The Van Allen Radiation Belts: How their discovery worried lay scientists hungry for human spaceflight.
Abstract not provided.
Porwitzky, Andrew↗
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Space radiation measurements during the Artemis I lunar mission
Space radiation is a notable hazard for long-duration human spaceflight. Associated risks include cancer, cataracts, degenerative diseases and tissue reactions from large, acute exposures. Space radiation originates from diverse sources, including galactic cosmic rays, trapped-particle (Van Allen) belts5 and solar-particle events. Previous radiation data are from the International Space Station and the Space Shuttle in low-Earth orbit protected by heavy shielding and Earth’s magnetic field and lightly shielded interplanetary robotic probes such as Mars Science Laboratory and Lunar Reconnaissance Orbiter. Limited data from the Apollo missions and ground measurements with substantial caveats are also available. Here we report radiation measurements from the heavily shielded Orion spacecraft on the uncrewed Artemis I lunar mission. At differing shielding locations inside the vehicle, a fourfold difference in dose rates was observed during proton-belt passes that are similar to large, reference solar-particle events. Interplanetary cosmic-ray dose equivalent rates in Orion were as much as 60% lower than previous observations. Furthermore, a change in orientation of the spacecraft during the proton-belt transit resulted in a reduction of radiation dose rates of around 50%. These measurements validate the Orion for future crewed exploration and inform future human spaceflight mission design.
79 ASTRONOMY AND ASTROPHYSICS↗
Astrovirology: how viruses enhance our understanding of life in the Universe
Abstract Viruses are the most numerically abundant biological entities on Earth. As ubiquitous replicators of molecular information and agents of community change, viruses have potent effects on the life on Earth, and may play a critical role in human spaceflight, for life-detection missions to other planetary bodies and planetary protection. However, major knowledge gaps constrain our understanding of the Earth's virosphere: (1) the role viruses play in biogeochemical cycles, (2) the origin(s) of viruses and (3) the involvement of viruses in the evolution, distribution and persistence of life. As viruses are the only replicators that span all known types of nucleic acids, an expanded experimental and theoretical toolbox built for Earth's viruses will be pivotal for detecting and understanding life on Earth and beyond. Only by filling in these knowledge and technical gaps we will obtain an inclusive assessment of how to distinguish and detect life on other planetary surfaces. Meanwhile, space exploration requires life-support systems for the needs of humans, plants and their microbial inhabitants. Viral effects on microbes and plants are essential for Earth's biosphere and human health, but virus–host interactions in spaceflight are poorly understood. Viral relationships with their hosts respond to environmental changes in complex ways which are difficult to predict by extrapolating from Earth-based proxies. These relationships should be studied in space to fully understand how spaceflight will modulate viral impacts on human health and life-support systems, including microbiomes. In this review, we address key questions that must be examined to incorporate viruses into Earth system models, life-support systems and life detection. Tackling these questions will benefit our efforts to develop planetary protection protocols and further our understanding of viruses in astrobiology.
37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗
Ionospheric Disturbances in GNSS TEC Data: SpaceX Falcon 9 Deorbit Maneuvers Over CONUS in April–May 2024
Traveling ionospheric disturbances (TIDs) driven by a large number of internal and external sources are detectable with dense networks of ground‐based Global Navigation Satellite System (GNSS) receivers' measurements of total electron content (TEC). We present the newly developed System for Rapid Analysis of Ionospheric Dynamics (S‐RAID), providing data and visual GNSS TEC products of TIDs of periods ~2–120 min and horizontal resolution up to tens of kilometers for years 2017–2024. The S‐RAID data reveal myriad natural and anthropogenic TIDs from meteorology and space weather, and from human spaceflight activities. In this report, we focus on new prominent disturbances found during SpaceX second stage deorbit maneuvers in April–May 2024. Signatures include waves emanating from the Falcon's trajectory above California and depletions following its deorbit and passage over Arizona. These findings suggest further opportunities to detect and quantify small‐scale events in the ionosphere as well as to understand the responses of the atmosphere‐ionosphere system to known inputs.
58 GEOSCIENCES↗
Crewmember microbiome may influence microbial composition of ISS habitable surfaces
The International Space Station (ISS) is a complex built environment physically isolated from Earth. Assessing the interplay between the microbial community of the ISS and its crew is important for preventing biomedical and structural complications for long term human spaceflight missions. In this study, we describe one crewmember’s microbial profile from body swabs of mouth, nose, ear, skin and saliva that were collected at eight different time points pre-, during and post-flight. Additionally, environmental surface samples from eight different habitable locations in the ISS were collected from two flights. Environmental samples from one flight were collected by the crewmember and samples from the next flight were collected after the crewmember departed. The microbial composition in both environment and crewmember samples was measured using shotgun metagenomic sequencing and processed using the Livermore Metagenomics Analysis Toolkit. Ordination of sample to sample distances showed that of the eight crew body sites analyzed, skin, nostril, and ear samples are more similar in microbial composition to the ISS surfaces than mouth and saliva samples; and that the microbial composition of the crewmember’s skin samples are more closely related to the ISS surface samples collected by the crewmember on the same flight than ISS surface samples collected by other crewmembers on different flights. In these collections, species alpha diversity in saliva samples appears to decrease during flight and rebound after returning to Earth. This is the first study to compare the ISS microbiome to a crewmember’s microbiome via shotgun metagenomic sequencing. We observed that the microbiome of the surfaces inside the ISS resemble those of the crew’s skin. These data support future crew and ISS microbial surveillance efforts and the design of preventive measures to maintain crew habitat onboard spacecraft destined for long term space travel.
59 BASIC BIOLOGICAL SCIENCES↗
Functional Meta-Analysis of the Proteomic Responses of Arabidopsis Seedlings to the Spaceflight Environment Reveals Multi-Dimensional Sources of Variability across Spaceflight Experiments
The human quest for sustainable habitation of extraterrestrial environments necessitates a robust understanding of life’s adaptability to the unique conditions of spaceflight. This study provides a comprehensive proteomic dissection of the Arabidopsis plant’s responses to the spaceflight environment through a meta-analysis of proteomics data from four separate spaceflight experiments conducted on the International Space Station (ISS) in different hardware configurations. Raw proteomics LC/MS spectra were analyzed for differential expression in MaxQuant and Perseus software. The analysis of dissimilarities among the datasets reveals the multidimensional nature of plant proteomic responses to spaceflight, impacted by variables such as spaceflight hardware, seedling age, lighting conditions, and proteomic quantification techniques. By contrasting datasets that varied in light exposure, we elucidated proteins involved in photomorphogenesis and skotomorphogenesis in plant spaceflight responses. Additionally, with data from an onboard 1 g control experiment, we isolated proteins that specifically respond to the microgravity environment and those that respond to other spaceflight conditions. This study identified proteins and associated metabolic pathways that are consistently impacted across the datasets. Notably, these shared proteins were associated with critical metabolic functions, including carbon metabolism, glycolysis, gluconeogenesis, and amino acid biosynthesis, underscoring their potential significance in Arabidopsis’ spaceflight adaptation mechanisms and informing strategies for successful space farming.
59 BASIC BIOLOGICAL SCIENCES↗
GeneLab Database Analyses Suggest Long-Term Impact of Space Radiation on the Cardiovascular System by the Activation of FYN Through Reactive Oxygen Species
Space radiation has recently been considered a risk factor for astronauts’ cardiac health. As an example, for the case of how to query and identify datasets within NASA’s GeneLab database and demonstrate the database utility, we used an unbiased systems biology method for identifying key genes/drivers for the contribution of space radiation on the cardiovascular system. This knowledge can contribute to designing appropriate experiments targeting these specific pathways. Microarray data from cardiomyocytes of male C57BL/6 mice followed-up for 28 days after exposure to 900 mGy of 1 GeV proton or 150 mGy of 1 GeV/n 56 Fe were compared to human endothelial cells (HUVECs) cultured for 7 days on the International Space Station (ISS). We observed common molecular pathways between simulated space radiation and HUVECs flown on the ISS. The analysis suggests FYN is the central driver/hub for the cardiovascular response to space radiation: the known oxidative stress induced immediately following radiation would only be transient and would upregulate FYN, which in turn would reduce reactive oxygen species (ROS) levels, protecting the cardiovascular system. The transcriptomic signature of exposure to protons was also much closer to the spaceflight signature than 56 Fe’s signature. To our knowledge, this is the first time GeneLab datasets were utilized to provide potential biological indications that the majority of ions on the ISS are protons, clearly illustrating the power of omics analysis. More generally, this work also demonstrates how to combine animal radiation studies done on the ground and spaceflight studies to evaluate human risk in space.
cardiomyocytes↗
Investigation of Spaceflight Induced Changes to Astronaut Microbiomes
The International Space Station (ISS) is a uniquely enclosed environment that has been continuously occupied for the last two decades. Throughout its operation, protecting the health of the astronauts on-board has been a high priority. The human microbiome plays a significant role in maintaining human health, and disruptions in the microbiome have been linked to various diseases. To evaluate the effects of spaceflight on the human microbiome, body swabs and saliva samples were collected from four ISS astronauts on consecutive expeditions. Astronaut samples were analyzed using shotgun metagenomic sequencing and microarrays to characterize the microbial biodiversity before, during, and after the astronauts’ time onboard the ISS. Samples were evaluated at an individual and population level to identify changes in microbial diversity and abundance. No significant changes in the number or relative abundance of taxa were observed between collection time points when samples from all four astronauts were analyzed together. When the astronauts’ saliva samples were analyzed individually, the saliva samples of some astronauts showed significant changes in the relative abundance of taxa during and after spaceflight. The relative abundance of Prevotella in saliva samples increased during two astronauts’ time onboard the ISS while the relative abundance of other commensal taxa such as Neisseria, Rothia, and Haemophilus decreased. The abundance of some antimicrobial resistance genes within the saliva samples also showed significant changes. Most notably, elfamycin resistance gene significantly increased in all four astronauts post-flight and a CfxA6 beta-lactam marker significantly increased during spaceflight but returned to normal levels post-flight. The combination of both shotgun metagenomic sequencing and microarrays showed the benefit of both technologies in monitoring microbes on board the ISS. There were some changes in each astronaut’s microbiome during spaceflight, but these changes were not universal for all four astronauts. Two antimicrobial resistance gene markers did show a significant change in abundance in the saliva samples of all four astronauts across their collection times. These results provide insight for future ISS microbial monitoring studies and targets for antimicrobial resistance screenings.
59 BASIC BIOLOGICAL SCIENCES↗
Relevance of the Unfolded Protein Response to Spaceflight-Induced Transcriptional Reprogramming in Arabidopsis
Plants are primary producers of food and oxygen on Earth and will likewise be indispensable to the establishment of large-scale sustainable ecosystems and human survival in space. To contribute to the understanding of how plants respond to spaceflight stress, we examined the significance of the unfolded protein response (UPR), a conserved signaling cascade that responds to a number of unfavorable environmental stresses, in the model plant Arabidopsis thaliana. To do so, we performed a large-scale comparative transcriptome profiling in wild type and various UPR-defective mutants during the SpaceX-CRS12 mission to the International Space Station. We established that orbital culture substantially alters the expression of hundreds of stress-related genes compared with ground control conditions. Although expression of those genes varied in the UPR mutants on the ground, it was largely similar across the genotypes in the spaceflight condition. Furthermore, our results have yielded new information on how plants respond to growth in orbit and support the hypothesis that spaceflight induces the activation of signaling pathways that compensate for the loss of UPR regulators in the control of downstream transcriptional regulatory networks.
59 BASIC BIOLOGICAL SCIENCES↗
Toll Mediated Infection Response Is Altered by Gravity and Spaceflight in Drosophila
Space travel presents unlimited opportunities for exploration and discovery, but requires better understanding of the biological consequences of long-term exposure to spaceflight. Immune function in particular is relevant for space travel. Human immune responses are weakened in space, with increased vulnerability to opportunistic infections and immunerelated conditions. In addition, microorganisms can become more virulent in space, causing further challenges to health. To understand these issues better and to contribute to design of effective countermeasures, we used the Drosophila model of innate immunity to study immune responses in both hypergravity and spaceflight. Focusing on infections mediated through the conserved Toll and Imd signaling pathways, we found that hypergravity improves resistance to Toll-mediated fungal infections except in a known gravitaxis mutant of the yuri gagarin gene. These results led to the first spaceflight project on Drosophila immunity, in which flies that developed to adulthood in microgravity were assessed for immune responses by transcription profiling on return to Earth. Spaceflight alone altered transcription, producing activation of the heat shock stress system. Space flies subsequently infected by fungus failed to activate the Toll pathway. In contrast, bacterial infection produced normal activation of the Imd pathway. We speculate on possible linkage between functional Toll signaling and the heat shock chaperone system. Our major findings are that hypergravity and spaceflight have opposing effects, and that spaceflight produces stress-related transcriptional responses and results in a specific inability to mount a Toll-mediated infection response.
59 BASIC BIOLOGICAL SCIENCES↗
The effects and mechanisms of clinorotation on proliferation and differentiation in bone marrow mesenchymal stem cells
Data from human and rodent studies have demonstrated that microgravity induces observed bone loss in real spaceflight or simulated experiments. The decrease of bone formation and block of maturation may play important roles in bone loss induced by microgravity. The aim of this study was to investigate the changes of proliferation and differentiation in bone marrow mesenchymal stem cells (BMSCs) induced by simulated microgravity and the mechanisms underlying it. We report here that clinorotation, a simulated model of microgravity, decreased proliferation and differentiation in BMSCs after exposure to 48 h simulated microgravity. The inhibited proliferation are related with blocking the cell cycle in G2/M and enhancing the apoptosis. While alterations of the osteoblast differentiation due to the decreased SATB2 expression induced by simulated microgravity in BMSCs. - Highlights: • Simulated microgravity inhibited proliferation and differentiation in BMSCs. • The decreased proliferation due to blocked cell cycle and enhanced the apoptosis. • The inhibited differentiation accounts for alteration of SATB2, Hoxa2 and Cbfa1.
60 APPLIED LIFE SCIENCES↗
Astronauts Plasma-Derived Exosomes Induced Aberrant EZH2-Mediated H3K27me3 Epigenetic Regulation of the Vitamin D Receptor
There are unique stressors in the spaceflight environment. Exposure to such stressors may be associated with adverse effects on astronauts' health, including increased cancer and cardiovascular disease risks. Small extracellular vesicles (sEVs, i.e., exosomes) play a vital role in intercellular communication and regulate various biological processes contributing to their role in disease pathogenesis. To assess whether spaceflight alters sEVs transcriptome profile, sEVs were isolated from the blood plasma of 3 astronauts at two different time points: 10 days before launch (L-10) and 3 days after return (R+3) from the Shuttle mission. AC16 cells (human cardiomyocyte cell line) were treated with L-10 and R+3 astronauts-derived exosomes for 24 h. Total RNA was isolated and analyzed for gene expression profiling using Affymetrix microarrays. Enrichment analysis was performed using Enrichr. Furthermore, transcription factor (TF) enrichment analysis using the ENCODE/ChEA Consensus TF database identified gene sets related to the polycomb repressive complex 2 (PRC2) and Vitamin D receptor (VDR) in AC16 cells treated with R+3 compared to cells treated with L-10 astronauts-derived exosomes. Further analysis of the histone modifications using datasets from the Roadmap Epigenomics Project confirmed enrichment in gene sets related to the H3K27me3 repressive mark. Interestingly, analysis of previously published H3K27me3–chromatin immunoprecipitation sequencing (ChIP-Seq) ENCODE datasets showed enrichment of H3K27me3 in the VDR promoter. Collectively, our results suggest that astronaut-derived sEVs may epigenetically repress the expression of the VDR in human adult cardiomyocytes by promoting the activation of the PRC2 complex and H3K27me3 levels.
59 BASIC BIOLOGICAL SCIENCES↗
Sixty days of head-down tilt bed rest with or without artificial gravity do not affect the neuromuscular secretome
Highlights: • Long-term bed rest with/without artificial gravity does not affect the neuromuscular secretome. • Serum concentrations of markers of muscle wasting are not affected by bed rest/artificial gravity. • C-terminal Agrin Fragment serum concentrations are not affected by bed rest/artificial gravity. • Human centrifugation during bed rest does not have a negative impact on the neuromuscular secretome. Artificial gravity is a potential countermeasure to attenuate effects of weightlessness during long-term spaceflight, including losses of muscle mass and function, possibly to some extent attributable to disturbed neuromuscular interaction. The 60-day AGBRESA bed-rest study was conducted with 24 participants (16 men, 8 women; 33 ± 9 years; 175 ± 9 cm; 74 ± 10 kg; 8 control group, 8 continuous (cAG) and 8 intermittent (iAG) centrifugation) to assess the impact of bed rest with or without daily 30-min continuous/intermittent centrifugation with 1G at the centre of mass. Fasting blood samples were collected before and on day 6, 20, 40 and 57 during 6° head-down tilt bed rest. Concentrations of circulating markers of muscle wasting (GDF-8/myostatin; slow skeletal muscle troponin T; prostaglandin E2), neurotrophic factors (BDNF; GDNF) and C-terminal Agrin Fragment (CAF) were determined by ELISAs. Creatine kinase activity was assessed by colorimetric enzyme assay. Repeated-measures ANOVAs were conducted with TIME as within-subject, and INTERVENTION and SEX as between-subject factors. The analyses revealed no significant effect of bed rest or sex on any of the parameters. Continuous or intermittent artificial gravity is a safe intervention that does not have a negative impact of the neuromuscular secretome.
60 APPLIED LIFE SCIENCES↗
Oxidative Stress and Skeletal Health with Low-Dose, Low-LET (Linear Energy Transfer) Ionizing Radiation
We performed in vivo and in vitro experiments to accomplish the following specific aims of this project: 1) determine if low dose, low LET radiation affects skeletal remodeling at structural, cellular and molecular levels and 2) determine if low dose, low LET radiation modulates skeletal health during aging via oxidative mechanisms. A third aim is supported by NASA supplement to this DOE grant focusing on the influence of high LET radiation on bone. A series of experiments were conducted at the NASA Space Radiation Laboratory at Brookhaven, NSRL-BNL, using iron (56Fe) or a sequential exposure to protons / iron / protons, and separate experiments at NASA Ames Research Center (ARC) using 137Cs. The following provides a summary of key findings. (1) Exposure of nine-week old female mice to priming doses of gamma radiation (10cGy x 5) did not significantly affect bone volume/total volume (BV/TV) or microarchitecture as analyzed by 3D microcomputed tomography. As expected, exposure to the challenge dose of 2 Gy gamma irradiation resulted in significant decreases in BV/TV. The priming dose combined with the 2Gy challenge dose had no further effect on BV/TV compared to challenge dose alone, with the sole exception of the Structural Model Index (SMI). SMI reflects the ratio of rods-to-plates in cancellous bone tissue, such that higher SMI values indicate a tendency toward a weaker structure compared to lower SMI values. Mice treated with both priming and challenge dose had 25% higher SMI values compared to sham-irradiated controls and 7% higher values compared to mice treated with the challenge dose alone. Thus, although this priming regimen had relatively modest effects on cancellous tissue, the difference in SMI suggests this fractionated priming doses have adverse, rather than beneficial, effects on bone structure. (2) In 10-week old male mice, a single exposure to 100cGy of 137Cs reduces trabecular bone number and connectivity density by 20% and 36% respectively one month after irradiation (IR). At four months post-IR, these animals were comparable to sham-treated controls with regards to the abovementioned structural parameters. Irradation at 1 or 10 cGy did not result in any significant changes in bone structural parameters. (3) Irradiation of 16-wk old male mice with high doses of 56Fe or proton (50 or 200cGy), but not at low doses (5 or 10cGy), showed a similar loss of cancellous BV/TV and trabecular number at five weeks post-IR. (4) Age-related bone loss overtook acute radiation-induced decrements in bone structure within four months post-IR with 100 cGy gamma and 12 months post-IR with 200 cGy iron. Transgenic mice globally overexpressing human catalase gene in mitochondria did not exhibit cancellous bone loss as assessed at four month post-IR with 10 cGy proton, 50 cGy iron, or in combination. (5) The cellular and molecular mechanisms responsible for loss of bone with radiation are mediated primarily through increased osteoclastogenesis. Our data provide evidence that there are increases in gene expression of TNF alpha and MCP1 in the bone marrow cells 24 hours post-IR and of osteoclastogenic differentiation factor RANKL by day 3. These cytokines in the marrow may stimulate mature osteoclasts or drive osteoclastogenesis from precursors. (6) Osteoblastogenesis from marrow progenitors evaluated ex vivo decreased following whole body 56Fe irradiation at a dose threshold between 20 and 50 cGy whereas osteoclastogenesis ex vivo increased with doses as low as 10cGy two days post-IR of mice. However, the latter finding was not observed in more than a single experiment. (7) Gamma irradiation of cells in vitro requires relatively high doses (200cGy) to disturb normal osteoblastogenesis and osteoclastogenesis as evidenced by decrements in mineralized nodule formation, osteoclast counts, and expression of osteoblast related genes such as runx2, col1a1. (8) We also investigated the effect of antioxidants on osteoblastogenesis following low dose in vitro gamma irradiation (15cGy) on day four bone marrow stromal cell cultures. Superoxide dismutase (SOD) was added to the cell culture medium for 2 or 3 days post-irradiation and cell colonies were counted on days 7 and 10. SOD treatment increased cell growth as measured by DNA content and colony forming units (CFU) in both irradiated cells and 0 cGy control groups. However, low dose radiation of 15cGy abolished SOD stimulatory effects on cell growth and CFU number. These results suggest that exogenous SOD increases osteoblast cell growth and colony formation and that low-dose radiation (15cGy) can interfere with the antioxidant effects. In summary, our findings indicate that acute, whole body irradiation at high doses (50-200 cGy) results in prompt tissue degradation and bone loss. Lower doses (<50 cGy) do not cause bone structural deterioration but may deplete stem/progenitor cell pools in the bone marrow.
59 BASIC BIOLOGICAL SCIENCES↗