Epitope cleavage by Leishmania endopeptidase(s) limits the efficiency of the exogenous pathway of major histocompatibility complex class I-associated antigen presentation

The activation of CD8+ T cell responses is commonplace during infection with a number of nonviral pathogens. Consequently, there has been much interest in the pathways of presentation of such exogenous antigens for major histocompatibility complex class I-restricted recognition. We had previously shown that Leishmania promastigotes transfected with the ovalbumin (OVA) gene could efficiently target OVA to the parasitophorous vacuole (PV), with subsequent recognition by class II-restricted T cells. We now report the results of studies aimed at evaluating the PV as a route of entry into the exogenous class I pathway. Bone marrow-derived macrophages can present soluble OVA (albeit at high concentrations) to the OVA(257-264)-specific T cell hybridoma 13.13. In contrast, infection with OVA-transfected Leishmania promastigotes failed to result in the stimulation of this hybridoma. This appeared unrelated to variables such as antigen concentration, parasite survival, and macrophage activation status. These results prompted an analysis of the effects of promastigotes on class I peptide binding using RMA-S cells and OVA(257-264). Our data indicate that the major surface protease of Leishmania, gp63, inhibits this interaction by virtue of its endopeptidase activity against the OVA(257-264) peptide. The data suggest that this activity, if maintained within the PV, would result in loss of the OVA(257-264) epitope. Although we can therefore draw no conclusions from these studies regarding the efficiency of the PV as a site of entry of antigen into the exogenous class I pathway, we have identified a further means by which parasites may manipulate the immune repertoire of their host.     

From outpost to outback: project career paths in Australia

With the growth in project management as a form of work organisation in many sectors of the economy has come the significant rise in the number of project managers and project team members. This change in work organisation brings issues in forging career paths and determining career support in work situations that are often dynamic, short lived and intense. In the relatively small but substantially robust Australian economy, a unique labour market and the tyranny of distance bring their own difficulties. Innovative and collaborative project structures and increasing prevalence of contract work provide both challenges and opportunities for new career pathways in many industries. A growing percentage of Australia's workforce is employed in project-based or project-oriented organisations, leading to the claim that Australia is a project-based economy. This provided a context for our research into the career paths and the issues of career management for project managers working in a project based economy. Using in-depth interviews with project managers from three industry areas we found generational and gender differences in experiences of work, workplace support and mentoring for career development. For a continued strong performance in this economy, organisations that employ project personnel will need to consider how they will ensure the supply of high quality project professionals into the future.     

Changes in the body size of UK and US children over the past three decades

The major sources of published anthropometric data on children are now over two decades old. Due to concern being expressed regarding the continued validity of such data, changes in the body sizes of the UK child population over the past three decades have been considered. Comparisons were also made between the size of the current UK child population to the current US child population, and to the most comprehensive source of measured data on US children (but which are now over 20 years old). The growth of children in the UK and US over the past three decades was assessed for an indication of secular growth trends. Stature increases were found to have generally been less than body weight increases (as a percentage) at 5th percentile, mean and 95th percentile levels for UK children, and UK children were found to be closer in size to US children now than they were 30 years ago.     

Influence of agronomic management of legume crops on soil accumulation with nitrate

Nitrate is known to accumulate under legume crops. The effects of legume crop, inoculation, row width, sowing rate, sowing date, and intra-cropping with wheat, on the amount and soil distribution of mineral N, residual soil water, crop biomass and crop N were studied at Wagga Wagga in south-east Australia. After removal of most of the above-ground plant material, the treatment effects on the biomass, N content, grain yield and grain N of wheat, established in the following season, were also measured. In a later experiment at Wagga, the recovery of 15N applied to the mid-row of lupin crops established at three row widths was estimated at crop maturity. At Condobolin, row width effects on the soil distribution of mineral N, biomass, N accumulation and N fixation of crop legumes and cereals, were determined. At physiological maturity, at Wagga Wagga, very little nitrate was left beneath cereals. Significantly more was left under legume crops, mostly below 30 cm of soil depth, and it was distributed differently depending on crop, inoculation, and sampling location. More nitrate was left under pea and faba than under lupin, and in response to inoculation. Mixing wheat with narrow-leaf lupin did not prevent nitrate accumulation in soil. For most of the legumes more nitrate was left in the mid-row than in the in-row; and more nitrate was left at the mid-row of lupin crops sown with wider rows. The additional nitrate left with wider rows increased the growth, N content, grain yield and protein of wheat established in the following season. 15N labelled nitrate applied mid-row was used less effectively by lupin as row width increased, in a dry season. At Condobolin, lupin established with wide rows used less soil nitrate than with narrower rows but maintained crop N by increased N fixation. In contrast, field pea maintained N demand by increasing nitrate uptake at intermediate row spacing. The study shows that the amount of nitrate accumulated in soil during legume cropping is susceptible to agronomic management, particularly crop selection, row width and inoculation; and that variation in the amount of this nitrate may carry forward to impact wheat production in the follow-on season.     

gp120-induced programmed cell death in recently activated T cells without subsequent ligation of the T cell receptor

In most individuals, HIV infection is characterized by a progressive decline in the number of peripheral blood CD4+ T lymphocytes, and while the number of CD4+ cells is within the normal range, defects in immune function are detectable. To date neither the decline in function nor the decline in cell number have been satisfactorily explained. Here we describe a mechanism which may contribute to the immunodeficiency and decline in CD4+ cell numbers in HIV-infected individuals. We show that recently activated T cells are susceptible to apoptosis when exposed to HIV gp120 in the presence of anti-gp120 antibody.     

Indoor Environmental Risk Factors for Respiratory Health in Children

Abstract The indoor environment of 80 houses in the Latrobe Valley, Victoria, Australia was assessed during six visits performed bi-monthly over a period of one year. Children between 7 and 14 years of age residing in the houses were included, resulting in 148 study children, 53 of whom were asthmatic. A respiratory health questionnaire was completed and skin prick tests performed. Significant risk factors for asthma were: exposure to a gas stove (OR=3.15, 95% CI 1.28-7.72), and indoor pets (OR = 2.68, 95% CI 1.07-6.70). Exposure to airborne Aspergillus spores (+10 CFU/m³, OR=1.51, 95% CI 1.05-2.18) was a risk factor for atopy, while exposure to a gas stove (OR=2.32, 95% CI 1.04-5.18) was a risk factor for respiratory symptoms. In conclusion, exposure to gas stoves, fungal spores and pets in the home were identified as statistically significant risk factors for respiratory health in children.