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NASA NTRS1981

Millimeter-wave experiments for cometary space missions

Predicted brightness temperatures, computed by means of radiative transfer techniques adapted from the modeling of terrestrial ice and snow fields, are given for cometary nucleus models consisting of homogeneous layers of water ice and refractory grain mixtures presented as functions of wavelength. The computed millimeter-wave spectra are sensitive to the values of such physically significant nucleus parameters as (1) crust thickness, (2) subsurface temperature gradient, and (3) sublimating surface boundary temperature. Although antenna beam dilution is a major obstacle for ground-based molecular spectral line radio observations of comets, a millimeter-wave radiometer in the vicinity of the comet would be immune to this effect and able to make observations of several candidate parent molecules in the gas phase.

Hobbs, R. W.↗

NASA NTRS2007

Recommendations for Refinement and Validation of Intermittent Artificial Gravity

The IMAG Pilot Study, recently completed at the University of Texas Medical Branch, filled in the second major gap in knowledge standing in the way of development of a practical Short Radius Centrifuge (SRC) and the use of Artificial Gravity (AG) as a multi-system countermeasure to combat the deconditioning associated with extended weightlessness. (The first challenge, to adapt rapidly rotating subjects to permit unlimited head movements without excessive motion sickness, was achieved in a series of studies at MIT involving incremental increases in head and centrifuge velocity.) It remained to be demonstrated that intermittent exposure to AG, at only one hour per day for 21 days, would have any positive effect on slowing or eliminating of deconditioning. Bed-rested normal subjects were used as a ground analog for astronauts in weightlessness. The results are clearly positive for the key physiological systems of interest: cardiovascular, muscle, and bone. No functionally relevant changes were observed in immune, cognitive, or sensory-motor function. Furthermore, we found that our initial concerns about the inability of deconditioned subjects to withstand daily centrifugation without syncope were misplaced. These encouraging initial results clearly support the further development of AG protocols. We recommend, as the next steps, the integration of a controlled exercise device on the SRC to determine the synergy between AG and exercise. Coupled with appropriate exercise device(s) the AG protocol will be tuned to-ward an optimal prescription for minimum exposure duration and frequency, maximum AG level and SRC speed.. Performance of these next steps will require extensive use of bed-rest/centrifuge facilities and eventually validation using an SRC in space. A space SRC could be placed in the ISS or on a planetary surface.

Young, Lauren R.↗

NASA NTRS2022

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↗

NASA NTRSDate not supplied

Oxidative Stress and the Neuroconsequences of Spaceflight Environment - Immune Dysregulation and Antioxidant Dietary Countermeasure Efficacy

In this project, we will test the hypothesis that 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. Specific Aims for this project are: (1) Determine dose-response curves for acute ‘Five-Ion GCR Simulation’ exposure for immune, brain and performance responses in crew age-matched adult male and female mice; (2) Determine effects of acute ‘Five-Ion GCR Simulation’ exposure singly and in combination with simulated microgravity and social isolation, on immune, brain and performance responses in crew age-matched male and female mice mimicking deep space missions; and (3) Determine efficacy of the dietary antioxidant, Nicotinamide Mononucleotide (NMN), a key intermediate in nicotinamide adenine dinucleotide (NAD+) biosynthesis. The project relies on established and highly translatable ground-based mouse models and assays with IR exposures to be performed at the NASA Space Radiation Laboratory (NSRL). The experimental approach will provide definitive data on the timing and mechanisms involved in the oxidative stress response, immune and brain changes, and ensuing functional (behavioral/cognitive) impairments expected during human transit to Mars. 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. The project will address NASA’s efforts to rapidly advance the characterization of risks and identify appropriate countermeasures in anticipation of future deep space missions. Ensuring crew health and performance during extended transits necessitates that sensorimotor and cognitive abilities remain strong to avoid potentially catastrophic health and safety outcomes. Further, despite historically low numbers of female astronauts, the two most recent NASA Astronaut Corps class selections, comprised of ~50% women as compared to men, signal the need to understand how sex differences affect physiological adaptation and health in the space environment. Here, we will determine how key features of the deep space environment may interact to increase risk to crewmembers by negatively impacting health and performance, and identify and develop strategies to characterize and mitigate the potential risks via countermeasures. Supported by the NASA Human Research Program (HRP) Human Factors Behavioral Performance Element Grant 18-18FLAG_2-0028.

radiation↗

NASA NTRS2025

Influence of Microgravity on Bacterial Pathogen Virulence and Immune Cell Function—Relevance for Infectious Disease Risk During Spaceflight

Spaceflight has measurable impacts on astronaut immune profiles as well as the virulence patterns of bacterial pathogens. Data with respect to human immunity indicate diminished T and NK cell function, altered cytokine profiles, persistent inflammation, and latent herpesvirus reactivation. Furthermore, evaluation of International Space Station (ISS) crewmembers gives evidence of compromised immunity, including atypical allergy, infectious disease, and dermatitis. Data with respect to certain human bacterial pathogens suggest modified virulence that may be enhanced. It is therefore critical to examine this interaction of immune dysregulation and increased microbial virulence and whether it might synergistically increase the risk of infectious disease to crew members. The goal of this study is to use modeled microgravity to study the impact of medically significant ISS bacteria that may have altered virulence on the immune response of the host. This study consists of two primary aims to assess this relationship. First, immune cells will be collected from healthy test subjects and cultured in static or in modeled microgravity conditions together with either control pathogens or with microgravity conditioned pathogens that were grown in bioreactors. Second, immune cells will be collected from astronauts before, during, and after flight and co-cultured with the control or the microgravity conditioned bacteria. Three pathogens were selected for this investigation: Pseudomonas aeruginosa , Salmonella enterica serovar Enteritidis and Burkholderia cepacia . Previously, the optimal cell to bacteria ratios that produce the greatest immune cell responses have been derived for these three bacteria. Cellular activation, as determined by the induction of cell surface activation markers and cytokine profiles, will be measured. Interactions between cells and bacteria will be assessed using fluorescent and electron microscopy techniques. This study will provide critical information to help understand how microgravity alters microbial virulence and the associated infectious disease risk to crewmembers during spaceflight missions. Over the past year, the Immunology and Microbiology laboratories at NASA Johnson Space Center have collaborated to process the astronaut subject samples to complete the last year of the flight portion of this study. This included the completion of four astronaut subjects full mission sampling sets. Sample processing included innate and adaptive cell flow cytometry as well as analysis of cytokine concentrations in the supernatant. The ground control segment of the study will take place during FY25 which involves parallel infections run under static and clinostat conditions. The acquired data sets over this 3-year study are now being analyzed to provide a comprehensive set of results and conclusions that will contribute to a more effective risk assessment for astronauts during spaceflight regarding this host-pathogen context.

Immunology↗

NASA NTRS2007

Multi-System Effects of Daily Artificial Gravity Exposures in Humans Deconditioned by Bed Rest

We have begun to explore the utility of intermittent artificial gravity (AG) as a multi-system countermeasure to the untoward health and performance effects of adaptation to decreased gravity during prolonged space flight. The first study in this exploration was jointly designed by an international, multi-disciplinary team of scientists interested in standardizing an approach so that comparable data could be obtained from follow-on studies performed in multiple international locations. Fifteen rigorously screened male volunteers participated in the study after providing written informed consent. All were subjected to 21 days of 6deg head-down-tilt (HDT) bed rest. Eight were treated with daily 1hr AG exposures (2.5g at the feet decreasing to 1.0g at the heart) aboard a short radius (3m) centrifuge, while the other seven served as controls. Multiple observations were made of dependent measures in the bone, muscle, cardiovascular, sensory-motor, immune, and behavioral systems during a 10 day acclimatization period prior to HDT bed rest and again during an 8 day recovery period after the bed rest period. Comparisons between the treatment and control subjects demonstrated salutary effects of the AG exposure on aspects of the muscle and cardiovascular systems, with no untoward effects on the vestibular system, the immune system, or cognitive function. Bone deconditioning was similar between the treatment and control groups, suggesting that the loading provided by this specific AG paradigm was insufficient to protect that system from deconditioning. Future work will be devoted to varying the loading duty cycle and/or coupling the AG loading with exercise to provide maximum physiological protection across all systems. Testing will also be extended to female subjects. The results of this study suggest that intermittent AG could be an effective multi-system countermeasure.

Paloski, William H.↗

NASA NTRS2016

Epigenetics Research on the International Space Station

The International Space Station (ISS) is a state-of-the orbiting laboratory focused on advancing science and technology research. Experiments being conducted on the ISS include investigations in the emerging field of Epigenetics. Epigenetics refers to stably heritable changes in gene expression or cellular phenotype (the transcriptional potential of a cell) resulting from changes in a chromosome without alterations to the underlying DNA nucleotide sequence (the genetic code), which are caused by external or environmental factors, such as spaceflight microgravity. Molecular mechanisms associated with epigenetic alterations regulating gene expression patterns include covalent chemical modifications of DNA (e.g., methylation) or histone proteins (e.g., acetylation, phorphorylation, or ubiquitination). For example, Epigenetics ("Epigenetics in Spaceflown C. elegans") is a recent JAXA investigation examining whether adaptations to microgravity transmit from one cell generation to another without changing the basic DNA of the organism. Mouse Epigenetics ("Transcriptome Analysis and Germ-Cell Development Analysis of Mice in Space") investigates molecular alterations in organ-specific gene expression patterns and epigenetic modifications, and analyzes murine germ cell development during long term spaceflight, as well as assessing changes in offspring DNA. NASA's first foray into human Omics research, the Twins Study ("Differential effects of homozygous twin astronauts associated with differences in exposure to spaceflight factors"), includes investigations evaluating differential epigenetic effects via comprehensive whole genome analysis, the landscape of DNA and RNA methylation, and biomolecular changes by means of longitudinal integrated multi-omics research. And the inaugural Genes in Space student challenge experiment (Genes in Space-1) is aimed at understanding how epigenetics plays a role in immune system dysregulation by assaying DNA methylation in immune cells directly in space using miniPCR technology. In addition, NASA's geneLAB campaign covers the epigenome as part of the "expressome", by employing an innovative open source science platform for multi-investigator high throughput utilization of the ISS. Earth benefits of Epigenetics research onboard the ISS range from contributions to the fundamental understanding of epigenetic phenomena with applications in countermeasure development for biomedical conditions, to the generation of integrated strategies for personalized medicine based on unique physiological responses.

Love, John↗

NASA NTRS1998

An Adaptable Power System with Software Control Algorithm

A low cost, flexible and modular spacecraft power system design was developed in response to a call for an architecture that could accommodate multiple missions in the small to medium load range. Three upcoming satellites will use this design, with one launch date in 1999 and two in the year 2000. The design consists of modular hardware that can be scaled up or down, without additional cost, to suit missions in the 200 to 600 Watt orbital average load range. The design will be applied to satellite orbits that are circular, polar elliptical and a libration point orbit. Mission unique adaptations are accomplished in software and firmware. In designing this advanced, adaptable power system, the major goals were reduction in weight volume and cost. This power system design represents reductions in weight of 78 percent, volume of 86 percent and cost of 65 percent from previous comparable systems. The efforts to miniaturize the electronics without sacrificing performance has created streamlined power electronics with control functions residing in the system microprocessor. The power system design can handle any battery size up to 50 Amp-hour and any battery technology. The three current implementations will use both nickel cadmium and nickel hydrogen batteries ranging in size from 21 to 50 Amp-hours. Multiple batteries can be used by adding another battery module. Any solar cell technology can be used and various array layouts can be incorporated with no change in Power System Electronics (PSE) hardware. Other features of the design are the standardized interfaces between cards and subsystems and immunity to radiation effects up to 30 krad Total Ionizing Dose (TID) and 35 Mev/cm(exp 2)-kg for Single Event Effects (SEE). The control algorithm for the power system resides in a radiation-hardened microprocessor. A table driven software design allows for flexibility in mission specific requirements. By storing critical power system constants in memory, modifying the system code for other programs is simple. These constants can be altered also by ground command, or in response to an anomolous event. All critical power system functions have backup hardware functions to prevent a software or computer glitch from propagating. A number of battery charge control schemes can be implemented by selecting the proper control terms in the code. The architecture allows the design engineer to tune the system response to various system components and anticipated load profiles without costly alterations. A design trade was made with the size, weight and power dissipation of the electronics versus the performance of the power bus to load variations. Linear, fine control is maintained with a streamlined electronics design. This paper describes the hardware design as well as the software control algorithm. The challenges of closing the system control loop digitally is discussed. Control loop margin and power system performance is presented. Lab measurements are shown and compared to the system response of a hardware model running actual flight software.

Castell, Karen↗

NASA NTRS1994

Physiological Adaptations and Countermeasures Associated with Long-Duration Space Flights

On earth, the presence of gravity imposes weight-bearing gradients on tissues which influence the functions of multiple integrative systems. On the other hand, conditions of actual or simulated microgravity can modify and/or nullify these gradients and subsequently alter structure and function. The purpose of this symposium is to discuss the results from short-term Shuttle flights, long term Skylab or Mir missions, or long-term ground based experiments which indicate or suggest that performance has been or could be compromised in space missions of long durations (>one year) or with space tasks (e.g. building space stations) with the goal of identifying countermeasures that could minimize or eliminate the expected anatomical and physiological consequences. After an overview by C. Tipton from the U. Arizona, the countermeasures necessary for the fluid shifts and select functions of the cardiovascular system will be discussed by A. Hargens from NASA Ames Research Center. He will be followed by K. Baldwin of the U. California at Irvine who will discuss the countermeasures needed to prevent the changes that alter the structure, function and control of skeletal muscles. Since changes in bone mass with microgravity are a major concern of NASA, V. Schneider from NASA Headquarters will present data and the countermeasures for bone. Although the results are limited, the changes in the endocrine and immune system deserve mentioning and C. Tipton will assume this responsibility. V. Convertino from the Air Force School of Aerospace Medicine has the challenge of discussing the role, importance, and the specificity of exercise as an effective countermeasure while I. Kozlovskaya from Moscow will elaborate on the Russian experiences with past countermeasures and provide a viewpoint on future ones. After the brief (25 min.) presentations, the speakers will assemble as a panel to discuss the issues raised and the concerns of the audience.

Tipton, C. M.↗

NASA NTRS2000

Blood Volume: Importance and Adaptations to Exercise Training, Environmental Stresses and Trauma/Sickness

This paper reviews the influence of several perturbations (physical exercise, heat stress, terrestrial altitude, microgravity, and trauma/sickness) on adaptations of blood volume (BV), erythrocyte volume (EV), and plasma volume (PV). Exercise training can induced BV expansion; PV expansion usually occurs immediately, but EV expansion takes weeks. EV and PV expansion contribute to aerobic power improvements associated with exercise training. Repeated heat exposure induces PV expansion but does not alter EV. PV expansion does not improve thermoregulation, but EV expansion improves thermoregulation during exercise in the heat. Dehydration decreases PV (and increases plasma tonicity) which elevates heat strain and reduces exercise performance. High altitude exposure causes rapid (hours) plasma loss. During initial weeks at altitude, EV is unaffected, but a gradual expansion occurs with extended acclimatization. BV adjustments contribute, but are not key, to altitude acclimatization. Microgravity decreases PV and EV which contribute to orthostatic intolerance and decreased exercise capacity in astronauts. PV decreases may result from lower set points for total body water and central venous pressure, which EV decrease bay result form increased erythrocyte destruction. Trauma, renal disease, and chronic diseases cause anemia from hemorrhage and immune activation, which suppressions erythropoiesis. The re-establishment of EV is associated with healing, improved life quality, and exercise capabilities for these injured/sick persons.

Sawka, Michael N.↗

NASA NTRSDate not supplied

BLOOD-BASED MULTI-SCALE MODEL FOR CANCER RISK FROM GCR IN GENETICALLY DIVERSE POPULATIONS

OBJECTIVES AND METHODS This project addresses the challenge of understanding and predicting individual radiation sensitivity by integrating genetics, demographics and biomarker characteristics across species (mice and humans). We hypothesize that ex vivo DNA repair response to GCR components is a central determinant of cancer risk from space radiation and can serve as a biomarker of radiation risk in combination with genetics. Automated image quantification of 53BP1+ radiation-induced foci (RIF) during the first 4-48 h post-irradiation was performed as a function of dose and LET in non-immortalized primary skin fibroblasts derived from 76 mice across 15 strains (5 inbred reference strains and 10 collaborative-cross strains) exposed to X rays (0.1, 1 and 4 Gy), 350 MeV/n 40Ar and 600 MeV/n 56Fe (1.1 and 3 particles/100μm2), as well as in peripheral blood mononuclear cells (PBMCs) from 768 healthy donors (matched ethnicity, 50/50 male/female, 18-70 years old) exposed to gamma rays (0.1 and 1 Gy), 350 MeV/n 28Si, 350 MeV/n 40Ar and 600 MeV/n 56Fe (1.1 and 3 particles/100μm2). QUANTIFICATION OF 53BP1+ FOCI IN VITRO AND ASSOCIATIONS TO IN VIVO RADIATION SUSCEPTIBILITY IN 15 MOUSE STRAINS We reported in vitro repair kinetic and repairable fractions of RIF for the 15 mouse strains and introduced a mathematical model for RIF as a function of time, dose and LET. We noted that the metabolic activity of cells modulates the RIF response, and we introduced the open access tool terRIFic (Tool for Enhanced Results of RIF In Cells, https://radbiolab.shinyapps.io/terrific/) to correct for such bias using confluence level. Notably, at 4h post-irradiation, RIF/Gy decreased with dose or LET: as the dose or LET increases, so does the proximity of DNA double-strand-breaks (DSB) and our data suggest that proximal DSBs are brought together inside isolated RIF for repair. The RIF/Gy trend was inverted at 24h, suggesting RIF with high DSB content are more difficult to repair. We showed that in vitro metrics correlate with in vivo measurements in the same 15 mouse strains, such as survival levels of immune cells or spontaneous cancer incidence, suggesting a relationship between the efficiency of DSB repair and cancer risk or radiation toxicity. In addition to the efficiency of repair and persistent RIF, the amount of spontaneous foci before irradiation was also found to be strain dependent. Finally, we performed genome-wide association study in the same 15 mouse strains using all RIF phenotypes measured in vitro, identifying genes of interest and validating RIF as an ideal biomarker for individual radiation sensitivity. BASELINE 53BP1+ FOCI PREDICTS INDIVIDUAL HUMAN RESPONSE TO GCR COMPONENTS Based on the analysis of radiation responses of 576 donor PBMCs (using quantification of 53BP1+ foci, oxidative stress and cell death), we observed a wide variability of subject- and LET-dependent radiation responses, with radiation-induced DNA repair foci increasing with LET, though oxidative stress being notably reduced by high-LET irradiation, potentially due to a switch between hydrogen peroxide and oxygen radical-based mechanisms. We identified a relationship between few spontaneous DNA foci at baseline and increased DNA repair after irradiation, accompanied by an alteration in immunoregulatory cytokine secretion, which might be adapted as biomarkers to predict ionizing radiation sensitivity. Among demographic variables, only latent cytomegalovirus infection and age were predictive of high baseline foci formation. Finally, we have performed low-throughput whole genome sequencing of all samples and are currently in the process of identifying the genes and pathways associated with low and high-LET ionizing radiation sensitivity in humans.

53BP1↗

NASA NTRS2007

Artificial Gravity as a Multi-System Countermeasure to Bed Rest Deconditioning: Pilot Study Overview

Efficient, effective, multi-system countermeasures will likely be required to protect the health, safety, and performance of crews aboard planned exploration-class space flight missions to Mars and beyond. To that end, NASA, DLR, and IMBP initiated a multi-center international project to begin systematically exploring the utility of artificial gravity (AG) as a multi-system countermeasure in ground based venues using test subjects deconditioned by bed rest. The goal of this project is to explore the efficacy of short-radius, intermittent AG as a countermeasure to bone, muscle, cardiovascular, and sensory-motor adaptations to hypogravity. This session reports the results from a pilot study commissioned to validate a standardized protocol to be used by all centers involved in the project. Subject selection criteria, medical monitoring requirements, medical care procedures, experiment control procedures, and standardized dependent measures were established jointly. Testing was performed on 15 rigorously screened male volunteers subjected to 21 days of 6deg HDT bed rest. (All provided written consent to volunteer after the nature of the study and its hazards were clearly explained to them.) Eight were treated with daily 1hr AG exposures (2.5g at the feet decreasing to 1.0g at the heart) aboard a short radius (3m) centrifuge, while the other seven served as controls. Multiple tests of multiple dependent measures were made in each of the primary physiological systems of interest during a 10 day acclimatization period prior to HDT bed rest and again during an 8 day recovery period after the bed rest period was complete. Analyses of these data (presented in other papers in this session) suggest the AG prescription had salutary effects on aspects of the bone, muscle, and cardiovascular systems, with no untoward effects on the vestibular system, the immune system, or cognitive function. Furthermore, treatment subjects were able to tolerate 153/160 centrifuge sessions over the 21 day deconditioning protocol, suggesting that tolerance was unaffected by deconditioning. These positive results set the stage for full implementation of the planned multi-center international AG project. Future work will be devoted to developing optimization techniques for AG prescriptions (likely supplemented by exercise) to provide maximum physiological protection across all systems subject to space flight deconditioning in both men and women with minimum time and/or side effects. While a continuous AG solution (rotating vehicle) would likely be more efficient, this study suggests that intermittent AG could be an effective multi-system countermeasure.

Paloski, William H.↗

NASA NTRS2016

Transcriptomic Response of Drosophila Melanogaster Pupae Developed in Hypergravity

The metamorphosis of Drosophila is evolutionarily adapted to Earth's gravity, and is a tightly regulated process. Deviation from 1g to microgravity or hypergravity can influence metamorphosis, and alter associated gene expression. Understanding the relationship between an altered gravity environment and developmental processes is important for NASA's space travel goals. In the present study, 20 female and 20 male synchronized (Canton S, 2 to 3day old) flies were allowed to lay eggs while being maintained in a hypergravity environment (3g). Centrifugation was briefly stopped to discard the parent flies after 24hrs of egg laying, and then immediately continued until the eggs developed into P6-staged pupae (25 - 43 hours after pupation initiation). Post hypergravity exposure, P6-staged pupae were collected, total RNA was extracted using Qiagen RNeasy mini kits. We used RNA-Seq and qRT-PCR techniques to profile global transcriptomic changes in early pupae exposed to chronic hypergravity. During the pupal stage, Drosophila relies upon gravitational cues for proper development. Assessing gene expression changes in the pupa under altered gravity conditions helps highlight gravity dependent genetic pathways. A robust transcriptional response was observed in hypergravity-exposed pupae compared to controls, with 1,513 genes showing a significant (q < 0.05) difference in gene expression. Five major biological processes were affected: ion transport, redox homeostasis, immune response, proteolysis, and cuticle development. This outlines the underlying molecular changes occurring in Drosophila pupae in response to hypergravity.

RNASeq↗

NASA NTRS2006

Microgravity and Immunity: Changes in Lymphocyte Gene Expression

Earlier studies had shown that modeled and true microgravity (MG) cause multiple direct effects on human lymphocytes. MG inhibits lymphocyte locomotion, suppresses polyclonal and antigen-specific activation, affects signal transduction mechanisms, as well as activation-induced apoptosis. In this study we assessed changes in gene expression associated with lymphocyte exposure to microgravity in an attempt to identify microgravity-sensitive genes (MGSG) in general and specifically those genes that might be responsible for the functional and structural changes observed earlier. Two sets of experiments targeting different goals were conducted. In the first set, T-lymphocytes from normal donors were activated with antiCD3 and IL2 and then cultured in 1g (static) and modeled MG (MMG) conditions (Rotating Wall Vessel bioreactor) for 24 hours. This setting allowed searching for MGSG by comparison of gene expression patterns in zero and 1 g gravity. In the second set - activated T-cells after culturing for 24 hours in 1g and MMG were exposed three hours before harvesting to a secondary activation stimulus (PHA) thus triggering the apoptotic pathway. Total RNA was extracted using the RNeasy isolation kit (Qiagen, Valencia, CA). Affymetrix Gene Chips (U133A), allowing testing for 18,400 human genes, were used for microarray analysis. In the first set of experiments MMG exposure resulted in altered expression of 89 genes, 10 of them were up-regulated and 79 down-regulated. In the second set, changes in expression were revealed in 85 genes, 20 were up-regulated and 65 were down-regulated. The analysis revealed that significant numbers of MGS genes are associated with signal transduction and apoptotic pathways. Interestingly, the majority of genes that responded by up- or down-regulation in the alternative sets of experiments were not the same, possibly reflecting different functional states of the examined T-lymphocyte populations. The responder genes (MGSG) might play an essential role in adaptation to MG and/or be responsible for pathologic changes encountered in Space and thus represent potential targets for molecular-based countermeasures

Risin, D.↗

NASA NTRS2022

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↗

NASA NTRS2017

Mapping by VESGEN of Blood Vessels in the Retinas of Astronauts Pre- and Post-Flight to the ISS

Research by NASA [1] established that significant risks for visual and ocular impairments associated with increased intracranial pressure (VIIP) are incurred by microgravity spaceflight, especially long-duration missions. It is well established in physiology and pathology that a fundamental role of the microvasculature is to mediate fluid transfers and remodel actively in response to environmental, immune and other stresses. We therefore hypothesize that remodeling of retinal blood vessels necessarily occurs during accommodation of microgravity-induced fluid shifts prior to subsequent development of visual and ocular impairments. Potential contributions of retinal vascular remodeling to VIIP etiology are therefore being investigated by NASA's innovative VESsel GENeration Analysis (VESGEN) software for two studies: (1) U.S. crew members before and after ISS missions, and (2) head-down tilt in human subjects before and after 70 days of bed rest. We anticipate that results of the two studies will be complete by the Investigators Workshop (January 22, 2017). METHODS: For the 2013 NASA NRA award, we are concluding the analysis of 30 degree infrared (IR) Heidelberg Spectralis images of retinal blood vessels by VESGEN (patents pending), a mature, automated software developed as a translational and basic vascular research discovery tool, particularly for retinal vascular disease. Subjects of our retrospective study include eight ISS crew members monitored for routine occupational surveillance pre- and post-flight, who provided their study consents to NASAs Lifetime Surveillance of Astronaut Health (LSAH) in coordination with approval of the VESGEN retrospective study protocol by NASAs Institutional Review Board (IRB). The ophthalmic retinal images (average image resolution, approximately 5.6 microns per pixel) are blinded as to pre and post ISS status until the second portion of our study, when VESGEN results will be correlated with other ophthalmic and medical findings for the crew members. Due to image resolution challenges, a novel Matlab tool was developed for aligning pre and post images, and comparing (querying) the two images for differences in the morphology of small vessels. RESULTS: During the past year, LSAH approved the release of all astronaut retinal images to our study for VESGEN analysis. Substantial progress on the initial blinded portion of the study is in place. We anticipate that VESGEN analysis of the 32 Spectralis IR retinal images will be complete for presentation at the 2017 IWS meeting. CONCLUSIONS: Modified retinal vascular patterning may offer early-stage predictions of ocular changes resulting in decreased visual acuity for the VIIP syndrome. Novel insights provided by VESGEN into progressively pathological and blinding vascular remodeling in the human retina currently help to guide other NIH- and NASA-supported therapeutic studies of retinal disease and modeling of the VIIP risk. Results of our vascular investigation of the retinas of astronauts pre- and post-flight may help advance the understanding of both healthy and pathological adaptations to fluid shifts in microgravity associated with the VIIP syndrome. Preliminary results indicate that imaging of higher resolution, such as the new OCT angiography (OCT-A) technology, will be required to determine conclusively the role of the smaller retinal and choroidal vessels in VIIP etiology.

VESGEN↗