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At least 145 records · Page 8

Dynamics of the G-excess illusion

The G-excess illusion is increasingly recognized as a cause of aviation mishaps especially when pilots perform high-speed, steeply banked turns at low altitudes. Centrifuge studies of this illusion have examined the perception of subject orientation and/or target displacement during maintained hypergravity with the subject's head held stationary. The transient illusory perceptions produced by moving the head in hypergravity are difficult to study onboard centrifuges because the high angular velocity ensures the presence of strong Coriolis cross-coupled semicircular canal effects that mask immediate transient otolith-organ effects. The present study reports perceptions following head movements in hypergravity produced by high-speed aircraft maintaining a banked attitude with low angular velocity to minimize cross-coupled effects. Methods: Fourteen subjects flew on the NASA KC-135 and were exposed to resultant gravity forces of 1.3, 1.5, and 1.8 G for 3 minute periods. On command, seated subjects made controlled head movements in roll, pitch, and yaw at 30 second intervals both in the dark and with faint targets at a distance of 5 feet. Results: head movement produced transient perception of target displacement and velocity at levels as low as 1.3 G. Reports of target velocity without appropriate corresponding displacement were common. At 1.8 G when yaw head movements were made from a face down position, 4 subjects reported oscillatory rotational target displacement with fast and slow alternating components suggestive of torsional nystagmus. Head movements evoked symptoms of nausea in most subjects, with 2 subjects and 1 observer vomiting. Conclusions: The transient percepts present conflicting signals, which introduced confusion in target and subject orientation. Repeated head movements in hypergravity generate nausea by mechanisms distinct from cross-coupled Coriolis effects.

Baylor, K. A.↗

Centrifugation of Cultured Osteoblasts And Macrophages as a Model To Study How Gravity Regulates The Function of Skeletal Cells

Mechanical loading helps define the architecture of weight-bearing bone via the tightly regulated process of skeletal turnover. Turnover occurs by the concerted activity of osteoblasts, responsible for bone formation. and osteoclasts, responsible for bone resorption. Osteoclasts are specialized megakaryon macrophages, which differentiate from monocytes in response to resorption stimuli, such as reduced weight-bearing. Habitation in space dramatically alters musculoskeletal loading, which modulates both cell function and bone structure. Our long-term objective is to define the molecular and cellular mechanisms that mediate skeletal adaptations to altered gravity environments. Our experimental approach is to apply hypergravity loads by centrifugation to rodents and cultured cells. As a first step, we examined the influence of centrifugation on the structure of cancellous bone in rats to test the ability of hypergravity to change skeletal architecture. Since cancellous bone undergoes rapid turnover we expected the most dramatic structural changes to occur in the shape of trabeculae of weight-bearing, cancellous bone. To define the cellular responses to hypergravity loads, we exposed cultured osteoblasts and macrophages to centrifugation. The intraosseous and intramedullary pressures within long bones in vivo reportedly range from 12-40 mm Hg, which would correspond to 18-59 gravity (g) in our cultures. We assumed that hydrostatic pressure from the medium above the cell layer is at least one major component of the mechanical load generated by centrifuging cultured cells. and therefore we exposed the cells to 10-50g. In osteoblasts, we examined the structure of their actin and microtubule networks, production of prostaglandin E2 (PGE2), and cell survival. Analysis of the shape of the cytoskeletal networks provides evidence for the ability of centrifugation to affect cell structure, while the production of PGE2 serves as a convenient marker for mechanical stimulation. We examined cell survival, reasoning that osteoblasts might mold skeletal structure in a hypergravity environment in part by regulating apoptosis and thus the duration of osteoblast productivity. Finally, we tested the influence of centrifugation on microbial activation of a macrophage cell line (RAW264.7). In response to the appropriate hormonal stimulation, this cell line is reportedly capable of undergoing differentiation to express osteoclast markers. In addition, a component of the cell wall of gram-negative bacteria, lipopolysaccaride (LPS), stimulates the formation of osteoclasts in vivo. Thus we tested the influence on centrifugation on RAW264.7 cells stimulated with LPS to provide an index of the function of osteoclast precursors.

Globus, Ruth K.↗

Altered Gravity Induces Oxidative Stress in Drosophila Melanogaster

Altered gravity environments can induce increased oxidative stress in biological systems. Microarray data from our previous spaceflight experiment (FIT experiment on STS-121) indicated significant changes in the expression of oxidative stress genes in adult fruit flies after spaceflight. Currently, our lab is focused on elucidating the role of hypergravity-induced oxidative stress and its impact on the nervous system in Drosophila melanogaster. Biochemical, molecular, and genetic approaches were combined to study this effect on the ground. Adult flies (2-3 days old) exposed to acute hypergravity (3g, for 1 hour and 2 hours) showed significantly elevated levels of Reactive Oxygen Species (ROS) in fly brains compared to control samples. This data was supported by significant changes in mRNA expression of specific oxidative stress and antioxidant defense related genes. As anticipated, a stress-resistant mutant line, Indy302, was less vulnerable to hypergravity-induced oxidative stress compared to wild-type flies. Survival curves were generated to study the combined effect of hypergravity and pro-oxidant treatment. Interestingly, many of the oxidative stress changes that were measured in flies showed sex specific differences. Collectively, our data demonstrate that altered gravity significantly induces oxidative stress in Drosophila, and that one of the organs where this effect is evident is the brain.

Oxidative Stress↗

Effects of Altered Gravity on the Central Nervous System of Drosophila melanogaster

A comprehensive understanding of the effects of spaceflight and altered gravity on human physiology is necessary for continued human space exploration and long-term space habitation. Spaceflight includes multiple factors such as microgravity, hypergravity, ionizing radiation, physiological stress, and disrupted circadian rhythms and these have been shown to contribute to pathophysiological responses that target immunity, bone and muscle integrity, cardiovascular and nervous systems. In terrestrial conditions, some of these factors can lead to cancer and neuroimmunological disorders. In this study, we used a well-established spaceflight model organism, Drosophila melanogaster, to assess spaceflight-associated changes in the nervous system. We hypothesize that exposure to altered gravity triggers the oxidative stress response, leading to impairments in the nervous system. To test this hypothesis, we used two experimental paradigms: 1) hypergravity, using the ground-based chronic acceleration model, and 2) spaceflight conditions, which includes exposure to microgravity and in-flight space 1g controls. In our ground studies, acute hypergravity resulted in an induction of oxidative stress-related genes with an increase in reactive oxygen species (ROS) in fly brains. Additionally, we observed a depressed locomotor phenotype in these flies (p<0.05). These flies also show a decreased dopaminergic neuron counts in the fly brain upon exposure to acute hypergravity (p<0.05). Thus, the data suggest that altered gravity has a profound effect on the fly nervous system. Similarly, we observe behavioral impairments (p<0.001) and synaptic deficits, including decreased synaptic connections (p<0.05), in 3rd instar larvae which were developed in space. Furthermore, space-grown adults show a decrease in neuronal (p<0.05) and dendritic field (p<0.01) in adult brains coupled with an increased number of apoptotic cells (p<0.001), suggesting increased neuronal loss under spaceflight conditions. In summary, we observe that altered gravity leads to gross neurological deficits. To better understand the long-term effects of spaceflight on the nervous system, longitudinal and multigenerational changes were also identified. This study will help elucidate the different approaches to prevent nervous system dysfunction in astronauts during spaceflight, while also contributing to a better understanding of the pathways that are related to some CNS disorders on Earth.

nervous system↗

Antibody binding in altered gravity: implications for immunosorbent assay during space flight

A single antibody-incubation step of an indirect, enzyme-linked immunosorbent assay (ELISA) was performed during microgravity, Martian gravity (0.38 G) and hypergravity (1.8 G) phases of parabolic flight, onboard the NASA KC-135 aircraft. Antibody-antigen binding occurred within 15 seconds; the level of binding did not differ between microgravity, Martian gravity and 1 G (Earth's gravity) conditions. During hypergravity and 1 G, antibody binding was directly proportional to the fluid volume (per microtiter well) used for incubation; this pattern was not observed during microgravity. These effects in microgravity may be due to "fluid spread" within the chamber (observed during microgravity with digital photography), leading to greater fluid-surface contact and subsequently antibody-antigen contact. In summary, these results demonstrate that: i) ELISA antibody-incubation and washing steps can be successfully performed by human operators during microgravity, Martian gravity and hypergravity; ii) there is no significant difference in antibody binding between microgravity, Martian gravity and 1 G conditions; and iii) a smaller fluid volume/well (and therefore less antibody) was required for a given level of binding during microgravity. These conclusions indicate that reduced gravity would not present a barrier to successful operation of immunosorbent assays during spaceflight.

NASA Discipline Environmental Health↗

Thermoregulation in unrestrained rats during and after exposure to 1.5-4 G

Unrestrained rats were exposed to cold for 1 h during and immediately after exposure to hypergravic fields (1.5-4 G) to determine if they recover their ability to thermoregulate on reentry to 1-G conditions. In contrast to the decreased body temperatures observed when cold exposure occurred concurrently with acceleration, hypothalamic, carotid, and brown fat temperatures did not fall when rats were exposed to cold immediately after return to 1 G. These results support the hypothesis that the thermoregulatory alterations seen under hypergravic conditions are manifestations of an effect of ongoing exposure to hypergravity and can be reversed on termination of acceleration. The reversibility of the thermoregulatory impairment is apparently unaffected by the magnitude of the acceleration field over a range of 1.5-4 G.

Giacchino, J.↗

The biological clock of Neurospora in a microgravity environment

The effects of simulated microgravity (via the use of a slowly rotating clinostat), altered orientation (via alterations in the vector of a 1-g force), and hypergravity (via centrifugation) on the circadian rhythm of conidiation in Neurospora crassa were investigated. It was found that the clinostat, while capable of producing some of the microgravity effects seen in space (Sulzman, 1984), did not produce major repeatable results. Similarly, alterations of the vector of a 1-g gravity load were not adequate simulations of space flight on the conidiation rhythm. The results on the acute and chronic exposures to hypergravity demonstrated that chronic exposure of Neurospora to a 3-g force had no damping effect. On the other hand, an acute 10-min exposure to this hypergravity (the lift-off conditions) was found to cause significant damping on the circadian rhythm of conidiation. This effect was eliminated by a brief light pulse given 36 hrs after the exposure to 3 g.

Ferraro, James S.↗

Some Pecularities of the Graviresponse in Vaucheria

The growth and position of nuclei in the siphonaceous alga Vaucheria sessilis were investigated under conditions of hypergravity and hypogravity. Under hypergravity conditions, active sporogenesis was observed. The accumulation of nuclei in the apical and branching zone preceeded the sporogenesis. The anti-microtubular agent, colchicine inhibits sporogenesis and the response of Vaucheria to hypergravity. Under hypogravity conditions, the quantity of nuclei increased throughout the whole branch. Colchicine prevents the migration of nuclei from the apical zone to the basal part of the branch. The anti-actin agent phalloidin prevents the formation of an actin network, and phalloidin-poisoned cells lose a cluster of nuclei in the apical zone. However, the gravity dependent response is less pronounced. It is supposed that, in Vaucheria sessilis, the primary stages of the reception and translation of gravitational signals coincide with those for light signals and active division of nuclei in the growth zone is an integral part of the graviresponse.

Gavrilova, O. V.↗

The Development of Vestibular Connections in Rat Embryos in Microgravity

Existing experimental embryological data suggests that the vestibular system initially develops in a very rigid and genetically controlled manner. Nevertheless, gravity appears to be a critical factor in the normal development of the vestibular system that monitors position with respect to gravity (saccule and utricle). In fact several studies have shown that prenatal exposure to microgravity causes temporary deficits in gravity-dependent righting behaviors, and prolonged exposure to hypergravity from conception to weaning causes permanent deficits in gravity-dependent righting behaviors. Data on hypergravity and microgravity exposure suggest some changes in the otolith formation during development, in particular the size although these changes may actually vary with the species involved. In adults exposed to microgravity there is a change in the synaptic density in the otic sensory epithelia suggesting that some adaptation may occur there. However, effects have also been reported in the brainstem. Several studies have shown synaptic changes in the lateral vestibular nucleus and in the nodulus of the cerebellum after neonatal exposure to hypergravity. We report here that synaptogenesis in the medial vestibular nucleus is retarded in developing rat embryos that were exposed to microgravity from gestation days 9 to 19.

Bruce, Laura L.↗

Effects of Prolonged Centrifugation on Orthostasis

A feasibility study conducted on the Ames 20-G Human Centrifuge examined how well humans can maintain orthostatic tolerance during and after prolonged exposures to hypergravity. Three adult males lived for periods of 22 hours in the centrifuge while it was at rest (1.00 G), and while it rotated at 9.38 RPM to provide 1.25 G-total at the mean radius of 7.62 m. Two participants also experienced 22-hour habitation sessions at 11.46 RPM, which provided 1.50 G-total. Both before and after each habitation session, the participants were given gradual onset rate (GOR) acceleration profiles at 0.067 G/sec to determine their Gz tolerance. In addition, cardiovascular responses were compared while subjects were supine, siting, and standing at various times during the habitation (stand test), and cardiovascular responsiveness was determined using a lower body negative pressure tilt table (LBNPTT) at the beginning of the experiment and after each session. Post-Pre changes in G tolerance were -0.33 (mean) +/- 0.11 (std. error) Gz for habitation at 1.00 G, -0.02 +/- 0.12 Gz for habitation at 1.25 G, and +0.41 +/- 0.13 Gz for habitation at 1.50 G. Performance on the stand test generally improved with duration of habitation in hypergravity. Our results suggest that habitation in a confined chamber at 1.00 G reduces G tolerance and leads to lowered LBNPTT tolerance. Exposure to increased G in the centrifuge leads to enhanced performance on the stand test, and to increased GOR acceleration tolerance, but only when fluid balance is maintained; when motion sickness and negative fluid balance were observed, G tolerance was reduced. The data indicate that enhanced G tolerance can result from prolonged exposure to hypergravity, but that these changes are complex and depend on multiple underlying physiological processes.

Cohen, Malcolm M..↗

Body Weight Gain during Altered Gravity: Spaceflight, Centrifugation and Transitions

Gravity is a force that influences all living systems, and is often disregarded in the study of environment on growth and development. To assess the effect of gravity exposure on growth, immature rats (130-200 g) were evaluated during chronic altered gravity exposure and during transition between gravity fields. The effects of 14 days of spaceflight on body weight gain were evaluated (n=12) and compared to controls. Spaceflight did not affect weight gain. In 6 rats, the transition from spaceflight to 1 G showed a significant (p less than 0.05) post flight weight loss over 48 hr of 13 g compared to controls. Over subsequent days this loss was compensated for with no difference noted after 5 days. Exposure to hypergravity, 2 G for 16 days, was evaluated in groups of n=6 (Control; On Center Control (OCC); Centrifuged). With centrifugation or OCC there was a reduction in body weight within 24 hr. The OCC regained control weights within 13 days. The weight difference, 26 +/- 1 g, persisted with 2 G with no subsequent difference in weight gain over days 3-16 compared to controls; 3.7 +/- 0.1 versus 3.9 +/- 0.1 g/day respectively. Transition from centrifugation to 1 G resulted in a weight increase within 48 hours. Over 16 days the rate of gain was increased 3.1 +/- 0.1 g/day for centrifuge compared to 2.1 +/- 0.1 g/day for controls between Day 3 to 16. However, differences from control were still noted on Day 16. Transition from one gravity field to another causes acute changes in body weight. Transition to microgravity or 1 G, following the acute changes, results in adjustments to attain a normal weight. In hypergravity the acute reduction in body weight persist, but weight gain is normal. Transitioning from hypergravity to 1G results in an increased weight gain to compensate for the persistent reduction during exposure.

Wade, Charles E.↗

Constant Applied Force Stimulates Osteoblast Proliferation Via Matrix-Integrin-Signaling Pathways

Reduced weight-bearing caused by immobilization, bed-rest or microgravity leads to atrophy in mechanosensitive tissue such as muscle and bone. We hypothesize that bone tissue requires earth s gravity (1-g) for the maintenance of extracellular matrix, integrin, and kinase-mediated cell growth and survival pathways. We investigate the role of matrix-integrin signaling in bone cells using cell culture centrifugation to provide different levels of hypergravity mechanostimulation. The 10-50-g range we use also mimics physiological intermedullary pressure (1.2 - 5 kPa). 24 hours at 50-g increased primary rat osteoblast proliferation on collagen Type I and fibronectin, but not laminin or uncoated plastic. BrdU incorporation in primary osteoblasts over 24 h showed hypergravity increased the number of cells actively synthesizing DNA from about 60% at 1-g to over 90% at 25-g. Primary rat fibroblasts grown at 50-g (24 h) showed no proliferation increase, suggesting this is a tissue-specific phenomenon. These results suggest that the betal and alpha4 integrins may be involved. To further test this, we used osteocytic-like MLO-Y4 cells that showed increased proliferation at 1-g with stable expression of a betal integrin cytoplasmic tail and transmembrane domain construct. At 50-g, MLO-Y4/betal cells showed greater MAPK activation than MLO-Y4 vector controls, suggesting that betal integrin is involved in transducing mitogenic signals in response to hypergravity. Preliminary results also show that interfering with the alpha4 integrin in primary osteoblasts grown on fibronectin blocked the proliferation response. These results indicate that cells from mechanosensitive bone tissue can respond to gravity-generated forces, and this response involves specific matrix and integrin-dependent signaling pathways.

Vercoutere, W.↗

Human ocular torsion during parabolic flights: an analysis with scleral search coil

Rotation of the eyes about the visual axis is known as ocular torsion. A lateral inclination (a "roll") of the head induces ocular torsion in the opposite direction, a response known as ocular counterrolling. For six subjects, we recorded the static (head still) and dynamic (head in oscillatory roll motion) ocular torsion in normal 1 g condition and also during the microgravity and hypergravity periods of parabolic flight, using the electromagnetic scleral search coil technique. With the head still, the direction and magnitude of torsion that occurred in response to microgravity and hypergravity differed substantially from one individual to another, but there was a significant difference in torsional magnitude between the microgravity and hypergravity periods, for all static head positions including the upright position. Under normal 1 g conditions, counterrolling compensated for about 16% of (voluntary) static head roll, while dynamic counterroll was much larger, up to 36% of head roll at 0.55 Hz. With increasing frequency of head oscillation between 0.33 Hz and 0.55 Hz, the gain of counterrolling increased and there was no change in the phase relationship. The gain of dynamic counterroll (in response to voluntary head rolling) was not significantly less in hypogravity, suggesting that on the ground at these frequencies the contribution of gravity and gravity receptors to this reflex is redundant: this reflex is probably driven by the semicircular canals. In some subjects, the torsional displacement in microgravity is accompanied by micro-torsional oscillatory motion.

Non-NASA Center↗

Gravisensing, apoptosis, and drug recovery in Taxus cell suspensions

Haploid and diploid cell suspensions of Taxus spp. were examined for their adaptive plasticity in response to simulated microgravity, unit gravity, and hypergravity. Cell suspensions produced the taxane, paclitaxel, (TAXOL (R)), which is useful for the treatment of various cancers. Amyloplasts contributed to taxane ring biosynthesis and to drug release at the cell wall. Drug-producing cells reacted as gravisensing osmotic tensiometers. In stressed cells, amyloplasts docked and fused in clusters to sites on the plasmalemma before taxane discharge into the culture medium. In simulated microgravity and compared to all other treatments, taxane production was reduced nearly 100-fold. The percent paclitaxel of total taxanes remained 3-to 6-fold greater, and biomass doubled. When p53-independent programmed cell death was induced, taxanes were released into the culture medium as free molecules (soluble and insoluble) or bound to membranes, nuclear fragments, xylan residues, and other particulate materials. Unit gravity and especially hypergravity promoted xylogenesis and significant drug overproduction. A model relating families of >touch = (TCH), taxane early response (TER), nuclear cycling, and apoptosis-regulating genes to gravisensing, cell wall modifications, and to taxane recovery accounted for most but not all of the observations.

Paclitaxel/biosynthesis↗

An Artificial-Gravity Space-Settlement Ground-Analogue Design Concept

The design concept of a modular and extensible hypergravity facility is presented. Several benefits of this facility are described including that the facility is suitable as a full-scale artificial-gravity space-settlement ground analogue for humans, animals, and plants for indefinite durations. The design is applicable as an analogue for on-orbit settlements as well as those on moons, asteroids, and Mars. The design creates an extremely long-arm centrifuge using a multi-car hypergravity vehicle travelling on one or more concentric circular tracks. This design supports the simultaneous generation of multiple-gravity levels to explore the feasibility and value of and requirements for such space-settlement designs. The design synergizes a variety of existing technologies including centrifuges, tilting trains, roller coasters, and optionally magnetic levitation. The design can be incrementally implemented such that the facility can be operational for a small fraction of the cost and time required for a full implementation. Brief concept of operation examples are also presented.

Space Settlement↗

Impact of the ISS Environment on CNS in Drosophila Melanogaster

Altered gravity and elevated carbon dioxide (CO 2 ) levels as experienced on the ISS can adversely affect human health across various organ systems, especially the Central Nervous System (CNS). Investigating these changes is essential for understanding the long-term effects of spaceflight on human physiology to ensure crew health. Ground-based analogs provide an efficient method to evaluate alterations induced by chronic spaceflight on a larger scale. This study focuses on CNS changes in response to hypergravity (HG) and elevated CO 2 levels via a ground-based analog using the well-established model organism, Drosophila melanogaster. We hypothesize behavior and physiological changes immediately post exposure to HG+CO 2 , along with chronic effects up to 25 days post-exposure. Adult male and female flies were exposed to varying gravity loads (1g, 1.2g, and 3g) and elevated CO 2 levels (~4000 ppm, mimicking CO 2 levels on the ISS) for 15 days and were assessed immediately and at 5-, 10-, and 25-days post-exposure, mirroring astronauts’ post-return profiling. The flies were assessed for neurobehavioral changes, including longevity and negative geotaxis; brain morphological changes, such as dopaminergic neuron count, apoptosis, and glial cell density; and bioenergetic changes in the brain, including mitochondrial abundance and membrane potential. Longevity remained unchanged under hypergravity, even with the addition of elevated CO 2 as a stressor. However, despite the stable lifespan, quality of life appeared to be affected, as shown by negative geotaxis and neuroanatomical changes. Negative geotaxis testing revealed a reduction in motor ability at R0 across all conditions, which correlated with a decrease in dopaminergic (DA) neuron count. Additional observations suggested further systemic alterations, including a decrease in glial cell count, an increase in apoptosis, and notable bioenergetic changes. Collectively, these findings contribute to our understanding of the long-term effects of spaceflight on the CNS.

spaceflight↗

Effects of a 2X gravity environment on the ultrastructure of the gerbil parathyroid gland

A number of studies concerning the effects of hypergravity on bone have shown increases in bone mass or bone dimensions. Correlative studies, which could provide clues to the mechanism for such a response, have been lacking. The purpose of the present study was to evaluate the ultrastructure of parathyroid glands of Mongolian gerbils exposed to a continuous 2 X gravity force for 60 d. It was found that the experimental animals had parathyroid glands which had a greater percentage of chief cells in the active stage of their secretory cycle when compared with control animals. This result was interpreted to indicate an increase in parathyroid gland secretory activity and, hence, an increase in parathyroid hormone release. It was suggested that increased parathyroid secretory activity was necessary to maintain serum calcium levels of hypergravity animals within normal limits. Cellular forms resembling water clear cells and highly compact, degenerating cells were described in experimental animals but not in controls. Areas suggestive of cellular dissolution and disorganization were also reported in experimental parathyroids.

Sannes, P. L.↗

Responses of articular and epiphyseal cartilage zones of developing avian radii to estrone treatment and a 2-G environment

Histological measurements of radii from chickens exposed to estrone and hypergravity are reported. Female chicks at two weeks post-hatch were maintained for two weeks at earth gravity or 2 G with daily injections of 0.2 or 0.4 mg estrone. Animals were sacrificed after the last injection, and the radii were processed by described histological techniques. The results suggest that proximal and distal epiphyses of developing radii show different morphological responses to estrone and hypergravity.

Negulesco, J. A.↗