Identification of Eusynstyelamide B as a Potent Cell Cycle Inhibitor Following the Generation and Screening of an Ascidian-Derived Extract Library Using a Real Time Cell Analyzer

Ascidians are marine invertebrates that have been a source of numerous cytotoxic compounds. Of the first six marine-derived drugs that made anticancer clinical trials, three originated from ascidian specimens. In order to identify new anti-neoplastic compounds, an ascidian extract library (143 samples) was generated and screened in MDA-MB-231 breast cancer cells using a real-time cell analyzer (RTCA). This resulted in 143 time-dependent cell response profiles (TCRP), which are read-outs of changes to the growth rate, morphology, and adhesive characteristics of the cell culture. Twenty-one extracts affected the TCRP of MDA-MB-231 cells and were further investigated regarding toxicity and specificity, as well as their effects on cell morphology and cell cycle. The results of these studies were used to prioritize extracts for bioassay-guided fractionation, which led to the isolation of the previously identified marine natural product, eusynstyelamide B (1). This bis-indole alkaloid was shown to display an IC₅₀ of 5 µM in MDA-MB-231 cells. Moreover, 1 caused a strong cell cycle arrest in G2/M and induced apoptosis after 72 h treatment, making this molecule an attractive candidate for further mechanism of action studies.     

Rigidin E,a New Pyrrolopyrimidine Alkaloid from a Papua New Guinea Tunicate Eudistoma Species

A new pyrrolopyrimidine alkaloid, rigidin E (1) and the known metabolites rigidin (2) and 1-methylherbipoline (3) have been isolated from a Papua New Guinea tunicate Eudistoma sp. A combination of spectroscopic data were used to determine the structures of these metabolites.     

Fire is a key element in the landscape-scale habitat requirements and global population status of a threatened bird: The Mallee Emu-wren (Stipiturus mallee)

The Mallee Emu-wren (Stipiturus mallee) is a threatened, narrow-range passerine endemic to south-eastern Australia. To inform future conservation measures for this poorly known species, we used ecological niche factor analysis, habitat suitability modelling and distance sampling to determine landscape-scale habitat requirements and estimate the population size. Using GIS software, we integrated digital layers of ecogeographic variables with; (1) presence-only observations to derive and validate a habitat suitability model using ecological niche factor analysis, and (2) distance sampling to determine population distribution and densities across vegetation types. We detected populations in only five of seven reserves which they had occupied in 2000. We estimate the global population size to be 16,821 individuals (range 8431-39, 104), 68% greater than the previously estimated 10,000 individuals, with a single large reserve containing the majority (∼92%) of the global population. The Mallee Emu-wren is a habitat specialist, primarily occurring in mallee-Triodia vegetation that has not been burnt for at least 15 years. The highest densities were in vegetation associations containing at least a 15% cover of Triodia, however, time since the habitat was last burnt was the overriding factor in determining densities. Large-scale wildfires are a pervasive threat to the global status of the Mallee Emu-wren, and the risk to remaining populations is exacerbated by the adverse impact of prolonged drought and the potential for altered fire regimes caused by global warming. Evaluation of the global population status, and the continued wildfire threat warranted recent reclassification of the Mallee Emu-wren from Vulnerable to Endangered according to IUCN Red List categories and criteria.     

Long-term impacts of prescribed burning on regional extent and incidence of wildfires—Evidence from 50 years of active fire management in SW Australian forests

Prescribed burning is advocated for the sustainable management of fire-prone ecosystems for its capacity to reduce fuel loads and mitigate large high-intensity wildfires. However, there is a lack of comprehensive field evidence on which to base predictions of the benefits of prescribed burning for meeting either wildfire hazard reduction or conservation goals. Australian eucalypt forests are among the very few forest types in the world where prescribed burning has been practised long enough and at a large enough spatial scale to quantify its effect on the incidence and extent of unplanned fires. Nevertheless even for Australian forests evidence of the effectiveness of prescribed burning remains fragmented and largely unpublished in the scientific literature.     

Glycaemic index, glycaemic load and ovarian cancer risk: a prospective cohort study

BACKGROUND: There is some evidence that plasma insulin levels might influence ovarian cancer risk. Glycaemic index (GI) and glycaemic load (GL) are measures that allow the carbohydrate content of individual foods to be classified according to their postprandial glycaemic effects and hence their effects on circulating insulin levels. Therefore, we examined ovarian cancer risk in association with GI and GL, and intake of dietary carbohydrate and sugar. METHODS: The study was conducted in a prospective cohort of 49 613 Canadian women enrolled in the National Breast Screening Study (NBSS) who completed a self-administered food-frequency questionnaire (FFQ) between 1980 and 1985. Linkages to national mortality and cancer databases yielded data on deaths and cancer incidence, with follow-up ending between 1998 and 2000. Data from the FFQ were used to estimate overall GI and GL, and Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between energy-adjusted quartile levels of GL, overall GI, total carbohydrates, total sugar and ovarian cancer risk. RESULTS: During a mean 16.4 years of follow-up, we observed 264 incident ovarian cancer cases. GI and total carbohydrate and sugar intakes were not associated with ovarian cancer risk in the total cohort. GL was positively associated with a 72% increase in risk of ovarian cancer (HR=1.72, 95% CI=1.13-2.62, Ptrend=0.01) and the magnitude of the association was slightly greater among postmenopausal (HR=1.89, 95% CI=0.98-3.65, Ptrend=0.03) than among premenopausal women (HR=1.64, 95% CI=0.95-2.88, Ptrend=0.07). CONCLUSIONS: Our data suggest that consumption of diets with high GL values may be associated with increased risk of ovarian cancer.     

Underestimated and severe: Small mammal decline from the forests of south-eastern Australia since European settlement, as revealed by a top-order predator

In Australia, numerous small mammal species have suffered extinction or severe declines in distribution and abundance following European settlement. The extent of these declines from forested areas of south-eastern Australia, however, remains poorly understood. In this paper we use sub-fossil deposits of the sooty owl (Tyto tenebricosa tenebricosa) as a tool for understanding the diversity of the small mammal palaeocommunity. These results are compared to the contemporary sooty owl diet from the same geographical region to investigate the degree of small mammal decline following European settlement.Of 28 mammal species detected in sub-fossil deposits and considered prey items of the sooty owl at the time of European settlement, only 10 species were detected in the contemporary sooty owl diet. Numerous small mammal species have not only recently suffered severe declines in distribution and abundance but have also recently undergone niche contraction, as they occupied a greater diversity of regions and habitats at the time of European settlement. For some species our understanding of their true ecological niche and ecological potential is therefore limited. The species that underwent the greatest declines occupied open habitat types or were terrestrial. The severity of decline is also likely to have resulted in severe disruption of ecosystem functions, with wide scale ecosystem consequences. There is an urgent need to improve small mammal conservation, to maintain crucial ecosystem functions performed by small mammals. It is recommended that broad-scale exotic predator control programs are conducted which may also provide suitable conditions for the re-introduction of locally extinct species.     

Implications of conserving an ecosystem modifier: Increasing green turtle (Chelonia mydas) densities substantially alters seagrass meadows

Ecosystem modifiers have the ability to significantly alter the ecosystem they inhabit sometimes with serious consequences for their own populations. We evaluated the ability of green turtles (Chelonia mydas) to modify seagrass ecosystems by their foraging activity. This study was conducted in a seagrass-dominated lagoon in the Lakshadweep Islands, Indian Ocean, where a stable high-density congregation of green turtles is present. We determined a gradient of turtle density in the lagoon and measured the intensity of turtle herbivory across the gradient. We then measured the impact of increasing grazing on seagrass structural parameters, growth and flowering along this gradient. Our results indicate that turtles substantially change seagrass meadow structure (canopy height, shoot length, width and density), reduce flowering and can potentially even cause changes in the species composition of the meadow. We discuss the implications of these results for seagrass ecosystem function, green turtle movement and human attitudes. When conserving ecosystem modifiers like the green turtle, any management strategy needs to include a detailed knowledge of the roles these species play in the ecosystems they inhabit.     

Ultraviolet-induced oxidation of ascorbic acid in a model juice system: identification of degradation products

Degradation products of ultraviolet (UV-C, 254 nm) treated ascorbic acid (AA) are reported. Analysis by high-performance liquid chromatography-mass spectroscopy (HPLC-MS) conducted in a 0.5% malic acid model juice system (pH 3.3) demonstrated increased degradation of AA above untreated controls with concomitant increases in dehydroascorbic acid (DHA) and 2,3-diketogulonic acid (DKGA) levels. Electron spin resonance (ESR) spectroscopy studies, conducted in phosphate buffer (pH 7.0) to increase detection sensitivity, demonstrated that ascorbyl radical (AA?) formation occurs simultaneously with AA degradation. Consistent with a previous study in which UV treatments were shown to accelerate dark storage degradation, AA? radicals continued to form for up to 200 min after an initial UV treatment. Results from this study suggest that the mechanism for UV-induced degradation is the same as the general mechanism for metal-catalyzed oxidation of AA in juice.