Succession of small mammal communities after fire and reintroduction of the swamp antechinus 'Antechinus minimus'

This thesis is involved with changes that have occurred to small mammal populations following a major disturbance in the Anglesea region as a result of the 1983 Ash Wednesday fires. Fire, with its effects on spatial and temporal heterogeneity, was found to be an important factor in the maintenance of vegetation and small mammal community structure and diversity in the region. Successional changes in vegetation and small mammal communities were described by multivariate analyses, using data collected annually from 22 study sites. The use of factor analysis techniques, in reducing the annual capture data content, enabled long-term changes in the structure of mammal communities to be interpreted. The small mammal communities in the coastal heath and forest vegetation in the Anglesea region show evidence of a general resilience, (the degree and speed of recovery), to disturbance. Two phases of successional response to fire by mammal species have been proposed; a ‘re-establishment’ phase which occurs in the initial 5-6 years post-fire and is accompanied by rapid increase in species’ abundance, and a subsequent ‘maintenance’ phase accompanied by relatively minor changes in abundance. Habitat Suitability Indices were produced relating to these phases. Vertical density measures of understorey shrubs and herb layers showed significant relationships with small mammal species abundance at the study sites. Long term studies following major disturbances are needed to distinguish between short term recovery of plant and animal species and long term changes in these species. Studies extending over a number of years enable a better directional view of changes in small mammal communities than can be determined from . observations made over a short period. As a part of the investigation into temporal change, it was proposed to undertake trial reintroductions of the Swamp antechinus, Ant echinus minimus, a marsupial dasyurid species which was trapped in the area prior to the 1983 fire, but rarely subsequently. Other more commonly observed native small mammal species (e.g. Rattus fuscipes,R. lutreolus, Antechinus stuartii, Sminthopsis leucopus) had re-invaded the proposed reintroduction site after this fire. Failure of A. minimus to re-establish may have been due to spatial separation of the pre-fire populations coupled with the extensive area burnt in 1983, A source population of the species was located about 100km to the west and habitat utilization and interspecific and niche relationships between the species making the small mammal community explored. Discriminant analysis revealed some spatial separation of species within a habitat based on structural vegetation factors rather than floristic factors. Temporal separation of species was observed, asA. minimus were more active than Rattus species during daylight periods. There was evidence of micro-habitat selection by species, and structural vegetation factors were most commonly identified in statistical analyses as contributing towards selection by small mammal species. Following a theoretical modelling study three reintroduction trials were carried out near Anglesea during 1992-94. Individuals were subsequently radio tracked, and habitat relationships between the species in the small mammal community investigated. Although successful breeding of A, minimus occurred during the latter two trials, the subsequent fate of offspring was not determined. Invasive techniques required to adequately monitor young animals were considered potentially too damaging. Telemetry studies indicated a preference of A. minimus for short, wet heath vegetation. Structural vegetation factors were identified as being significant in discriminating between capture locations of species. Small scale and inexpensive trial reintroductions have yielded valuable additional data on this species and may be viewed as a useful tool in the conservation of other small native mammals.

Therapeutic effects of matrine on primary and metastatic breast cancer

Matrine, one of the main components extracted from a traditional Chinese herb, Sophora flavescens Ait, has displayed anti-cancer activity in several types of cancer cells. This study aims to evaluate the therapeutic benefits of matrine on primary and metastatic breast cancer. Matrine inhibited the viability of and induced apoptosis in human MCF-7 and mouse 4T1 breast cancer cells in a dose-dependent manner in vitro as shown by MTT assay, flow cytometry and laser scanning confocal microscopy. Administration of matrine inhibited the growth of primary tumors and their metastases to lungs and livers, in a dose-dependent manner, in a highly metastatic model of 4T1 breast cancer established in syngeneic Balb/c mice. Tumors from matrine-treated mice had a smaller proliferation index, shown by immunostaining with an anti-Ki-67 antibody, a greater apoptosis index, shown by TUNEL-staining, and a less microvessel density, shown by immunostaining with an anti-CD31 A antibody, compared to the controls. Western blot analysis of tumoral homogenates indicated that matrine therapy reduced the ratio of Bcl-2/Bax, downregulated the expressions of VEGF and VEGFR-2, and increased the activation of caspase-3 and caspase-9. This study suggests matrine may be a potent agent, from a natural resource, for treating metastatic breast cancer because of its anti-apoptotic, anti-proliferative and anti-angiogenic activities.

Regulation of human pregnane X receptor and its target gene cytochrome P450 3A4 by Chinese herbal compounds and a molecular docking study

1. The pregnane X receptor (PXR) plays a critical role in the regulation of human cytochrome P450 3A4 (CYP3A4) gene. In this study, we investigated the effect of an array of compounds isolated from Chinese herbal medicines on the activity of PXR using a luciferase reporter gene assay in transiently transfected HepG2 and Huh7 cells and on the expression of PXR and CYP3A4 in LS174T cells. Furthermore, molecular docking was performed to investigate the binding modes of herbal compounds with PXR.

2. Praeruptorin A and C, salvianolic acid B, sodium danshensu, protocatechuic aldehyde, cryptotanshinone, emodin, morin, and tanshinone IIA significantly transactivated the CYP3A4 reporter gene construct in either HepG2 or Huh7 cells. The PXR mRNA expression in LS174T cells was significantly induced by physcion, protocatechuic aldehyde, salvianolic acid B, and sodium danshensu. However, epifriedelanol, morin, praeruptorin D, mulberroside A, tanshinone I, and tanshinone IIA significantly down-regulated the expression of PXR mRNA in LS174T cells.

3. All the herbal compounds tested can be readily docked into the ligand-binding cavity of PXR mainly through hydrogen bond and aromatic interactions with Ser247, Gln285, His407, and Arg401.

4. These findings suggest that herbal medicines can significantly regulate PXR and CYP3A4 and this has important implication in herb–drug interactions.