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The Biological Flight Research Facility.

NASA Ames Research Center (ARC) is building a research facility, the Biological Flight Research Facility (BFRF), to meet the needs of life scientists to study the long-term effects of variable gravity on living systems. The facility will be housed on Space Station Freedom and is anticipated to operate for the lifetime of the station, approximately 30 years. It will allow plant and animal biologists to study the role of gravity, or its absence, at varying gravity intensities for varying periods of time and with various organisms. The principal difference between current Spacelab missions and those on Space Station Freedom, other than length of mission, will be the capability to perform on-orbit science procedures and the capability to simulate Earth gravity. Initially the facility will house plants and rodents in habitats which can be maintained at microgravity or can be placed on a 2.5 m diameter centrifuge. However, the facility is also being designed to accommodate future habitats for small primates, avian and aquatic specimens. The centrifuge will provide 1 g for controls and will also be able to provide gravity from 0.01 to 2.0 g for threshold gravity studies as well as hypergravity studies. Included in the facility are a service unit for providing clean chambers for the specimens and a glovebox for manipulating the plant and animal specimens and for performing experimental protocols. The BFRF will provide the means to conduct basic experiments to gain an understanding of the effects of microgravity on the structure and function of plants and animals, as well as investigate the role of gravity as a potential countermeasure for the physiological changes observed in microgravity.

Adaptation, Physiological↗

Effects of the 120 days of head-down bed rest on cytokine secretion and its in vitro modulation by glucocorticoids.

Antiorthostatic hypokinesia or head-down bed rest (HDBR), is a ground-based model system used to simulate some of the physioloical responses observed during space flight. Several studies involving humans and animals have demonstrated the effects of HDBR on different physioloical systems. HDBR produced a large thoracic fluid shift similar to that reported for space flight. Exposure to the combination of -6 degrees HDBR, emotional stress, and hypergravity led to an elevation of plasma histamine and serotinin and a dramatic decrease in the concentration of prostaglandins E, F2-alpha, and erthropoietin. These responses indicated the HDBR produces significant alterations in the neuroendocrine regulatory pathways. The proliferative response of immune cells in response to activators was significantly enhanced in antiorthostatically suspended mice; plasma corticosterone also was higher but splenic natural killer cell cytotoxicity remained unchanged after suspension. Bone-resporbing activity of supernatatants increased in mitogen-stimulated PBMC cultures of subjects exposed to -5 degrees HDBR for 370 days of HDBR. Proliferative activity of PBMCs had declined at the end of a 320-day HDBR and during the initial days of recovery, but the numbers of active rosette-forming T cells increased. These and other results suggest that most stress-induced immune changes are neuroendocrine modulated, and that corticosteroids play a significant role in this modulation. It is expected that HDBR-induced immune changes could result from similar mechanisms. In this study, we investigated the effect of 120 days of HDBR on Type-1 vs. Type-2 cytokine equilibrium in mitogen-activated PBMC culture, and how these reactions may correlate with changes in the neuroendocrine status.

Adult↗

Changes in muscle sympathetic nerve activity and effect of breathing maneuvers during microgravity induced by parabolic flight in humans.

UNLABELLED: This study aimed to clarify how muscle sympathetic nerve activity (MSNA) in humans, which plays an important role in blood pressure control against gravity, is altered under microgravity (microG) conditions, and how the MSNA change is modified by breathing maneuvers. Ten subjects seated themselves in a jet aircraft with their knees extended. MSNA was recorded microneurographically from the left tibial nerve with simultaneous monitoring of ECG, blood pressure, respiration, and intrathoracic blood volume estimated by the impedance method during parabolic flight in a jet aircraft. In half of the parabolas, their respiration was controlled at 0.25 Hz by a metronome. RESULTS: MSNA was enhanced under hypergravity just before microG entry, and immediately suppressed by microG induced by parabolic flight. The suppression was more marked with controlled than with uncontrolled respiration (51.6 +/- 7.2 vs 82.8 +/- 2.5%, mean +/- SE, 1G=100%). MSNA changes during microG correlated significantly to changes in blood pressure and intrathoracic blood volume. The blood pressure fall 10 to 15 sec after microG entry was less prominent with controlled than with uncontrolled respiration. We conclude that changes in arterial blood pressure and intrathoracic blood volume modulate MSNA during microG induced by parabolic flight, depending largely on breathing maneuvers.

Adult↗

Altering the position of the first horizontal cleavage furrow of the amphibian (Xenopus) egg reduces embryonic survival.

The animal/vegetal cleavage ratio (AVCR), defined as the ratio of the height of the animal blastomere to the height of the Xenopus embryo at the 8 cell stage, can be shifted by placing embryos in novel gravitational fields: clinostating (microgravity simulation) increases AVCR, and centrifugation (hypergravity simulation) reduces AVCR. This report contributes to an understanding of the subcellular mechanism responsible for the furrow relocation and assesses its significance. Embryo inversion and D2O immersion were found to increase AVCR, and cold shock was found to reduce AVCR. Based on the additive or antagonistic effects of combined treatments, it is postulated that the primary cause of AVCR changes is an alteration in the distribution of yolk platelets and the rearrangement of microtubule arrays. Embryos with a decreased AVCR exhibited reduced survival in early developmental stages, indicating serious difficulties in cleavage, blastulation and/or gastrulation. Cold-shocked embryos with a reduced AVCR could be rescued by D2O pretreatment or clinostating, an observation which supports the notion that changes accompanying AVCR modifications represent the primary cause of the reduction in percent survival.

Animals↗

Accuracy of aimed arm movements in changed gravity.

We studied the accuracy of aimed arm movements in normal gravity, and during the hypergravity (hyper-G) and microgravity (micro-G) episodes of KC-135 parabolic flights. Subjects pointed at mirror-viewed targets without sight of their arm, and final pointing position was measured by a digitizing pad. Compared with the normal gravity (normal-G) baseline, subjects pointed consistently higher in hyper-G, and still higher in micro-G. Results were not different if subjects viewed targets only during normal-G and pointed at their memorized position under changed gravity (changed-G); this suggests that the "elevator illusion" played a minor role in our study. The observed impairments were attributed to degraded proprioceptive feedback and/or inappropriate motor programs in changed-G. Pointing accuracy improved movement-to-movement but not parabola-to-parabola, indicating that prolonged exposure is needed for sustained adaptation.

Aerospace Medicine↗

Gravity: It's the law.

Based on experience in microgravity and on centrifuge induced hypergravity, exposure to either altered force field causes marked effects in animals and humans. It would seem logical that changes from unit gravity would have different effects depending on whether gravity is increased or decreased. Examples will be presented of responses to altered gravitational fields and changes in human and animal musculoskeletal, cardiopulmonary neurovestibular and metabolic responses.

Journal Article↗

The influence of 2.5 g exposure on the morphology of rat vestibular epithelia.

Several studies have shown that altered gravity causes changes in vestibular induced reflexes and behaviour, and in vestibular morphology. How the level of gravity affects the morphology of vestibular epithelia, however, is largely unknown. Vestibular epithelia of hypergravity (HG) exposed animals and control animals were histochemically labeled for actin and tubulin (two characteristic proteins for specific cytoskeletal structures in hair cells and supporting cells). Cellular organization, cytoskeletal structure and apical cross-sectional area were investigated.

Research Support, N.I.H., Extramural↗

Neuronal regulation of otolith growth and kinetotic behaviour.

Inner ear stones (otoliths) of larval cichlid fish were labelled with the calcium-tracer alizarin-complexone (AC) before animals were subjected to hypergravity (hg; 3 g). After the experiment, the otoliths' area between the two AC-labellings was measured. Growth of hg-otoliths was significantly slowed down as compared to 1 g-control specimens. In the course of a second experiment, the vestibular nerve was unilaterally transacted in neonate swordtail fish which were subsequently incubated in AC. Incorporation of AC was considerably lower in the otoliths of the transacted side. The results strongly suggest that otolith growth is continuously regulated in dependence of the environmental gravity vector. Since the otolithic calcium incorporation ceased on the transected head sides, it is concluded that the regulation of otolith growth is based on the central nervous efferent vestibular system.

Research Support, Non-U.S. Gov't↗

Gravity induced postponed potentiation as a result of repeated 2 G influence on rats.

On the base of electron- and light microscopical, immunocytochemical and morphometrical studies it was found that repeated 5-days' 2 G influence on the rats induced in the cells of the brain, pituitary and thyroid the alteration of structure, enzyme and hormone content which differed in quantity or quality from the changes arisen under the primary 5-days' 2 G and directed to increase in effectiveness of neuronal circuit, facilitation of synaptic transmission and elevation of hormone production. These structural and metabolic changes point out the animal capability for memorizing the change of gravity level and can be considered as an evidence of arise, hypergravity induced postponed potentiation that characterized the functional state of studied systems and presumably the functional state of whole organism which repeatedly was in the state of increased weightness.

Journal Article↗

Noninvasive beat-to-beat stroke volume computation during acute hydrostatic pressure changes in parabolic flight.

A three-element model of the cardiovascular system was used to monitor stroke volume (SV) changes during parabolic flight. Aortic blood flow was estimated from continuous arterial finger pressure and SV computed by integrating simulated aortic flow during each systole. SV was significantly higher in microgravity (microgravity) compared to 1 G whereas in hypergravity (hG), SV was significantly lower. Exponential SV transients were observed after the transitions to and from microgravity and the succeeding or preceeding hG phases. These SV transients present different time constants, which reflect two different mechanisms of cardiovascular adaptation to sudden gravitational changes. These results show that beat-to-beat computation of SV provides noninvasive information on circulatory adaptation to acute hydrostatic pressure changes.

Comparative Study↗

Responses of Hoffman-reflex in human soleus to gravity and/or fluid shift.

Responses of Hoffman (H)-reflex in human soleus to changes in the levels of gravity, activities of skeletal muscles, and/or fluid distribution of lower limbs during the parabolic flight of a jet airplane and/or using a tilting table were studied. The time interval between the electrical stimulation and the appearance of either M- or H-wave and the amplitude of M-wave were not influenced by the changes in gravity and fluid distribution levels. However, the H-wave amplitude was increased when the subjects were exposed to microgravity (microgravity-G). Hypergravity at 1.5- or 2-G had no effect on the H-wave amplitude. The H-reflex had no relation with the changes of electromyogram activities of skeletal muscles and fluid volume in lower limbs. Further, the H-wave amplitude was even decreased insignificantly when the distribution of lower limb fluid was reduced at head-down position on the table. It is suggested that an acute exposure to microgravity-G increases the excitability of soleus motor pool, but the mechanism is still unclear.

Journal Article↗

Variable acceleration influences cyclic AMP levels in Paramecium biaurelia.

Paramecium is used as a model system to analyse the gravity signal transduction pathway, that leads to gravitaxis and gravikinesis. In order to prove whether gravistimulation is coupled with second messenger production (cyclic AMP: hyperpolarization, cyclic GMP: depolarization) Paramecium was fixated under variable accelerations (1 x g, 9 x g and 10(-4) x g) on a centrifuge and during a sounding rocket flight (TEXUS 39). The analysis of cAMP and cGMP levels revealed an acceleration-dependent change in cAMP, while cGMP-levels showed gravity-independent variations. Hypergravity did not only induce an amplification of gravitaxis and gravikinesis, but also an increase in cAMP compared to the 1 x g-data. We conclude that the increased pressure of the cytoplasm on the lower membrane of upward swimming cells enhance the number of open K+(-)channels, thus causing hyperpolarization and change in cAMP concentration. Consequently, transition to microgravity declines gravitaxis and gravikinesis, and decreases cAMP concentration due to the loss of pressure on the cell membrane.

Journal Article↗

Remote controlled equipment for multiple blood withdrawal in gravitational physiology experiments.

Electro-mechanical equipment for multiple blood withdrawal from small experimental animals applied to a centrifuge with maximal 6g gravitational overloading has been developed and tested. The equipment consists of a transmitter and receiver equipped by microcomputers. Active rotor stepping motors are driving four pairs of syringes. It is also possible to measure the instantaneous gravitational force using an accelerometric transducer. This telemetrically regulated blood sampling allows studying selective effects of hypergravity during centrifugation. It can be also used for study of microgravity effects in the animal organism during space flights for the understanding of the mechanism of the changes of the activity of neuroendocrine system and metabolic processes.

Journal Article↗

"Critical periods" in vestibular development or adaptation of gravity sensory systems to altered gravitational conditions?

1. A feature of sensory, neuronal and motor systems is the existence of a critical period during their development. Modification of environmental conditions during this specific period of life affects development in a long-term manner, or even irreversibly. Deprivation is the prefered approach to study the existence and duration of critical periods. For gravity sensory systems, space flights offer the only opportunity for deprivation conditions. 2. Studies in a fish (Oreochromis mossambicus) and an amphibian (Xenopus laevis) revealed a significant sensitivity of their roll-induced static vestibuloocular reflex (rVOR) to a 9- to 10-day gravity deprivation (microgravity) during a spaceflight. In some instances, the rVOR was augmented after the flight as demonstrated in young Oreochromis which were launched when their rVOR had not been developed, and in Xenopus tadpoles launched after their rVOR had developed. Fish which could perform the rVOR at launch were insensitive to microgravity exposure. A similar insensitivity to microgravity was observed in Xenopus tadpoles with normal body shape which had not yet developed their rVOR at launch. Some tadpoles, however, developed an upward bended tail during their space flight; their rVOR was significantly depressed after termination of microgravity independent of the age at onset of the flight. Hypergravity depressed the rVOR for all so far tested developmental stages in both Oreochromis and Xenopus. 3. Both adaptive processes during exposure to altered gravity as well as the existence of a critical period in vestibular development might be responsible for the modulation of the rVOR recorded after exposure to altered gravity. Deprivation studies have to be extended to older developmental stages to test the possibility of a critical period; however, this approach is limited due to the low number of space flights.

Adaptation, Physiological↗

Cyclic stretch induced MAPK phosphorylation stronger than static stretch.

The environment for living organism in space has microgravity and/or hypergravity and/or any kind of mechanical stresses. Cellular response may differ from the variety of mechanical stress. Mitogen-activated protein kinases (MAPKs) pathway is related to various cellular events. In the present study it was investigated the serial measurement of MAPK phosphorylation using western-blotting analysis following with three types of cyclic stretch, static, 0.1 Hz and 0.25 Hz. The result was that induction of MAPK phosphorylation had peaks within 2 to 4 hours and attenuated, while induction of p38 phosphorylation in 0.1 Hz stretch had a peak at 6 hours later and the strongest. Thus, there might be differential cellular response depends upon the frequency of cyclic stretch .

Blotting, Western↗

BIOPACK: the ground controlled late access biological research facility.

Future Space Shuttle flights shall be characterized by activities necessary to further build the International Space Station, ISS. During these missions limited resources are available to conduct biological experiments in space. The Shuttles' Middeck is a very suitable place to conduct science during the ISS assembly missions or dedicated science missions. The BIOPACK, which flew its first mission during the STS-107, provides a versatile Middeck Locker based research tool for gravitational biology studies. The core facility occupies the space of only two Middeck Lockers. Experiment temperatures are controlled for bacteria, plant, invertebrate and mammalian cultures. Gravity levels and profiles can be set ranging from 0 to 2.0 x g on three independent centrifuges. This provides the experimenter with a 1.0 x g on-board reference and intermediate hypogravity and hypergravity data points to investigate e.g. threshold levels in biological responses. Temperature sensitive items can be stored in the facilities' -10 degrees C and +4 degrees C stowage areas. During STS-107 the facility also included a small glovebox (GBX) and passive temperature controlled units (PTCU). The GBX provides the experimenter with two extra levels of containment for safe sample handling. This biological research facility is a late access (L-10 hrs) laboratory, which, when reaching orbit, could automatically be starting up reducing important experiment lag-time and valuable crew time. The system is completely telecommanded when needed. During flight system parameters like temperatures, centrifuge speeds, experiment commanding or sensor readouts can be monitored and changed when needed. Although ISS provides a wide range of research facilities there is still need for an STS-based late access facility such as the BIOPACK providing experimenters with a very versatile research cabinet for biological experiments under microgravity and in-flight control conditions.

Acceleration↗

The pituitary-testicular axis in microgravity: analogies with the aging male syndrome.

Extraterrestrial exploration has gone on for decades before reversible testicular failure was shown to be a consequence of space flight in humans and animals at the end of the XXth century. This phenomenon was initially thought to depend on the psycho-physical stress expected to derive from a decidedly unusual environment, but the lack of consistent data concerning cortisol increase and/or gonadotrophin suppression pointed to the possibility of a primary defect. This was indirectly confirmed by the observation that a continuum of testicular androgen secretion potential exists from microgravity to centrifuge-derived hypergravity. Further experiments using tissue slices and suspended cells confirmed a direct inhibitory effect of microgravity upon testicular androgen production. A parallel deterioration of major physiological parameters, such as bone density, muscle mass/force, red blood cell mass, hydration and cardiopulmonary performance, has been repeatedly described during space missions, which, luckily enough, fully recover within days to weeks after landing, the time lag depending on single organ/system adaptation rates. According to the Authors of the present review, when taking together all reported changes occurring in space, a picture emerges closely resembling the so-called aging male syndrome, which is currently the object of daily screening and clinical care in their endocrine unit, so that microgravity may become a tool for better understanding subtle mechanisms of testicular senescence.

Aging↗

[Dynamics of ECG voltage in changing gravity].

Comparative analysis of the QRS voltage response to gravity variations was made using the data about 26 normal human subjects collected in parabolic flights (CNERS-AIRBUS A300 Zero-G, n=23; IL-76MD, n=3) and during the tilt test (head-up tilt at 70 degrees for a min and head-down tilt at-15 degrees for 5 min, n=14). Both the parabolic flights and provocative tilt tests affected R-amplitude in the Z lead. During the hypergravity episodes it was observed in 95% of cases with the mean gain of 16% and maximal--56%. On transition to the horizontal position, the Rz-amplitude showed a rise in each subject (16% on the average). In microgravity, the Rz-amplitude reduced in 95% of the observations. The voltage decline averaged 18% and reached 49% at the maximum. The head-down tilt was conducive to Rz reduction in 78% of observations averaging 2%. Analysis of the ECG records under changing gravity when blood redistribution developed within few seconds not enough for serious metabolic shifts still revealed QRS deviations associated exclusively with the physical factors, i.e., alteration in tissue conduction and distance to electrodes. Our findings can stand in good stead in evaluation of the dynamics of predictive ECG parameters during long-term experiments leading to changes as in tissue conduction, so metabolism.

Adaptation, Physiological↗