Comparison of established and emerging biodosimetry assays

Rapid biodosimetry tools are required to assist with triage in the case of a large-scale radiation incident. Here, we aimed to determine the dose-assessment accuracy of the well-established dicentric chromosome assay (DCA) and cytokinesis-block micronucleus assay (CBMN) in comparison to the emerging γ-H2AX foci and gene expression assays for triage mode biodosimetry and radiation injury assessment. Coded blood samples exposed to 10 X-ray doses (240 kVp, 1 Gy/min) of up to 6.4 Gy were sent to participants for dose estimation. Report times were documented for each laboratory and assay. The mean absolute difference (MAD) of estimated doses relative to the true doses was calculated. We also merged doses into binary dose categories of clinical relevance and examined accuracy, sensitivity and specificity of the assays. Dose estimates were reported by the first laboratories within 0.3-0.4 days of receipt of samples for the γ-H2AX and gene expression assays compared to 2.4 and 4 days for the DCA and CBMN assays, respectively. Irrespective of the assay we found a 2.5-4-fold variation of interlaboratory accuracy per assay and lowest MAD values for the DCA assay (0.16 Gy) followed by CBMN (0.34 Gy), gene expression (0.34 Gy) and γ-H2AX (0.45 Gy) foci assay. Binary categories of dose estimates could be discriminated with equal efficiency for all assays, but at doses ≥1.5 Gy a 10% decrease in efficiency was observed for the foci assay, which was still comparable to the CBMN assay. In conclusion, the DCA has been confirmed as the gold standard biodosimetry method, but in situations where speed and throughput are more important than ultimate accuracy, the emerging rapid molecular assays have the potential to become useful triage tools

The rate of X-ray-induced DNA double-strand break repair in the embryonic mouse brain is unaff ected by exposure to 50 Hz magnetic fi elds

Following in utero exposure to low dose radiation (10 – 200 mGy), we recently observed a linear induction of DNA double-strand breaks (DSB) and activation of apoptosis in the embryonic neuronal stem/progenitor cell compartment. No signifi cant induction of DSB or apoptosis was observed following exposure to magnetic fi elds (MF). In the present study, we exploited this in vivo system to examine whether exposure to MF before and after exposure to 100 mGy X-rays impacts upon DSB repair rates. Materials and methods : 53BP1 foci were quantifi ed following combined exposure to radiation and MF in the embryonic neuronal stem/progenitor cell compartment. Embryos were exposed in utero to 50 Hz MF at 300 m T for 3 h before and up to 9 h after exposure to 100 mGy X-rays. Controls included embryos exposed to MF or X-rays alone plus sham exposures. Results : Exposure to MF before and after 100 mGy X-rays did not impact upon the rate of DSB repair in the embryonic neuronal stem cell compartment compared to repair rates following radiation exposure alone. Conclusions : We conclude that in this sensitive system MF do not exert any signifi cant level of DNA damage and do not impede the repair of X-ray induced damage

Epigenetic clock for skin and blood cells applied to Hutchinson Gilford Progeria Syndrome and ex vivo studies

DNA methylation (DNAm)-based biomarkers of aging have been developed for many tissues and organs. However, these biomarkers have sub-optimal accuracy in fibroblasts and other cell types used in ex vivo studies. To address this challenge, we developed a novel and highly robust DNAm age estimator (based on 391 CpGs) for human fibroblasts, keratinocytes, buccal cells, endothelial cells, lymphoblastoid cells, skin, blood, and saliva samples. High age correlations can also be observed in sorted neurons, glia, brain, liver, and even bone samples. Gestational age correlates with DNAm age in cord blood. When used on fibroblasts from Hutchinson Gilford Progeria Syndrome patients, this age estimator (referred to as the skin & blood clock) uncovered an epigenetic age acceleration with a magnitude that is below the sensitivity levels of other DNAm-based biomarkers. Furthermore, this highly sensitive age estimator accurately tracked the dynamic aging of cells cultured ex vivo and revealed that their proliferation is accompanied by a steady increase in epigenetic age. The skin & blood clock predicts lifespan and it relates to many age-related conditions. Overall, this biomarker is expected to become useful for forensic applications (e.g. blood or buccal swabs) and for a quantitative ex vivo human cell aging assay

A Bioinformatics Filtering Strategy for Identifying Radiation Response Biomarker Candidates

The number of biomarker candidates is often much larger than the number of clinical patient data points available, which motivates the use of a rational candidate variable filtering methodology. The goal of this paper is to apply such a bioinformatics filtering process to isolate a modest number (<10) of key interacting genes and their associated single nucleotide polymorphisms involved in radiation response, and to ultimately serve as a basis for using clinical datasets to identify new biomarkers. In step 1, we surveyed the literature on genetic and protein correlates to radiation response, in vivo or in vitro, across cellular, animal, and human studies. In step 2, we analyzed two publicly available microarray datasets and identified genes in which mRNA expression changed in response to radiation. Combining results from Step 1 and Step 2, we identified 20 genes that were common to all three sources. As a final step, a curated database of protein interactions was used to generate the most statistically reliable protein interaction network among any subset of the 20 genes resulting from Steps 1 and 2, resulting in identification of a small, tightly interacting network with 7 out of 20 input genes. We further ranked the genes in terms of likely importance, based on their location within the network using a graph-based scoring function. The resulting core interacting network provides an attractive set of genes likely to be important to radiation response

Investigations into MIMO systems from an electromagnetic perspective

The paper presents investigations into multiple input multiple output wireless communication systems, which are carried out from an electromagnetic perspective. The first part of the paper focuses on signal propagation models, which can be used for determining the MIMO system capacity or its performance when various space-time coding schemes are applied. Two types of models are considered. In the first model, array antennas are treated in an exact electromagnetic manner but interactions with scattering objects are incorporated using an approximate single bounce scattering approach. The other model is a simple but exact electromagnetic (EM) model, which takes into account EM interactions between antennas and scatterers. In this model, parallel wire dipoles represent antennas as well as scatterers. The second part of the paper reports on investigations into two types of MIMO testbeds. The first one is a simple transmit/receive diversity tested while the other one is a full MIMO testbed. The paper briefly describes the results obtained during the undertaken investigation

Biomarkers for Uranium Risk Assessment for the Development of the CURE (Concerted Uranium Research in Europe) Molecular Epidemiological Protocol

International audienceDespite substantial experimental and epidemiological research, there is limited knowledge of the uranium-induce health effects after chronic low-dose exposures in humans. Biological markers can objectively characterize pathological processes or environmental responses to uranium and confounding agents. The integration of such biological markers into a molecular epidemiological study would be a useful approach to improve and refine estimations of uranium-induced health risks. To initiate such a study, Concerted Uranium Research in Europe (CURE) was established, and involves biologists, epidemiologists and dosimetrists. The aims of the biological work package of CURE were 1. To identify biomarkers and biological specimens relevant to uranium exposure; 2. To define standard operating procedures (SOPs); and 3. To set up a common protocol (logistic, questionnaire, ethical aspects) to perform a large-scale molecular epidemiologic study in uranium-exposed cohorts. An intensive literature review was performed and led to the identification of biomarkers related to 1. retention organs (lungs, kidneys and bone); 2. other systems/organs with suspected effects (cardiovascular system, central nervous system and lympho-hematopoietic system); 3. target molecules (DNA damage, genomic instability); and 4. high-throughput methods for the identification of new biomarkers. To obtain high-quality biological materials, SOPs were established for the sampling and storage of different biospecimens. A questionnaire was developed to assess potential confounding factors. The proposed strategy can be adapted to other internal exposures and should improve the characterization of the biological and health effects that are relevant for risk assessment. © 2017 by Radiation Research Society