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At least 343 records · Page 19

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NASA NTRSDate not supplied

Genomic and phenotypic predictors of human ex vivo sensitivity to simulated deep space 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 this risk requires understanding the factors underlying individual radiation sensitivity. We started to address this challenge by identifying the genomic and phenotypic associations with sensitivity to low and high-LET ionizing radiation ex vivo in over 750 healthy human donors. We exposed primary human blood mononuclear cells to simulated galactic cosmic ray components: 350MeV/n (28)Si, 350MeV/n (40)Ar and 600MeV/n (56)Fe particles, at 1.1 and 3 particles/100µm^(2) fluences, as well as 0.1 Gy and 1 Gy doses of gamma rays, and analyzed the outcomes at 4 and 24 hours post-irradiation. We quantified DNA damage and repair responses based on 53BP1^(+) radiation-induced foci formation, together with oxidative stress and changes in secreted factors including immune cytokines and exosomes. We also analyzed phenotypic associations with spontaneous DNA repair foci at baseline prior to irradiation. We identified an increase in spontaneous DNA repair associated with age and latent viral infection, and observed that human spontaneous DNA repair foci at baseline can serve as a negative predictor of DNA repair and immunoregulatory cytokine production after irradiation. Furthermore, we observed a wide variability of subject- and LET-dependent radiation responses, with radiation-induced DNA repair foci increasing by dose and LET, and high-LET particle radiation resulting in more residual DNA damage compared to low-LET particles and gamma rays. We have developed multiple metrics to quantify human radiosensitivity across the spectrum of conditions. Here we present their dependence on radiation quality and phenotypic variables, including an age-dependent decrease in DNA repair after irradiation, and genomic associations with radiosensitivity based on low-coverage whole genome sequencing. We anticipate that our work will pave the way for understanding the spectrum of human radiosensitivity and identifying targets for countermeasure development to reduce DNA and cellular damage and radiation carcinogenesis during deep space exploration.

GWAS↗

NASA NTRSDate not supplied

Efficacy of Dried Plum to Countermeasure Simulated Spaceflight Exposure

Human exploration of the space environment has been a topic of interest for decades; however, the threat to physiological health posed by ionizing radiation and microgravity effects remains a concern. Previous research utilizing combined hindlimb unloading and irradiation to simulate spaceflight effects found that a dried plum diet can mitigate adverse effects of simulated spaceflight on skeletal health. Though the mechanism is not fully understood we believe this protective effect is due to its high antioxidant capacity and polyphenolic content. This study seeks to extend these findings to investigate if dried plum is an effective countermeasure in other tissues relating to aging and neurotoxicity. Male C57BL/6 J mice were assigned to one of eight groups (n = 10/group) and were fed either a controlled diet or dried plum diet, underwent normal loading or hindlimb unloading as well as exposure 2 Gy gamma radiation or sham exposure. At the end of the experiment, mice were euthanized, and RNA was extracted from brain and bone marrow tissue and PCR was employed to analyze significant changes in gene expression profiles. Analysis of five house-keeping genes revealed genes B2M (neurotoxicity) and GUSB (aging) to be the most stable genes across all treatments and were used to find the fold change within our genes of interest. Through this, and analysis via ANOVA, we were able to identify genes with significant altered expression levels within brain and bone marrow tissues related to neurotoxicity and aging. Considering previous research, we hypothesize that the dried plum diet’s antioxidative properties ameliorated the oxidative stress from irradiation and microgravity via altered levels of gene expression. Identified expression changes will provide insights into molecular mechanisms behind the observed protective effects. These findings present potential avenues for future interventions to alleviate negative impacts of spaceflight on astronaut health.

Faisal Ahmad↗

NASA NTRSDate not supplied

NASA Hypersonic Technology Project (HTP) Sic/Sic Research for Hypersonic Airframe Hot Structures

NASA, DoD, and industry have a vision for reusable hypersonic vehicles (Mach > 5). The realization of this vision will require high-specific-strength, high-temperature, reusable structures. In the sub-sonic and super-sonic flight regimes, high-specific-strength structures can be obtained via the use of aluminum, titanium, and composite materials. In the high-temperature environments associated with hypersonic flight, high specific strength is obtained via refractory-composite materials. NASA Langley Research Center has multiple efforts focused on evaluating refractory-composites for use as airframe hot structures for reusable hypersonic vehicles. Current efforts span the entire building-block approach, including coupon, element, subcomponent, and component manufacturing and testing. The coupon level work includes progressive damage testing and analysis, restrained thermal growth testing, stressed oxidation testing, and evaluation of laminate properties for several layup architectures. Element testing includes evaluation of over-temperature capability and co-processed bonding, fastener development, and analysis and testing of beaded (corrugated) panels. Subcomponent level work includes a solid rocket motor booster fin and a portion of a control surface, and component level work includes a control surface static test article. The current presentation will provide an update of work being performed at NASA, which is expected to transition refractory-composite materials to reusable hypersonic vehicles.

Hot structures↗

NASA NTRSDate not supplied

Plasma and Brain Cytokine Responses to Single and Combinatorial Spaceflight Stressors in Male and Female Mice

Spaceflight involves exposure to multiple environmental stressors, including Ionizing Radiation (IR), microgravity, and social isolation. We hypothesize that spaceflight stressors combine synergistically to trigger an oxidative stress response that, in turn, alters immune homeostasis, brain structure/function, and neurobehavioral/cognitive performance. Here, we report plasma and brain cytokine findings from two studies of crew age-matched (24-week-old) male and female mice exposed to simulated 5-Ion GCRsim at the NASA Space Radiation Laboratory (NSRL). In Study 1, mice were exposed to 0, 5, 15, or 50cGy 5-ion GCRsim. Immune and brain measures were acquired either at ‘Acute’ (within 3 days post-irradiation; IR), ‘Intermediate’ (IR+14 days) or ‘Delayed’ (IR+125 days) timepoints. In Study 2, mice were exposed singly and in combination to 15cGy 5-ion GCRsim, simulated microgravity via continuous head-down tilt/hindlimb unloading (HU), and social isolation. Plasma and brain cytokine cytokine profiling revealed sex-specific as well as sex-common responses. Notably, plasma granulocyte colony stimulating factor (GCSF) levels showed significant regulation compared to a single stressor alone, suggesting a potential biomarker responder. Increased GCSF was correlated with corresponding increased blood neutrophil populations. Futhermore, our study provides evidence for robust effects of HU relative to IR alone. This project addresses NASA’s efforts to characterize risks in both women and men in anticipation of future space missions beyond low earth orbit (BLEO). Ensuring crew health and performance during extended transits to the moon and beyond necessitates that sensorimotor and cognitive abilities remain strong to avoid potentially catastrophic health and safety outcomes.

mouse radiation hindlimb unloading spaceflight↗

NASA NTRSDate not supplied

Effects Of Five-Ion Galactic Cosmic Radiation Simulation On Immune Function, Brain, And Behavior In Male And Female Mice

Exposure to galactic cosmic radiation is a principal consideration of spaceflight missions, and with upcoming missions to the Moon and Mars, it is increasingly imperative to elucidate the effects of space travel beyond the lower Earth orbit. Additionally, with the first female astronaut to soon travel to the Moon there is a strong need to understand the biological sex differences to adaptation to the deep space environment. While the effects of spaceflight on the nervous system are not fully known, studies in animal models have shown that exposure to ionizing radiation can cause neuronal damage and lead to downstream cognitive and behavioral deficits. To simulate the type of radiation exposure occurring during spaceflight, model organisms can be exposed to relevant doses via Five-Ion Galactic Cosmic Radiation Simulation at the NASA National Space Radiation Laboratory at Brookhaven National Laboratory. We have investigated the neurobehavioral responses to space environment-like radiation exposure. Male and female 23–24-week-old mice (age-matched to average astronaut age) were exposed to 5, 15 and 50 cGy. Following exposure, immune, brain and behavioral (sensorimotor, risk-taking and cognitive) measures were acquired at ‘Acute’ (IR+24hrs, IR+72hrs), ‘Intermediate’ (IR+14 days) and ‘Delayed’ (IR+28 to IR+124 days) to inform biological responses anticipated during a transit to Moon and Mars. There were pronounced sex differences observed in all outcome measurements, while very few radiation induced effects were observed. Those dose effects that were observed were primarily in cytokine expression and less so in behavioral measurements. Further studies will investigate if radiation, microgravity and social isolation combine synergistically to trigger an oxidative stress response that alters immune homeostasis, brain structure/function, and neurobehavioral/cognitive performance, ultimately to characterize risks and identify appropriate countermeasures in both women and men in anticipation of future deep space missions.

Stephanie Puukila↗

NASA NTRSDate not supplied

The Efficacy of Dried Plum to Counter Spaceflight Microgravity and Radiation

Faisal Ahmad↗

NASA NTRS2024

Long-term effects of acute irradiation and isolation on crew age-matched mice

The future of space missions beyond low-Earth orbit presents exciting opportunities but may come with formidable health challenges. Astronauts face a unique combination of space stressors capable of exerting effects on the central nervous system (CNS) with possible sex-dependent differences. The interaction of these combined spaceflight stressors may induce oxidative stress, thereby altering brain integrity and behavioral performance. Understanding these changes is critical for safeguarding astronaut health and enabling successful exploration. By understanding the physiological responses to the combined effects of ionizing radiation (IR) and social isolation in the brain through immunohistochemistry (IHC), proteomics and cytokine expression analyses, we aim to identify CNS pathways ripe for countermeasure development to mitigate adverse brain changes with future deep space exploration. Here, we study the combined effects of simulated 5-ion galactic cosmic radiation (GCRsim) at acute dosage (5, 15, and 50 cGy) and social isolation on crew age-matched male and female mice at 124 days post-irradiation. We conducted analyses of hippocampal cytokine biomarkers and proteomic profiling on hippocampal lysates. Our findings reveal sex-specific regulation of hippocampal cytokines and proteomic profiles. Ongoing immunohistochemistry findings on the hippocampus will provide qualitative information regarding key protein expression and cellular changes such as microglial activation, blood brain barrier integrity, and neuroinflammation. With future plans for long-duration space missions, such as Mars exploration, understanding CNS changes over extended periods in mice can provide insights into potential long-term health impacts on astronauts. This project will provide us with valuable insights into sex-differences in neurobiological processes and disease mechanisms impacting men and women in space.

space radiation↗

NASA NTRSDate not supplied

The ABCs of Spaceflight: Evaluating the Impact of Spaceflight on ABC Proteins (P-Glycoprotein) in the Blood Brain Barrier

Both astronauts and other model organisms experience negative effects from spaceflight, such as Blood-Brain Barrier (BBB) leakage—this vital barrier protects the brain from harmful substances. This leakage results from oxidative stress and neuroinflammation caused by proinflammatory cytokines which damage surrounding tissue. Thus, our proposal uses Drosophila Melanogaster(Fruit fly) transcriptomics data from OSD-588 to investigate the role of microgravity on the BBB and methods to mitigate these implications,

drosophila↗

NASA NTRS2011

Defining the Relationship Between Biomarkers of Oxidative and Inflammatory Stress and the Risk for Atherosclerosis in Astronauts During and After Long-Duration Spaceflight

Future human space travel will primarily consist of long-duration missions aboard the International Space Station (ISS) or exploration class missions to Mars, its moons, or nearby asteroids. These missions will expose astronauts to increased risk of oxidative and inflammatory damage primarily from radiation, but also from psychological stress, reduced physical activity, diminished nutritional status, and, in the case of extravehicular activity, hyperoxic exposure. There is evidence that increased oxidative damage and inflammation can accelerate the development of atherosclerosis. PURPOSE The purpose of this proposal is to identify biomarkers of oxidative and inflammatory stress and to correlate them to indices of atherosclerosis risk before, during, and after long-duration spaceflight. METHODS To meet the objectives of the study, we will study astronauts before, during, and up to 5 years after long-duration missions aboard ISS. Biomarkers of oxidative and inflammatory stress, some of which we have previously shown to be elevated with spaceflight, will be measured before, during, and after spaceflight. Arterial structure will be monitored using ultrasound to measure carotid intima-medial thickness before, during, and after weightlessness. Carotid intima-medial thickness has been shown to be a better indicator than Framingham Risk scores for prediction of atherosclerosis. Arterial function will be monitored using brachial flow-mediated dilation before flight and after landing. Brachial flow-mediated dilation is a good index of endothelium-dependent vasodilation, which is a sensitive predictor of atherosclerotic risk. This is the first study to propose assessing atherosclerotic risk using biochemical, structural, and functional measures before, during, and immediately after spaceflight and structural functional measures for up to 5 years after landing. EXPECTED RESULTS We hypothesize that these biomarkers of oxidative and inflammatory stress will be increased with spaceflight and will correlate with increased carotid intima-medial thickness in- and postflight and with decreased flow-mediated dilation after the mission. Furthermore, we hypothesize that measures of oxidative stress will return to baseline after flight, but that biomarkers of inflammatory stress and vascular indices of atherosclerosis risk will remain elevated.

Lee, Stuart M. C.↗

NASA NTRS2014

Defining the Relationship between Biomarkers of Oxidative and Inflammatory Stress and the Risk for Atherosclerosis in Astronauts during and after Long-duration Spaceflight

Future human space travel will consist primarily of long-duration missions onboard the International Space Station (ISS) or exploration-class missions to Mars, its moons, or nearby asteroids. These missions will expose astronauts to increased risk of oxidative and inflammatory damage from a variety of sources, including radiation, psychological stress, reduced physical activity, diminished nutritional status, and hyperoxic exposure during extravehicular activity. Evidence exists that increased oxidative damage and inflammation can accelerate the development of atherosclerosis. PURPOSE The purpose of this investigation is to determine whether biomarkers of oxidative and inflammatory stress are elevated during and after long-duration spaceflight and investigate if a relation exists between levels of these biomarkers and structural and functional indices of atherosclerotic risk measured in the carotid and brachial arteries. This is the first study to propose assessing atherosclerotic risk using biochemical, structural, and functional measures before, during, and immediately after spaceflight, and structural and functional measures for up to 5 years after landing. METHODS We will study 12 astronauts before, during, and up to 5 years after long-duration ISS missions. A panel of biomarkers of oxidative and inflammatory stress will be measured twice before flight, early (flight days 15 and 60) and late (2 weeks before landing) during the mission, and early in the postflight recovery phase (approx 3 days after landing). Arterial structure and vascular compliance will be measured at the same times and also at 1, 3, and 5 years after landing (surveillance). Arterial function will be measured using the same preflight, postflight, and surveillance schedule as arterial structure and vascular compliance measures, but will not be measured inflight. Biomarkers, some of which we have previously shown to be elevated with spaceflight, will be measured in venous blood samples and 24-h (in-flight) and 48-h (pre- and post-flight) urine pools. Arterial structure will be assessed from measures of carotid intima-media thickness, which have been shown to be better indicators of atherosclerotic than the Framingham Risk Score. Arterial function will be assessed using brachial flow-mediated dilation, a well-validated measure used to assess endothelium-dependent vasodilation and is a sensitive predictor of atherosclerotic risk. Arterial pulse pressure measured in the brachial artery and stroke volume measured from cardiac ultrasound will be used to assess hemodynamic status, cardiac function, and systemic vascular compliance. Three astronauts are actively participating in the preflight data collection and training activities. One astronaut has completed all preflight activities and will participate in the first in-flight data collection sessions by the end of 2013. The first post-flight data collection sessions will occur in the spring of 2014. EXPECTED RESULTS We hypothesize that biomarkers of oxidative and inflammatory stress will increased with spaceflight and will correlate with increased carotid intima-media thickness during and after flight and with decreased flow-mediated dilation after the mission. Furthermore, we hypothesize that measures of oxidative stress will return to baseline after flight, but biomarkers of inflammatory stress and vascular indices of atherosclerotic risk will remain elevated.

Lee, Stuart M. C.↗

NASA NTRS1998

Effect of Layer-Graded Bond Coats on Edge Stress Concentration and Oxidation Behavior of Thermal Barrier Coatings

Thermal barrier coating (TBC) durability is closely related to design, processing and microstructure of the coating Z, tn systems. Two important issues that must be considered during the design of a thermal barrier coating are thermal expansion and modulus mismatch between the substrate and the ceramic layer, and substrate oxidation. In many cases, both of these issues may be best addressed through the selection of an appropriate bond coat system. In this study, a low thermal expansion and layer-graded bond coat system, that consists of plasma-sprayed FeCoNiCrAl and FeCrAlY coatings, and a high velocity oxyfuel (HVOF) sprayed FeCrAlY coating, is developed to minimize the thermal stresses and provide oxidation resistance. The thermal expansion and oxidation behavior of the coating system are also characterized, and the strain isolation effect of the bond coat system is analyzed using the finite element method (FEM). Experiments and finite element results show that the layer-graded bond coat system possesses lower interfacial stresses. better strain isolation and excellent oxidation resistance. thus significantly improving the coating performance and durability.

Zhu, Dongming↗

DOE OSTI2026

Transcriptomic data sets examining several stress responses in Zymomonas mobilis strains

We used RNA-seq to compare gene expression from Zymomonas mobilis ZM4 grown under various conditions: aerobic ± paraquat, anaerobic ± hydrogen peroxide, or an iron chelator. We analyzed two mutant strains lacking predicted transcription factors (ZMO_0442 and ZMO_1411) grown under aerobic or anaerobic conditions. We report the RNA-seq data from these experiments.

Bacterial Stress Response↗

NASA NTRS2016

Defining the Relationship Between Biomarkers of Oxidation and Inflammatory Stress and the Risk for Atherosclerosis in Astronauts During and After Long-Duration Spaceflight

Lee, Stuart M. C.↗

NASA NTRS2002

Acetylcholine released from cholinergic nerves contributes to cutaneous vasodilation during heat stress

Nitric oxide (NO) contributes to active cutaneous vasodilation during a heat stress in humans. Given that acetylcholine is released from cholinergic nerves during whole body heating, coupled with evidence that acetylcholine causes vasodilation via NO mechanisms, it is possible that release of acetylcholine in the dermal space contributes to cutaneous vasodilation during a heat stress. To test this hypothesis, in seven subjects skin blood flow (SkBF) and sweat rate were simultaneously monitored over three microdialysis membranes placed in the dermal space of dorsal forearm skin. One membrane was perfused with the acetylcholinesterase inhibitor neostigmine (10 microM), the second membrane was perfused with the NO synthase inhibitor N(G)-nitro-l-arginine methyl ester (l-NAME; 10 mM) dissolved in the aforementioned neostigmine solution (l-NAME(Neo)), and the third membrane was perfused with Ringer solution as a control site. Each subject was exposed to approximately 20 min of whole body heating via a water-perfused suit, which increased mean body temperature from 36.4 +/- 0.1 to 37.5 +/- 0.1 degrees C (P < 0.05). After the heat stress, SkBF at each site was normalized to its maximum value, identified by administration of 28 mM sodium nitroprusside. Mean body temperature threshold for cutaneous vasodilation was significantly lower at the neostigmine-treated site relative to the other sites (neostigmine: 36.6 +/- 0.1 degrees C, l-NAME(Neo): 37.1 +/- 0.1 degrees C, control: 36.9 +/- 0.1 degrees C), whereas no significant threshold difference was observed between the l-NAME(Neo)-treated and control sites. At the end of the heat stress, SkBF was not different between the neostigmine-treated and control sites, whereas SkBF at the l-NAME(Neo)-treated site was significantly lower than the other sites. These results suggest that acetylcholine released from cholinergic nerves is capable of modulating cutaneous vasodilation via NO synthase mechanisms early in the heat stress but not after substantial cutaneous vasodilation.

Non-NASA Center↗

DOE OSTI2023

Evaluation of air oxidation and internal stresses induced by quenching of partially Cr-coated and uncoated optimized ZIRLO part I: Materials characterization

Not provided.

Chemistry↗

DOE OSTI2023

Modeling the two-way coupling of stress, diffusion, and oxidation in heterogeneous CMC microstructures

Not Available

36 MATERIALS SCIENCE↗

NASA NTRS1972

A common modality of action of simulated space stresses on the oxidative metabolism of ethylmorphine, aniline and p-nitroanisole by male rat liver.

High gravity, cold and starvation elicited similar responses in male Simonson rats. These responses included a decreased rate in body weight gain, increased metabolism of aniline and p-nitroanisole, and no consistent pattern of change in the metabolism of ethylmorphine. Cold and starvation increased the amount of hepatic cytochrome P-450, while hypobaric-hyperoxia caused no change in any of the parameters measured. When 1% acetone was given to the rats in their drinking water, the effects on drug metabolism were similar to those produced by food restriction in that the metabolism of aniline and p-nitroanisole was increased, and the metabolism of ethylmorphine unchanged. The type I binding spectrum of acetone suggests that it is either a substrate, inhibitor, or both for hepatitic oxidative enzymes.

Furner, R. L.↗

NASA NTRS1984

Literature survey on oxidations and fatigue lives at elevated temperatures

Nickel-base superalloys are the most complex and the most widely used for high temperature applications such as aircraft engine components. The desirable properties of nickel-base superalloys at high temperatures are tensile strength, thermomechanical fatigue resistance, low thermal expansion, as well as oxidation resistance. At elevated temperature, fatigue cracks are often initiated by grain boundary oxidation, and fatigue cracks often propagate along grain boundaries, where the oxidation rate is higher. Oxidation takes place at the interface between metal and gas. Properties of the metal substrate, the gaseous environment, as well as the oxides formed all interact to make the oxidation behavior of nickel-base superalloys extremely complicated. The important topics include general oxidation, selective oxidation, internal oxidation, grain boundary oxidation, multilayer oxide structure, accelerated oxidation under stress, stress-generation during oxidation, composition and substrate microstructural changes due to prolonged oxidation, fatigue crack initiation at oxidized grain boundaries and the oxidation accelerated fatigue crack propagation along grain boundaries.

Liu, H. W.↗