Bridging plant and human radiation response and DNA repair through an in silico approach

The mechanisms of response to radiation exposure are conserved in plants and animals. The DNA damage response (DDR) pathways are the predominant molecular pathways activated upon exposure to radiation, both in plants and animals. The conserved features of DDR in plants and animals might facilitate interdisciplinary studies that cross traditional boundaries between animal and plant biology in order to expand the collection of biomarkers currently used for radiation exposure monitoring (REM) in environmental and biomedical settings. Genes implicated in trans-kingdom conserved DDR networks often triggered by ionizing radiation (IR) and UV light are deposited into biological databases. In this study, we have applied an innovative approach utilizing data pertinent to plant and human genes from publicly available databases towards the design of a ‘plant radiation biodosimeter’, that is, a plant and DDR gene-based platform that could serve as a REM reliable biomarker for assessing environmental radiation exposure and associated risk. From our analysis, in addition to REM biomarkers, a significant number of genes, both in human and Arabidopsis thaliana, not yet characterized as DDR, are suggested as possible DNA repair players. Last but not least, we provide an example on the applicability of an Arabidopsis thaliana—based plant system monitoring the role of cancer-related DNA repair genes BRCA1, BARD1 and PARP1 in processing DNA lesions

Bridging plant and human radiation response and DNA repair through an in silico approach

The mechanisms of response to radiation exposure are conserved in plants and animals. The DNA damage response (DDR) pathways are the predominant molecular pathways activated upon exposure to radiation, both in plants and animals. The conserved features of DDR in plants and animals might facilitate interdisciplinary studies that cross traditional boundaries between animal and plant biology in order to expand the collection of biomarkers currently used for radiation exposure monitoring (REM) in environmental and biomedical settings. Genes implicated in trans-kingdom conserved DDR networks often triggered by ionizing radiation (IR) and UV light are deposited into biological databases. In this study, we have applied an innovative approach utilizing data pertinent to plant and human genes from publicly available databases towards the design of a ‘plant radiation biodosimeter’, that is, a plant and DDR gene-based platform that could serve as a REM reliable biomarker for assessing environmental radiation exposure and associated risk. From our analysis, in addition to REM biomarkers, a significant number of genes, both in human and Arabidopsis thaliana, not yet characterized as DDR, are suggested as possible DNA repair players. Last but not least, we provide an example on the applicability of an Arabidopsis thaliana—based plant system monitoring the role of cancer-related DNA repair genes BRCA1, BARD1 and PARP1 in processing DNA lesions. © 2017 by the authors. Licensee MDPI, Basel, Switzerland

Emerging molecular networks common in ionizing radiation, immune and inflammatory responses by employing bioinformatics approaches

Efficient radiation therapy is characterized by enhanced tumor cell killing involving the activation of the immune system (tumor immunogenicity) but at the same time minimizing chronic inflammation and radiation adverse effects in healthy tissue. The aim of this study was to identify gene products involved in immune and inflammatory responses upon exposure to ionizing radiation by using various bioinformatic tools. Ionizing radiation is known to elicit different effects at the level of cells and organism i.e. DNA Damage Response (DDR), DNA repair, apoptosis and, most importantly, systemic effects through the instigation of inflammatory 'danger' signals and innate immune response activation. Genes implicated both in radiation and immune/inflammatory responses were collected manually from the scientific literature with a combination of relevant keywords. The experimentally validated and literature-based results were inspected, and genes involved in radiation, immune and inflammatory response were pooled. This kind of analysis was performed for the first time, for both healthy and tumor tissues. In this way, a set of 24 genes common in all three different phenomena was identified. These genes were found to form a highly connected network. Useful conclusions are drawn regarding the potential application of these genes as markers of response to radiation for both healthy and tumor tissues through the modulation of immune and/or inflammatory mechanisms. © 2015 Elsevier Ireland Ltd

Key biological mechanisms involved in high-LET radiation therapies with a focus on DNA damage and repair

DNA damage and repair studies are at the core of the radiation biology field and represent also the fundamental principles informing radiation therapy (RT). DNA damage levels are a function of radiation dose, whereas the type of damage and biological effects such as DNA damage complexity, depend on radiation quality that is linear energy transfer (LET). Both levels and types of DNA damage determine cell fate, which can include necrosis, apoptosis, senescence or autophagy. Herein, we present an overview of current RT modalities in the light of DNA damage and repair with emphasis on medium to high-LET radiation. Proton radiation is discussed along with its new adaptation of FLASH RT. RT based on α-particles includes brachytherapy and nuclear-RT, that is proton-boron capture therapy (PBCT) and boron-neutron capture therapy (BNCT). We also discuss carbon ion therapy along with combinatorial immune-based therapies and high-LET RT. For each RT modality, we summarise relevant DNA damage studies. Finally, we provide an update of the role of DNA repair in high-LET RT and we explore the biological responses triggered by differential LET and dose. © The Author(s), 2022. Published by Cambridge University Press

Cross-check of Analysis Modules and Reasoner Interactions

This deliverable presents an extended set of Analysis Modules, including both the improvements done to those presented in deliverable D4.1 as well as the new analysis algorithms designed and developed to address use-cases. The deliverable also describes a complete workflow description for the different use-cases, including both stream processing for real-time monitoring applications as well as batch processing for “off-line” analysis. This workflow description specifies the iterative interaction loop between WP2, WP3, T4.1, and T4.2, thereby allowing for a cross-checking of the analysis modules and the reasoner interactions.mPlane – an Intelligent Measurement Plane for Future Network and Application Managemen

Investigation on the correlation between energy deposition and clustered DNA damage induced by low-energy electrons

This study presents the correlation between energy deposition and clustered DNA damage, based on a Monte Carlo simulationof the spectrum of direct DNA damage induced by low-energy electrons including the dissociative electron attachment.Clustered DNA damage is classified as simple and complex in terms of the combination of single-strand breaks (SSBs) ordouble-strand breaks (DSBs) and adjacent base damage (BD). The results show that the energy depositions associated withabout 90% of total clustered DNA damage are below 150 eV. The simple clustered DNA damage, which is constituted of thecombination of SSBs and adjacent BD, is dominant, accounting for 90% of all clustered DNA damage, and the spectra of theenergy depositions correlating with them are similar for different primary energies. One type of simple clustered DNA damageis the combination of a SSB and 1–5 BD, which is denoted as SSB+BD. The average contribution of SSB+BD to totalsimple clustered DNA damage reaches up to about 84% for the considered primary energies. In all forms of SSB+BD, theSSB+BD including only one base damage is dominant (above 80%). In addition, for the considered primary energies, there isno obvious difference between the average energy depositions for a fixed complexity of SSB+BD determined by the numberof base damage, but average energy depositions increase with the complexity of SSB+BD. In the complex clustered DNAdamage constituted by the combination of DSBs and BD around them, a relatively simple type is a DSB combining adjacentBD, marked as DSB+BD, and it is of substantial contribution (on average up to about 82%). The spectrum of DSB+BD isgiven mainly by the DSB in combination with different numbers of base damage, from 1 to 5. For the considered primaryenergies, the DSB combined with only one base damage contributes about 83% of total DSB+BD, and the average energydeposition is about 106 eV. However, the energy deposition increases with the complexity of clustered DNA damage, andtherefore, the clustered DNA damage with high complexity still needs to be considered in the study of radiation biologicaleffects, in spite of their small contributions to all clustered DNA damage