Molecular evolutionary dynamics of Ross River virus and implications for vaccine efficacy

Ross River virus (RRV) is a mosquito-borne member of the genus Alphavirus that causes epidemic polyarthritis in humans, costing the Australian health system at least US$10 million annually. Recent progress in RRV vaccine development requires accurate assessment of RRV genetic diversity and evolution, particularly as they may affect the utility of future vaccination. In this study, we provide novel RRV genome sequences and investigate the evolutionary dynamics of RRV from time-structured E2 gene datasets. Our analysis indicates that, although RRV evolves at a similar rate to other alphaviruses (mean evolutionary rate of approx. 8x10(-4) nucleotide substitutions per site year(-1)), the relative genetic diversity of RRV has been continuously low through time, possibly as a result of purifying selection imposed by replication in a wide range of natural host and vector species. Together, these findings suggest that vaccination against RRV is unlikely to result in the rapid antigenic evolution that could compromise the future efficacy of current RRV vaccines.

A novel corepressor, BCoR-L1, represses transcription through an interaction with CtBP

Corepressors play a crucial role in negative gene regulation and are defective in several diseases. BCoR is a corepressor for the BCL6 repressor protein. Here we describe and functionally characterize BCoR-L1, a homolog of BCoR. When tethered to a heterologous promoter, BCoR-L1 is capable of strong repression. Like other corepressors, BCoR-L1 associates with histone deacetylase (HDAC) activity. Specifically, BCoR-L1 coprecipitates with the Class II HDACs, HDAC4, HDAC5, and HDAC7, suggesting that they are involved in its role as a transcriptional repressor. BCoR-L1 also interacts with the CtBP corepressor through a CtBP-interacting motif in its amino terminus. Abrogation of the CtBP binding site within BCoR-L1 partially relieves BCoR-L1-mediated transcriptional repression. Furthermore, BCoR-L1 is located on the E-cadherin promoter, a known CtBP-regulated promoter, and represses the E-cadherin promoter activity in a reporter assay. The inhibition of BCoR-L1 expression by RNA-mediated interference results in derepression of E-cadherin in cells that do not normally express E-cadherin, indicating that BCoR-L1 contributes to the repression of an authentic endogenous CtBP target.

Substrate recognition and catalysis by the Holliday junction resolving enzyme Hje

Two archaeal Holliday junction resolving enzymes, Holliday junction cleavage (Hjc) and Holliday junction endonuclease (Hje), have been characterized. Both are members of a nuclease superfamily that includes the type II restriction enzymes, although their DNA cleaving activity is highly specific for four-way junction structure and not nucleic acid sequence. Despite 28% sequence identity, Hje and Hjc cleave junctions with distinct cutting patterns—they cut different strands of a four-way junction, at different distances from the junction centre. We report the high-resolution crystal structure of Hje from Sulfolobus solfataricus. The structure provides a basis to explain the differences in substrate specificity of Hje and Hjc, which result from changes in dimer organization, and suggests a viral origin for the Hje gene. Structural and biochemical data support the modelling of an Hje:DNA junction complex, highlighting a flexible loop that interacts intimately with the junction centre. A highly conserved serine residue on this loop is shown to be essential for the enzyme's activity, suggesting a novel variation of the nuclease active site. The loop may act as a conformational switch, ensuring that the active site is completed only on binding a four-way junction, thus explaining the exquisite specificity of these enzymes.

Cultivating Innovation through Social Relationships: A Qualitative Study of Outstanding Australian Innovators in Science, Technology and the Creative Industries

In this chapter, we describe and explore social relationship patterns associated with outstanding innovation. In doing so, we draw upon the findings of 16 in-depth interviews with award-winning Australian innovators from science & technology and the creative industries. The interviews covered topics relating to various influences on individual innovation capacity and career development. We found that for all of the participants, innovation was a highly social process. Although each had been recognised individually for their innovative success, none worked in isolation. The ability to generate innovative outcomes was grounded in certain types of interaction and collaboration. We outline the distinctive features of the social relationships which seem to be important to innovation, and ask which ‘social network capabilities’ might underlie the ability to create an optimal pattern of interpersonal relationships. We discuss the implications of these findings for universities, which we argue play a key role in the development of nascent innovators.

Chlamydia pneumoniae is genetically diverse in animals and appears to have crossed the host barrier to humans on (at least) two occasions

Chlamydia pneumoniae is a common human and animal pathogen associated with a wide range of diseases. Since the first isolation of C. pneumoniae TWAR in 1965, all human isolates have been essentially clonal, providing little evolutionary insight. To address this gap, we investigated the genetic diversity of 30 isolates from diverse geographical locations, from both human and animal origin (amphibian, reptilian, equine and marsupial). Based on the level of variation that we observed at 23 discreet gene loci, it was clearly evident that the animal isolates were more diverse than the isolates of human origin. Furthermore, we show that C. pneumoniae isolates could be grouped into five major genotypes, A-E, with A, B, D and E genotypes linked by geographical location, whereas genotype C was found across multiple continents. Our evidence strongly supports two separate animal-to-human cross species transfer events in the evolutionary history of this pathogen. The C. pneumoniae human genotype identified in the USA, Canada, Taiwan, Iran, Japan, Korea and Australia (non- Indigenous) most likely originated from a single amphibian or reptilian lineage, which appears to have been previously geographically widespread. We identified a separate human lineage present in two Australian Indigenous isolates (independent geographical locations). This lineage is distinct and is present in Australian amphibians as well as a range of Australian marsupials.

Analysis of HapMap tag-SNPs in dysbindin (DTNBP1) reveals evidence of consistent association with schizophrenia

Dystrobrevin binding protein 1 (DTNBP1), or dysbindin, is thought to be critical in regulating the glutamatergic system. While the dopamine pathway is known to be important in the aetiology of schizophrenia, it seems likely that glutamatergic dysfunction can lead to the development of schizophrenia. DTNBP1 is widely expressed in brain, levels are reduced in brains of schizophrenia patients and a DTNBP1 polymorphism has been associated with reduced brain expression. Despite numerous genetic studies no DTNBP1 polymorphism has been strongly implicated in schizophrenia aetiology. Using a haplotype block-based gene-tagging approach we genotyped 13 SNPs in DTNBP1 to investigate possible associations with DTNBP1 and schizophrenia. Four polymorphisms were found to be significantly associated with schizophrenia. The strongest association was found with an A/C SNP in intron 7 (rs9370822). Homozygotes for the C allele of rs9370822 were more than two and a half times as likely to have schizophrenia compared to controls. The other polymorphisms showed much weaker association and are less likely to be biologically significant. These results suggest that DTNBP1 is a good candidate for schizophrenia risk and rs9370822 is either functionally important or in disequilibrium with a functional SNP, although our observations should be viewed with caution until they are independently replicated.

Shifting the technology context : career-change entrants’ transition into teaching

Becoming a teacher in technology-rich classrooms is a complex and challenging transition for career-change entrants. Those with generic or specialist Information and Communication Technology (ICT) expertise bring a mindset about purposeful uses of ICT that enrich student learning and school communities. The transition process from a non-education environment is both enhanced and constrained by shifting the technology context of generic or specialist ICT expertise, developed through a former career as well as general life experience. In developing an understanding of the complexity of classrooms and creating a learner centred way of working, perceptions about learners and learning evolve and shift. Shifts in thinking about how ICT expertise supports learners and enhances learning preceded shifts in perceptions about being a teacher, working with colleagues, and functioning in schools that have varying degrees of intensity and impact on evolving professional identities. Current teacher education and school induction programs are seen to be falling short of meeting the needs of career-change entrants and, as a flow on, the students they nurture. Research (see, for example, Tigchelaar, Brouwer, & Korthagen, 2008; Williams & Forgasz, 2009) highlights the value of generic and specialist expertise career-change teachers bring to the profession and draws attention to the challenges such expertise begets (Anthony & Ord, 2008; Priyadharshini & Robinson-Pant, 2003). As such, the study described in this thesis investigated perceptions of career-change entrants, who have generic (Mishra & Koehler, 2006) or specialist expertise, that is, ICT qualifications and work experience in the use of ICT. The career-change entrants‘ perceptions were sought as they shifted the technology context and transitioned into teaching in technology-rich classrooms. The research involved an interpretive analysis of qualitative data and quantitative data. The study used the explanatory case study (Yin, 1994) methodology enriched through grounded theory processes (Strauss & Corbin, 1998), to develop a theory about professional identity transition from the perceptions of the participants in the study. The study provided insights into the expertise and experiences of career change entrants, particularly in relation to how professional identities that include generic and specialist ICT knowledge and expertise were reconfigured while transitioning into the teaching profession. This thesis presents the Professional Identity Transition Theory that encapsulates perceptions about teaching in technology-rich classrooms amongst a selection of the increasing number of career-change entrants. The theory, grounded in the data, (Strauss & Corbin, 1998) proposes that career-change entrants experience transition phases of varying intensity that impact on professional identity, retention and development as a teacher. These phases are linked to a shift in perceptions rather than time as a teacher. Generic and specialist expertise in the use of ICT is a weight of the past and an asset that makes the transition process more challenging for career-change entrants. The study showed that career-change entrants used their experiences and perceptions to develop a way of working in a school community. Their way of working initially had an adaptive orientation focussed on immediate needs as their teaching practice developed. Following a shift of thinking, more generative ways of working focussed on the future emerged to enable continual enhancement and development of practice. Sustaining such learning is a personal, school and systemic challenge for the teaching profession.

Technology, design and process innovation in the built environment

Buildings and infrastructure represent principal assets of any national economy as well as prime sources of environmental degradation. Making them more sustainable represents a key challenge for the construction, planning and design industries and governments at all levels; and the rapid urbanisation of the 21st century has turned this into a global challenge. This book embodies the results of a major research programme by members of the Australia Co-operative Research Centre for Construction Innovation and its global partners, presented for an international audience of construction researchers, senior professionals and advanced students. It covers four themes, applied to regeneration as well as to new build, and within the overall theme of Innovation: Sustainable Materials and Manufactures, focusing on building material products, their manufacture and assembly – and the reduction of their ecological ‘fingerprints’, the extension of their service lives, and their re-use and recyclability. It also explores the prospects for applying the principles of the assembly line. Virtual Design, Construction and Management, viewed as increasing sustainable development through automation, enhanced collaboration (such as virtual design teams), real time BL performance assessment during design, simulation of the construction process, life-cycle management of project information (zero information loss) risk minimisation, and increased potential for innovation and value adding. Integrating Design, Construction and Facility Management over the Project Life Cycle, by converging ICT, design science engineering and sustainability science. Integration across spatial scales, enabling building–infrastructure synergies (such as water and energy efficiency). Convergences between IT and design and operational processes are also viewed as a key platform increased sustainability.

Ureaplasma parvum and ureaplasma urealyticum detected in semen after washing prior to assisted reproductive technology procedures

Objective: This study investigated: (i) the prevalence of ureaplasmas in semen and washed semen and (ii) the effect of ureaplasmas on semen andrology parameters. Design: Prospective study. Setting: IVF unit -private hospital, Brisbane, Australia. Patient(s): Three hundred and forty three men participating in an assisted reproductive technology (ART) treatment cycle. Intervention(s): Semen and washed semen tested by culture, PCR assays and indirect immunofluorescent antibody assays. Statistical differences were determined by a t-test, Wilcoxon or Pearson’s Chi- square test where appropriate. Main Outcome Measure(s): The prevalence of ureaplasmas in semen and washed semen and the effect of these microorganisms on semen andrology parameters. Result(s): Ureaplasmas were detected in 73/343 (22%) semen samples and 29/343 (8.5%) washed semen samples. Ureaplasmas adherent to the surface of spermatozoa were demonstrated by indirect immunofluorescent antibody testing. U. parvum serovar 6 (36.6%) and U. urealyticum (30%) were the most prevalent isolates in washed semen. A comparison of the semen andrology parameters of washed semen ureaplasma positive and negative groups demonstrated a lower proportion of non-motile sperm in the washed semen ureaplasma positive group. Conclusion(s): Ureaplasmas are not always removed from semen by a standard ART washing procedure and can remain adherent to the surface of spermatozoa.

Project managers and technical change : curriculum development in strategic technology management

Traditional business approaches do not take account of the rapid technological developments underpinning today's world. Further understanding the role of technology and its efficient management to build and maintain a competitive edge in business can allow project managers to more successfully manage organisations, and to adapt to and capitalise on, today’s rapidly changing environment. Strategic Technology Management links engineering, science and management principles to identify, choose, and implement the most effective means of attaining compatibility between internal skills and resources of an organisation and its competitive, economic and social environment. This paper reviews the rationale and the development of a new Strategic Technology Management subject in QUT’s Master of Project Management program. It discusses recent developments in the area of technology management from an international perspective, provides details of the curriculum developed and discusses the experience of completing two years of teaching the new program.

Technology strategy for re-engineering design and construction

Automation technology can provide construction firms with a number of competitive advantages. Technology strategy guides a firm's approach to all technology, including automation. Engineering management educators, researchers, and construction industry professionals need improved understanding of how technology affects results, and how to better target investments to improve competitive performance. A more formal approach to the concept of technology strategy can benefit the construction manager in his efforts to remain competitive in increasingly hostile markets. This paper recommends consideration of five specific dimensions of technology strategy within the overall parameters of market conditions, firm capabilities and goals, and stage of technology evolution. Examples of the application of this framework in the formulation of technology strategy are provided for CAD applications, co-ordinated positioning technology and advanced falsework and formwork mechanisation to support construction field operations. Results from this continuing line of research can assist managers in making complex and difficult decisions regarding reengineering construction processes in using new construction technology and benefit future researchers by providing new tools for analysis. Through managing technology to best suit the existing capabilities of their firm, and addressing the market forces, engineering managers can better face the increasingly competitive environment in which they operate.

Mesenchymal stem cells in osteoarthritis therapy : current status of theory, technology, and applications

Osteoarthritis (OA) is a chronic, non-inflammatory type of arthritis, which usually affects the movable and weight bearing joints of the body. It is the most common joint disease in human beings and common in elderly people. Till date, there are no safe and effective diseases modifying OA drugs (DMOADs) to treat the millions of patients suffering from this serious and debilitating disease. However, recent studies provide strong evidence for the use of mesenchymal stem cell (MSC) therapy in curing cartilage related disorders. Due to their natural differentiation properties, MSCs can serve as vehicles for the delivery of effective, targeted treatment to damaged cartilage in OA disease. In vitro, MSCs can readily be tailored with transgenes with anti-catabolic or pro-anabolic effects to create cartilage-friendly therapeutic vehicles. On the other hand, tissue engineering constructs with scaffolds and biomaterials holds promising biological cartilage therapy. Many of these strategies have been validated in a wide range of in vitro and in vivo studies assessing treatment feasibility or efficacy. In this review, we provide an outline of the rationale and status of stem-cell-based treatments for OA cartilage, and we discuss prospects for clinical implementation and the factors crucial for maintaining the drive towards this goal.

Technology strategy and competitive performance in bridge construction

Pragmatic construction professionals, accustomed to intense price competition and focused on the bottom line, have difficulty justifying investments in advanced technology. Researchers and industry professionals need improved tools to analyze how technology affects the performance of the firm. This paper reports the results of research to begin answering the question, “does technology matter?” The researchers developed a set of five dimensions for technology strategy, collected information regarding these dimensions along with four measures of competitive performance in five bridge construction firms, and analyzed the information to identify relationships between technology strategy and competitive performance. Three technology strategy dimensions—competitive positioning, depth of technology strategy, and organizational fit—showed particularly strong correlations with the competitive performance indicators of absolute growth in contract awards and contract award value per technical employee. These findings indicate that technology does matter. The research also provides ways to analyze options for approaching technology and ways to relate technology to competitive performance for use by managers. It also provides a valuable set of research measures for technology strategy.