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I Plante

Publications and source records attributed to I Plante.

10 records
All sourcesNASA NTRSDOE OSTI
NASA NTRSDate not supplied

Individual Variability and Predictive Biomarkers of Human Sensitivity to Ionizing Radiation

High-linear energy transfer (LET) ionizing radiation is a major health hazard for astronauts who will be exposed to galactic cosmic rays during upcoming lunar and Mars missions. Predicting and mitigating personalized health risks from space radiation exposure requires understanding the factors underlying individual radiation sensitivity, which currently remain unknown. We started to address this challenge by identifying the genomic and demographic associations with sensitivity to low and high-LET ionizing radiation in the largest human sample cohort to date and by evaluating baseline DNA damage as a potential predictor of radiation responses. We have collected and irradiated peripheral blood mononuclear cells (PBMCs) from 768 healthy donors of matched ethnicity, 50/50 male/female, 18-70 years old. We have analyzed the responses of 576 donor PBMCs to irradiation with simulated galactic cosmic ray components: 350MeV/n 28Si, 350MeV/n 40Ar and 600MeV/n 56Fe, at 1.1 and 3 particles/100μm2 fluences, as well as 0.1Gy and 1Gy doses of gamma rays, at 4 and 24 hours post irradiation. We quantified post-irradiation DNA repair based on radiation-induced 53BP1+ foci formation, together with oxidative stress and cell death using a flow cytometry-based assay. We also assessed baseline levels of DNA repair in PBMCs at the time of sample collection prior to irradiation experiments. We observed a wide variability of subject- and LET-dependent radiation responses, with radiation-induced DNA repair foci increasing with LET, though oxidative stress being notably reduced by high-LET irradiation, potentially due to a switch between hydrogen peroxide and oxygen radical-based mechanisms. We also identified a relationship between few DNA repair foci at baseline and increased DNA repair after irradiation, accompanied by an alteration in immunoregulatory cytokine secretion, which might be adapted as biomarkers to predict ionizing radiation sensitivity. Among demographic variables, baseline foci levels were positively associated with age and latent cytomegalovirus infection. Finally, we have performed low-throughput whole genome sequencing of all samples and are currently in process of identifying the genes and pathways associated with low and high-LET ionizing radiation sensitivity in humans.

Space radiation, human spaceflight, DNA damage↗
NASA NTRSDate not supplied

Impact of Space Radiation on Plants: from Arabidopsis thaliana to Crops

One of the major concerns for long-term exploration missions beyond the Earth’s magnetosphere is radiation risk, primarily from solar particle events (SPE) and galactic cosmic rays (GCR). With the goal of manned Mars exploration, the production of fresh food during long-duration space missions provides critical nutritional supplementation and may also benefit astronauts’ behavioral health. However, the effects of space radiation on plants and plant propagules have not been sufficiently investigated and characterized. In this study, we evaluated the effect of simulated GCR (using dry seeds) or SPE (using hydrated seeds) on seeds of Arabidopsis, Mizuna mustard, ‘Outredgeous’ red romaine lettuce, and ‘Red Robin’ dwarf tomato. Seeds were exposed to various doses of simulated space radiation scenarios, either acutely or at a low dose rate (LDR), using the NASA Space Radiation Laboratory (NSRL) facility at Brookhaven National Lab (BNL). Exposure to simulated GCR or SPE at the levels tested had no significant impact on the germination rate in Arabidopsis and crop seeds; however, GCR reduced the viability of lettuce and tomato seeds. Overall, the morphological changes of the seedlings cultured from irradiated seeds were dose- and ion quality- dependent, with heavier ions causing more severe damage. These changes ranged from cotyledon deformation, shortened root length, smaller seedling size, and other signs of stress, depending on the seed types. Both 40 and 80 cGy (LDR) exposures of GCR or SPE significantly affected tomato early seedling development, delayed tomato fruiting, and reduced the total yield of tomato. Altered nutritional values were also found in edible biomass, especially for the GCR 80 cGy (LDR) groups. For both GCR and SPE, 40 cGy showed some effects, but to a much lesser extent compared with 80 cGy, which can be considered as the “maximum permissible exposure” for the seed types we evaluated in this study. The impact of space radiation on seeds potentially affects the ability of plants to adapt to other environmental stresses (e.g. microgravity, water stress, and hardware constraints) as well as susceptibility to plant diseases, which need to be furtherly investigated. This research is funded by NASA’s Human Research Program.

J T Richards↗
NASA NTRSDate not supplied

Impact of Space Radiation on Plant Seeds: from Arabidopsis thaliana to Crops

One of the major concerns for long-term exploration missions beyond the Earth’s magnetosphere is radiation risk, primarily from solar particle events (SPE) and galactic cosmic rays (GCR). With the goal of manned Mars exploration, the production of fresh food during long-duration space missions provides critical nutritional supplementation and may also benefit astronauts’ behavioral health. However, the effects of space radiation on plants and plant propagules have not been sufficiently investigated and characterized. In this study, we evaluated the effect of simulated GCR (using dry seeds) or SPE (using hydrated seeds) on seeds of Arabidopsis, Mizuna mustard, ‘Outredgeous’ red romaine lettuce, and ‘Red Robin’ dwarf tomato. Seeds were exposed to various doses of simulated space radiation scenarios, either acutely or at a low dose rate (LDR), using the NASA Space Radiation Laboratory (NSRL) facility at Brookhaven National Lab (BNL). Exposure to simulated GCR or SPE at the levels tested had no significant impact on the germination rate in Arabidopsis and crop seeds; however, GCR reduced the viability of lettuce and tomato seeds. Overall, the morphological changes of the seedlings cultured from irradiated seeds were dose- and ion quality- dependent, with heavier ions causing more severe damage. These changes ranged from cotyledon deformation, shortened root length, smaller seedling size, and other signs of stress, depending on the seed types. Both 40 and 80 cGy (LDR) exposures of GCR or SPE significantly affected tomato early seedling development, delayed tomato fruiting, and reduced the total yield of tomato. Altered nutritional values were also found in edible biomass, especially for the GCR 80 cGy (LDR) groups. For both GCR and SPE, 40 cGy showed some effects, but to a much lesser extent compared with 80 cGy, which can be considered as the “maximum permissible exposure” for the seed types we evaluated in this study. The impact of space radiation on seeds potentially affects the ability of plants to adapt to other environmental stresses (e.g. microgravity, water stress, and hardware constraints) as well as susceptibility to plant diseases, which need to be furtherly investigated. This research is funded by NASA’s Human Research Program.

J T Richards↗
NASA NTRSDate not supplied

Impact of Space Radiation on Plant Seeds: from Arabidopsis thaliana to Crops

One of the major concerns for long-term exploration missions beyond the Earth’s magnetosphere is radiation risk, primarily from solar particle events (SPE) and galactic cosmic rays (GCR). With the goal of manned Mars exploration, the production of fresh food during long-duration space missions provides critical nutritional supplementation and may also benefit astronauts’ behavioral health. However, the effects of space radiation on plants and plant propagules have not been sufficiently investigated and characterized. This is the final report of our project to summarize the findings of the effect of space radiation exposure on plant seeds from morphometrics, nutritional values, to molecular machenisms. In this study, we evaluated the effect of simulated GCR (using dry seeds) or SPE (using hydrated seeds) on seeds of Arabidopsis, Mizuna mustard, ‘Outredgeous’ red romaine lettuce, and ‘Red Robin’ dwarf tomato. Seeds were exposed to various doses of simulated space radiation scenarios, either acutely or at a low dose rate (LDR), using the NASA Space Radiation Laboratory (NSRL) facility at Brookhaven National Lab (BNL). Exposure to simulated GCR or SPE at the levels tested had no significant impact on the germination rate in Arabidopsis and crop seeds; however, GCR reduced the viability of lettuce and tomato seeds. Overall, the morphological changes of the seedlings cultured from irradiated seeds were dose- and ion quality- dependent, with heavier ions causing more severe damage. These changes ranged from cotyledon deformation, shortened root length, smaller seedling size, and other signs of stress, depending on the seed types. Both 40 and 80 cGy (LDR) exposures of GCR or SPE significantly affected tomato early seedling development, delayed tomato fruiting, and reduced the total yield of tomato. Altered nutritional values were also found in edible biomass, especially for the GCR 80 cGy (LDR) groups. Underlying mechanisms were furtherly evaluated using transcriptomic analysis. For both GCR and SPE, 40 cGy showed some effects, but to a much lesser extent compared with 80 cGy, which can be considered as the “maximum permissible exposure” for the seed types we evaluated in this study. The impact of space radiation on seeds potentially affects the ability of plants to adapt to other environmental stresses (e.g. microgravity, water stress, and hardware constraints) as well as susceptibility to plant diseases, which need to be furtherly investigated. This research is funded by NASA’s Human Research Program.

J T Richards↗
NASA NTRSDate not supplied

Integration of the Cardiovascular Clinical Risk Prediction Model Astro-CHARM Into the NASA Radiation Risk Model

Space radiation poses an increased risk for cardiovascular diseases (CVD) during and after spaceflight, that should be quantified to plan future space missions such as the flight to Mars. The radiation-induced CVD risk is evaluated using a linear no-threshold dose response excess relative risk (ERR) model, so that the risk is function of the radiation dose and of the background (i.e., non-exposed) incidence rate. The background CVD risk can be evaluated using clinical prediction models (CPMs). The first CPMs developed in the 1960’s have identified CVD risk factors such as blood pressure, diabetes, cholesterol, and smoking. In this work, the steps used to integrate the CVD risk provided by a CPM into the NASA Radiation Risk Model are described. Simulation results calculated using available data for relevant mission scenarios are also shown, and the challenges in CVD risk predictions are discussed.

I Plante↗
NASA NTRSDate not supplied

Analytical Calculation of the Energy Deposition Spectrum and Average Dose to A Spherical Target By Ion Tracks at All Impact Parameters

Microdosimetry is used to estimate quality factors for risk assessment in radiation protection [1] and to quantify relative biological effectiveness (RBE) for treatment planning of hadron radiation therapy [2]. Radiation physics has shown that energetic ions deposit energy in a complex manner: the track structure. The Local Effect Model (LEM) [3] is often used as an approximation to describe this complex track structure. We have previously calculated an analytical expression for the dose to a spherical target fully located in the penumbra of an ion track using the LEM [4]. In this work, the calculation has been extended to all impact parameters. Furthermore, using these analytical expressions, it was possible to obtain the theoretical energy deposition spectra to a sphere irradiated uniformly.

I Plante↗
NASA NTRSDate not supplied

Simulation of Radiation-Induced DNA Damage With the Code RITRACKS

INTRODUCTION DNA damage is one of the most physiologically important effects of ionizing radiation. Clustered DNA damage events, like double-strand breaks (DSBs), have the most notable biological consequences. DNA damage types depend on both the track structure of the radiation and the spatial organization of the DNA. High linear energy transfer (LET) charged nuclei, found in galactic cosmic rays (GCR), are known to produce large numbers of complex DNA damage events. The human genome is packaged into chromatin, which can take on locus-dependent and cell type-dependent spatial conformations that correspond to epigenetic states, such as more open, extended structures in transcriptionally active chromatin. These epigenetic differences can affect DNA break patterns in response to ionizing radiation, potentially creating distinct DNA repair and signaling outcomes across the genome in different cells. MATERIAL AND METHODS The code RITRACKS (Relativistic Ion Tracks), which simulates stochastic radiation track structures and radiation chemistry, was used to model damage on isolated and histone-bound DNA by various types of ions and photons. The changes made to the code to perform radiation-induced DNA damage, and simulation results on single nucleosomes are given in our recent paper. In this work, the DNA building capabilities of RITRACKS have been extended to simulate more complex DNA structures build on the coarse-grain simulation framework meso-WLCsim. This code can sample generic chromatin fiber conformation ensembles based on the geometry of nucleosomes and mechanical properties of DNA. Using RITRACKS, we simulated the fragment length distributions (FLD) of irradiated DNA structures built using the chromatin conformations of WLCsim and obtained results representative of those obtained with Radiation-Induced Correlated Cleavage with sequencing (RICC-Seq) experiments [6]. We have also performed Fe ion and photon irradiations of K562, IMR90, BJ and RPE-1 cells at NSRL to experimentally validate results. Sample processing and data analysis are in progress and any available preliminary results will be discussed. DISCUSSION The recent updates in the code RITRACKS allow the calculation of several quantities such as the DNA damage yield and the FLD. This approach can be used to model epigenetic state-specific chromatin structure parameters to leverage the epigenetic state data available for many human cell types to infer relative DNA damage sensitivity among genomic loci.

I Plante↗