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Neurovascular effects of simulated space radiation

A major health risk for human deep space exploration is central nervous system (CNS) damage by ionizing radiation. Simulated galactic cosmic rays or their components, especially high-linear energy transfer particles such as 56Fe ions, have been shown to cause CNS damage, neuroinflammation and cognitive dysfunction in rodent models, but their effects on human CNS remain to be investigated. CNS damage from any insult, including ionizing radiation, is partially mediated by the blood-brain barrier (BBB), which regulates interactions between CNS and the rest of the body. Astrocytes are major cellular regulators of BBB permeability and also modulate neuroinflammation and neurodegeneration. However, BBB and astrocyte functions in regulating CNS responses to space radiation remain little investigated, especially in human organ analogs. Therefore, we developed and utilized a high-throughput 3D human neurovascular organ-on-a-chip model, seeded with induced pluripotent stem cell-derived cells. The effects of time course, ionizing radiation dose and dose rate were mapped by exposing the model to either acute, high dose rate radiation with simulated galactic cosmic rays or 600 MeV/n 56Fe particles, or protracted, low dose rate gamma radiation using a 57Co sealed source setup. We investigated BBB permeability, oxidative stress, cellular damage and secreted factors over the time period between 24 hours – 2 weeks after 0.1 – 0.8 Gy irradiation. We observed that ionizing radiation exposure increased BBB permeability, caused oxidative stress, damaged endothelial cells and altered expression of inflammatory cytokines with a subset of outcomes dependent on ionizing radiation dose rate. Furthermore, our results indicated that astrocyte functions were primarily deleterious at early time points and protective later after irradiation, resembling CNS responses to injury in vivo. Our findings in organ models were complemented by studies on true spaceflight using mouse spatial and single cell multi-omics, which similarly indicated spaceflight-mediated changes in astrocyte functions. In summary, our study evaluates the regulation of neurovascular responses to simulated space radiation, suggesting astrocytes as targets for countermeasures to mitigate CNS damage in deep space exploration.

Radiation↗

NASA NTRS2015

NASA's Functional Task Test: High Intensity Exercise Improves the Heart Rate Response to a Stand Test Following 70 Days of Bedrest

Cardiovascular adaptations due to spaceflight are modeled with 6deg head-down tilt bed rest (BR) and result in decreased orthostatic tolerance. We investigated if high-intensity resistive and aerobic exercise with and without testosterone supplementation would improve the heart rate (HR) response to a 3.5-min stand test and how quickly these changes recovered following BR. During 70 days of BR male subjects performed no exercise (Control, n=10), high intensity supine resistive and aerobic exercise (Exercise, n=9), or supine exercise plus supplemental testosterone (Exercise+T, n=8; 100 mg i.m., weekly in 2-week on/off cycles). We measured HR for 2 min while subjects were prone and for 3 min after standing twice before and 0, 1, 6, and 11 days after BR. Mixed-effects linear regression models were used to evaluate group, time, and interaction effects. Compared to pre-bed rest, prone HR was elevated on BR+0 and BR+1 in Control, but not Exercise or Exercise+T groups, and standing HR was greater in all 3 groups. The increase in prone and standing HR in Control subjects was greater than either Exercise or Exercise+T groups and all groups recovered by BR+6. The change in HR from prone to standing more than doubled on BR+0 in all groups, but was significantly less in the Exericse+T group compared to the Control, but not Exercise group. Exercise reduces, but does not prevent the increase in HR observed in response to standing. The significantly lower HR response in the Exercise+T group requires further investigation to determine physiologic significance.

Laurie, Steven S.↗

NASA NTRS2017

Skeletal Responses to Long-Duration Simulated Weightlessness in Rats

Damaging effects due to spaceflight and long-duration weightlessness are seen in the musculoskeletal system, specifically with regards to bone loss, bone resorption, and changes in overall bone structure. These adverse effects are all seen with indicators of oxidative stress and a variation in the levels of oxidative gene expression. Once gravity is restored, however, the recovery is slow and incomplete. Despite this, few reports have investigated the correlation between oxidative damage and general modifications within the bone. In this project, we will make use of a ground-based model of simulated weightlessness (hindlimb unloading, HU) in order to observe skeletal changes in response to induced microgravity due to changes in oxidative pressures. With this model we will analyze samples at 14-day and 90-day time points following HU for the determination of acute and chronic effects, each with corresponding controls. We hypothesize that simulated microgravity will lead to skeletal adaptations including time-dependent activation of pro-oxidative processes and pro-osteoclastogenic signals related to the progression, plateau, and recovery of the bone. Microcomputed tomography techniques will be utilized to measure skeletal changes in response to HU. With the results of this study, we hope to further the understanding of skeletal affects as a result of long-duration weightlessness and develop countermeasures to combat bone loss in spaceflight and osteoporosis on Earth.

hindlimb unloading↗

NASA NTRS1976

Report of 14-day bedrest simulation of Skylab

Part one of a two-phase bedrest project in which the physiological effects of weightlessness were simulated is presented. The project was designed to approximate the medical testing and dietary control of Skylab. The test period included a three week pre-flight period, a two week bedrest period and a two week post-flight period. The test subjects ate measured amounts of the Skylab diet and drank deionized water to recreate the metabolic balance studies of Skylab. The medical testing program, pre- and postbedrest, was similar to that of Skylab including: lower body negative pressure testing the orthostatic intolerance noted after both spaceflights and bedrest, bicycle ergometry testing the cardiovascular response to graded exercise, postural equilibrium, vestibular studies and electromyograms. Fluid and electrolyte shifts and balance were documented with intake and output records and radionuclide studies. The subjects were observed by a psychiatrist who watched for signs of mental stress in the test environment and changes in mental status.

Johnson, P. C.↗

NASA NTRS2002

Models to study gravitational biology of Mammalian reproduction

Mammalian reproduction evolved within Earth's 1-g gravitational field. As we move closer to the reality of space habitation, there is growing scientific interest in how different gravitational states influence reproduction in mammals. Habitation of space and extended spaceflight missions require prolonged exposure to decreased gravity (hypogravity, i.e., weightlessness). Lift-off and re-entry of the spacecraft are associated with exposure to increased gravity (hypergravity). Existing data suggest that spaceflight is associated with a constellation of changes in reproductive physiology and function. However, limited spaceflight opportunities and confounding effects of various nongravitational factors associated with spaceflight (i.e., radiation, stress) have led to the development of ground-based models for studying the effects of altered gravity on biological systems. Human bed rest and rodent hindlimb unloading paradigms are used to study exposure to hypogravity. Centrifugation is used to study hypergravity. Here, we review the results of spaceflight and ground-based models of altered gravity on reproductive physiology. Studies utilizing ground-based models that simulate hyper- and hypogravity have produced reproductive results similar to those obtained from spaceflight and are contributing new information on biological responses across the gravity continuum, thereby confirming the appropriateness of these models for studying reproductive responses to altered gravity and the underlying mechanisms of these responses. Together, these unique tools are yielding new insights into the gravitational biology of reproduction in mammals.

Review, Tutorial↗

NASA NTRS1999

Nutrition and muscle loss in humans during spaceflight

The protein loss in humans during spaceflight is partly due to a normal adaptive response to a decreased work load on the muscles involved in weight bearing. The process is mediated by changes in prostaglandin release, secondary to the decrease in tension on the affected muscles. On missions, where there is a high level of physical demands on the astronauts, there tends to be an energy deficit, which adds to the muscle protein loss and depletes the body fat reserves. While the adaptive response is a normal part of homeostasis, the additional protein loss from an energy deficit can, in the long run, have a negative effect on health and capability of humans to live and work in space and afterward return to Earth.

NASA Program Biomedical Research and Countermeasur↗

NASA NTRS2013

Evidence Report: Risk of Crew Adverse Health Event Due to Altered Immune Response

The Risk of Crew Adverse Health Event Due to Altered Immune Response is identified by the National Aeronautics and Space Administration (NASA) Human Research Program (HRP) as a recognized risk to human health and performance in space. The HRP Program Requirements Document (PRD) defines these risks. This Evidence Report provides a summary of the evidence that has been used to identify and characterize this risk. It is known that human immune function is altered in‐ and post‐flight, but it is unclear at present if such alterations lead to increased susceptibility to disease. Reactivation of latent viruses has been documented in crewmembers, although this reactivation has not been directly correlated with immune changes or with observed diseases. As described in this report, further research is required to better characterize the relationships between altered immune response and susceptibility to disease during and after spaceflight. This is particularly important for future deep‐space exploration missions.

Crucian, Brian↗

NASA NTRS2016

Sex-Specific Effects of Unpredictable Variable Prenatal Stress: Implications for Mammalian Developmental Programming During Spaceflight

During adaptation to the microgravity environment, adult mammals experience stress mediated by the Hypothalamic-Pituitary-Adrenal axis. In our previous studies of pregnant rats exposed to 2-g hypergravity via centrifugation, we reported decreased corticosterone and increased body mass and leptin in adult male, but not female, offspring. In this study, we utilized Unpredictable Variable Prenatal Stress to simulate the stressors of spaceflight by exposing dams to different stressors. Stress response modulation occurs via both positive and negative feedback in the hypothalamus, anterior pituitary gland, and adrenal cortex resulting in the differential release of corticosterone (CORT), a murine analog to human cortisol.

Prenatal Stress↗

NASA NTRS2017

Group Housing During Hindlimb Unloading to Simulate Weightlessness

The rodent hindlimb unloading (HU) model was developed in the 1980s to faciliate the study of mechanisms, responses, and treatments for the adverse effects of spaceflight. A number of variations on unloading systems and cage designs have been developed, although most entail individually housing the HU animals. In this study, we performed hindlimb unloading under group housing conditions. Our preliminary results indicate that HU animals that were group housed for 30 days, displayed musculoskeletal decrements associated with disuse, and further, body weights did not differ compared to age-matched controls. In conclusion, group housing of HU mice provides a novel means to simulate weightlessness under conditions that more closely resemble living conditions of Rodent Research Project ISS flight hardware habitats, and minimizes the social stress of isolation, which is consistent with current animal welfare standards (Guide for the Care and Use of Laboratory Animals: Eighth Edition, National Research Council).

group housing↗

NASA NTRS2019

Science Driven By Space Biology Omics Data Utilizing NASA's GeneLab Platform

Determining the biological impact of spaceflight through novel approaches is essential to reduce the health risks to astronauts for long-term space missions. The current established health risks due to spaceflight are only reflecting known symptomatic and physiologic responses and do not reflect early onset of other potential diseases. There are many unknown variables which still need to be identified to fully understand the health impacts due to the environmental factors in space. One method to uncover potential novel biological mechanisms responsible for health risks in astronauts is by utilizing NASA's GeneLab Data Systems (genelab.nasa.gov). GeneLab is public repository that hosts multiple omics datasets generated from space biology experiments that include experiments flown in space, simulated cosmic radiation.

Beheshti, Afshin↗

NASA NTRS2006

Modification of Eye Movements and Motion Perception during Off-Vertical Axis Rotation

Constant velocity Off-Vertical Axis Rotation (OVAR) imposes a continuously varying orientation of the head and body relative to gravity. The ensuing ocular reflexes include modulation of both torsional and horizontal eye movements as a function of the varying linear acceleration along the lateral plane, and modulation of vertical and vergence eye movements as a function of the varying linear acceleration along the sagittal plane. Previous studies have demonstrated that tilt and translation otolith-ocular responses, as well as motion perception, vary as a function of stimulus frequency during OVAR. The purpose of this study is to examine normative OVAR responses in healthy human subjects, and examine adaptive changes in astronauts following short duration space flight at low (0.125 Hz) and high (0.5 Hz) frequencies. Data was obtained on 24 normative subjects (14 M, 10 F) and 14 (13 M, 1F) astronaut subjects. To date, astronauts have participated in 3 preflight sessions (n=14) and on R+0/1 (n=7), R+2 (n= 13) and R+4 (n= 13) days after landing. Subjects were rotated in darkness about their longitudinal axis 20 deg off-vertical at constant rates of 45 and 180 deg/s, corresponding to 0.125 and 0.5 Hz. Binocular responses were obtained with video-oculography. Perceived motion was evaluated using verbal reports and a two-axis joystick (pitch and roll tilt) mounted on top of a two-axis linear stage (anterior-posterior and medial-lateral translation). Eye responses were obtained in ten of the normative subjects with the head and trunk aligned, and then with the head turned relative to the trunk 40 deg to the right or left of center. Sinusoidal curve fits were used to derive amplitude, phase and bias of the responses over several cycles at each stimulus frequency. Eye responses during 0.125 Hz OVAR were dominated by modulation of torsional and vertical eye position, compensatory for tilt relative to gravity. While there is a bias horizontal slow phase velocity (SPV), the modulation of horizontal and vergence SPV is negligible at this lower stimulus frequency. Eye responses during 0.5 Hz OVAR; however, are characterized by modulation of horizontal and vergence SPV, compensatory for translation in the lateral and sagittal planes, respectively. Neither amplitude nor bias velocities were significantly altered by head-on-trunk position. The phases of the ocular reflexes, on the other hand, shifted towards alignment with the head. During the lower frequency OVAR, subjects reported the perception of progressing along the edge of a cone. During higher frequency OVAR, subjects reported the perception of progressing along the edge of an upright cylinder. In contrast to the eye movements, the phase of both perceived tilt and translation motion is not altered by stimulus frequency. Preliminary results from astronaut data suggest that the ocular responses are not substantially altered by short-duration spaceflight. However, compared to preflight averages, astronauts reported greater amplitude of both perceived tilt and translation at low and high frequency, respectively, during early post-flight testing. We conclude that the neural processing to distinguish tilt and translation linear acceleration stimuli differs between eye movements and motion perception. The results from modifying head-on-trunk position are consistent with the modulation of ocular reflexes during OVAR being primarily mediated by the otoliths in response to the sinusoidally varying linear acceleration along the interaural and naso-occipital head axis. While the tilt and translation ocular reflexes appear to operate in an independent fashion, the timing of perceived tilt and translation influence each other. We conclude that the perceived motion path during linear acceleration in darkness results from a composite representation of tilt and translation inputs from both vestibular and somatosensory systems.

Wood, S. J.↗

NASA NTRS2016

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

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

Hypergravity↗

NASA NTRS1995

Increased beta-adrenergic responsiveness induced by 14 days exposure to simulated microgravity

Increased sensitivity of end-organ responses to neuroendocrine stimuli as a result of prolonged exposure to the relative inactivity of microgravity has recently been hypothesized. This notion is based on the inverse relationship between circulating norepinephrine and beta-adrenoreceptor sensitivity. The beta-adrenoreceptor activity is reduced in individuals who have elevated plasma norepinephrine as a result of regular exposure to upright posture and physical exercise. In contrast, adrenoreceptor hypersensitivity has been reported in patients with dysautonomias in which circulating catecholamines are absent or reduced. Taken together, these studies and the observation that circulating plasma norepinephrine has been reduced during spaceflight and in groundbased simulations of microgravity prompt the suggestion that adrenoreceptor hypersensitivity may be a consequence of the adaptation to spaceflight. We conducted an experiment designed to measure cardiovascular responses to adrenoreceptor agonists in human subjects before and after prolonged exposure to 6 deg head-down tilt (HDT) to test the hypothesis that adaptation to microgravity increases adrenoreceptor responsiveness, and that this adaptation is associated with reduced levels of circulating norepinephrine.

Convertino, V. A.↗

NASA NTRS2017

The Effects of CDKN1a/p21 on Oxidative Stress and Mitochondrial Function During Long Duration Spaceflight

Spaceflight factors, such as microgravity and space radiation, are known to put astronauts at risk for negative effects to their tissue regeneration and degenerative conditions. On our previous spaceflight research, we found that long duration spaceflight produced increased oxidative stress and activation of the inflammatory response as a major contributor to physiological changes, including alterations to the cardiovascular and musculoskeletal systems, metabolism, and the liver. Proliferation, apoptosis, and ion-channel remodeling of vascular smooth muscle cells, as well as endothelial inflammation, and nitric oxide synthase-nitric oxide system regulation have been shown by spaceflight and simulated spaceflight projects. CDKN1ap21 is a regulatory gene for tissue regeneration and also plays an important role in upregulating oxidative stress caused by radiation. In further research, we have also determined CDKN1ap21 to be overexpressed during spaceflight. When knocked out in mice, however, it protects against unloading-induced changes to the morphology and physiology of carotid arteries. In this proposal, we seek to test a potential dietary countermeasure to down-regulate CDKN1ap21 in the mice and protect against oxidative stress in the rodents. Specifically, we will expose both Wildtype and CDKN1ap21-null mice to hydrogen peroxide to induce oxidative stress and observe the molecular mechanisms in which a dietary supplement protects vascular smooth muscle cells against the consequences of the apoptotic environment within Wildtype mice versus the, hypothetically, sound physiology of CDKN1ap21-null mice. The successful completion of this experiment will conclusively determine accuracy of a dietary supplement as a CDKN1ap21 suppressor. This will provide a new perspective on the problem of increased oxidative stress developing into cardiovascular disease as a result of long-term space flight. This research will address the Human Research Plan Roadmaps Risk of Cardiac Rhythm Problems including CV-8, the Risk of Cardiovascular Disease and Other Degenerative Tissue Effects from Radiation Exposure including Degen-6 and Degen-7, and the Risk of Adverse Health Event from Radiation Exposure including IM-8. Additionally, this research will address Space Biology Research Plans questions SBP CMB-1, SBP CMB-3, and SB AN-2.

Oxidative Stress↗

NASA NTRS2000

Effect of spaceflight on the isotonic contractile properties of single skeletal muscle fibers in the rhesus monkey

Experiments from both Cosmos and Space Shuttle missions have shown weightlessness to result in a rapid decline in the mass and force of rat hindlimb extensor muscles. Additionally, despite an increased maximal shortening velocity, peak power was reduced in rat soleus muscle post-flight. In humans, declines in voluntary peak isometric ankle extensor torque ranging from 15-40% have been reported following long- and short-term spaceflight and prolonged bed rest. Complete understanding of the cellular events responsible for the fiber atrophy and the decline in force, as well as the development of effective countermeasures, will require detailed knowledge of how the physiological and biochemical processes of muscle function are altered by spaceflight. The specific purpose of this investigation was to determine the extent to which the isotonic contractile properties of the slow- and fast-twitch fiber types of the soleus and gastrocnemius muscles of rhesus monkeys (Macaca mulatta) were altered by a 14-day spaceflight.

Non-NASA Center↗

NASA NTRS2022

The Cooling Loop A Anomaly of 2013: A Case Study in Human-Systems Resilience

Throughout the history of human spaceflight, NASA has employed an operational paradigm of 24/7 dependence on experts in Mission Control Center (MCC). In addition to nominal flight control and mission operations, these 85+ experts per shift manage anomaly detection, diagnosis, and response, and support the crew in real-time in performing maintenance and repair, procedure execution, and other complex mission operations. Future long-duration exploration missions (LDEMs) beyond low-Earth orbit (LEO) will not operate successfully using this same Human-Systems Integration Architecture (HSIA) where crew rely on ground controllers, have ready access to resupply, and have a fallback plan of evacuation. As distance from Earth increases and the communication delay grows, crews will need to respond independently and adequately to time-critical vehicle malfunctions. It will not always be sufficient or even possible to ‘safe the system’ and then wait upon ground intervention. A new and radically different HSIA is needed to accommodate the paradigm shift of deep-space travel. Historical International Space Station (ISS) data show that for a 30-day mission, the likelihood of a high-consequence vehicle anomaly of uncertain origin that requires rapid response is greater than 10%. The likelihood of such an event is 50% by the fourth month of the mission, and it grows exponentially with time. Our team has conducted in-depth investigations into these events and their corresponding anomaly resolution activities. Using MCC and Mission Evaluation Room (MER) anomaly resolution artifacts (including meeting summaries, caution and warning data, and ISS daily summaries), we created timelines detailing ground actions and in-orbit events for two significant anomalies. We then mapped these timelines onto Mars transit conditions, introducing a ground-crew communications time delay and shifting immediate response, time-critical task execution, and vehicle commanding to the crew. In detailing successful anomaly resolution in transit to Mars, the timelines highlight where effective resolution requires drastically evolved onboard capabilities. Though this research has yielded a rich data set based on ground response in past missions, there is still insufficient knowledge to assess the potential impact of inflight anomalies on a small autonomous crew on future LDEMs beyond LEO. To begin building an evidence base that will inform future HSIA standards and requirements, we are developing an approach to systematically capture crew anomaly response and procedure execution during early Artemis missions. Being the first human spaceflight beyond LEO since Apollo, early Artemis missions provide a rare and unique opportunity to serve as a testbed for Mars missions. Our work aims to capitalize on planned data collection to derive crew operational responses to anomalous events in real-time. Our team is also researching the level of simulation fidelity required for empirically validating proposed HSIA standards and evaluating HSIA implementations for LDEMs beyond LEO. This work will produce a trade space study of HSIA simulation objectives and fidelity requirements. Ultimately, these research efforts will assist in developing the standards and technologies needed to build a next-generation HSIA for LDEMs beyond LEO.

human-systems integration architecture↗

NASA NTRS2021

Chapter 4: Aerospace Neurology

In the practice of medicine, the neurologist is called upon to answer the following questions: (1) Does the patient have neurologic disease? (2) If so, what is the localization of the lesion or lesions? (3) What is the pathophysiology of the process? (4) What is the preliminary differential diagnosis? Utilizing the tools of the neurologic and medical history, the neurologic examination, ancillary studies, and one’s education, training, and experience, the neurologist arrives at a diagnosis. The aerospace medicine physician (evaluator) has the additional challenge of relating the neurologic condition to aviation safety and achieving an appropriate aeromedical disposition. Whether it is the aviation medical examiner (AME), flight surgeon, or Federal Aviation Administration (FAA) regulator, the aerospace medicine physician shoulders the responsibility of a determination that may decide one’s career in aviation or spaceflight. Considering the individual, and yet preserving aerospace safety, is a never-ending challenge for the aerospace medicine physician. The evaluator has the dual responsibility of applying the standards and also considering exceptions to the standards in allowing waivers from standards, while assuring aerospace safety.

Joseph I Sirven↗

NASA NTRS2001

Changes in gene expression and signal transduction in microgravity

Studies from space flights over the past three decades have demonstrated that basic physiological changes occur in humans during space flight. These changes include cephalic fluid shifts, loss of fluid and electrolytes, loss of muscle mass, space motion sickness, anemia, reduced immune response, and loss of calcium and mineralized bone. The cause of most of these manifestations is not known and until recently, the general approach was to investigate general systemic changes, not basic cellular responses to microgravity. This laboratory has recently studied gene growth and activation of normal osteoblasts (MC3T3-El) during spaceflight. Osteoblast cells were grown on glass coverslips and loaded in the Biorack plunger boxes. The osteoblasts were launched in a serum deprived state, activated in microgravity and collected in microgravity. The osteoblasts were examined for changes in gene expression and signal transduction. Approximately one day after growth activation significant changes were observed in gene expression in 0-G flight samples. Immediate early growth genes/growth factors cox-2, c-myc, bcl2, TGF beta1, bFGF and PCNA showed a significant diminished mRNA induction in microgravity FCS activated cells when compared to ground and 1-G flight controls. Cox-1 was not detected in any of the samples. There were no significant differences in the expression of reference gene mRNA between the ground, 0-G and 1-G samples. The data suggest that quiescent osteoblasts are slower to enter the cell cycle in microgravity and that the lack of gravity itself may be a significant factor in bone loss in spaceflight. Preliminary data from our STS 76 flight experiment support our hypothesis that a basic biological response occurs at the tissue, cellular, and molecular level in 0-G. Here we examine ground-based and space flown data to help us understand the mechanism of bone loss in microgravity.

manned↗