Clinical research:Developing an appropriate career structure

The veterinary profession needs to become more successful in producing the next generation of clinician scientists, say Richard Mellanby and others, who set out a roadmap for future academic postgraduate clinical training

An approach for the identification of targets specific to bone metastasis using cancer genes interactome and gene ontology analysis

Metastasis is one of the most enigmatic aspects of cancer pathogenesis and is a major cause of cancer-associated mortality. Secondary bone cancer (SBC) is a complex disease caused by metastasis of tumor cells from their primary site and is characterized by intricate interplay of molecular interactions. Identification of targets for multifactorial diseases such as SBC, the most frequent complication of breast and prostate cancers, is a challenge. Towards achieving our aim of identification of targets specific to SBC, we constructed a 'Cancer Genes Network', a representative protein interactome of cancer genes. Using graph theoretical methods, we obtained a set of key genes that are relevant for generic mechanisms of cancers and have a role in biological essentiality. We also compiled a curated dataset of 391 SBC genes from published literature which serves as a basis of ontological correlates of secondary bone cancer. Building on these results, we implement a strategy based on generic cancer genes, SBC genes and gene ontology enrichment method, to obtain a set of targets that are specific to bone metastasis. Through this study, we present an approach for probing one of the major complications in cancers, namely, metastasis. The results on genes that play generic roles in cancer phenotype, obtained by network analysis of 'Cancer Genes Network', have broader implications in understanding the role of molecular regulators in mechanisms of cancers. Specifically, our study provides a set of potential targets that are of ontological and regulatory relevance to secondary bone cancer.Comment: 54 pages (19 pages main text; 11 Figures; 26 pages of supplementary information). Revised after critical reviews. Accepted for Publication in PLoS ON

Evidence of Endemic Hendra Virus Infection in Flying-Foxes (Pteropus conspicillatus)—Implications for Disease Risk Management

This study investigated the seroepidemiology of Hendra virus in a spectacled flying-fox (Pteropus conspicillatus) population in northern Australia, near the location of an equine and associated human Hendra virus infection in late 2004. The pattern of infection in the population was investigated using a serial cross-sectional serological study over a 25-month period, with blood sampled from 521 individuals over six sampling sessions. Antibody titres to the virus were determined by virus neutralisation test. In contrast to the expected episodic infection pattern, we observed that seroprevalence gradually increased over the two years suggesting infection was endemic in the population over the study period. Our results suggested age, pregnancy and lactation were significant risk factors for a detectable neutralizing antibody response. Antibody titres were significantly higher in females than males, with the highest titres occurring in pregnant animals. Temporal variation in antibody titres suggests that herd immunity to the virus may wax and wane on a seasonal basis. These findings support an endemic infection pattern of henipaviruses in bat populations suggesting their infection dynamics may differ significantly from the acute, self limiting episodic pattern observed with related viruses (e.g. measles virus, phocine distemper virus, rinderpest virus) hence requiring a much smaller critical host population size to sustain the virus. These findings help inform predictive modelling of henipavirus infection in bat populations, and indicate that the life cycle of the reservoir species should be taken into account when developing risk management strategies for henipaviruses

Evidence of Endemic Hendra Virus Infection in Flying-Foxes (Pteropus conspicillatus)—Implications for Disease Risk Management

This study investigated the seroepidemiology of Hendra virus in a spectacled flying-fox (Pteropus conspicillatus) population in northern Australia, near the location of an equine and associated human Hendra virus infection in late 2004. The pattern of infection in the population was investigated using a serial cross-sectional serological study over a 25-month period, with blood sampled from 521 individuals over six sampling sessions. Antibody titres to the virus were determined by virus neutralisation test. In contrast to the expected episodic infection pattern, we observed that seroprevalence gradually increased over the two years suggesting infection was endemic in the population over the study period. Our results suggested age, pregnancy and lactation were significant risk factors for a detectable neutralizing antibody response. Antibody titres were significantly higher in females than males, with the highest titres occurring in pregnant animals. Temporal variation in antibody titres suggests that herd immunity to the virus may wax and wane on a seasonal basis. These findings support an endemic infection pattern of henipaviruses in bat populations suggesting their infection dynamics may differ significantly from the acute, self limiting episodic pattern observed with related viruses (e.g. measles virus, phocine distemper virus, rinderpest virus) hence requiring a much smaller critical host population size to sustain the virus. These findings help inform predictive modelling of henipavirus infection in bat populations, and indicate that the life cycle of the reservoir species should be taken into account when developing risk management strategies for henipaviruses

Lower edge of locked Main Himalayan Thrust unzipped by the 2015 Gorkha earthquake

Large earthquakes are thought to release strain on previously locked faults. However, the details of how earthquakes are initiated, grow and terminate in relation to pre-seismically locked and creeping patches is unclear ^1-4. The 2015 Mw 7.8 Gorkha, Nepal earthquake occurred close to Kathmandu in a region where the prior pattern of fault locking is well documented ^5. Here we analyze this event using seismological records measured at teleseismic distances and Synthetic Aperture Radar imagery. We show that the earthquake originated northwest of Kathmandu within a cluster of background seismicity that fringes the bottom of the locked portion of the Main Himalayan Thrust fault (MHT). The rupture propagated eastwards for about 140 km, unzipping the lower edge of the locked portion of the fault. High-frequency seismic waves radiated continuously as the slip pulse propagated at about 2.8 km s-1 along this zone of presumably high and heterogeneous pre-¬seismic stress at the seismic-aseismic transition. Eastward unzipping of the fault resumed during the Mw 7.3 aftershock on May 12. The transfer of stress to neighbouring regions during the Gorkha earthquake should facilitate future rupture of the areas of the MHT adjacent and up-dip of the Gorkha earthquake rupture.This is the author accepted manuscript. The final version is available from Nature Publishing Group via http://dx.doi.org/10.1038/ngeo251

Satellite Telemetry and Long-Range Bat Movements

Background: Understanding the long-distance movement of bats has direct relevance to studies of population dynamics, ecology, disease emergence, and conservation. Methodology/Principal Findings: We developed and trialed several collar and platform terminal transmitter (PTT) combinations on both free-living and captive fruit bats (Family Pteropodidae: Genus Pteropus). We examined transmitter weight, size, profile and comfort as key determinants of maximized transmitter activity. We then tested the importance of bat-related variables (species size/weight, roosting habitat and behavior) and environmental variables (day-length, rainfall pattern) in determining optimal collar/PTT configuration. We compared battery- and solar-powered PTT performance in various field situations, and found the latter more successful in maintaining voltage on species that roosted higher in the tree canopy, and at lower density, than those that roost more densely and lower in trees. Finally, we trialed transmitter accuracy, and found that actual distance errors and Argos location class error estimates were in broad agreement. Conclusions/Significance: We conclude that no single collar or transmitter design is optimal for all bat species, and that species size/weight, species ecology and study objectives are key design considerations. Our study provides a strategy for collar and platform choice that will be applicable to a larger number of bat species as transmitter size and weight continue to decrease in the future

Search for supersymmetric particles in scenarios with a gravitino LSP and stau NLSP

Sleptons, neutralinos and charginos were searched for in the context of scenarios where the lightest supersymmetric particle is the gravitino. It was assumed that the stau is the next-to-lightest supersymmetric particle. Data collected with the DELPHI detector at a centre-of-mass energy near 189 GeV were analysed combining the methods developed in previous searches at lower energies. No evidence for the production of these supersymmetric particles was found. Hence, limits were derived at 95% confidence level.Comment: 31 pages, 14 figure