FGFR2 mutations are rare across histologic subtypes of ovarian cancer

OBJECTIVE: Ovarian cancer is the leading cause of death from gynecologic malignancies in the Western world. Fibroblast growth factor receptor (FGFR) signaling has been implicated to play a role in ovarian tumorigenesis. Mutational activation of one member of this receptor family, FGFR2, is a frequent event in endometrioid endometrial cancer. Given the similarities in the histologic and molecular genetics of ovarian and endometrial cancers, we hypothesized that activating FGFR2 mutations may occur in a subset of endometrioid ovarian tumors, and possibly other histotypes. METHODS: Six FGFR2 exons were sequenced in 120 primary ovarian tumors representing the major histologic subtypes. RESULTS: FGFR2 mutation was detected at low frequency in endometrioid (1/46, 2.2%) and serous (1/41, 2.4%) ovarian cancer. No mutations were detected in clear cell, mucinous, or mixed histology tumors or in the ovarian cancer cell lines tested. Functional characterization of the FGFR2 mutations confirmed that the mutations detected in ovarian cancer result in receptor activation. CONCLUSIONS: Despite the low incidence of FGFR2 mutations in ovarian cancer, the two FGFR2 mutations identified in ovarian tumors (S252W, Y376C) overlap with the oncogenic mutations previously identified in endometrial tumors, suggesting activated FGFR2 may contribute to ovarian cancer pathogenesis in a small subset of ovarian tumors.

Mutations in exon 3 of the beta-catenin gene are rare in melanoma cell lines

Mutations in exon 3 of the CTNNB1 gene encoding beta-catenin have been reported in colorectal cancer cell lines and tumours. Although one study reported mutations or deletions affecting beta-catenin in 20% of melanoma cell lines, subsequent reports detected a much lower frequency of aberrations in uncultured melanomas. To determine whether this difference in mutation frequency reflected an in vitro culturing artefact, exon 3 of CTNNB1 was screened in a panel of 62 melanoma cell lines. In addition, reverse transcription-polymerase chain reaction (RT-PCR) was performed to detect intragenic deletions affecting exon 3. One out of 62 (1.6%) cell lines was found to carry a mutation, indicating that aberration of the Wnt-1/wingless pathway through activation of beta-catenin is a rare event, even in melanoma cell lines.

PTEN inactivation is rare in melanoma tumours but occurs frequently in melanoma cell lines

Deletions detected in cytogenetic and loss of heterozygosity (LOH) studies indicate that at least one tumour suppressor gene maps to the long arm of chromosome 10. Previous deletion mapping studies have observed LOH on 10q in about 30% of melanomas analysed. The PTEN gene, mapping to chromosome band 10q23.3, encodes a protein with both lipid and protein phosphatase activity. Somatic mutations and deletions in have been detected in a variety of cell lines and tumours, including melanoma samples. We performed mutation analyses and extensive allelic loss studies to investigate the role this gene plays in melanoma pathogenesis. We found that a total of 34 out of 57 (60%) melanoma cell lines carried hemizygous deletions of chromosome 10q encompassing the PTEN locus. A further three cell lines carried smaller deletions excluding PTEN. Inactivation of both PTEN alleles by exon-specific homozygous deletion or mutation was observed in 13 out of 57 (23%) melanoma cell lines. The mutation spectrum observed does not indicate an important role for ultraviolet radiation in the genesis of these mutations, and evidence from three cell lines supports the acquisition of PTEN aberrations in culture. Ten out of 49 (20%) matched melanoma tumour/normal samples harboured hemizygous deletions of either the whole chromosome or most of the long arm. Mutations within were detected in only one of the 10 tumours demonstrating LOH at 10q23 that were analysed. These results suggest that PTEN inactivation may be important for the propagation of melanoma cells in culture, and that another chromosome 10 tumour suppressor gene may be important for melanoma pathogenesis.

Look before you leap : a confidence-based method for selecting species criticality while avoiding negative populations in τ-leaping

The stochastic simulation algorithm was introduced by Gillespie and in a different form by Kurtz. There have been many attempts at accelerating the algorithm without deviating from the behavior of the simulated system. The crux of the explicit τ-leaping procedure is the use of Poisson random variables to approximate the number of occurrences of each type of reaction event during a carefully selected time period, τ. This method is acceptable providing the leap condition, that no propensity function changes “significantly” during any time-step, is met. Using this method there is a possibility that species numbers can, artificially, become negative. Several recent papers have demonstrated methods that avoid this situation. One such method classifies, as critical, those reactions in danger of sending species populations negative. At most, one of these critical reactions is allowed to occur in the next time-step. We argue that the criticality of a reactant species and its dependent reaction channels should be related to the probability of the species number becoming negative. This way only reactions that, if fired, produce a high probability of driving a reactant population negative are labeled critical. The number of firings of more reaction channels can be approximated using Poisson random variables thus speeding up the simulation while maintaining the accuracy. In implementing this revised method of criticality selection we make use of the probability distribution from which the random variable describing the change in species number is drawn. We give several numerical examples to demonstrate the effectiveness of our new method.

Acoustic component detection for automatic species recognition in environmental monitoring

Automatic species recognition plays an important role in assisting ecologists to monitor the environment. One critical issue in this research area is that software developers need prior knowledge of specific targets people are interested in to build templates for these targets. This paper proposes a novel approach for automatic species recognition based on generic knowledge about acoustic events to detect species. Acoustic component detection is the most critical and fundamental part of this proposed approach. This paper gives clear definitions of acoustic components and presents three clustering algorithms for detecting four acoustic components in sound recordings; whistles, clicks, slurs, and blocks. The experiment result demonstrates that these acoustic component recognisers have achieved high precision and recall rate.

Rare chicken rescue

Sound design for documentary is an under-researched field. The specific context of representation of emotional or mental states is particularly open to clichéd treatment. Such treatment in the media often ‘perpetuates inaccurate or negative assumptions about mental health issues in the wider community’ (Francis et al 2005: 11) by employing, for example, either jarring sound/music combinations to signify ‘madness’ or overtly saccharine music to educe sympathy. This project adopted a practice-based approach to discovering a considered aesthetic treatment designed to elicit a more empathetic audience response. A more discriminating engagement with the intentions of the film was cultivated by abandoning both the ‘representational naturalism’ and the ‘distilled, evocative realism’ of documentary sound design (Davies 2007: 18) in favour of a more lyrical or musical approach. To achieve this we manipulated perspective, tonal character and perceptions of space in the final mixing stage. The project was funded by the Film Australia National Interest Program, ABC TV and the Pacific Film and Television Commission. As a crucial contributor to the aesthetic of the project I was nominated in the funding application, and ultimately received an AFI Award for Best Sound in a Documentary in 2008. The film was honoured by The Film Critics Circle of Australia, The Slamdance Film Festival in Utah and The Sydney Film Festival. It has been favourably reviewed in national and international print media (The Age, Sydney Morning Herald, among others) as well as online film/culture zines and blogs.

Impacts of experimental warming and fire on phenology of subalpine open-heath species

The present study examined experimentally the phenological responses of a range of plant species to rises in temperature. We used the climate-change field protocol of the International Tundra Experiment (ITEX), which measures plant responses to warming of 1 to 2°C inside small open-topped chambers. The field study was established on the Bogong High Plains, Australia, in subalpine open heathlands; the most common treeless plant community on the Bogong High Plains. The study included areas burnt by fire in 2003, and therefore considers the interactive effects of warming and fire, which have rarely been studied in high mountain environments. From November 2003 to March 2006, various phenological phases were monitored inside and outside chambers during the snow-free periods. Warming resulted in earlier occurrence of key phenological events in 7 of the 14 species studied. Burning altered phenology in 9 of 10 species studied, with both earlier and later phenological changes depending on the species. There were no common phenological responses to warming or burning among species of the same family, growth form or flowering type (i.e. early or late-flowering species), when all phenological events were examined. The proportion of plants that formed flower buds was influenced by fire in half of the species studied. The findings support previous findings of ITEX and other warming experiments; that is, species respond individualistically to experimental warming. The inter-year variation in phenological response, the idiosyncratic nature of the responses to experimental warming among species, and an inherent resilience to fire, may result in community resilience to short-term climate change. In the first 3 years of experimental warming, phenological responses do not appear to be driving community-level change. Our findings emphasise the value of examining multiple species in climate-change studies.

Interaction of myxomatosis and Rabbit Haemorrhagic Disease in wild rabbit

Increasing resistance of rabbits to myxomatosis in Australia has led to the exploration of Rabbit Haemorrhagic Disease, also called Rabbit Calicivirus Disease (RCD) as a possible control agent. While the initial spread of RCD in Australia resulted in widespread rabbit mortality in affected areas, the possible population dynamic effects of RCD and myxomatosis operating within the same system have not been properly explored. Here we present early mathematical modelling examining the interaction between the two diseases. In this study we use a deterministic compartment model, based on the classical SIR model in infectious disease modelling. We consider, here, only a single strain of myxomatosis and RCD and neglect latent periods. We also include logistic population growth, with the inclusion of seasonal birth rates. We assume there is no cross-immunity due to either disease. The mathematical model allows for the possibility of both diseases to be simultaneously present in an individual, although results are also presented for the case where co infection is not possible, since co-infection is thought to be rare and questions exist as to whether it can occur. The simulation results of this investigation show that it is a crucial issue and should be part of future field studies. A single simultaneous outbreak of RCD and myxomatosis was simulated, while ignoring natural births and deaths, appropriate for a short timescale of 20 days. Simultaneous outbreaks may be more common in Queensland. For the case where co-infection is not possible we find that the simultaneous presence of myxomatosis in the population suppresses the prevalence of RCD, compared to an outbreak of RCD with no outbreak of myxomatosis, and thus leads to a less effective control of the population. The reason for this is that infection with myxomatosis removes potentially susceptible rabbits from the possibility of infection with RCD (like a vaccination effect). We found that the reduction in the maximum prevalence of RCD was approximately 30% for an initial prevalence of 20% of myxomatosis, for the case where there was no simultaneous outbreak of myxomatosis, but the peak prevalence was only 15% when there was a simultaneous outbreak of myxomatosis. However, this maximum reduction will depend on other parameter values chosen. When co-infection is allowed then this suppression effect does occur but to a lesser degree. This is because the rabbits infected with both diseases reduces the prevalence of myxomatosis. We also simulated multiple outbreaks over a longer timescale of 10 years, including natural population growth rates, with seasonal birth rates and density dependent(logistic) death rates. This shows how both diseases interact with each other and with population growth. Here we obtain sustained outbreaks occurring approximately every two years for the case of a simultaneous outbreak of both diseases but without simultaneous co-infection, with the prevalence varying from 0.1 to 0.5. Without myxomatosis present then the simulation predicts RCD dies out quickly without further introduction from elsewhere. With the possibility of simultaneous co-infection of rabbits, sustained outbreaks are possible but then the outbreaks are less severe and more frequent (approximately yearly). While further model development is needed, our work to date suggests that: 1) the diseases are likely to interact via their impacts on rabbit abundance levels, and 2) introduction of RCD can suppress myxomatosis prevalence. We recommend that further modelling in conjunction with field studies be carried out to further investigate how these two diseases interact in the population.