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NASA NTRSDate not supplied

Developing High-Throughput Organ-on-a-Chip Models to Investigate the Effects of Ionizing Radiation on the Central Nervous System

One of the main health risks in human space exploration is central nervous system (CNS) damage by ionizing radiation due to exposure to the galactic cosmic rays (GCRs). In animal models, irradiation with simulated GCRs or their components has been shown to cause neuronal damage and neuroinflammation associated with cognitive and behavioral dysfunction. In general, the extent of CNS damage is partially regulated by the blood-brain barrier (BBB), which enables immune cells to enter the CNS. The main cellular regulators of BBB permeability are astrocytes, which also modulate neuronal death, immune responses and oxidative stress, and thus could serve as a robust CNS-specific target for countermeasure development. However, studies on BBB permeability and astrocyte functions in regulating CNS responses to ionizing radiation have been limited, especially in human tissue/organ analogs. Therefore, we established a high-throughput 3D organ-on-a-chip system to study human CNS and BBB impairments in response to ionizing radiation, based on commercially available OrganoPlates (Mimetas, Inc.) seeded with primary or induced pluripotent stem cell-derived human cells. We investigated both immediate and delayed CNS responses to major GCR components: 0.15-0.5 Gy 250MeV/n 4-He, and 0.3-0.8 Gy 600 MeV/n 56-Fe; as well as to 0.5-1 Gy X-rays. We observed ionizing radiation-mediated increases in BBB permeability that was exacerbated by astrocyte presence and accompanied by morphological changes in endothelial cells and tight junctions, altered cytokine profile including TNFa upregulation, and increased oxidative stress. We also quantified irradiation-mediated changes in astrocyte activation and neuronal functions, revealing major astrocyte damage mediated by 600MeV/n 56-Fe particles. Thus, we demonstrate that deep space radiation may contribute to CNS damage by disrupting both astrocyte and endothelial cell components of the blood-brain barrier. Our next steps include mapping and validating the transcriptomic changes induced by simulated GCRs and their components in human CNS models. Ultimately, we aim to uncover potential novel targets for countermeasure developments to mitigate CNS damage in long duration spaceflight.

Radiation↗
NASA NTRSDate not supplied

A Multi Targeted Dietary Supplement as a Potential Countermeasure for Prolonged, Deep Space Exploration

Deep space exploration, particularly to the Moon and Mars, are currently major goals of NASA and other international space agencies. Long-term space flight presents unique challenges to the human physiology from microgravity, social isolation, altered circadian rhythm and radiation. Oxidative stress has been implicated as a crucial factor in space environment induced injury. Elucidating these detrimental effects on the central nervous system and brain is a primary objective, as they may result in adverse changes in astronaut behavior, mood and performance of critical tasks. We were recently funded by HRP Human Factors Behavioral Performance (HFBP) Element to test the hypothesis that Galactic Cosmic Ray Simulation (GCRsim) Ionizing Radiation (IR), microgravity and social isolation combine synergistically to trigger an oxidative stress response that alters immune homeostasis, brain structure and function, and neurobehavioral and cognitive performance. This project will identify potential biomarkers for, and mechanisms underlying, structural and functional changes in the immune and nervous systems leading to behavioral/cognitive performance deficits, and its potential application to develop effective countermeasures to mitigate negative health effects of long duration space habitation. Countermeasures to offset neurological damaged and cognitive deficits are paramount for protecting astronauts during deep space transits, but many countermeasures have been found to be unsuitable in ground-based model studies. We have developed a multi targeted dietary supplement (MTDS) designed to simultaneously ameliorate oxidative stress, inflammatory processes, energetic shortfalls, and membrane and mitochondrial deterioration. Administration of this MTDS has improved cognition and longevity in age accelerated and normal aging mice. Specifically, the MTDS was found to prevent a decline in mitochondrial complex III activity and cell loss, as well as prevent an increase in protein carbonyls and mitochondrial 3-nitrotyrosine in the brain of these mice. Further, administration of the MTDS was also found to reduce bone marrow chromosomal aberrations, DNA damage, lymphocyte apoptosis after whole body exposure of 2 Gy γ radiation. Mice exposed to a high dose cranially (10 Gy) had decreased cognitive responses (seen as increased latency time to uncover buried food and decreased novel object recognition), increased plasma 8-OHdG levels, increased markers of cell stress in the brain, decreased hippocampal brain-derived neurotrophic factor (BDNF) protein and decreased plasma levels of cytokines, all of which were ameliorated with treatment of the MTDS. As we have shown the supplement is protective in models of cognitive damage similar space environment stressors, particularly increased oxidative stress, we propose it may be a suitable countermeasure for upcoming deep space exploration.

radiation↗
NASA NTRSDate not supplied

Immunological Consequences of the Spaceflight Environment on Macrophage Function

The role of macrophages in the protection of multicellular organisms is critical and multifaceted.Regulation of macrophage populations and functions is key to maintaining tissue home ostasis and a healthy organism. As the bridge between the innate and adaptive immune systems, macrophages patrol every tissue in the body and show remarkable heterogeneity. Primarily, macrophages phagocytose harmful pathogens and release cytokines to regulate pro-inflammatory responses to infections and anti-inflammatory responses for wound healing. Prior research has demonstrated that spaceflight conditions, including microgravity and deep space radiation, have a detrimental effect on macrophage populations and functions. However, tissue-specific and individual spaceflight stressor-specific effects remain to be untangled. Furthermore, prior research into the effects of spaceflight on macrophages lacks experimental standardization, creating difficulty in reconciling disparate studies. Finally, due to their presence in various human tissues, easy accessibility in the bloodstream, and fast responses to immune status and spaceflight, macrophages present a unique opportunity for developing new diagnostic tools for spaceflight applications. Therefore, further targeted research on macrophage functions may support astronaut health in long-duration crewed space missions, both within and beyond lowEarth orbit. Here we present a review that summarizes previous findings on macrophagedys regulation in spaceflight, details key areas for further research and investment, and recommends potential investigations into spaceflight dysfunctions, diagnostics, and countermeasures.

immunology↗
NASA NTRSDate not supplied

A MULTI TARGETED DIETARY SUPPLEMENT AS A POTENTIAL COUNTERMEASURE FOR DEEP SPACE EXPLORATION

Future deep space exploration to the Moon and Mars and beyond are currently major goals of NASA. Space flight presents unique challenges to the human physiology from the combined effects of microgravity, social isolation, altered circadian rhythm and radiation. Oxidative stress has been implicated as a crucial factor in space environment induced injury. Elucidating these detrimental effects on the central nervous system and brain is a primary objective, as they may result in adverse changes in astronaut behavior, mood and performance of critical tasks. We were recently funded by HRP Human Factors Behavioral Performance (HFBP) Element to test the hypothesis that Galactic Cosmic Ray Simulation (GCRsim) Ionizing Radiation (IR), microgravity and social isolation combine synergistically to trigger an oxidative stress response that alters immune homeostasis, brain structure and function, and neurobehavioral and cognitive performance. This project will identify potential biomarkers for, and mechanisms underlying, structural and functional changes in the immune and nervous systems leading to behavioral/cognitive performance deficits, and its potential application to develop effective countermeasures to mitigate negative health effects of long duration space habitation. Countermeasures to offset neurological damaged and cognitive deficits are paramount for protecting astronauts during deep space transits, but many countermeasures have been found to be unsuitable in ground-based model studies. We have developed a multi targeted dietary supplement (MTDS) designed to simultaneously ameliorate oxidative stress, inflammatory processes, energetic shortfalls, and membrane and mitochondrial deterioration. Administration of this MTDS has improved cognition and longevity in age accelerated and normal aging mice. Specifically, the MTDS was found to prevent a decline in mitochondrial complex III activity and cell loss, as well as prevent an increase in protein carbonyls and mitochondrial 3-nitrotyrosine in the brain of these mice. Further, administration of the MTDS was also found to reduce bone marrow chromosomal aberrations, DNA damage, lymphocyte apoptosis after whole body exposure of 2 Gy γ radiation. Mice exposed to a high dose cranially (10 Gy) had decreased cognitive responses (seen as increased latency time to uncover buried food and decreased novel object recognition), increased plasma 8-OHdG levels, increased markers of cell stress in the brain, decreased hippocampal brain-derived neurotrophic factor (BDNF) protein and decreased plasma levels of cytokines, all of which were ameliorated with treatment of the MTDS. As we have shown the supplement is protective in models of cognitive damage similar space environment stressors, particularly increased oxidative stress, we propose it may be a suitable countermeasure for upcoming deep space exploration.

Stephanie Puukila↗
NASA NTRSDate not supplied

Method Development for In-situ Detection of Latent Herpesvirus DNA from Saliva using Nanopore Sequencing

Research toward latent herpesvirus reactivation has been intensively addressed through Space Shuttle and International Space Station (ISS) investigations. This work has provided the understanding that persistent reactivation of herpesviruses from asymptomatic crew can be detected through viral shedding in saliva, urine, and blood. Occasionally, viral reactivation from the latency stage can pose a threat to crew health (clinical manifestation) before, during, and after flight missions. Furthermore, previous work detailing correlations with immunity indicate that monitoring viral reactivation could be implemented to assess potential immune dysfunction. While in-flight monitoring is desirable, there is no well-established procedure or method for real-time evaluations, and research to date has relied on postflight, ground-based analysis. The development of portable molecular technologies like the miniPCR™ (miniPCR Bio) thermal cycler and the MinION™ sequencer (Oxford Nanopore Technologies) have confirmed that real-time monitoring is possible in extreme and low resource environments. These devices, combined with simple sample preparation methods, have been used to demonstrate bacterial identification onboard the ISS, as well as rapid viral detection in remote locations on Earth. The work here builds upon previous molecular advancements onboard the ISS toward the development and validation of a spaceflight-compatible method for viral detection from crew samples. Several herpesviruses can be detected in saliva, which provides a non-invasive means to collect samples for monitoring. While the basis for this method lies in previous spaceflight investigations, key points for method optimization include DNA extraction from saliva, viral primer selection, and bioinformatic processes for data analysis. To increase viral yield, numerous DNA extraction methods have been evaluated and will be discussed in detail. For initial development and testing, varicella-zoster virus (VZV) is being targeted though open reading frame 51 and 63 (ORF51, ORF63), as the replication origin-binding protein is highly expressed during latency. Optimization of the thermal cycling parameters has resulted in the ability to test the entire process. The full method has been tested with both viral VZV DNA standards and saliva spiked with varying concentrations of VZV. Viral sequence data were mapped to the reference sequence using minimap2. Prior to mapping, DNA sequencing reads were filtered for length and quality, barcodes were removed, and alignment identity calculated. Following further assessments, statistics were compared across multiple sequencing experiments and are being used to determine the success of the protocols. Forward work will include the incorporation of herpes simplex virus 1 (HSV-1) and Epstein-Barr virus (EBV) primers as well as the validation of results to the terrestrial qPCR standard assay. Upon full validation of the developed method, saliva will be collected from 20 healthy subjects and spiked with viral DNA. These samples will be split and assayed with the MinION and standard qPCR assay.

Hang N Nguyen↗
NASA NTRSDate not supplied

Spaceflight Food System Impacts to Nutritional Adequacy, Health, Performance, and Resources in Space Exploration

Despite high physical standards and training protocols, physiological and behavioral decrements have been documented in astronauts on both short (1-2 weeks) and long (6+ month) missions in spaceflight, including dysregulation of the immune system, cardiovascular and musculoskeletal deconditioning, ophthalmic changes, weight loss, and increased stress and fatigue. Optimizing food and nutrition intakes are key underpinnings for the proper function and performance of all physiological systems and the resulting physical and behavioral health and performance outcomes of astronauts. Much has been learned about the role of nutrition in human health on Earth over the past hundred years, from the identity and role of specific vitamins to the importance of the quantities of some nutrients to immune function. The requirements for providing adequate nutrition to astronauts seem obvious. However, providing a safe, reliable, and nutritious food system for space exploration missions remains a challenge. In fact, food is one of the greatest resource and logistical challenges, which is part of why it remains a “red” risk for Mars missions.

Grace L Douglas↗
NASA NTRSDate not supplied

HemoCue ISS Tech Demo - Results and Lessons Learned

During long duration space missions, astronauts experience immune system dysregulation [1], and white blood cell (WBC) count can give vital information about the body’s immune response. The ability to measure WBC count is currently an unmet need on the International Space Station (ISS) and for future exploration missions. To address this need, the Human Research Program’s (HRP) Exploration Medical Capability (ExMC) Element, along with the Research Operations and Integration (ROI) Element and the NASA Johnson Space Center Immunology Lab, flew HemoCue®, a commercial-off-the-shelf analyzer with the ability to measure whole blood WBC count with 5-part differential to ISS in December 2020.

Exploration Medical Capability↗
NASA NTRS2022

Dermatitis during Spaceflight Associated with HSV-1 Reactivation

Human alpha herpesviruses herpes simplex virus (HSV-1) and varicella zoster virus (VZV) establish latency in various cranial nerve ganglia and often reactivate in response to stress-associated immune system dysregulation. Reactivation of Epstein Barr virus (EBV), VZV, HSV-1, and cytomegalovirus (CMV) is typically asymptomatic during spaceflight, though live/infectious virus has been recovered and the shedding rate increases with mission duration. The risk of clinical disease, therefore, may increase for astronauts assigned to extended missions (>180 days). Here, we report, for the first time, a case of HSV-1 skin rash (dermatitis) occurring during long-duration spaceflight. The astronaut reported persistent dermatitis during flight, which was treated onboard with oral antihistamines and topical/oral steroids. No HSV-1 DNA was detected in 6-month pre-mission saliva samples, but on flight day 82, a saliva and rash swab both yielded 4.8 copies/ng DNA and 5.3 × 104 copies/ng DNA, respectively. Post-mission saliva samples continued to have a high infectious HSV-1 load (1.67 × 107 copies/ng DNA). HSV-1 from both rash and saliva samples had 99.9% genotype homology. Additional physiological monitoring, including stress biomarkers (cortisol, dehydroepiandrosterone (DHEA), and salivary amylase), immune markers (adaptive regulatory and inflammatory plasma cytokines), and biochemical profile markers, including vitamin/mineral status and bone metabolism, are also presented for this case. These data highlight an atypical presentation of HSV-1 during spaceflight and underscore the importance of viral screening during clinical evaluations of in-flight dermatitis to determine viral etiology and guide treatment.

Satish K. Mehta↗
NASA NTRSDate not supplied

Gene expression changes in peripheral blood mononuclear cells of ISS crewmembers suggest impacts of spaceflight on cell death

In space, living organisms are exposed to numerous stress factors including microgravity and space radiation. For humans, these harmful environmental factors have been known to cause negative health impacts such as immune dysfunction. Understanding the mechanisms by which spaceflight impacts human health at the molecular level is critical not only for accurately assessing the risks associated with spaceflight, but also for developing effective countermeasures. This study is part of the Functional Immune Project, intended to determine alterations in crewmembers` immunobiology before, during, and after spaceflight. For this project, blood samples were collected from International Space Station (ISS) crewmembers at the following time points: i) at two pre-flight time points of 180 days (L180) and 45 days (L45) before launch. ii) During flight, blood was drawn at approximately the midpoint (mid-flight, MF) of the mission, and shortly before egress from the ISS (late-flight, LF). iii) Post-flight blood samples were collected within 24 hrs (R0), 30 days (R30) and 90 days (R90) after landing. For each crewmember, blood was also drawn from a matching test subject on the ground at the corresponding time point. For both the ISS crewmembers and the ground control subjects, total RNA was isolated from peripheral blood mononuclear cells (PBMC) and mRNA was analysed using next generation RNA-sequencing (NGS). Differentially expressed genes were determined by performing contrast analysis. Using the data from all of the time points from the ground control subjects as a control, a number of dysregulated genes were identified in astronauts at MF, LF and R0, including downregulations of several cell cycle related genes including CDKN1A and VEGFA at MF and LF. Pathway analysis of these differentially expressed genes indicated that, in space, pathways associated with autophagy and senescence were affected. Our analysis also indicated that the genes related to metabolisms were downregulated in the microgravity environment. Taken together, our data suggests that PBMC in the ISS crewmembers may be starved, resulting in autophagy and delayed senescence in space. Such findings are in agreement with delayed cell death in PBMC under simulated microgravity conditions on the ground and offer an explanation for telomere lengthening that has been reported among the ISS astronauts in flight.

Maria Moreno-Villanueva↗
NASA NTRSDate not supplied

Gene Expression Changes in Peripheral Blood Mononuclear Cells of ISS Crewmembers Suggest Impacts of Spaceflight on Cell Death

In space, living organisms are exposed to numerous stress factors including microgravity and space radiation. For humans, these harmful environmental factors have been known to cause negative health impacts such as immune dysfunction. Understanding the mechanisms by which spaceflight impacts human health at the molecular level is critical not only for accurately assessing the risks associated with spaceflight, but also for developing effective countermeasures. This study is part of the Functional Immune Project, intended to determine alterations in crewmembers` immunobiology before, during, and after spaceflight. For this project, blood samples were collected from International Space Station (ISS) crewmembers at the following time points: i) at two pre-flight time points of 180 days (L180) and 45 days (L45) before launch. ii) During flight, blood was drawn at approximately the midpoint (mid-flight, MF) of the mission, and shortly before egress from the ISS (late-flight, LF). iii) Post-flight blood samples were collected within 24 hrs (R0), 30 days (R30) and 90 days (R90) after landing. For each crewmember, blood was also drawn from a matching test subject on the ground at the corresponding time point. For both the ISS crewmembers and the ground control subjects, total RNA was isolated from peripheral blood mononuclear cells (PBMC) and mRNA was analysed using next generation RNA-sequencing (NGS). Differentially expressed genes were determined by performing contrast analysis. Using the data from all of the time points from the ground control subjects as a control, a number of dysregulated genes were identified in astronauts at MF, LF and R0, including downregulations of several cell cycle related genes including CDKN1A and VEGFA at MF and LF. Pathway analysis of these differentially expressed genes indicated that, in space, pathways associated with autophagy and senescence were affected. Our analysis also indicated that the genes related to metabolisms were downregulated in the microgravity environment. Taken together, we hypothesize that PBMC in the ISS crewmembers may be starved, resulting in autophagy and delayed senescence in space. Such findings are in agreement with delayed cell death in PBMC under simulated microgravity conditions on the ground and offer an explanation for telomere lengthening that has been reported among the ISS astronauts in flight

Maria Moreno-Villanueva↗
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

Dry Saliva Development-Artemis

Prior to the deployment of prolonged deep space missions which may carry increased crew health risks, it is essential to determine the effect that missions beyond the Van Allen Belt will have on physiology. Historically the National Aeronautics and Space Administration (NASA), Human Research Program (HRP) has developed, conducted, and delivered research findings and countermeasures that will maintain the health and safety of crews aboard the International Space Station (ISS) in anticipation of future exploration class missions. To support these objectives, research operations on ISS typically include the collection and storage of human physiological samples and their return to Earth for analysis. Transition to Gateway and Artemis lunar exploration will limit the available up mass and biosample return capability resulting in new challenges to monitor crew health during the mission. The Artemis lunar missions provide a perfect opportunity to assess new technology that could support crew biosample return that is compatible with the severe operational constraints of Artemis mission design. Dried biosample chemistry analysis is a potential technology that can enable the collection of samples and tracking of crew health during these exploration class missions. The development and implementation of dried biosample chemistry technology for tracking immune health, viral reactivation and hormone fluctuations provide a simple alternative strategy for sample collection and sample return (light weight non-conditioned stowage option) for the continuation of human research during Artemis missions. Saliva is established as an informative biosample that has both its own unique available analytes as well as others that are also present in blood. Saliva is already routinely collected from ISS astronauts for the detection of stress hormones and latent virus DNA. The ‘Dry Saliva’ book sample collection/storage protocol, already successfully deployed to ISS, represents a perfect method for collecting biosamples from Gateway and Artemis astronauts because it requires a simple, non-invasive sample collection protocol, minimum volume, and uses non-conditioned storage. We are currently conducting an expanded stability study of the dry saliva analyte platform to include additional stress hormones, cytokines, antimicrobial proteins, and latent virus DNA as well as other markers of immunity and inflammation. Validation testing on parabolic flight will establish collection methods for saliva and blood to dry sampling substrates to finalize the collection protocols for flight. For the new expanded analyte stability study, a short-term stability study with time points out to 14 days has been completed with analysis underway to determine whether additional analytes could be recovered, as well as assessing the best storage conditions for the samples collected. In parallel, a long-term stability study is being conducted out to 1 year to improve the stability of some unstable analytes. To this end, the NASA Johnson Space Center’s Immunology/Virology lab is currently finalizing the saliva dry chemistry platform, including assay compatibility and stability studies. This technology is approved to be implemented, as part of the ‘Biomarkers’ study, during Artemis II through Artemis IV lunar missions.

Mayra Nelman-Gonzalez↗
NASA NTRS2002

Opportunities for nutritional amelioration of radiation-induced cellular damage

The closed environment and limited evasive capabilities inherent in space flight cause astronauts to be exposed to many potential harmful agents (chemical contaminants in the environment and cosmic radiation exposure). Current power systems used to achieve space flight are prohibitively expensive for supporting the weight requirements to fully shield astronauts from cosmic radiation. Therefore, radiation poses a major, currently unresolvable risk for astronauts, especially for long-duration space flights. The major detrimental radiation effects that are of primary concern for long-duration space flights are damage to the lens of the eye, damage to the immune system, damage to the central nervous system, and cancer. In addition to the direct damage to biological molecules in cells, radiation exposure induces oxidative damage. Many natural antioxidants, whether consumed before or after radiation exposure, are able to confer some level of radioprotection. In addition to achieving beneficial effects from long-known antioxidants such as vitamins E and C and folic acid, some protection is conferred by several recently discovered antioxidant molecules, such as flavonoids, epigallocatechin, and other polyphenols. Somewhat counterintuitive is the protection provided by diets containing elevated levels of omega-3 polyunsaturated fatty acids, considering they are thought to be prone to peroxidation. Even with the information we have at our disposal, it will be difficult to predict the types of dietary modifications that can best reduce the risk of radiation exposure to astronauts, those living on Earth, or those enduring diagnostic or therapeutic radiation exposure. Much more work must be done in humans, whether on Earth or, preferably, in space, before we are able to make concrete recommendations.

Review↗
NASA NTRS2001

Research activities at the Loma Linda University and Proton Treatment Facility--an overview

The Loma Linda University (LLU) Radiobiology Program coordinates basic research and proton beam service activities for the university and extramural communities. The current focus of the program is on the biological and physical properties of protons and the operation of radiobiology facilities for NASA-sponsored projects. The current accelerator, supporting facilities and operations are described along with a brief review of extramural research projects supported by the program. These include space craft electronic parts and shielding testing as well as tumorigenesis and animal behavior experiments. An overview of research projects currently underway at LLU is also described. These include: 1) acute responses of the C57Bl/6 mouse immune system, 2) modulation of gene expression in the nematode C. elegans and rat thyroid cells, 3) quantitation of dose tolerance in rat CNS microvasculature, 4) behavioral screening of whole body proton and iron ion-irradiated C57Bl/6 mice, and 5) investigation of the role of cell integration into epithelial structures on responses to radiation.

Non-NASA Center↗
NASA NTRS1993

Overview of spaceflight immunology studies

The effects of spaceflight and analogues of spaceflight are discussed here and in nine accompanying articles. In this summary we present spaceflight studies with human subjects, animal subjects, and cell cultures and we review ground-based systems used to model the observed effects of spaceflight on the immune system. Human paradigms include bed rest, academic or psychological stress, physical stress, hypobaric or high altitude stress, and confinement. Animal models include antiorthostatic and orthostatic suspension, hypobarism, and confinement. The ten manuscripts in this collection were selected to provide a summary that should give the reader an overview of the various activities of spaceflight immunology researchers throughout the history of space travel. This manuscript identifies the major contributors to the study of spaceflight immunology, explains what types of studies have been conducted, and how they have changed over the years. Also presented is a discussion of the unusual limitations associated with spaceflight research and the efforts to develop appropriate ground-based surrogate model systems. Specific details, data, and mechanistic speculations will be held to a minimum, because they will be discussed in depth in the other articles in the collection.

NASA Discipline Number 18-10↗
NASA NTRS2016

Elucidating the Gravome: Quantitative Proteomic Profiling of the Response to Chronic Hypergravity in Drosophila

Altered gravity conditions, such as experienced by organisms during spaceflight, is known to cause transcriptomic and proteomic changes. We describe the proteomic changes in the whole body of adult Drosophila melanogaster (fruit fly), but focus specifically on the localized changes in the adult head in response to chronic hypergravity (3G) treatment. Canton S adult female flies (2-3 days old) were exposed to chronic hypergravity for 9 days and compared with parallel 1G controls. After hypergravity treatment, whole flies and fly heads were separated, and evaluated for quantitative comparison of the two gravity conditions using an isobaric tagging liquid chromatography-tandem mass spectrometry approach. Data revealed a total of 1948 (whole flies) and 1480 (head) proteins to be differentially present in hypergravity-treated flies. Gene Ontology analysis of head specific proteomics revealed host immune response and humoral stress proteins were significantly upregulated. Proteins related to calcium signaling, ion transport and ATPase were decreased. Enhanced expression of cuticular proteins may suggest an alteration in chitin metabolism and in chitin-based cuticle development. We therefore present a comprehensive quantitative survey of proteomic changes in response to chronic hypergravity in Drosophila, which will help elucidate the underlying molecular mechanisms associated with altered gravity environments.

Hypergravity↗
NASA NTRS2021

SMD Technology Highlights

Seven technology highlights from the Science Mission Directorate (SMD) Astrophysics, Planetary Science, Heliophysics, and Biological and Physical Sciences, and Earth Science divisions are featured: 1. Technology using precisely controlled ultraviolet light source that to suppress electrostatic noise in gravitational wave observatories 2. New micro-shutter technology that will enable space telescopes to perform spectroscopy on a large number of objects simultaneously 3. An optical seismometer that is micro-fabricated, easy to manufacture, immune to radiation damage, and operates with low power consumption to characterize ice sheets and mantle on icy worlds 4. Rediscovering the lost art of fluxgate magnetometer cores 5. Innovative technology to measure muscle strength of worms in space to prepare astronauts for future missions 6. A new state-of-the-art sensor and satellite platform to enable continued monitoring of Earth’s radiant energy system 7. Novel Algorithms to merge ground- and space-based data to forecast air pollution events

ultraviolet↗
NASA NTRS2023

Palmer Station, Antarctica: A Ground-Based Spaceflight Analog Suitable for Validation of Biomedical Countermeasures for Deep Space Missions

Astronauts are known to exhibit a variety of immunological alterations during spaceflight including changes in leukocyte distribution and plasma cytokine concentrations, a reduction in T-cell function, and subclinical reactivation of latent herpesviruses. These alterations are most likely due to mission-associated stressors including circadian misalignment, microgravity, isolation, altered nutrition, and increased exposure to cosmic radiation. Some of these stressors may also occur in terrestrial situations. This study sought to determine if crewmembers performing overwinter deployment at Palmer Station, Antarctica displayed similar immune alterations. The larger goal was to validate a ground analog suitable for the evaluation of countermeasures designed to protect astronauts during future deep space missions. For this pilot study, plasma, saliva, hair, and health surveys were collected from Palmer Station, Antarctica winterover participants at baseline, and at five overwinter timepoints. Twenty-six subjects consented to participate over the course of two seasons. Initial sample processing was performed at Palmer, and eventually stabilized samples were returned to the Johnson Space Center for analysis. A white blood cell differential was performed (real time) using a fingerstick blood sample to determine alterations in basic leukocyte subsets throughout the winterover. Plasma and saliva samples were analyzed for 30 and 13 cytokines, respectively. Saliva was analyzed for cortisol concentration and three latent herpesviruses (DNA by qPCR), EBV, HSV1, and VZV. Hair samples were analyzed for several hormones, as a measure of stress over prolonged periods of time. Voluntary surveys related to general health and adverse clinical events were distributed to participants. It is noteworthy that due to logistical constraints due to COVID-19, the baseline samples for each season were collected in Punta Arenas, Chile, after long international travel and during isolation. Therefore, the palmer pre mission samples may not reflect a true normal ‘baseline’. Minimal alterations were observed in leukocyte distribution during overwinter. The mean percentage of monocyte concentration elevated at one timepoint. Plasma G-CSF, IL1RA, MCP-1, MIP-1β, TNFα and VEGF were decreased during at least one overwinter timepoint, whereas RANTES was significantly increased. No statistically significant changes were observed in mean saliva cytokine concentrations. Salivary cortisol was substantially elevated throughout the entire winterover compared to baseline. Compared to shedding levels observed in healthy controls (23%), the percentage of participants who shed EBV was higher throughout all winterover timepoints (52-60%). Five subjects shed HSV1 during at least one timepoint throughout the season compared to no subjects shedding during pre-deployment. Finally, VZV reactivation, common in astronauts but exceptionally rare in ground-based stress analogs, was observed in one subject during pre-deployment and a different subject at WO2 and WO3. These pilot data, somewhat influenced by the COVID-19 situation, do suggest that participants at Palmer Station do undergo immunological alterations similar to, but likely in reduced magnitude, as those observed in astronauts. We suggest that overwinter at Palmer Station may be suitable test analog for spaceflight biomedical countermeasures designed to mitigate clinical risks for deep space missions.

Space↗