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The robustness of the international system of radiological protection relies on regularly updating its scientific underpinnings while providing a clear understanding of the assumptions needed to cope with the remaining uncertainties associated to radiation-induced health risks at low dose/low dose rate (i.e. below 100 mSv or below 0.1 mSv/minute). Recent reviews of biological and epidemiological data tend to provide additional support to the assumption that, for low dose, low dose rate exposures, stochastic effects (e.g. cancer risk) follow a dose response with no threshold. However, the adoption of this Linear-Non-Threshold (LNT) model remains controversial because of the large uncertainties persisting about health risks associated with low dose/low dose rate radiation exposures. Current knowledge in low dose or low dose rate radiobiology shows that the mechanisms involved in carcinogenesis are extremely complex. The integration of biological evidence on radiation-induced cancers with epidemiological results offers a promising mechanism-based approach for a less uncertain inference from high doses/dose rates to low doses/dose rates. This approach also applies to non-cancer effects (e.g. circulatory diseases, cognitive effects, lens opacities), where interpretation of epidemiological and animal studies could be reconciled through the development of Adverse Outcome Pathways (AOP), adopting the strategy used for chemical toxicity and its regulation. Given the importance placed on such research by public funding bodies and the broad amount of research being conducted and continued in this area across the globe, while noting national and regional ongoing efforts to effectively collaborate and co-ordinate research, ongoing and planned work merits consideration under an international meta-coordination. One way to reduce uncertainties in low dose/low dose rate health risks is to advance related research strategically, ensuring better use of key results in policy making and improving the way research findings and policies are communicated to stakeholders. To address these issues, the High-Level Group on Low-Dose Research (HLG-LDR) operating under the auspices of the Nuclear Energy Agencies (NEA���s) Committee on Radiological Protection and Public Health (CRPPH), aims to facilitate global networking of low dose research funding organisations and research implementing organisations. This initiative will also integrate a policy-oriented communication strategy on risk uncertainties. Finally, the HLG-LDR activities will enhance the impact of research and have implications for radiological protection policy, regulation and implementation, which will contribute to the revision of the International Commission on Radiological Protection system and beyond., License: Creative Commons Attribution Non Commercial No Derivatives 2.5 Generic Grants: I would like to leave it blank.

1.Animals must tailor their life history strategies to suit the prevailing conditions and respond to hazards in the environment. Animals with lethal infections are faced with a difficult choice: to allocate more resources to reproduction and suffer higher mortality or to reduce reproduction with the expectation of enhanced immunity and late-age reproduction. But, how they do this is largely unknown. 2.Here, we have investigated the temperature preference of the fruit fly, Drosophila melanogaster, during infection with the fungal pathogen, Metarhizium robertsii, and the consequences of temperature preference on life history traits. We have used multiple measurements to assess the fitness consequences of temperature including age-specific changes in mortality rate and reproduction, providing more sensitive measures of accounting for variation in fitness with age. 3.We report that D. melanogaster optimizes its life history by exploiting thermal variation. Fungus-infected fruit flies seek out cooler temperatures, which immediately reduces their fecundity but, ultimately, increases their lifetime reproductive success. Colder temperatures reduced fungal growth rates both in vivo and in vitro, indicating that cooler temperatures increased resistance to the infection. 4.By comparing life history responses in infected and control animals, we found that cold seeking in infected animals facilitates a trade off between early- and late-age reproduction, but does not otherwise provide life history benefits that are specific to infected animals. These results indicate that cold-seeking is a mechanism for reducing the reproductive costs of infection. In contrast, uninfected control flies prefer warmer temperatures that optimise reproductive success via a rapid propagation strategy. 5.These findings help explain how life history trade-offs are mediated and how animals cope with infection, which will be increasingly important given the recent emergence of fungal pathogens and global climate change.

Epidemiological studies indicate long-term risks of ionizing radiation on the heart, even at moderate doses. In this study, we investigated the inflammatory, thrombotic and fibrotic late responses of the heart after low-dose irradiation (IR) with specific emphasize on the dose rate. Hypercholesterolemic ApoE-deficient mice were sacrificed 3 and 6 months after total body irradiation (TBI) with 0.025, 0.05, 0.1, 0.5 or 2 Gy at low (1 mGy/min) or high dose rate (150 mGy/min). The expression of inflammatory and thrombotic markers was quantified in frozen heart sections (CD31, E-selectin, thrombomodulin, ICAM-1, VCAM-1, collagen IV, Thy-1, and CD45) and in plasma samples (IL6, KC, MCP-1, TNFα, INFγ, IL-1β, TGFβ, INFγ, IL-10, sICAM-1, sE-selectin, sVCAM-1 and fibrinogen) by fluorescence analysis and ELISA. We found that even very low irradiation doses induced adaptive late responses, such as increases of capillary density and changes in collagen IV and Thy-1 levels indicating compensatory regulation. Slight decreases of ICAM-1 levels and reduction of Thy 1 expression at 0.025–0.5 Gy indicate anti-inflammatory effects, whereas at the highest dose (2 Gy) increased VCAM-1 levels on the endocardium may represent a switch to a pro-inflammatory response. Plasma samples partially confirmed this pattern, showing a decrease of proinflammatory markers (sVCAM, sICAM) at 0.025–2.0 Gy. In contrast, an enhancement of MCP-1, TNFα and fibrinogen at 0.05–2.0 Gy indicated a proinflammatory and prothrombotic systemic response. Multivariate analysis also revealed significant age-dependent increases (KC, MCP-1, fibrinogen) and decreases (sICAM, sVCAM, sE-selectin) of plasma markers. This paper represents local and systemic effects of low-dose irradiation, including also age- and dose rate-dependent responses in the ApoE-/- mouse model. These insights in the multiple inflammatory/thrombotic effects caused by low-dose irradiation might facilitate an individual evaluation and intervention of radiation related, long-term side effects but also give important implications for low dose anti-inflammatory radiotherapy.

This work is supported by the EC-FP7 program no. 245500 and the BBSRC Microbial virulence is a complex and often multifactorial phenotype, intricately linked to a pathogen's evolutionary trajectory. Toxicity, the ability to destroy host cell membranes, and adhesion, the ability to adhere to human tissues, are the major virulence factors of many bacterial pathogens, including Staphylococcus aureus. Here, we assayed the toxicity and adhesiveness of 90 MRSA (methicillin resistant S. aureus) isolates and found that while there was remarkably little variation in adhesion, toxicity varied by over an order of magnitude between isolates, suggesting different evolutionary selection pressures acting on these two traits. We performed a genome-wide association study (GWAS) and identified a large number of loci, as well as a putative network of epistatically interacting loci, that significantly associated with toxicity. Despite this apparent complexity in toxicity regulation, a predictive model based on a set of significant single nucleotide polymorphisms (SNPs) and insertion and deletions events (indels) showed a high degree of accuracy in predicting an isolate's toxicity solely from the genetic signature at these sites. Our results thus highlight the potential of using sequence data to determine clinically relevant parameters and have further implications for understanding the microbial virulence of this opportunistic pathogen. Publisher PDF