We employed a novel cuing paradigm to assess whether dynamically versus statically presented facial expressions differentially engaged predictive visual mechanisms. Participants were presented with a cueing stimulus that was either the static depiction of a low intensity expressed emotion; or a dynamic sequence evolving from a neutral expression to the low intensity expressed emotion. Following this cue and a backwards mask, participants were presented with a probe face that displayed either the same emotion (congruent) or a different emotion (incongruent) with respect to that displayed by the cue although expressed at a high intensity. The probe face had either the same or different identity from the cued face. The participants' task was to indicate whether or not the probe face showed the same emotion as the cue. Dynamic cues and same identity cues both led to a greater tendency towards congruent responding, although these factors did not interact. Facial motion also led to faster responding when the probe face was emotionally congruent to the cue. We interpret these results as indicating that dynamic facial displays preferentially invoke predictive visual mechanisms, and suggest that motoric simulation may provide an important basis for the generation of predictions in the visual system.

Facial emotion modulates the neural mechanisms responsible for short interval time perception

Emotionally arousing events can distort our sense of time. We used mixed block/event-related fMRI design to establish the neural basis for this effect. Nineteen participants were asked to judge whether angry, happy and neutral facial expressions that varied in duration (from 400 to 1,600 ms) were closer in duration to either a short or long duration they learnt previously. Time was overestimated for both angry and happy expressions compared to neutral expressions. For faces presented for 700 ms, facial emotion modulated activity in regions of the timing network Wiener et al. (NeuroImage 49(2):1728–1740, 2010) namely the right supplementary motor area (SMA) and the junction of the right inferior frontal gyrus and anterior insula (IFG/AI). Reaction times were slowest when faces were displayed for 700 ms indicating increased decision making difficulty. Taken together with existing electrophysiological evidence Ng et al. (Neuroscience, doi: 10.3389/fnint.2011.00077, 2011), the effects are consistent with the idea that facial emotion moderates temporal decision making and that the right SMA and right IFG/AI are key neural structures responsible for this effect.

Insights into a multidrug resistant Escherichia coli pathogen of the globally disseminated ST131 lineage : genome analysis and virulence mechanisms

Escherichia coli strains causing urinary tract infection (UTI) are increasingly recognized as belonging to specific clones. E. coli clone O25b:H4-ST131 has recently emerged globally as a leading multi-drug resistant pathogen causing urinary tract and bloodstream infections in hospitals and the community. While most molecular studies to date examine the mechanisms conferring multi-drug resistance in E. coli ST131, relatively little is known about their virulence potential. Here we examined E. coli ST131 clinical isolates from two geographically diverse collections, one representing the major pathogenic lineages causing UTI across the United Kingdom and a second representing UTI isolates from patients presenting at two large hospitals in Australia. We determined a draft genome sequence for one representative isolate, E. coli EC958, which produced CTX-M-15 extended-spectrum β-lactamase, CMY-23 type AmpC cephalosporinase and was resistant to ciprofloxacin. Comparative genome analysis indicated that EC958 encodes virulence genes commonly associated with uropathogenic E. coli (UPEC). The genome sequence of EC958 revealed a transposon insertion in the fimB gene encoding the activator of type 1 fimbriae, an important UPEC bladder colonization factor. We identified the same fimB transposon insertion in 59% of the ST131 UK isolates, as well as 71% of ST131 isolates from Australia, suggesting this mutation is common among E. coli ST131 strains. Insertional inactivation of fimB resulted in a phenotype resembling a slower off-to-on switching for type 1 fimbriae. Type 1 fimbriae expression could still be induced in fimB-null isolates; this correlated strongly with adherence to and invasion of human bladder cells and bladder colonisation in a mouse UTI model. We conclude that E. coli ST131 is a geographically widespread, antibiotic resistant clone that has the capacity to produce numerous virulence factors associated with UTI.

Conjugation of carcinogens by 6 class glutathione S-transferases : mechanisms and relevance to variations in human risk

Conjugation of chemicals with glutathione (GSH) can lead to decreased or increased toxicity. A genetic deficiency in the GSH S-transferase μ class gene M1 has been hypothesized to lead to greater risk of lung cancer in smokers. Recently a gene deletion polymorphism involving the human θ enzyme T1 has been described; the enzyme is present in erythrocytes and can be readily assayed. A rat θ class enzyme, 5-5, has structural and catalytic similarity and the protein was expressed in the Salmonella typhimurium tester strain TA1535. Expression of the cDNA vector increased the mutagenicity of ethylene dibromide and several methylene dihalides. Mutations resulting from the known GSH S-transferase substrate 1,2-epoxy-3-(4′nitrophenoxy)propane were decreased in the presence of the transferase. Expression of transferase 5-5 increased mutations when 1,2,3,4-diepoxybutane (butadiene diepoxide), 4-bromo-1,2-epoxybutane, or 1,3-dichloracetone were added. The latter compound is a model for the putative 1,2-dibromo-3-chloropropane oxidation product 1-bromo-3-chloroacetone. These genotoxicity and genotyping assays may be of use in further studies of the roles of GSH S-transferase θ enzymes in bioactivation and detoxication and any changes in risk due to polymorphism.

Coordination and plasticity in leaf anatomical traits of invasive and native vine species

Premise of the study: Plant invasiveness can be promoted by higher values of adaptive traits (e.g., photosynthetic capacity, biomass accumulation), greater plasticity and coordination of these traits, and by higher and positive relative influence of these functionalities on fitness, such as increasing reproductive output. However, the dataset for this premise rarely include linkages between epidermal-stomatal traits, leaf internal anatomy, and physiological performance. Methods: Three ecological pairs of invasive vs non-invasive (native) woody vine species of South-East Queensland, Australia were investigated for trait differences in leaf morphology and anatomy under varying light intensity. The linkages of these traits with physiological performance (e.g. water use efficiency, photosynthesis, and leaf construction cost) and plant adaptive traits of specific leaf area, biomass, and relative growth rates were also explored. Key results: Mean leaf anatomical trait differed significantly between the two groups, except for stomatal size. Plasticity of traits, and to a very limited extent, their phenotypic integration were higher in the invasive relative to the native species. ANOVA, ordination, and analysis of similarity suggest that for leaf morphology and anatomy, the three functional strategies contribute to the differences between the two groups in the order phenotypic plasticity > trait means > phenotypic integration. Conclusions: The linkages demonstrated in the study between stomatal complex/gross anatomy and physiology are scarce in the ecological literature of plant invasiveness, but the findings suggest that leaf anatomical traits need to be considered routinely as part of weed species assessment and in the worldwide leaf economic spectrum.

Fred’s Flow (Canada) and Murphy Well (Australia) : thick komatiitic lava flows with contrasting compositions, emplacement mechanisms and water contents

Two Archaean komatiitic flows, Fred’s Flow in Canada and the Murphy Well Flow in Australia, have similar thicknesses (120 and 160 m) but very different compositions and internal structures. Their contrasting differentiation profiles are keys to determine the cooling and crystallization mechanisms that operated during the eruption of Archaean ultramafic lavas. Fred’s Flow is the type example of a thick komatiitic basalt flow. It is strongly differentiated and consists of a succession of layers with contrasting textures and compositions. The layering is readily explained by the accumulation of olivine and pyroxene in a lower cumulate layer and by evolution of the liquid composition during downward growth of spinifex-textured rocks within the upper crust. The magmas that erupted to form Fred’s Flow had variable compositions, ranging from 12 to 20 wt% MgO, and phenocryst contents from 0 to 20 vol%. The flow was emplaced by two pulses. A first ~20-m-thick pulse was followed by another more voluminous but less magnesian pulse that inflated the flow to its present 120 m thickness. Following the second pulse, the flow crystallized in a closed system and differentiated into cumulates containing 30–38 wt% MgO and a residual gabbroic layer with only 6 wt% MgO. The Murphy Well Flow, in contrast, has a remarkably uniform composition throughout. It comprises a 20-m-thick upper layer of fine-grained dendritic olivine and 2–5 vol% amygdales, a 110–120 m intermediate layer of olivine porphyry and a 20–30 m basal layer of olivine orthocumulate. Throughout the flow, MgO contents vary little, from only 30 to 33 wt%, except for the slightly more magnesian basal layer (38–40 wt%). The uniform composition of the flow and dendritic olivine habits in the upper 20 m point to rapid cooling of a highly magnesian liquid with a composition like that of the bulk of the flow. Under equilibrium conditions, this liquid should have crystallized olivine with the composition Fo94.9, but the most magnesian composition measured by electron microprobe in samples from the flow is Fo92.9. To explain these features, we propose that the parental liquid contained around 32 wt% MgO and 3 wt% H2O. This liquid degassed during the eruption, creating a supercooled liquid that solidified quickly and crystallized olivine with non-equilibrium textures and compositions.

Critical factors for waste management in office building retrofit projects in Australia

Office building retrofit is a sector being highlighted in Australia because of the mature office building market characterised by a large proportion of ageing properties. The increasing number of office building retrofit projects strengthens the need for waste management. Retrofit projects possess unique characteristics in comparison to traditional demolition and new builds such as partial operation of buildings, constrained site spaces and limited access to as-build information. Waste management activities in retrofit projects can be influenced by issues that are different from traditional construction and demolition projects. However, previous research on building retrofit projects has not provided an understanding of the critical issues affecting waste management. This research identifies the critical factors which influence the management of waste in office building retrofit projects through a literature study and a questionnaire survey to industry practitioners. Statistical analysis on a range of potential waste issues reveals the critical factors, as agreed upon by survey respondents in consideration of their different professional responsibilities and work natures. The factors are grouped into five dimensions, comprising industry culture, organisational support and incentive, existing building information, design, and project delivery process. The discussions of the dimensions indicate that the waste management factors of office building retrofit projects are further intensified compared to those for general demolition and construction because retrofit projects involve existing buildings which are partially operating with constrained work space and limited building information. Recommendations for improving waste management in office building retrofit projects are generalised such as waste planning, auditing and assessment in the planning and designing stage, collaboration and coordination of various stakeholders and different specialists, optimised building surveying and BIM technologies for waste analysis, and new design strategies for waste prevention.

Numerical investigation of deformation and failure mechanisms of osteopontin-hydroxyapatite interfaces and mineralized collagen fibril arrays

This thesis is a comprehensive study of deformation and failure mechanisms in bone at nano- and micro-scale levels. It explores the mechanical behaviour of osteopontin-hydroxyapatite interfaces and mineralized collagen fibril arrays, through atomistic molecular dynamics and finite element simulations. This thesis shows some main factors contributing to the excellent material properties of bone and provides some guidelines for development of new artificial biological materials and medical implants.