The use of an acetoacetyl-CoA synthase in place of a -ketothiolase enhances poly-3-hydroxybutyrate production in sugarcane mesophyll cells

Engineering the production of polyhydroxyalkanoates (PHAs) into high biomass bioenergy crops has the potential to provide a sustainable supply of bioplastics and energy from a single plant feedstock. One of the major challenges in engineering C-4 plants for the production of poly[(R)-3-hydroxybutyrate] (PHB) is the significantly lower level of polymer produced in the chloroplasts of mesophyll (M) cells compared to bundle sheath (BS) cells, thereby limiting the full PHB yield-potential of the plant. In this study, we provide evidence that the access to substrate for PHB synthesis may limit polymer production in M chloroplasts. Production of PHB in M cells of sugarcane is significantly increased by replacing -ketothiolase, the first enzyme in the bacterial PHA pathway, with acetoacetyl-CoA synthase. This novel pathway enabled the production of PHB reaching an average of 6.3% of the dry weight of total leaf biomass, with levels ranging from 3.6 to 11.8% of the dry weight (DW) of individual leaves. These yields are more than twice the level reported in PHB-producing sugarcane containing the -ketothiolase and illustrate the importance of producing polymer in mesophyll plastids to maximize yield. The molecular weight of the polymer produced was greater than 2x10(6)Da. These results are a major step forward in engineering a high biomass C-4 grass for the commercial production of PHB.

A reanalysis of 409 European-Ancestry and African American schizophrenia pedigrees reveals significant linkage to 8p23.3 with evidence of locus heterogeneity

The detection and replication of schizophrenia risk loci can require substantial sample sizes, which has prompted various collaborative efforts for combining multiple samples. However, pooled samples may comprise sub-samples with substantial population genetic differences, including allele frequency differences. We investigated the impact of population differences via linkage reanalysis of Molecular Genetics of Schizophrenia 1 (MGS1) affected sibling-pair data, comprising two samples of distinct ancestral origin: European (EA: 263 pedigrees) and African-American (AA: 146 pedigrees). To exploit the linkage information contained within these distinct continental samples, we performed separate analyses of the individual samples, allowing for within-sample locus heterogeneity, and the pooled sample, allowing for both within-sample and between-sample heterogeneity. Significance levels, corrected for the multiple tests, were determined empirically. For all suggestive peaks, stronger linkage evidence was obtained in either the EA or AA sample than the combined sample, regardless of how heterogeneity was modeled for the latter. Notably, we report genomewide significant linkage of schizophrenia to 8p23.3 and evidence for a second, independent susceptibility locus, reaching suggestive linkage, 29 cM away on 8p21.3. We also detected suggestive linkage on chromosomes 5p13.3 and 7q36.2. Many regions showed pronounced differences in the extent of linkage between the EA and AA samples. This reanalysis highlights the potential impact of population differences upon linkage evidence in pooled data and demonstrates a useful approach for the analysis of samples drawn from distinct continental groups.

No evidence for association of ataxia-telangiectasia mutated gene T2119C and C3161G amino acid substitution variants with risk of breast cancer

Background There is evidence that certain mutations in the double-strand break repair pathway ataxia-telangiectasia mutated gene act in a dominant-negative manner to increase the risk of breast cancer. There are also some reports to suggest that the amino acid substitution variants T2119C Ser707Pro and C3161G Pro1054Arg may be associated with breast cancer risk. We investigate the breast cancer risk associated with these two nonconservative amino acid substitution variants using a large Australian population-based case–control study. Methods The polymorphisms were genotyped in more than 1300 cases and 600 controls using 5' exonuclease assays. Case–control analyses and genotype distributions were compared by logistic regression. Results The 2119C variant was rare, occurring at frequencies of 1.4 and 1.3% in cases and controls, respectively (P = 0.8). There was no difference in genotype distribution between cases and controls (P = 0.8), and the TC genotype was not associated with increased risk of breast cancer (adjusted odds ratio = 1.08, 95% confidence interval = 0.59–1.97, P = 0.8). Similarly, the 3161G variant was no more common in cases than in controls (2.9% versus 2.2%, P = 0.2), there was no difference in genotype distribution between cases and controls (P = 0.1), and the CG genotype was not associated with an increased risk of breast cancer (adjusted odds ratio = 1.30, 95% confidence interval = 0.85–1.98, P = 0.2). This lack of evidence for an association persisted within groups defined by the family history of breast cancer or by age. Conclusion The 2119C and 3161G amino acid substitution variants are not associated with moderate or high risks of breast cancer in Australian women.

Reducing the global burden of depression : population level analysis of intervention cost-effectiveness in 14 world regions

International evidence on the cost and effects of interventions for reducing the global burden of depression remain scarce. Aims: To estimate the population-level cost-effectiveness of evidence-based depression interventions and their contribution towards reducing current burden. Method: Primary-care-based depression interventions were modelled at the level of whole populations in 14 epidemiological subregions of the world. Total population-level costs (in international dollars or I$) and effectiveness (disability adjusted life years (DALYs) averted) were combined to form average and incremental cost-effectiveness ratios. Results: Evaluated interventions have the potential to reduce the current burden of depression by 10–30%. Pharmacotherapy with older antidepressant drugs, with or without proactive collaborative care, are currently more cost-effective strategies than those using newer antidepressants, particularly in lower-income subregions. Conclusions: Even in resource-poor regions, each DALYaverted by efficient depression treatments in primary care costs less than 1 year of average per capita income, making such interventions a cost-effective use of health resources. However, current levels of burden can only be reduced significantlyif there is a substantialincrease substantial increase intreatment coverage.

Regioregular poly(3-hexyl-thiophene) helical self-organization on carbon nanotubes

Mixtures of Regioregular Poly(3-hexyl-thiophene) (rrP3HT) and multi wall carbon nanotubes have been investigated by Scanning Tunneling Microscopy in Ultra High Vacuum. Carbon nanotubes covered by rrP3HT have been imaged and analyzed, providing a clear evidence that this polymer self assembles on the nanotube surface following geometrical constraints and adapting its equilibrium chain-to-chain distance. Largely spaced covered nanotubes have been analyzed to investigate the role played by nanotube chirality in the polymer wrapping, evidencing strong rrP3HT interactions along well defined directions.

Ex vivo investigation of novel wound healing therapies and development of a 3-D human skin equivalent wound model

It has previously been found that complexes comprised of vitronectin and growth factors (VN:GF) enhance keratinocyte protein synthesis and migration. More specifically, these complexes have been shown to significantly enhance the migration of dermal keratinocytes derived from human skin. In view of this, it was thought that these complexes may hold potential as a novel therapy for healing chronic wounds. However, there was no evidence indicating that the VN:GF complexes would retain their effect on keratinocytes in the presence of chronic wound fluid. The studies in this thesis demonstrate for the first time that the VN:GF complexes not only stimulate proliferation and migration of keratinocytes, but also these effects are maintained in the presence of chronic wound fluid in a 2-dimensional (2-D) cell culture model. Whilst the 2-D culture system provided insights into how the cells might respond to the VN:GF complexes, this investigative approach is not ideal as skin is a 3-dimensional (3-D) tissue. In view of this, a 3-D human skin equivalent (HSE) model, which reflects more closely the in vivo environment, was used to test the VN:GF complexes on epidermopoiesis. These studies revealed that the VN:GF complexes enable keratinocytes to migrate, proliferate and differentiate on a de-epidermalised dermis (DED), ultimately forming a fully stratified epidermis. In addition, fibroblasts were seeded on DED and shown to migrate into the DED in the presence of the VN:GF complexes and hyaluronic acid, another important biological factor in the wound healing cascade. This HSE model was then further developed to enable studies examining the potential of the VN:GF complexes in epidermal wound healing. Specifically, a reproducible partial-thickness HSE wound model was created in fully-defined media and monitored as it healed. In this situation, the VN:GF complexes were shown to significantly enhance keratinocyte migration and proliferation, as well as differentiation. This model was also subsequently utilized to assess the wound healing potential of a synthetic fibrin-like gel that had previously been demonstrated to bind growth factors. Of note, keratinocyte re-epitheliasation was shown to be markedly improved in the presence of this 3-D matrix, highlighting its future potential for use as a delivery vehicle for the VN:GF complexes. Furthermore, this synthetic fibrin-like gel was injected into a 4 mm diameter full-thickness wound created in the HSE, both keratinocytes and fibroblasts were shown to migrate into this gel, as revealed by immunofluorescence. Interestingly, keratinocyte migration into this matrix was found to be dependent upon the presence of the fibroblasts. Taken together, these data indicate that reproducible wounds, as created in the HSEs, provide a relevant ex vivo tool to assess potential wound healing therapies. Moreover, the models will decrease our reliance on animals for scientific experimentation. Additionally, it is clear that these models will significantly assist in the development of novel treatments, such as the VN:GF complexes and the synthetic fibrin-like gel described herein, ultimately facilitating their clinical trial in the treatment of chronic wounds.

The influence of ad model ethnicity and self-referencing on attitudes evidence from New Zealand

This paper examines consumers self-referencing as a mechanism for explaining ethnicity effects in advertising. Data was collected from a 2 (model ethnicity: Asian, white) x 2 (product stereotypicality: stereotypical, non-stereotypical) experiment. Measured independent variables included participant ethnicity and self-referencing. Results shows that (1) Asian exhibit greater self-referencing of Asian models than whites do; (2) self-referencing mediates ethnicity effects on attitude ( ie, attitude towards the model, attitude toward the add, brand attitude, and purchase intentions); (3) high self-referencing Asian have more favourable attitude towards the add and purchase intentions than low self referencing Asians; and (4) Asian models advertising atypical products generate more self-referencing and more favourable attitudes toward the model, A, and purchase intentions for both Asians and whites.

FIA : an open foresic integration architecture for composing digital evidence

The analysis and value of digital evidence in an investigation has been the domain of discourse in the digital forensic community for several years. While many works have considered different approaches to model digital evidence, a comprehensive understanding of the process of merging different evidence items recovered during a forensic analysis is still a distant dream. With the advent of modern technologies, pro-active measures are integral to keeping abreast of all forms of cyber crimes and attacks. This paper motivates the need to formalize the process of analyzing digital evidence from multiple sources simultaneously. In this paper, we present the forensic integration architecture (FIA) which provides a framework for abstracting the evidence source and storage format information from digital evidence and explores the concept of integrating evidence information from multiple sources. The FIA architecture identifies evidence information from multiple sources that enables an investigator to build theories to reconstruct the past. FIA is hierarchically composed of multiple layers and adopts a technology independent approach. FIA is also open and extensible making it simple to adapt to technological changes. We present a case study using a hypothetical car theft case to demonstrate the concepts and illustrate the value it brings into the field.

Biological performance of a polycaprolactone-based scaffold used as fusion cage device in a large animal model of spinal reconstructive surgery

A bioactive and bioresorbable scaffold fabricated from medical grade poly (epsilon-caprolactone) and incorporating 20% beta-tricalcium phosphate (mPCL–TCP) was recently developed for bone regeneration at load bearing sites. In the present study, we aimed to evaluate bone ingrowth into mPCL–TCP in a large animal model of lumbar interbody fusion. Six pigs underwent a 2-level (L3/4; L5/6) anterior lumbar interbody fusion (ALIF) implanted with mPCL–TCP þ 0.6 mg rhBMP-2 as treatment group while four other pigs implanted with autogenous bone graft served as control. Computed tomographic scanning and histology revealed complete defect bridging in all (100%) specimen from the treatment group as early as 3 months. Histological evidence of continuing bone remodeling and maturation was observed at 6 months. In the control group, only partial bridging was observed at 3 months and only 50% of segments in this group showed complete defect bridging at 6 months. Furthermore, 25% of segments in the control group showed evidence of graft fracture, resorption and pseudoarthrosis. In contrast, no evidence of graft fractures, pseudoarthrosis or foreign body reaction was observed in the treatment group. These results reveal that mPCL–TCP scaffolds could act as bone graft substitutes by providing a suitable environment for bone regeneration in a dynamic load bearing setting such as in a porcine model of interbody spine fusion.

A University Support Model for eResearch

Queensland University of Technology (QUT) is faced with a rapidly growing research agenda built upon a strategic research capacity-building program. This presentation will outline the results of a project that has recently investigated QUT’s research support requirements and which has developed a model for the support of eResearch across the university. QUT’s research building strategy has produced growth at the faculty level and within its research institutes. This increased research activity is pushing the need for university-wide eResearch platforms capable of providing infrastructure and support in areas such as collaboration, data, networking, authentication and authorisation, workflows and the grid. One of the driving forces behind the investigation is data-centric nature of modern research. It is now critical that researchers have access to supported infrastructure that allows the collection, analysis, aggregation and sharing of large data volumes for exploration and mining in order to gain new insights and to generate new knowledge. However, recent surveys into current research data management practices by the Australian Partnership for Sustainable Repositories (APSR) and by QUT itself, has revealed serious shortcomings in areas such as research data management, especially its long term maintenance for reuse and authoritative evidence of research findings. While these internal university pressures are building, at the same time there are external pressures that are magnifying them. For example, recent compliance guidelines from bodies such as the ARC, and NHMRC and Universities Australia indicate that institutions need to provide facilities for the safe and secure storage of research data along with a surrounding set of policies, on its retention, ownership and accessibility. The newly formed Australian National Data Service (ANDS) is developing strategies and guidelines for research data management and research institutions are a central focus, responsible for managing and storing institutional data on platforms that can be federated nationally and internationally for wider use. For some time QUT has recognised the importance of eResearch and has been active in a number of related areas: ePrints to digitally publish research papers, grid computing portals and workflows, institutional-wide provisioning and authentication systems, and legal protocols for copyright management. QUT also has two widely recognised centres focused on fundamental research into eResearch itself: The OAK LAW project (Open Access to Knowledge) which focuses upon legal issues relating eResearch and the Microsoft QUT eResearch Centre whose goal is to accelerate scientific research discovery, through new smart software. In order to better harness all of these resources and improve research outcomes, the university recently established a project to investigate how it might better organise the support of eResearch. This presentation will outline the project outcomes, which include a flexible and sustainable eResearch support service model addressing short and longer term research needs, identification of resource requirements required to establish and sustain the service, and the development of research data management policies and implementation plans.

Evidence-based practice and information literacy

Evidence-based Practice (EBP) has recently emerged as a topic of discussion amongst professionals within the library and information services (LIS) industry. Simply stated, EBP is the process of using formal research skills and methods to assist in decision making and establishing best practice. The emerging interest in EBP within the library context serves to remind the library profession that research skills and methods can help ensure that the library industry remains current and relevant in changing times. The LIS sector faces ongoing challenges in terms of the expectation that financial and human resources will be managed efficiently, particularly if library budgets are reduced and accountability to the principal stakeholders is increased. Library managers are charged with the responsibility to deliver relevant and cost effective services, in an environment characterised by rapidly changing models of information provision, information access and user behaviours. Consequently they are called upon not only to justify the services they provide, or plan to introduce, but also to measure the effectiveness of these services and to evaluate the impact on the communities they serve. The imperative for innovation in and enhancements to library practice is accompanied by the need for a strong understanding of the processes of review, measurement, assessment and evaluation. In 2001 the Centre for Information Research was commissioned by the Chartered Institute of Library and Information Professionals (CILIP) in the UK to conduct an examination into the research landscape for library and information science. The examination concluded that research is “important for the LIS [library and information science] domain in a number of ways” (McNicol & Nankivell, 2001, p.77). At the professional level, research can inform practice, assist in the future planning of the profession, raise the profile of the discipline, and indeed the reputation and standing of the library and information service itself. At the personal level, research can “broaden horizons and offer individuals development opportunities” (McNicol & Nankivell, 2001, p.77). The study recommended that “research should be promoted as a valuable professional activity for practitioners to engage in” (McNicol & Nankivell, 2001, p.82). This chapter will consider the role of EBP within the library profession. A brief review of key literature in the area is provided. The review considers issues of definition and terminology, highlights the importance of research in professional practice and outlines the research approaches that underpin EBP. The chapter concludes with a consideration of the specific application of EBP within the dynamic and evolving field of information literacy (IL).

Dopamine and visually regulated eye growth in chick

Retinal image properties such as contrast and spatial frequency play important roles in the development of normal vision. For example, visual environments comprised solely of low contrast and/or low spatial frequencies induce myopia. The visual image is processed by the retina and it then locally controls eye growth. In terms of the retinal neurotransmitters that link visual stimuli to eye growth, there is strong evidence to suggest involvement of the retinal dopamine (DA) system. For example, effectively increasing retinal DA levels by using DA agonists can suppress the development of form-deprivation myopia (FDM). However, whether visual feedback controls eye growth by modulating retinal DA release, and/or some other factors, is still being elucidated. This thesis is chiefly concerned with the relationship between the dopaminergic system and retinal image properties in eye growth control. More specifically, whether the amount of retinal DA release reduces as the complexity of the image degrades was determined. For example, we investigated whether the level of retinal DA release decreased as image contrast decreased. In addition, the effects of spatial frequency, spatial energy distribution slope, and spatial phase on retinal DA release and eye growth were examined. When chicks were 8-days-old, a cone-lens imaging system was applied monocularly (+30 D, 3.3 cm cone). A short-term treatment period (6 hr) and a longer-term treatment period (4.5 days) were used. The short-term treatment tests for the acute reduction in DA release by the visual stimulus, as is seen with diffusers and lenses, whereas the 4.5 day point tests for reduction in DA release after more prolonged exposure to the visual stimulus. In the contrast study, 1.35 cyc/deg square wave grating targets of 95%, 67%, 45%, 12% or 4.2% contrast were used. Blank (0% contrast) targets were included for comparison. In the spatial frequency study, both sine and square wave grating targets with either 0.017 cyc/deg and 0.13 cyc/deg fundamental spatial frequencies and 95% contrast were used. In the spectral slope study, 30% root-mean-squared (RMS) contrast fractal noise targets with spectral fall-off of 1/f0.5, 1/f and 1/f2 were used. In the spatial alignment study, a structured Maltese cross (MX) target, a structured circular patterned (C) target and the scrambled versions of these two targets (SMX and SC) were used. Each treatment group comprised 6 chicks for ocular biometry (refraction and ocular dimension measurement) and 4 for analysis of retinal DA release. Vitreal dihydroxyphenylacetic acid (DOPAC) was analysed through ion-paired reversed phase high performance liquid chromatography with electrochemical detection (HPLC-ED), as a measure of retinal DA release. For the comparison between retinal DA release and eye growth, large reductions in retinal DA release possibly due to the decreased light level inside the cone-lens imaging system were observed across all treated eyes while only those exposed to low contrast, low spatial frequency sine wave grating, 1/f2, C and SC targets had myopic shifts in refraction. Amongst these treatment groups, no acute effect was observed and longer-term effects were only found in the low contrast and 1/f2 groups. These findings suggest that retinal DA release does not causally link visual stimuli properties to eye growth, and these target induced changes in refractive development are not dependent on the level of retinal DA release. Retinal dopaminergic cells might be affected indirectly via other retinal cells that immediately respond to changes in the image contrast of the retinal image.