Development of cyanide for feral pig and fox control

This report provides an overview of a series of pig- and fox-baiting research projects conducted 2005–2010. It is intended to collate and summarise the outcomes of these unpublished projects, including the completed pen and field trials, and provide recommendations for future research. This review will provide a useful reference document to support further research.

Kidney Induction: control by Notch, Wnt and GDNF/Ret signalling

The permanent mammalian kidney (metanephros) develops as a result of complex reciprocal tissue interactions between a ureteric epithelium and the renal mesenchyme. The overall goal of the research in this thesis was to gain data that will eventually help in elucidating the formation of congenital renal malformations. The experiments in my thesis aimed to reveal the mechanisms by which Notch, Wnt and GDNF/Ret signalling pathways regulate the development of functional kidney. The function of Notch pathway was studied by a transgenic mouse model, where it was shown that overactivation of Notch signalling disturbs kidney development and alters the expression of Gdnf and Ret/GFRa1. This indicates that Notch signalling interplays with GDNF/Ret in the regulation of the primary ureteric budding and its subsequent branching. The data also suggested that strict spatio-temporal regulation of these two pathways is required for determination of ureteric tip-identity, which appeared to be crucial for the branch formation. The function of Wnt signalling in the ureteric morphogenesis was studied by in vivo and in vitro methods to show that a canonical pathway is required for ureteric branching. Stabilisation and deletion of the canonical pathway mediator, b-catenin specifically in the ureteric epithelium result in renal aplasia/hypodysplasia. These defects originate from severe blockage of ureteric branching due to the disrupted Ret signalling. Consequently, ureteric tip specific markers are lost and ureteric stalk identity is expanded throughout the whole epithelium. Thus, the data demonstrates that the Wnt/b-catenin pathway plays an essential role in the patterning and branching of the ureteric epithelium. A novel in vitro method was generated and utilised in nephron induction studies to reveal the mechanisms through which nephrogenesis is induced. Transient GSK3 inhibition results in stabilisation of b-catenin in the isolated renal mesenchyme, which efficiently triggers nephron formation. Also genetic stabilisation of b-catenin specifically in the mesenchyme results in spontaneous nephrogenesis. The results show that activation of the canonical Wnt pathway is sufficient to initiate nephrogenesis, and suggest that this pathway mediates the nephron induction in murine kidney mesenchymes. Taken together, this thesis demonstrates Notch and Wnt signalling pathways as novel regulators of ureteric branching morphogenesis, and that activation of the canonical Wnt pathway is sufficient for nephron induction. The studies also indicate that the Notch and Wnt pathways cross-talk with GDNF/Ret signalling in the patterning of ureteric epithelium.

To reactivate or not to reactivate : Control of KSHV lytic replication is essential for apoptosis in response to p53 restoration

Kaposi's sarcoma herpesvirus (KSHV) is an oncogenic human virus and the causative agent of three human malignancies: Kaposi's sarcoma (KS), Multicentric Castleman's Disease (MCD), and primary effusion lymphoma (PEL). In tumors, KSHV establishes latent infection during which it produces no infectious particles. Latently infected cells can enter the lytic replication cycle, and upon provision of appropriate cellular signals, produce progeny virus. PEL, commonly described in patients with AIDS, represents a diffuse large-cell non-Hodgkin's lymphoma, with median survival time less than six months after diagnosis. As tumor suppressor gene TP53 mutations occur rarely in PEL, the aim of this thesis was to investigate whether non-genotoxic activation of the p53 pathway can eradicate malignant PEL cells. This thesis demonstrates that Nutlin-3, a small-molecule inhibitor of the p53-MDM2 interaction, efficiently restored p53 function in PEL cells, leading to cell cycle arrest and massive apoptosis. Furthermore, we found that KSHV infection activated DNA damage signaling, rendering the cells more sensitive to p53-dependent cell death. We also showed in vivo the therapeutic potential of p53 restoration that led to regression of subcutaneous and intraperitoneal PEL tumor xenografts without adversely affecting normal cells. Importantly, we demonstrated that in a small subset of intraperitoneal PEL tumors, spontaneous induction of viral reactivation dramatically impaired Nutlin-3-induced p53-mediated apoptosis. Accordingly, we found that elevated KSHV lytic transcripts correlated with PEL tumor burden in animals and that inhibition of viral reactivation in vitro restored cytotoxic activity of a small-molecule inhibitor of the p53-MDM2 interaction. Latency provides a unique opportunity for KSHV to escape host immune surveillance and to establish persistent infections. However, to maintain viral reservoirs and spread to other hosts, KSHV must be reactivated from latency and enter into the lytic growth phase. We showed that phosphorylation of nucleolar phosphoprotein nucleophosmin (NPM) by viral cyclin-CDK6 is critical for establishment and maintenance of the KSHV latency. In short, this study provides evidence that the switch between latent phase and lytic replication is a critical step that determines the outcome of viral infection and the pathogenesis of KSHV-induced malignancies. Our data may thus contribute to development of novel targeted therapies for intervention and treatment of KSHV-associated cancers.

Performance Study of a Centralized Concurrency Control Algorithm for Distributed Database Systems using SIMULA

The stimulation technique has gained much importance in the performance studies of Concurrency Control (CC) algorithms for distributed database systems. However, details regarding the simulation methodology and implementation are seldom mentioned in the literature. One objective of this paper is to elaborate the simulation methodology using SIMULA. Detailed studies have been carried out on a centralised CC algorithm and its modified version. The results compare well with a previously reported study on these algorithms. Here, additional results concerning the update intensiveness of transactions and the degree of conflict are obtained. The degree of conflict is quantitatively measured and it is seen to be a useful performance index. Regression analysis has been carried out on the results, and an optimisation study using the regression model has been performed to minimise the response time. Such a study may prove useful for the design of distributed database systems.

Assessing the biological control potential of an adventitiously-established "pest", Scirtothrips aurantii (Faure), on a weed, Bryophyllum delagoense (Eckl. & Zeyh.), in Queensland

South African citrus thrips (Scirtothrips aurantii) established adventitiously in Australia. Although it is a major horticultural pest in Africa, it is now advocated as a possible biological control agent against Bryophyllum delagoense Eckl. & Zeyh. (Crassulaceae). To evaluate the biocontrol potential of S. aurantii a two year field study was conducted on the western Darling Downs of southern Queensland. Imidacloprid insecticide was applied to two quadrats at each of 18 field sites to assess, in the absence of S. aurantii, the persistence of individual plants and to quantify propagule production and recruitment by this declared weed. A third quadrat was left, as a control, to be infested naturally by S. aurantii. When released from herbivory by thrips in the field, plants grew significantly more, flowered more, and were significantly more fecund than plants in the quadrats with S. aurantii. Increases in growth and fecundity translated into significantly increased plant numbers but not increased recruitment. Recruitment even declined in experimental quadrats, through the indirect effects of releasing plants from herbivory. Field sampling also revealed that S. aurantii may be sensitive to seasonal climatic fluctuations. These and other local climatic influences may limit the biological control potential of the insect.

Gear selectivity of large-mesh nets and drumlines used to catch sharks in the Queensland Shark Control Program.

Catches of sharks and bycatch in large-mesh nets and baited drumlines used by the Queensland Shark Control Program were examined to determine the efficacy of both gear types and assess fishing strategies that minimise their impacts. There were few significant differences in the size of both sharks and bycatch in the two gear types, apart from significantly smaller (p < 0.05) tiger sharks Galeocerdo cuvier being taken on drumlines and smaller green turtles Chelonia mydas in nets. Catch per unit effort showed orders of magnitude differences among species, even within the same family. Hammerhead sharks and rays were particularly vulnerable to net capture, whereas higher catch rates of tiger sharks were observed for drumlines. Nets caught more marine mammals, teleost fish and rays, whereas drumlines exhibited higher catch rates of the threatened loggerhead turtle Caretta caretta. Survival of most taxa (particularly obligate ram ventilators) was lower in nets than drumlines. Bycatch species (turtles and marine mammals) were able to swim to the surface to breathe when they were hooked on drumlines, enhancing their survival potential. Fishing strategies that recognise the different selectivity patterns of the gear can be developed to suit local biotic and abiotic conditions, although it is recognised that quantification of both ecological risk and risk to bathers is not a simple task.