Expression of a truncated Brca1 protein delays lactational mammary development in transgenic mice

To address the hypothesis that certain disease-associated mutants of the breast-ovarian cancer susceptibility gene BRCA1 have biological activity in vivo, we have expressed a truncated Brca1 protein (trBrca1) in cell-lines and in the mammary gland of transgenic mice. Immunofluorescent analysis of transfected cell-lines indicates that trBRCA1 is a stable protein and that it is localized in the cell cytoplasm. Functional analysis of these cell-lines indicates that expression of trBRCA1 confers an increased radiosensitivity phenotype on mammary epithelial cells, consistent with abrogation of the BRCA1 pathway. MMTV-trBrca1 transgenic mice from two independent lines displayed a delay in lactational mammary gland development, as demonstrated by altered histological profiles of lobuloalveolar structures. Cellular and molecular analyses indicate that this phenotype results from a defect in differentiation, rather than altered rates of proliferation or apoptosis. The results presented in this paper are consistent with trBrca1 possessing dominant-negative activity and playing an important role in regulating normal mammary development. They may also have implications for germline carriers of BRCA1 mutations.

Brca1 inactivation induces p27Kip1-dependent cell cycle arrest and delayed development in the mouse mammary gland

One common characteristic of breast cancers arising in carriers of the predisposition gene BRCA1 is a loss of expression of the CDK inhibitor p27(Kip1) (p27), suggesting that p27 interacts epistatically with BRCA1. To investigate this relationship, we examined expression of p27 in mice expressing a dominant negative allele of Brca1 (MMTV-trBr) in the mammary gland. While these mice rarely develop tumors, they showed a 50% increase in p27 protein and a delay in mammary gland development associated with reduced proliferation. In contrast, on a p27 heterozygote background, MMTV-trBrca1 mice showed an increase in S phase cells, and normal mammary development. p27 was the only protein in the cyclin cyclin-dependent kinase network to show altered expression, suggesting that it may be a central mediator of cell cycle arrest in response to loss of function of BRCA1. Furthermore, in human mammary epithelial MCF7 cells expressing BRCA1-specific RNAi and in the BRCA1-deficient human tumor cell line HCC1937, p27 is elevated at the mRNA level compared to cells expressing wild-type BRCA1. We hypothesize that disruption of BRCA1 induces an increase in p27 that inhibits proliferation. Accordingly, reduction in p27 expression leads to enhancement of cellular proliferation in the absence of BRCA1.

Pax9 and Jagged1 act downstream of Gli3 in vertabrate limb development

From early in limb development the transcription factor Gli3 acts to define boundaries of gene expression along the anterior-posterior (AP) axis, establishing asymmetric patterns required to provide positional information. As limb development proceeds, posterior mesenchyme expression of Sonic hedgehog (Shh) regulates Gli3 transcription and post-translational processing to specify digit number and identity. The molecular cascades dependent on Gli3 at later stages of limb development, which link early patterning events with final digit morphogenesis, remain poorly characterised. By analysing the transcriptional consequences of loss of Gli3 in the anterior margin of the E11.5 and E12.5 limb bud in the polydactylous mouse mutant extra-toes (Gli3(Xt/Xt)), we have identified a number of known and novel transcripts dependent on Gli3 in the limb. In particular, we demonstrated that the genes encoding the paired box transcription factor Pax9, the Notch ligand Jagged1 and the cell surface receptor Cdo are dependent on Gli3 for correct expression in the anterior limb mesenchyme. Analysis of expression in compound Shh;Gli3 mutant mouse embryos and in both in vitro and in vivo Shh signaling assays, further defined the importance of Shh regulated processing of Gli3 in controlling gene expression. In particular Pax9 regulation by Shh and Gli3 was shown to be context dependent, with major differences between the limb and somite revealed by Shh bead implantation experiments in the chick. Jagged1 was shown to be induced by Shh in the chick limb and in a C3H10T1/2 cell based signaling assay, with Shh;Gli3 mutant analysis indicating that expression is dependent on Gli3 derepression. Our data have also revealed that perturbation of early patterning events within the Gli3(Xt/Xt), limb culminates in a specific delay of anterior chondrogenesis which is subsequently realised as extra digits. (c) 2005 Elsevier Ireland Ltd. All rights reserved.

Development of a non-intrusive heat transfer coefficient gauge and its application to high pressure die casting Effect of the process parameters

A heat transfer coefficient gauge has been built, obeying particular rules in order to ensure the relevance and accuracy of the collected information. The gauge body is made out of the same materials as the die casting die (H13). It is equipped with six thermocouples located at different depths in the body and with a sapphire light pipe. The light pipe is linked to an optic fibre, which is connected to a monochromatic pyrometer. Thermocouples and pyrometer measurements are recorded with a data logger. A high pressure die casting die was instrumented with one such gauge. A set of 150 castings was done and the data recorded. During the casting, some process parameters have been modified such as piston velocity, intensification pressure, delay before switch to the intensification stage, temperature of the alloy, etc.... The data was treated with an inverse method in order to transform temperature measurements into heat flux density and heat transfer coefficient plots. The piston velocity and the initial temperature of the die seem to be the process parameters that have the greatest influence on the heat transfer. (c) 2005 Elsevier B.V. All rights reserved.

First development of a polyurethane keratoprosthesis and its Australian connection: An unbeknown episode in the history of artificial cornea

This paper is aimed at establishing a particular chronological priority issue in the convoluted history of artificial cornea. According to existing records, the first keratoprosthesis made from polyurethane was developed by Caldwell and Jacob-Labarre in the late 1980s. This paper demonstrates that in fact the first polyurethane keratoprosthesis was proposed and designed in 1985 by Lawrence Hirst, an Australian ophthalmologist then working in St Louis, USA. The first prototype was manufactured in January 1986 by Thermedics Inc according to Dr Hirst's instructions from Tecoflex, a transparent polyurethane developed by the same company. This keratoprosthesis, which also had a porous skirt, was inserted intralamellarly in a monkey cornea and followed up clinically for about 3 months. There were no significant postoperative complications, and the histology of the explant indicated proper biointegration of the prosthetic skirt within the host stromal tissue. Because of a delay in the manufacture of further prototypes and to Dr Hirst's decision to return to Australia, the project was eventually abandoned. As no report was published on this development, the present paper is entirely based on original documents held in Dr Hirst's archives.

Minimising cold damage during reproductive development among temperate rice genotypes. I. Avoiding low temperature with the use of appropriate sowing time and photoperiod-sensitive varieties

Multiple-sown field trials in 4 consecutive years in the Riverina region of south-eastern Australia provided 24 different combinations of temperature and day length, which enabled the development of crop phenology models. A crop model was developed for 7 cultivars from diverse origins to identify if photoperiod sensitivity is involved in determining phenological development, and if that is advantageous in avoiding low-temperature damage. Cultivars that were mildly photoperiod-sensitive were identified from sowing to flowering and from panicle initiation to flowering. The crop models were run for 47 years of temperature data to quantify the risk of encountering low temperature during the critical young microspore stage for 5 different sowing dates. Cultivars that were mildly photoperiod-sensitive, such as Amaroo, had a reduced likelihood of encountering low temperature for a wider range of sowing dates compared with photoperiod-insensitive cultivars. The benefits of increased photoperiod sensitivity include greater sowing flexibility and reduced water use as growth duration is shortened when sowing is delayed. Determining the optimal sowing date also requires other considerations, e. g. the risk of cold damage at other sensitive stages such as flowering and the response of yield to a delay in flowering under non-limiting conditions. It was concluded that appropriate sowing time and the use of photoperiod-sensitive cultivars can be advantageous in the Riverina region in avoiding low temperature damage during reproductive development.

Development of the student placement evaluation form: A tool for assessing student fieldwork performance

Evaluation of students undertaking fieldwork education placements is a critical process in the health professions. As training programs and practice evolve, systems for assessing students need to be reviewed and updated constantly. In 1995, staff of the occupational therapy training program at the University of Queensland, Australia decided to develop a new tool for assessing student fieldwork performance. Using an action research methodology, a team developed the Student Placement Evaluation Form, a flexible and comprehensive criterion-referenced evaluation tool. The present paper examines action research as an appropriate methodology for considering real-life organisational problems in a systematic and participatory manner. The action research cycles undertaken, including preliminary information gathering, tool development, trial stages and current use of the tool, are detailed in the report. Current and future development of the tool is also described.

Development of a physical and genetic map of the virulent Wolbachia strain wMelPop

We report here the construction of a physical and genetic map of the virulent Wolbachia strain, wMelPop. This map was determined by ordering 28 chromosome fragments that resulted from digestion with the restriction endonucleases FseI, ApaI, SmaI, and AscI and were resolved by pulsed-field gel electrophoresis. Southern hybridization was done with 53 Wolbachia-specific genes as probes in order to determine the relative positions of these restriction fragments and use them to serve as markers. Comparison of the resulting map with the whole genome sequence of the closely related benign Wolbachia strain, wMel, shows that the two genomes are largely conserved in gene organization with the exception of a single inversion in the chromosome.

Workgroup emotional intelligence: Scale development and relationship to team process effectiveness and goal focus

Over the last decade, ambitious claims have been made in the management literature about the contribution of emotional intelligence to success and performance. Writers in this genre have predicted that individuals with high emotional intelligence perform better in all aspects of management. This paper outlines the development of a new emotional intelligence measure, the Workgroup Emotional Intelligence Profile, Version 3 (WEIP-3), which was designed specifically to profile the emotional intelligence of individuals in work teams. We applied the scale in a study of the link between emotional intelligence and two measures of team performance: team process effectiveness and team goal focus. The results suggest that the average level of emotional intelligence of team members, as measured by the WEIP-3, is reflected in the initial performance of teams. In our study, low emotional intelligence teams initially performed at a lower level than the high emotional intelligence teams. Over time, however, teams with low average emotional intelligence raised their performance to match that of teams with high emotional intelligence.

Flirting with Spirituality within Community Development Practice

In this paper Peter will consider some contemporary discourses of spirituality, the potential dangers of some spirituality, and then discuss how spirituality can contribute to an ‘enchanted’ framework of community development.

Personal Reflexive Instruments for Monitoring Engineering Development (PRIMED) Project

This was an early pre-Catalyst collaboration about developing reflexivity in student engineers. It was funded by (then) CUTSD.

Closing the gap in curriculum development leadership

“Closing the gap in curriculum development leadership” is a Carrick-funded University of Queensland project which is designed to address two related gaps in current knowledge and in existing professional development programs for academic staff. The first gap is in our knowledge of curriculum and pedagogical issues as they arise in relation to multi-year sequences of study, such as majors in generalist degrees, or core programs in more structured degrees. While there is considerable knowledge of curriculum and pedagogy at the course or individual unit of study level (e.g. Philosophy I), there is very little properly conceptualised, empirically informed knowledge about student learning (and teaching) over, say, a three-year major sequence in a traditional Arts or Sciences subject. The Carrick-funded project aims to (begin to) fill this gap through bottom-up curriculum development projects across the range of UQ’s offerings. The second gap is in our professional development programs and, indeed, in our recognition and support for the people who are in charge of such multi-year sequences of study. The major convener or program coordinator is not as well supported, in Australian and overseas professional development programs, as the lecturer in charge of a single course (or unit of study). Nor is her work likely to be taken account of in workload calculations or for the purposes of promotion and career advancement more generally. The Carrick-funded project aims to fill this gap by developing, in consultation with crucial stakeholders, amendments to existing university policies and practices. The attached documents provide a useful introduction to the project. For more information, please contact Fred D’Agostino at f.dagostino@uq.edu.au.

A Step-by-Step Approach to Transit Oriented Development Project Delivery

A major challenge in successfully implementing transit-oriented development (TOD) is having a robust process that ensures effective appraisal, initiation and delivery of multi-stakeholder TOD projects. A step-by step project development process can assist in the methodic design, evaluation, and initiation of TOD projects. Successful TOD requires attention to transit, mixed-use development and public space. Brisbane, Australia provides a case-study where recent planning policies and infrastructure documents have laid a foundation for TOD, but where barriers lie in precinct level planning and project implementation. In this context and perhaps in others, the research effort needs to shift toward identification of appropriate project processes and strategies. This paper presents the outcomes of research conducted to date. Drawing on the mainstream approach to project development and financial evaluation for property projects, key steps for potential use in successful delivery of TOD projects have been identified, including: establish the framework; location selection; precinct context review; preliminary precinct design; the initial financial viability study; the decision stage; establishment of project structure; land acquisition; development application; and project delivery. The appropriateness of this mainstream development and appraisal process will be tested through stakeholder research, and the proposed process will then be refined for adoption in TOD projects. It is suggested that the criteria for successful TOD should be broadened beyond financial concerns in order to deliver public sector support for project initiation.

Reconceptualising social sustainability in urban development

Although the social dimension is often cited as the third leg of triple bottom line sustainability, there is at present general agreement on the difficulty of saying just what social sustainability is and how it can be related to enivironmental sustainability. This paper proposes that a sociotechnical understanding of the relationship beween human behaviour and technical developments provides a way of making the social dimension accessible to engineers, designers and developers. We draw on early work in master planned urban developments to show how a sociotechnical model, married to a life cycle assessment approach can help us understand and design for effective and efficient implementation of sustainability systems