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At least 235 records · Page 13

Drosophila Habitat Developed to Support Research on the International Space Station

The Fruit Fly Lab is a hardware suite being designed to support research on the International Space Station (ISS) for use by the entire Drosophila research community. A validation mission will launch and return on SpaceX-5 in late 2014, followed by Principal Investigator-lead science flights thereafter. Space flight experiments are selected via peer-reviewed proposals open to the Drosophila community. The cassettes (containers) that will house the Drosophila cultures were successfully used to conduct an immunity study on the Space Shuttle. Results showed that the innate immune system of Drosophila melanogaster was affected by space flight with a reduction in phagocytosis function of plasmatocytes, changes in antimicrobial peptides and other gene expression levels, as well as changes in development of the animals. Scientific research topics that are of interest to NASA will be presented. Each cassette used to house the Drosophila has a removable food tray that can be replaced to sustain the growth of the culture, or can be transferred to another cassette, along with embryos and burrowed larvae, enabling multi-generational studies. The cassette can be frozen in the Minus Eighty Laboratory Freezer for ISS to preserve samples until post-flight analysis, expanding the applications of the hardware. Utilization of a centrifuge allows for on-orbit 1g controls for microgravity experiments, as well as variable g-levels for lunar or Mars environment studies. The standard form factor used also allows for implementation of modular upgrades. An observation system, circadian rhythm lighting system, and fixation capability are upgrades currently in development for near-term implementation. This hardware suite, with its flight- proven design and ability to utilize existing on-board facilities, offers the whole Drosophila research community a platform to address several key areas of the National Research Councils decadal survey, supporting the utilization of ISS for science discovery.

Drosophila↗

The Role of CDKN1a/p21 in Cellular Senescence of Bone Marrow Stem Cells Under Spaceflight Stressors

Spaceflight environments and their associated conditions, such as microgravity and space radiation, cause many biological functions formerly considered to be standard to behave in nonstandard ways. Exposure to microgravity has shown to induce deleterious effects in stem cell-based tissue regeneration, leading to immune system and healing response impairments as well as muscle and bone density loss. Such risks must be mitigated in order for long-term human space exploration to proceed. Thus, our work seeks to explore mechanisms of stem cell-based tissue regeneration that experience changes in spaceflight environments. Cellular senescence is a process of inducing cell cycle arrest that can be initiated by various stimuli. This function is influenced by two major pathways, controlled by p53 and pRB tumor suppressor proteins. p53 activity targets the cyclin-dependent kinase inhibitor gene p21Cdkn1a in osteogenic cell cycle arrest. Under conditions of mechanical unloading, stem cell-based tissue regeneration has shown to be decreased in both proliferation and differentiation, as many cells are arrested in progenitor states. p21 has shown upregulation in expression under conditions of microgravity, suggesting its role in regenerative bone formation arrest in space. p21 levels are found to be elevated independent of p53, suggesting a decrease in proliferation and regeneration without apoptosis, but rather through cell cycle arrest alone. Thus, we hypothesize that p21 is a mediator of cellular senescence in bone marrow stem cells. Culturing of bone marrow stem cells from wild type and p21 knockout mice under osteoblastogenic conditions will be completed to explore the role of p21Cdkn1a in stem cell proliferation and maturation. We believe that decreases in somatic stem cell differentiation may occur after spaceflight due to signal pathway alterations that result in downstream inhibition of genes involved in differentiation, preventing tissue from repairing and regenerating normally.

Stem Cells↗

Spacecraft Lighting to Mitigate Microbial Growth

ISS crew health research indicate risk for immune system degradation for long duration missions, necessitating the need to maximize countermeasures on microbial growth (1). This project will investigate applications using violet (400nm) LEDs to mitigate growth of bacteria on architectural surfaces. The application is primarily for architectures and surfaces where a higher amount of bacterial growth is expected. The project will build two different types of violet light sources that represent lamp types that could be installed in spacecraft applications. Under a controlled setting, using violet LEDs, the evaluation will test the effectiveness of a glowing work surface using LED Panel verses an LED array overhead lamp. The effectiveness of the lighting systems to attenuate bacterial growth will be compared to a control. The results of this study can be used to inform spacecraft system architects on novel ways to improve habitat health, and reduce reliance on manual cleaning methods.

Clark, Toni A.↗

The problem of partial gravity on the Moon and Mars

Astronauts who spend many weeks or months in space in zero g suffer serious health problems including muscle atrophy, cardiovascular deconditioning, bone calcium loss, impaired vision, and immune system change. The debilitating effects of weightlessness were first demonstrated on the early Skylab, Salyut, and Mir missions, but it was too optimistically hoped that in-flight exercise and resistance training could prevent these problems. Similar problems are anticipated in the partial gravity of the Moon and Mars. Partial gravity exposure below 0.4 g seems too low to maintain musculoskeletal and cardiopulmonary conditioning in the long term. Some studies show a strong correlation between heart rate, oxygen consumption, net metabolic rate and simulated gravity from 0 to 1 g. Exposure to Moon and Mars gravities probably will cause less severe physiological deconditioning than experienced in 0 g, but the benefit of partial gravity seems likely to be roughly proportional to the 1/6 or 1/3 gravity experienced. As in 0 g, exercise countermeasures seem necessary but insufficient to preserve all physiological systems to a 1 g standard.

Harry W Jones↗

The Partial Gravity of the Moon and Mars Appears Insufficient to Maintain Human Health

Astronauts who spend many weeks or months in space in microgravity suffer serious health problems including muscle atrophy, cardiovascular deconditioning, bone calcium loss, impaired vision, and immune system changes. The debilitating effects of weightlessness were first demonstrated on the early Skylab, Salyut, and Mir missions, but it was then hoped that countermeasures including in-flight exercise and resistance training could reduce most of these problems. Similar effects are anticipated in the partial gravity of the Moon and Mars. Direct evidence of the long-term effects of partial gravity on humans is not yet available, but indirect evidence suggests that partial gravity exposure below 0.4 g will be insufficient to maintain musculoskeletal and cardiopulmonary conditioning over the long term. Some studies show a strong correlation between heart rate, oxygen consumption, net metabolic rate, and simulated gravity from 0 to 1 g. Exposure to moon and Mars gravities will probably cause less severe physiological deconditioning than microgravity, but the benefit of partial gravity seems likely to be roughly proportional to the level of gravity experienced. As in microgravity, exercise countermeasures seem useful but insufficient to preserve all physiological systems as they would be in Earth gravity.

Harry W. Jones↗

Space Radiation Technologies for Human Missions beyond Low-Earth-Orbit

Ionizing radiation exposure is a pervasive occupational risk to astronauts and remains a major health risk associated with human exploration beyond low-Earth-orbit. Sustained lunar and Mars exploration crew will be at increased risk of radiogenic cancers and cardiovascular disease, as well as, the potential for in-mission performance decrements, immune system decrements, and late neurodegenerative conditions impacting crew health. Optimizing astronaut space radiation protection will incorporate both physical and biological radiological aspects and will implement protection strategies that span pre-mission, in-flight, and post mission timelines. Major facets of physical risk mitigation include accuracy in predicting the space radiation solar environment, monitoring environmental and human exposures, and minimizing exposure through vehicle shielding and design. Biological mitigation facets include understanding and predicting biological response to the space environment, developing advanced medical countermeasures, and identifying appropriate surveillance strategies to preserve long-term health. Coordinated investments in these major capability areas will support development of an integrated radiation protection solution to minimize astronaut risk for moon to Mars exploration missions.

Lisa C Simonsen↗

Topical: Stem Cell-Based Tissue Regenerative Health in Space

The maintenance of healthy adult tissues in mammals requires a complex homeostasis of molecular, cellular, tissue, and metabolic processes which are fundamentally different from the development and aging processes that bookend life. Cellular homeostasis in the adult requires molecular maintenance and repair of non-dividing cells such as cardiomyocytes and neurons, but also stem cell-based tissue regeneration via direct replacement of cell loss, such as in the blood, immune system, bone, skin, liver, intestine, and other tissues. Because stem cell-based tissue regenerative health requires constant proliferation and differentiation of stem cell progenitors in the bone marrow, and other adult stem cell niches, it is uniquely sensitive to the stresses of spaceflight including exposure to space radiation and mechanical unloading in microgravity. A key central hypothesis in this field is that those spaceflight stress factors can have profound negative effects on long-term tissue regenerative health mediated by adult stem cells, and that unmitigated, they may lead to premature tissue aging and functional failure. Specifically, it is thought that mechanical unloading due to lack of weight-bearing in space reduces mitogenic mechanotransduction necessary to promote adult stem cell proliferation and differentiation, and that space radiation can also lead to activation of cell cycle arrest mechanisms, further reducing adult stem cell proliferation. These hypotheses are being tested in low earth orbit(LEO)using a variety of cellular and whole organism tissue model systems, suggesting that spaceflight consistently interferes with stem cell tissue regenerative processes such as in mammalian embryoid bodies, regenerating newt tails, and mouse bone marrow hematopoietic and osteoprogenitor cells. Furthermore, potential molecular mechanisms integrating both space radiation and mechanical disuse via oxidative stress and the cell cycle inhibitor Cdkn1aare now under study using single cell (scRNAseq) expressome analysis of bone marrow osteoprogenitors, both under stretch loading, and spaceflight conditions including in various mouse transgenic null backgrounds relevant to these mechanisms. Future work in the area of tissue regenerative health in space for the coming decade should seek to understand the responses the various tissue regenerative stem cell niches in humans and relevant model organisms, and how they respond to long-term exposure to the space environment. Special emphases of future work should be on how regenerative deficits in whole-organism stem cell niches may lead to tissue degeneration and premature aging, and on the long-term proliferation and differentiation of stem cell derived tissue organoid models in the deep space environment outside of LEO.

Eduardo A C Almeida↗

International Standard Measures During the AGBRESA Bed Rest Study

The Artificial Gravity Bed Rest with European Space Agency (AGBRESA) study involved 2 campaigns of 60-day bed rest at 6° head down tilt in the:envihab facility in Cologne, Germany, in 2019. The objective was to determine whether centrifugation of supine subjects mitigates physiological changes that occur due to the exposure to the spaceflight analog of 6° head down tilt. A set of international standard measures was used to evaluate bone, muscle, nutritional status, ocular changes, and psychological state and to assess cardiovascular, sensorimotor, and immune systems functions. After 60 days of bed rest, the subjects who were not exposed to centrifugation had significant decreases in mineral density at the hip and lumbar spine, decreased muscle strength of the knee and ankle, reduced maximal aerobic capacity, orthostatic intolerance, and impaired balance and locomotion, as well as significant biochemical, immunological, and psychological alterations. A daily 30-min exposure to 1 Gz supine centrifugation at the center of mass (0.3 Gz at the head, 2 Gz at the feet) mitigated mineral density loss in the femur neck and lumbar spine; and lessened the effects of bed rest on aerobic capacity, biochemistry, and immunology. However, low statistical power could contribute to the non-significant effects that are reported.

Bed rest↗

Isolation Standard Measures: A Set of Validated and Feasible Measurements Ensuring Comparability Across Isolation and Confinement Studies

Isolation and confinement studies have been essential to the preparation of crewed long-duration space missions, acting as analogues that facilitate the study of psychological and physiological responses to isolation and confinement. They also serve as opportunities for the development, testing, and validation of countermeasures and coping methods to handle the challenges that arise in such scenarios. Due to the small sample sizes in combination with high inter-individual variability, single isolation campaigns are not always sufficient for obtaining statistically significant scientific findings. To address this issue and improve comparability between different studies, the need for standardized measures to be collected in all future isolation and confinement studies was identified. Additionally, these measures should also be shown to be generally valid, reliable, feasible and acceptable in analogue and spaceflight environments. Standard measures in isolation and confinement studies allow for more direct comparisons of results and synthesis of data across isolation and confinement studies as well as provide an important step toward standard measures in spaceflight. An international expert group with representatives from different space agencies worldwide was brought together to define a core set of standard measures for isolation and confinement studies. This paper provides an overview of the expert group’s recommendations for international standard measures for future isolation and confinement studies, along with subsequent updates coordinated by the International Countermeasures Working Group (ICMWG), which was established as a sub-Working Group under the International Space Life Sciences Working Group (ISLSWG). Additional experts were consulted by the ICMWG partner agencies as required. The collection of the described set of isolation standard measures will provide data on the following parameters: sleep, mood, psychological state, psychophysiology, cognitive performance, stress and the immune system, general health and well-being, team measures, nutritional measures, and environmental conditions. For each measure, recommendations were made about duration and frequency of administration, along with specific implementation recommendations in relation to the duration of the isolation study. The set of isolation standard measures will be reassessed every two years at a minimum to ensure they are up to date and reflect the current state-of-the-art.

Isolation↗

Brain Aging Hallmarks: A Primer for Future Studies on Space Radiation Effects

As humankind endeavors to travel farther away from Earth, many questions remain to be solved to ensure proper preparation for deep space. Multiple spaceflight stressors can elicit adverse health outcomes including exposure to space radiation. Space radiation exposure has been identified by the National Aeronautics and Space Administration (NASA) as an important contributor to cancer, degenerative tissue diseases including cataracts, cardiovascular disease, immune system dysfunction and possible central nervous system decrements. The complexity of the human central nervous system makes it difficult to adequately recapitulate in experimental model systems, which hinders quantitative description of associated decrements. The brain aging hallmarks, as introduced by Mattson and Arumugam in 2018, are measurable cellular and molecular hallmarks that generally contribute to the aging process, describe an aging phenotype, and are part of the etiology of age-related neurodegenerative diseases. These hallmarks include mitochondrial dysfunction, accumulation of oxidatively damaged molecules (oxidative stress), impaired lysosome and proteasome function, dysregulation of neuronal calcium homeostasis, compromised adaptive cellular stress response, aberrant neuronal network activity, impaired deoxyribonucleic acid (DNA) repair, inflammation, impaired neurogenesis and dysregulated energy metabolism. Cellular senescence and telomere attrition may also be considered, though more evidence is needed to regard them as brain-specific hallmarks of aging. Radiation exposure has previously been correlated with aging etiology; therefore, investigating the effects of radiation exposure within the context of the hallmarks of brain aging may provide insights into potential health risks facing NASA astronauts, and may provide a means to identify disease processes that may be important targets for disease prevention or intervention. This work describes the hallmarks of brain aging and serves as a primer for future investigation into how the hallmarks of brain aging may compare and contrast with outcomes associated with exposure to the space radiation environment. Further, it will be useful in future identification of hallmarks that may be appropriate to target for radiation countermeasures specific to the central nervous system.

Vivian Lu↗

Impact of Simulated Galactic Cosmic Radiation and Hindlimb Unloading on the Mouse Adrenal Gland Morphology and Histology

Stress related impact of Galactic Cosmic Radiation (GCR) combined with microgravity in space are concerns for astronauts going beyond the Van Allen belts on their way to the Moon and Mars. The adrenal gland is the central endocrine tissue involved in stress management, adrenal hormones regulate the immune system, cellular and tissue metabolism, and glucose and sodium balances. Adult (6 m old) female (n=18) and male (n=18) C57BL/6J mice were divided evenly into 6 treatment groups (control, hindlimb unloading (HU), irradiated (IR), HU+IR, group house control, and group house IR). Adrenals were dissected and fixed for 24 h in 4% paraformaldehyde, followed by transfer to 70% EtOH, and shipment to KUMC. Adrenals were then embedded in paraffin and serial sectioned and 4 central sections from each were stained with H&E, prior to imaging on a Nikon 80i microscope. Whole adrenal cross section area, medullary area, and cortex area were determined. General adrenal gland morphology and histology did not appear to be affected by hindlimb unloading or GCR exposure. Total cross-sectional area, medullary region, and cortex of the adrenal were not different across treatment groups. Male adrenal cross-sectional areas are half the size of the female adrenals, due to a difference in cortex area. In conclusion, simulated microgravity and GCR did not dramatically affect the adrenal gland histology or size. Support from Accelerate Cancer Education Internship Program (KUCC) and KINBRE Summer Scholars Program (KUMC) and NASA Human Research Program (HRP) Human Factors Behavioral Performance Element Grant 18 18FLAG 2 0028

radiation↗

Long Term Human Presence in Space Requires Artificial Gravity and Radiation Shielding

Astronauts who spend many months in microgravity suffer serious health problems including muscle atrophy, cardiovascular deconditioning, bone calcium loss, impaired vision, and immune system changes. Exercise countermeasures have been insufficient to maintain normal human performance. Similar problems can be expected in the partial gravity of the Moon and Mars. Achieving the long-term presence of healthy humans in space requires providing artificial Earth level gravity. This can be done on the Moon and Mars by using horizontally rotating habitats with angled floors, but it is easier in space habitats. Astronauts travelling beyond the protection of the Earth’s magnetic field can suffer harm from cosmic background radiation and occasional strong solar flares. Supporting healthy long-term human lives will require radiation shielding on the Moon and Mars as well as in space. Human space settlement will probably begin with artificial rotating space habitats in Low Earth Orbit (LEO) where they will be shielded from radiation. The earlier anticipated human communities in pressurized domes on the Moon or Mars appear unrealistic because of the now known problems of partial gravity and radiation.

Astronauts↗

Long Term Human Presence in Space Requires Artificial Gravity and Radiation Shielding

Astronauts who spend many months in microgravity suffer serious health problems including muscle atrophy, cardiovascular deconditioning, bone calcium loss, impaired vision, and immune system changes. Exercise countermeasures have been insufficient to maintain normal human performance. Similar problems can be expected in the partial gravity of the Moon and Mars. Achieving the long-term presence of healthy humans in space requires providing artificial Earth level gravity. This can be done on the Moon and Mars by using horizontally rotating habitats with angled floors, but it is easier in space habitats. Astronauts travelling beyond the protection of the Earth’s magnetic field can suffer harm from cosmic background radiation and occasional strong solar flares. Supporting healthy long-term human lives will require radiation shielding on the Moon and Mars as well as in space. Human space settlement will probably begin with artificial rotating space habitats in Low Earth Orbit (LEO) where they will be shielded from radiation. The earlier anticipated human communities in pressurized domes on the Moon or Mars appear unrealistic because of the now known problems of partial gravity and radiation.

Astronauts↗

Plausible Biological Mechanisms Underlying Sex Differences in Radiation-Induced Lung Cancer Risk

Some epidemiological studies suggest that women are at greater risk for radiation-induced lung cancer than men, but this observation is not consistent across all studies. A scientific committee formed by the National Council on Radiation Protection and Measurement evaluated evidence for a sex difference in lung cancer risk from radiation exposuresby reviewing animal studies and assessing the biological plausibility that such a difference might exist. The committee identified four mechanisms that could potentially result in greater radiogenic lung cancer risks for women. The first of these is that radiation exposure increases the relative risk for a molecular subtype of spontaneous lung cancer that occurs predominantly in women. The second is that is that sex chromosome or gene expression differences between men and women places women at greater risk. The third is that hormonal differences between men and women, particularly for estrogen levels, puts women at greater risk. The fourth mechanism is that sex differences in immune system function underlie a sex difference in radiation associated lung cancer risk.None of these mechanisms hasyet been proven to play a role in radiogenic lung cancer risk.

radiation↗

Analyzing the Impact of Lunar Dust on Astronaut Health – an Update to the Risk Modeling

INTRODUCTION Lunar dust exposure is an unavoidable hazard during lunar surface operations. Given the large number of surface EVAs expected to be performed during Artemis missions, it is critical that the incidence and extent of symptoms resulting from contact with lunar dust be fully understood in order to accurately predict the resources needed to treat Artemis astronauts. The purpose of this study will be to gather the latest data regarding the risk of and severity of symptoms associated with lunar dust exposure and refine the estimates of the impact of lunar dust on astronaut health for PRA models, both those in operational use and those currently being developed. METHODS The latest data on the pathophysiologic effects of lunar dust on humans will be gathered by querying the peer-reviewed literature as well as NASA technical documents. This data will be supplemented with discussions with hardware designers regarding methods used to mitigate exposure to lunar dust during lunar surface operations. Taken together, this data will be used to refine both the estimates for exposure to lunar dust for astronauts inside and outside lunar habitats, as well as provide evidence to guide estimates for the percentage of astronauts who are exposed to lunar dust who will be symptomatic. RESULTS Querying the peer-reviewed literature and NASA technical documents will begin in October of 2024, with the goal of codifying this information by the end of October. In parallel, discussions will begin with hardware engineering teams, also in October. Using the evidence found will help refine the estimate for resources needed to treat astronauts who exhibit symptoms from lunar dust exposure. DISCUSSION Lunar dust exposure is expected to be a major risk for upcoming exploration missions that include a lunar surface interval. Until recently, most of the information to inform the risk associated with lunar dust exposure has come from anecdotal evidence from Apollo astronauts about their symptoms while on the lunar surface; however, this evidence is sparse. Newer studies are now coming out, looking at the impact of lunar dust on human physiology, including studies on effects to the immune system. Additionally, there are new engineering efforts to attempt to mitigate the exposure to lunar dust from the space suits of astronauts returning to the lunar habitat after surface operations. Thus, developing an updated risk assessment, based on our current understanding of human physiology and our current resources for risk mitigation, is prudent to best estimate overall human health and performance risk for future Artemis missions. This project will lead to an updated and more accurate assessment of the risk of lunar dust exposure for exploration missions and will therefore allow mission planners to more accurately predict resources needed for these exploration-class missions.

D M Nusbaum↗

Spaceflight-Induced Changes in Microbial Virulence and the Impact to the Host Immune Response

Many microbial pathogens have repeatedly exhibited unexpected responses relevant to infectious disease when grown in microgravity and microgravity analogue environments, including changes in final cell concentration, biofilm production, stress resistance, antibiotic sensitivity, gene expression, host-pathogen interactions, and virulence. Notably, the classic foodborne pathogen Salmonella enterica serovar Typhimurium displayed increased virulence in animals when cultured in either the spaceflight analogue or true spaceflight environment. Recently, Serratia marcescens also was shown to increase virulence when cultured in the spaceflight environment. In parallel, astronaut studies have characterized a persistent spaceflight-induced dysregulation of the human immune system at multiple levels, which suggests an increased risk of infectious diseases. Moreover, astronauts have some degree of clinical infectious disease incidence. However, the contribution of the microgravity environment on host-pathogen interactions and potential for clinical disease remains understudied and poorly characterized. The goal of this study is to gain insight into the breadth of other medically significant microbial pathogens that may exhibit altered virulence and pathogenesis-related responses when cultured in spaceflight analogue conditions. Specifically, we are characterizing the effect of spaceflight analogue culture (Low Shear Modeled Microgravity/LSMMG) on microbial pathogenesis-related stress responses, in vitro host-pathogen interactions, gene expression, and virulence potential in animals using five important model bacterial pathogens, Salmonella enterica Enteritidis, Pseudomonas aeruginosa, Burkholderia cepacia, Streptococcus pneumoniae, and enterohemorrhagic Escherichia coli. The information to date is providing a better understanding into the potential impact of microgravity on alterations in microbial virulence and associated infectious disease risk to crew health during spaceflight missions.

C M Ott↗

An Immunized Aircraft Maneuver Selection System

The objective of this project, as stated in the original proposal, was to develop an immunized aircraft maneuver selection (IAMS) system. The IAMS system was to be composed of computational and informational building blocks that resemble structures in natural immune systems. The ultimate goal of the project was to develop a software package that could be flight tested on aircraft models. This report describes the work performed in the first year of what was to have been a two year project. This report also describes efforts that would have been made in the final year to have completed the project, had it been continued for the final year. After introductory material is provided in Section 2, the end-of-year-one status of the effort is discussed in Section 3. The remainder of the report provides an accounting of first year efforts. Section 4 provides background information on natural immune systems while Section 5 describes a generic ar&itecture developed for use in the IAMS. Section 6 describes the application of the architecture to a system identification problem. Finally, Section 7 describes steps necessary for completing the project.

Karr, Charles L.↗

Constant current loop impedance measuring system that is immune to the effects of parasitic impedances

A constant current loop measuring system is provided for measuring a characteristic of an environment. The system comprises a first impedance positionable in the environment, a second impedance coupled in series with said first impedance and a parasitic impedance electrically coupled to the first and second impedances. A current generating device, electrically coupled in series with the first and second impedances, provides a constant current through the first and second impedances to produce first and second voltages across the first and second impedances, respectively, and a parasitic voltage across the parasitic impedance. A high impedance voltage measuring device measures a voltage difference between the first and second voltages independent of the parasitic voltage to produce a characteristic voltage representative of the characteristic of the environment.

Anderson, Karl F.↗