C-peptide and PGE2 activity during human spaceflight
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NASA Experiment Number 178120 1/2↗
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Femoral Head Bone Loss Following Short and Long-Duration Spaceflight
Exposure to mechanical unloading during spaceflight is known to have significant effects on the musculoskeletal system. Our ongoing studies with the mouse bone model have identified the failure of normal stem cell-based tissue regeneration, in addition to tissue degeneration, as a significant concern for long-duration spaceflight, especially in the mesenchymal and hematopoietic tissue lineages. The 30-day BionM1 and the 37-day Rodent Research 1 (RR1) missions enabled the possibility of studying these effects in long-duration microgravity experiments. We hypothesized that the inhibition of stem cell-based tissue regeneration in short-duration spaceflight would continue during long-duration spaceflight and furthermore would result in significant tissue alterations. MicroCT analysis of BionM1 femurs revealed 31% decrease in bone volume ratio, a 14% decrease in trabecular thickness, and a 20% decrease in trabecular number in the femoral head of space-flown mice. Furthermore, high-resolution MicroCT and immunohistochemical analysis of spaceflight tissues revealed a severe disruption of the epiphyseal boundary, resulting in endochondral ossification of the femoral head and perforation of articular cartilage by bone. This suggests that spaceflight in microgravity may cause rapid induction of an aging-like phenotype with signs of osteoarthritic disease in the hip joint. However, mice from RR1 exhibited significant bone loss in the femoral head but did not exhibit the severe aging and disease-like phenotype observed during BionM1.This may be due to increased physical activity in the RH hardware. Immunohistochemical analysis of the epiphyseal plate and investigation of cellular proliferation and differentiation pathways within the marrow compartment and whole bone tissue is currently being conducted to determine alterations in stem cell-based tissue regeneration between these experiments. Our results show that the observed inhibition of stem cell-based tissue regeneration persists during long-duration spaceflight. Furthermore, spaceflight femurs from BionM1 indicate onset of an accelerated aging-like phenotype with signs of osteoarthritic disease shown by disruption of the epiphyseal boundary and endochondral ossification. These effects are likely caused by a failure of stem cells to regenerate degraded tissues and may have significant implications for bone and cartilage health following extensive periods of mechanical unloading during long-duration spaceflight.
microgravity↗
Femoral Head Bone Loss Following Short and Long-Duration Spaceflight
Exposure to mechanical unloading during spaceflight is known to have significant effects on the musculoskeletal system. Our ongoing studies with the mouse bone model have identified the failure of normal stem cell-based tissue regeneration, in addition to tissue degeneration, as a significant concern for long-duration spaceflight, especially in the mesenchymal and hematopoietic tissue lineages. The 30-day BionM1 and the 37-day Rodent Research 1 (RR1) missions enabled the possibility of studying these effects in long-duration microgravity experiments. We hypothesized that the inhibition of stem cell-based tissue regeneration in short-duration spaceflight would continue during long-duration spaceflight and furthermore would result in significant tissue alterations. MicroCT analysis of BionM1 femurs revealed 31 decrease in bone volume ratio, a 14 decrease in trabecular thickness, and a 20 decrease in trabecular number in the femoral head of space-flown mice. Furthermore, high-resolution MicroCT and immunohistochemical analysis of spaceflight tissues revealed a severe disruption of the epiphyseal boundary, resulting in endochondral ossification of the femoral head and perforation of articular cartilage by bone. This suggests that spaceflight in microgravity may cause rapid induction of an aging-like phenotype with signs of osteoarthritic disease in the hip joint. However, mice from RR1 exhibited significant bone loss in the femoral head but did not exhibit the severe aging and disease-like phenotype observed during BionM1. This may be due to increased physical activity in the RH hardware. Immunohistochemical analysis of the epiphyseal plate and investigation of cellular proliferation and differentiation pathways within the marrow compartment and whole bone tissue is currently being conducted to determine alterations in stem cell-based tissue regeneration between these experiments. Our results show that the observed inhibition of stem cell-based tissue regeneration persists during long-duration spaceflight. Furthermore, spaceflight femurs from BionM1 indicate onset of an accelerated aging-like phenotype with signs of osteoarthritic disease shown by disruption of the epiphyseal boundary and endochondral ossification. These effects are likely caused by a failure of stem cells to regenerate degraded tissues and may have significant implications for bone and cartilage health following extensive periods of mechanical unloading during long-duration spaceflight.
stem cells↗
Preliminary Results of Bisphosphonate ISS Flight Experiment
Bone loss has been recognized as a potential problem from the beginning of human spaceflight. With the spaceflight missions lasting 6 months to potentially 3 years or longer this issue has assumed increased significance. Detailed measurements from the Mir and ISS long duration missions have documented losses in bone mineral density (BMD) from the total skeleton and critical sub-regions. The most important losses are from the femoral hip averaging about -1.6%/mo integral to -2.3%/mo trabecular BMD. Importantly these studies have documented the wide range in individual response from -0.5 to -5%/mo in BMD. Given the small size of any expedition crew, the wide range of responses has to be considered in the implementation of any countermeasure. Assuming that it is unlikely that the susceptibility for bone loss in any given crewmember will be known, a suite of bone loss countermeasures will likely be needed to insure protection of all crewmembers. The hypothesis for this experiment is that the combined effect of anti-resorptive drugs plus the standard in-flight exercise regimen will have a measurable effect on preventing space flight induced bone loss and strength and will reduce renal stone risk. To date, 4 crewmembers have completed the flight portion of the protocol in which crewmembers take a 70-mg alendronate tablet once a week before and during flight, starting 17 days before launch. Compared to previous ISS crewmembers (n=14) not taking alendronate, DXA measurements of the total hip BMD were significantly changed from -1.1 0.5%/mo to 0.04 0.3%/mo (p<0.01); QCT-determined trabecular BMD of the total hip was significantly changed from -2.3 1.0%/mo to -0.3 1.6%/mo (p<0.01). Significance was calculated from a one-tailed t test. While these results are encouraging, the current n (4) is small, and the large SDs indicate that while the means are improved there is still high variability in individual response. Four additional crewmembers have been recruited to participate in this experiment, with expected completion of these flights by late 2011.
LeBlanc, Adrian↗
National Institutes of Health, Rodent 4 (NIH.R4); Calcium Metabolism and Vascular Function After Spaceflight: A Collaborative Series with NASA and NIH
The NIH.R4 payload was a collaborative experiment conducted by NASA's Ames Research Center in conjunction with the National Institutes of Health (NIH). This middeck payload was the fourth in a series of experiments focusing on developmental biology and the effects of microgravity on mammalian systems. The NIH.R4 payload was flown onboard STS-80, which launched November 19, 1996, and landed at Kennedy Space Center on December 7, 1996, and was the longest shuttle mission to date. Fourteen male Spontaneously Hypertensive rats (SHR) were flown; seven in each of two Animal Enclosure Modules (AEM) in the shuttle middeck. The flight animals were exposed to 18 days of microgravity. Two synchronous control groups were utilized for this study in addition to an asynchronous post-flight AEM control study conducted at the PI lab. The animals were fed two different calcium diets in the NASA food bar (2.0% and 0.2%) three weeks prior to launch and insight. Blood pressures were taken at pre-determined intervals and were the basis for flight selection. Upon recovery Dwight animals blood pressure was measured and a variety of tissues were collected. Project testing and data will be presented.
Reiss-Bubenheim, Debra↗
HUMAN FACTORS AND BEHAVIORAL PERFORMANCE EXPLORATION MEASURES: ASSESSING ASTRONAUT RISK
INTRODUCTION: The Human Factors and Behavioral Performance Exploration Measures (HFBP-EM) suite is a set of standardized measures to assess behavioral health and performance risk related to future exploration class missions, and to support reduction of the Human Research Program’s (HRP) Behavioral Medicine (BMed), Team, Sleep, and Human Systems Integration Architecture (HSIA) risks. This presentation will provide an overview of the HFBP-EM program, describe its implementation across spaceflight analogs and the international space station (ISS), and discuss its applicability to audience members. TOPIC: HFBP-EM is a research program designed to develop a standard set of measures that can be used in space and space-analog research to characterize BMed, Team, Sleep, and HSIA risks. It is an ongoing research project that is used examine the validity and reliability of HFBP measures, as well as their shorter forms. It also serves as a test bed for HFBP measures being considered for the spaceflight standard measures. The suite of measures is used to test the efficacy of countermeasures. To date, HFBP-EM has been collected in Human Exploration Research Analogs campaigns 4 and 5, and the SIRIUS 19 mission in the Russian Ground Based Experiment Complex. A subset of the HFBP-EM suite was collected during spaceflight as part of HRP’s Standard Measures in Spaceflight Project. Data was collected from a total of 55 multinational astronaut and astronaut-like crewmembers (mean age: 39.5, SD = 7.6; 31% female; 91% with advanced degrees). Three broad categories of HFBP-EM measures and their relevance to HRP risks will be discussed: 1) surveys that assess team functioning (Teams risk) as well as mood and affect (Bmed risk), 2) performance-based tasks of cognitive functioning and operationally relevant performance (Bmed risk), and 3) physiological biomarkers of sleep (sleep risk) and heart rate (Bmed risk). We will provide an overview of the background of the HFBP-EM program, what the suite currently includes, and next steps in its future development. We will also discuss the application to aerospace practitioners and researchers. APPLICATION: Astronaut teams selected for future space exploration missions will face several challenges that pose significant yet still unknown risks to the behavioral health and performance of astronauts. The HFBP-EM suite provides a comprehensive assessment of behavioral health and performance in space analog and spaceflight settings. This suite can be applied to both operational and research settings to advance risk reduction research for long duration space exploration missions.
S T Bell↗
Tailoring Systems Engineering Projects for Small Satellite Missions
NASA maintains excellence in its spaceflight systems by utilizing rigorous engineering processes based on over 50 years of experience. The NASA systems engineering process for flight projects described in NPR 7120.5E was initially developed for major flight projects. The design and development of low-cost small satellite systems does not entail the financial and risk consequences traditionally associated with spaceflight projects. Consequently, an approach is offered to tailoring of the processes such that the small satellite missions will benefit from the engineering rigor without overly burdensome overhead. In this paper we will outline the approaches to tailoring the standard processes for these small missions and describe how it will be applied in a proposed small satellite mission.
Horan, Stephen↗
Earth based approaches to enhancing the health and safety of space operations
This paper provides an overview of the current state of our earth based knowledge of space safety hazards; identification of several key areas of concern for space operations; and proposed approaches to providing technology enhancement and information needed to improve the health and safety to those conducting space operations. Included are a review of the identified hazards for space oeprations by hazard classification; a summarization of the information currently available on space experiences and an assessment of potential hazards for long duration spaceflight; a discussion of potential failure modes and their significance for Space Station work: and an assessment of current work which indicates additional research and experimentation which can only be accomplished in actual space missions.
Koller, A. M., Jr.↗
Experiment K-6-09. Morphological and biochemical investigation of microgravity-induced nerve and muscle breakdown. Part 1: Investigation of nerve and muscle breakdown during spaceflight; Part 2: Biochemical analysis of EDL and PLT muscles
The present findings on rat hindlimb muscles suggest that skeletal muscle weakness induced by prolonged spaceflight can result from a combination of muscle fiber atrophy, muscle fiber segmental necrosis, degeneration of motor nerve terminals and destruction of microcirculatory vessels. Damage was confined to the red adductor longus (AL) and soleus muscles. The midbelly region of the AL muscle had more segmental necrosis and edema than the ends. Macrophages and neutrophils were the major mononucleated cells infiltrating and phagocytosing the cellular debris. Toluidine blue-positive mast cells were significantly decreased in Flight AL muscles compared to controls; this indicated that degranulation of mast cells contributed to tissue edema. Increased ubiquitination of disrupted myofibrils may have promoted myofilament degradation. Overall, mitochondria content and SDH activity were normal, except for a decrease in the subsarcolemmal region. The myofibrillar ATPase activity shifted toward the fast type in the Flight AL muscles. Some of the pathological changes may have occurred or been exacerbated during the 2 day postflight period of readaptation to terrestrial gravity. While simple atrophy should be reversible by exercise, restoration of pathological changes depends upon complex processes of regeneration by stem cells. Initial signs of muscle and nerve fiber regeneration were detected. Even though regeneration proceeds on Earth, the space environment may inhibit repair and cause progressive irreversible deterioration during long term missions. Muscles obtained from Flight rats sacrificed immediately (within a few hours) after landing are needed to distinguish inflight changes from postflight readaptation.
Riley, D. A.↗
Auroral X-ray imaging from high- and low-earth orbit
Observations of bremsstrahlung X-rays emitted by energetic electrons impacting the earth's atmosphere can be used for remotely sensing the morphology, intensity, and energy spectra of electron precipitation from the magnetosphere. Two auroral X-ray imagers, developed for future spaceflight, will be discussed. Polar Ionospheric X-ray Imaging Experiment is scheduled for launch on the NASA International Solar-Terrestrial Physics/Global Geospace Science program POLAR satellite in May, 1994. The POLAR orbit, with an apogee and perigee of 9 and 1.8 R(E) (earth radii), respectively, affords the opportunity to image the aurora from high altitude above the north pole continuously for several hours. The Magnetospheric Atmospheric X-ray Imaging Experiment is scheduled for launch aboard the NOAA-I satellite in late 1992. The 800-km polar orbit passes over both the northern and southern auroral zones every 101 minutes. The presentation emphasizes the experimental approaches used to exploit these very different orbits for remote sensing of the earth's auroral zones.
Mckenzie, D. L.↗
The effects of autogenic-feedback training on motion sickness severity and heart rate variability in astronauts
Space motion sickness (SMS) affects 50 percent of all people during early days of spaceflight. This study describes the results of two Shuttle flight experiments in which autogenic-feedback training (AFT), a physiological conditioning method, was tested as a treatment for this disorder. Of the six who were designated as flight subjects (two women and four men), three were given treatment and three served as controls (i.e., no AFT). Treatment subjects were given 6 hours of preflight AFT. Preflight results showed that AFT produced a significant increase in tolerance to rotating chair motion sickness tests. Further, this increased tolerance was associated with changes in specific physiological responses and reports of reduced malaise. Flight results showed that two of the three control subjects experienced repeated vomiting on the first mission day, while one subject experienced only moderate malaise. Of the three treatment subjects, one experienced mild discomfort, one moderate discomfort, and one severe motion sickness. Only the three control subjects took medication for symptom suppression. Measures of cardiac function reflective of vagal control were shown to be affected especially strongly on the first day of space flight. AFT given for control of heart rate, respiration, and other autonomic activity influenced both the vagal control measures and SMS. These data suggest that AFT may be an effective treatment for space motion sickness; however, this cannot be demonstrated conclusively with the small number of subjects described.
Toscano, William B.↗
Antiorthostatic suspension as a model for the effects of spaceflight on the immune system
We describe the use and appropriateness of antiorthostatic suspension in immunological investigations. This manuscript describes the model and discusses how well data obtained by using the model correlate with spaceflight data. This review concludes with some suggestions for future experiments using antiorthostatic suspension.
short duration↗
Batch Effect Correction Methods for NASA GeneLab Transcriptomic Datasets
RNA sequencing (RNA-seq) data from space biology experiments promise to yield invaluable insights into the effects of spaceflight on terrestrial biology. However, sample numbers from each study are low due to limited crew availability, hardware, and space. To increase statistical power, spaceflight RNA-seq datasets from different missions are often aggregated together. However, this can introduce technical variation or "batch effects", often due to differences in sample handling, sample processing, and sequencing platforms. Several computational methods have been developed to correct for technical batch effects, thereby reducing their impact on true biological signals. In this study, we combined 7 mouse liver RNA-seq datasets from NASA GeneLab (part of the NASA Open Science Data Repository) to evaluate several common batch effect correction methods (ComBat and ComBat-seq from the sva R package, and Median Polish, Empirical Bayes, and ANOVA from the MBatch R package). We quantitatively evaluated the ability of these methods to correct for technical batch variables in space biology RNA-seq data using the following criteria: BatchQC, principal component analysis, dispersion separability criterion, log fold change correlation, and differential gene expression analysis. Each batch variable / correction method combination was then assessed using a custom scoring approach to identify the optimal correction method for the combined dataset, by geometrically probing the space of all allowable scoring functions to yield an aggregate volume-based scoring measure. Finally, we describe the way in which the GeneLab multi-study analysis and visualization portal will allow users to examine the presence or absence of batch effects using multiple metrics. If the user chooses to perform batch effect correction, the scoring approach described here can be implemented to identify the optimal correction method to use for their specific combined dataset prior to analysis.
Lauren M. Sanders↗
HERA in the Artemis ERA
As NASA shifts its mission objectives to the lunar surface and the return of humans to the moon in the next few years, analogs that simulate lunar transit or surface exploration are in a unique position to support spaceflight research that is aligned with future Artemis missions, especially a sustained lunar presence. NASA’s spaceflight analogs have historically focused on mission scenarios and operations for Mars exploration, including recent campaigns staged at the Human Exploration Research Analog (HERA) analog at Johnson Space Center. However, beginning in Campaign 8, future HERA missions are planned to mimic lunar operations and support research objectives that directly address knowledge gaps for lunar exploration and habitation. The Research Operations and Integration (ROI) HERA team will present a look-back over HERA mission scenarios and operations supporting NASA’s Human Research Program and international partners’ spaceflight research. An overview of critical capabilities in HERA and other similar analogs will also be presented, such as methods of simulating EVAs. Presenters will then discuss the transition to a high-fidelity lunar surface exploration mission scenario envisioned for Campaign 8, slated to begin in 2026. Operations changes that will be discussed will include simulated lunar surface exploration using a two-person simulated pressurized rover in combination with virtual reality, lunar-relevant communication delays, changes to concepts of how crew communicate with Earth-based mission supports, increased access to family & friends’ communication compared to prior campaigns, and a new mission scenario referencing Artemis mission objectives and tasks. ROI analog mission designs are driven by science objectives. The ROI HERA team will describe how the changes for Campaign 8 support ongoing spaceflight research interests and provide opportunities for investigators to design experiments more closely aligned to lunar missions. A questions and answers session will follow with attendees encouraged to ask questions.
B J Caldwell↗
Materials processing in space - Review of the early experiments
Basic research performed to study various aspects of fluid behavior in a microgravity environment during the first two decades of spaceflight is described. The uniqueness of space was recognized in the 1950s as a place where buoyancy-driven convective flows and sedimentation would effectively be absent. The conditions were favorable for experiments in crystal growth, alloy solidification, combustion, thermocapillary flows, electroosmotic flows, Stefan flows, Soret diffusion, and solidification processes. Pre-Skylab NASA drop tower experiments and Apollo 14 and 17 experiments made in preparation for Skylab are described. Skylab welding and brazing, crystal growth, metallurgy and liquid float zone trials and Apollo-Soyuz crystal growth, electrophoresis and metallurgical experiments are summarized. SPAR rocket trials along similar lines are also outlined.
Naumann, Robert J.↗
Abrogation of TNF-mediated cytotoxicity by space flight involves protein kinase C
Experiments conducted on STS-50 indicated that space flight significantly inhibited tumor necrosis factor (TNF)-mediated killing of LM929 cells compared to ground controls. In ground-based studies, activation of protein kinase C (PKC) with phorbol 12-myristate 13-acetate (PMA) also inhibited TNF-mediated killing of LM929 cells. Therefore, we used PKC inhibitors to determine if the inhibitory effects of spaceflight on TNF-mediated cytotoxicity involved the activation of PKC. In experiments conducted onboard space shuttle mission STS-54, we saw that in the presence of the protein kinase C inhibitors H7 and H8, TNF-mediated cytotoxicity was restored to levels of those observed in the ground controls. Subsequent experiments done during the STS-57 mission tested the dose response of two protein kinase inhibitors, H7 and HA1004. We again saw that killing was restored in a dose-dependent manner, with inhibitor concentrations known to inhibit PKC being most effective. These data suggest that space flight ameliorates the action of TNF by affecting PKC in target cells.
STS-54 Shuttle Project↗
Anesthesia during and Immediately after Spaceflight
The increasing presence of humans in space and long-duration manned missions to the Moon or Mars pose novel challenges to the delivery of medical care. Even now, cumulative person-days in space exceed 80 years and preparations for a return to the Moon are actively underway. Medical care after an emergent de-orbit or an accident during a non-nominal landing must not only address the specific disease or injuries but also the challenges posed by physiologic adaptations to microgravity. In the highly autonomous situation of a long-term space mission the situation is even more complex, because personnel, equipment, specific training, and clinical experience are by definition limited. To summarize our current knowledge specifically for anesthetic care during and immediately after spaceflight, we will review physiologic adaptations to microgravity with particular emphasis on the resulting anesthetic risks, discuss veterinary experiences with anesthesia in weightlessness or in animals adapted to microgravity, describe current research that pertains to anesthesia and spaceflight and point out unresolved questions for future investigation.
Seubert, Christoph N.↗
RESOLVE Project
The RESOLVE project is a lunar prospecting mission whose primary goal is to characterize water and other volatiles in lunar regolith. The Lunar Advanced Volatiles Analysis (LAVA) subsystem is comprised of a fluid subsystem that transports flow to the gas chromatograph- mass spectrometer (GC-MS) instruments that characterize volatiles and the Water Droplet Demonstration (WDD) that will capture and display water condensation in the gas stream. The LAVA Engineering Test Unit (ETU) is undergoing risk reduction testing this summer and fall within a vacuum chamber to understand and characterize C!Jmponent and integrated system performance. Ray will be assisting with component testing of line heaters, printed circuit heaters, pressure transducers, temperature sensors, regulators, and valves in atmospheric and vacuum environments. He will be developing procedures to guide these tests and test reports to analyze and draw conclusions from the data. In addition, he will gain experience with preparing a vacuum chamber with fluid and electrical connections. Further testing will include integrated testing of the fluid subsystem with the gas supply system, near-infrared spectrometer, WDD, Sample Delivery System, and GC-MS in the vacuum chamber. This testing will provide hands-on exposure to a flight forward spaceflight subsystem, the processes associated with testing equipment in a vacuum chamber, and experience working in a laboratory setting. Examples of specific analysis Ray will conduct include: pneumatic analysis to calculate the WOO's efficiency at extracting water vapor from the gas stream to form condensation; thermal analysis of the conduction and radiation along a line connecting two thermal masses; and proportional-integral-derivative (PID) heater control analysis. In this Research and Technology environment, Ray will be asked to problem solve real-time as issues arise. Since LAVA is a scientific subsystem, Ray will be utilizing his chemical engineering background to operate the near-infrared spectrometer and GC-MS instruments during ETU testing. Ray will be working with Modified Commercial off the Shelf (MCOTS) instruments and characterizing their analytical behavior for optimization. Ray will be offered the opportunity to suggest testing modifications or configuration changes at any time to improve the experimental effectiveness. He will gain many skills needed for working in a technical team setting requiring flexibility and critical thinking.
Parker, Ray O.↗