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At least 271 records · Page 15Linked to original sources

Key gravity-sensitive signaling pathways drive T cell activation.

Returning astronauts have experienced altered immune function and increased vulnerability to infection during spaceflights dating back to Apollo and Skylab. Lack of immune response in microgravity occurs at the cellular level. We analyzed differential gene expression to find gravity-dependent genes and pathways. We found inhibited induction of 91 genes in the simulated freefall environment of the random positioning machine. Altered induction of 10 genes regulated by key signaling pathways was verified using real-time RT-PCR. We discovered that impaired induction of early genes regulated primarily by transcription factors NF-kappaB, CREB, ELK, AP-1, and STAT after crosslinking the T-cell receptor contributes to T-cell dysfunction in altered gravity environments. We have previously shown that PKA and PKC are key early regulators in T-cell activation. Since the majority of the genes were regulated by NF-kappaB, CREB, and AP-1, we studied the pathways that regulated these transcription factors. We found that the PKA pathway was down-regulated in vg. In contrast, PI3-K, PKC, and its upstream regulator pLAT were not significantly down-regulated by vectorless gravity. Since NF-kappaB, AP-1, and CREB are all regulated by PKA and are transcription factors predicted by microarray analysis to be involved in the altered gene expression in vectorless gravity, the data suggest that PKA is a key player in the loss of T-cell activation in altered gravity.

Astronauts↗

Center of body mass and the evolution of female body shape.

Among primates, the genus Homo has a unique sexual dimorphism in general body shape. The stenotypic female "hourglass figure" has often been attributed to sexual selection. Sexual dimorphism both in shape and in position of the center of body mass (CoM) emerges during puberty and is related to hormonal influences. These are only the proximal and not the ultimate causes of this feature. This article explores the hypothesis that the evolutionary (i.e., ultimate) reason for female body shape and male preference for a lower waist-to-hip ratio (WHR) is due to the acquisition of bipedal locomotion and different biomechanical constraints on each sex. The demands of pregnancy and subsequently carrying infants may have more tightly constrained CoM in females than in males. A lower-position of CoM relative to height (RCoM=(CoM/height)*100%) would contribute to better stability during pregnancy and infant carrying. Using body measurements from 119 female students, we show that RCoM correlates negatively with only maximal thigh circumference and positively with only WHR and shoulder width. The relationship between RCoM and traits that best characterize female body shape seems to confirm a hypothesis of biomechanical selection pressure that may have acted on Homo female morphology, thus contributing to sexual dimorphism.

Adult↗

Hypoxia suppresses runx2 independent of modeled microgravity.

Bone loss is a consequence of skeletal unloading as seen in bed rest and space flight. Unloading decreases oxygenation and osteoblast differentiation/function in bone. Previously we demonstrated that simulation of unloading in vitro, by culturing differentiating mouse osteoblasts in a horizontal rotating wall vessel (RWV), results in suppressed expression of runx2, a master transcriptional regulator of osteoblast differentiation. However, the RWV is able to reproduce in a controlled fashion at least two aspects of disuse that are directly linked, model microgravity and hypoxia. Hypoxia in the RWV is indicated by reduced medium oxygen tension and increased expression of GAPDH and VEGF. To uncouple the role of model microgravity from hypoxia in suppressed runx2 expression, we cultured osteoblasts under modeled microgravity (oxygenated, horizontal RWV rotation), hypoxia (vertical RWV rotation), or both conditions (horizontal RWV rotation). The expression, DNA binding activity and promoter activity of runx2, was suppressed under hypoxic but not normoxic modeled microgravity RWV conditions. Consistent with a role for hypoxia in suppression of runx2, direct exposure to hypoxia alone is sufficient to suppress runx2 expression in osteoblasts grown in standard tissue culture plates. Taken together, our findings indicate that hypoxia associated with skeletal unloading could be major suppressor of runx2 expression leading to suppressed osteoblast differentiation and bone formation.

3T3 Cells↗

Effects of intermittent or continuous gravitational stresses on cell-matrix adhesion: quantitative analysis of focal contacts in osteoblastic ROS 17/2.8 cells.

The relationship between cell morphology and cell metabolism and the role of mechanical load in bone remodeling is well known. Mechanical stimulation induces changes in the shape of osteoblasts, probably mediated by reorganization of focal contacts. We studied the influence of gravity (Gz) variations occurring during parabolic flight on osteoblast focal adhesion of ROS 17/2.8 osteosarcoma cells subjected to 15 or 30 parabolic flights. Significant flight-induced shape changes consisted of decreased cell area associated with focal contact plaque reorganization. Identical durations of continuous mechanical stress induced by centrifugation (2 Gz) or clinorotation (Gz randomization) had no major effect on cell focal adhesion. ROS 17/2.8 G2/M synchronization by treatment with nocodazole inhibited the flight-induced decrease in adhesion parameters. We concluded that ROS 17/2.8 cells are sensitive to Gz switches and that their adaptation is at least dependent on microtubule function.

Animals↗

Mutants of Arabidopsis thaliana with altered responses to auxins and gravity.

Auxin-resistant mutants of Arabidopsis have been induced and isolated by screening for survivors on a medium containing the herbicide 2,4-D. Thirty independently arisen mutants have been isolated in this way and one of them, P 83, has been investigated in detail. When wild type and P 83 are compared in concentration/response curves, where the response is the inhibition of root growth, the ED50 values of the auxins, 2,4-D and IAA, are 14-fold higher for the mutant. The mutant also responds differently to gravity: its roots do not show positive geotropism, but tend to grow with a clockwise curvature on agar surfaces. The seedling roots of the mutant also grow more rapidly than those of the wild type in the absence of 2,4-D, following faster germination. The F1 between P 83 and wild type is similar to the latter, but has a slightly increased resistance to 2,4-D. Results obtained from the F2, F3 and backcross generations suggest monofactorial inheritance. Most of the other 29 mutants have the P 83 phenotype, but at least five are different. Four have lower levels of resistance to 2,4-D and P 83, and their roots appear to respond normally to gravity. One mutant has an abnormal georesponse and a much higher level of resistance to 2,4-D than P 83.

Dose-Response Relationship, Drug↗

Escherichia coli growth under modeled reduced gravity.

Bacteria exhibit varying responses to modeled reduced gravity that can be simulated by clino-rotation. When Escherichia coli was subjected to different rotation speeds during clino-rotation, significant differences between modeled reduced gravity and normal gravity controls were observed only at higher speeds (30-50 rpm). There was no apparent affect of removing samples on the results obtained. When E. coli was grown in minimal medium (at 40 rpm), cell size was not affected by modeled reduced gravity and there were few differences in cell numbers. However, in higher nutrient conditions (i.e., dilute nutrient broth), total cell numbers were higher and cells were smaller under reduced gravity compared to normal gravity controls. Overall, the responses to modeled reduced gravity varied with nutrient conditions; larger surface to volume ratios may help compensate for the zone of nutrient depletion around the cells under modeled reduced gravity.

Colony Count, Microbial↗

Ion channel are sensitive to gravity changes.

The effects of gravity on alamethicin doped planar lipid bilayers and on reconstituted porins of Escherichia coli outer membrane, respectively, have been investigated in this paper. The aim of the study was to find out whether and how gravity influences the highly stratified system: membrane-ion channel, in order to provide a novel approach to the explanation of gravity effects on living systems. This is necessary, as even single cells can react to gravity changes without having perceptive organelles. The mechanism of this detection is not clear yet. One possibility might be the detection of gravity by the membrane itself, or by the interaction of integral membrane proteins with gravity. Here we show for the first time that gravity directly influences the integral open state probability of native ion channels (porins) incorporated into planar lipid bilayers. Under hypergravity, especially the open state probability of porins is increased, whereas it is decreased in the microgravity case. The dependency is sigmoidal with the steepest region at 1 to 1.3 g. In the light of these experiments, a general effect of gravity on ion channels and membranes seems to be reasonable, possibly providing an explanation for several impacts of gravity on living systems.

Alamethicin↗

Balance in a rotating artificial gravity environment.

When subjects stand at the center of a fully enclosed room that is rotating at constant velocity, their natural postural sway generates Coriolis forces that destabilize their center of mass and head. We quantitatively assessed how exposure to constant velocity rotation at 10 rpm affected postural control. Twelve subjects stood in a heel-to-toe stance in the rotating room. Each test session involved three phases: (1) pre-rotation, (2) per-rotation, and (3) post-rotation. In each phase, subjects were tested in both eyes open and eyes closed conditions. Four measures were used to characterize center of mass movement and head movement: mean sway amplitude, total power, mean power frequency, and frequency of maximum power. Each measure was computed for anterior-posterior and medial-lateral sway. Both anterior-posterior and medial-lateral head and center of mass sway during rotation had significantly greater mean sway amplitude and total power compared with pre- and post-rotation values. Mean power frequency and frequency of maximum power were little affected. Eyes open conditions were significantly more stable in all test phases than eyes-closed, but vision did not completely suppress the effects of rotation. The greatest effect of rotation was in the eyes-closed condition with mean sway amplitude and total power increasing more than twofold. Inverted pendulum sway was maintained in all phases of both test conditions. No aftereffects of rotation were present after the four 25-s exposures each subject received. We expect that with longer exposure periods and with active generation of body sway subjects would both adapt to rotation and exhibit post-rotary aftereffects.

Adult↗

Accuracy of spatial localization depending on head posture in a perturbed gravitoinertial force field.

Spatial orientation is crucial when subjects have to accurately reach memorized visual targets. In previous studies modified gravitoinertial force fields were used to affect the accuracy of pointing movements in complete darkness without visual feedback of the moving limb. Target mislocalization was put forward as one hypothesis to explain this decrease in accuracy of pointing movements. The aim of this study was to test this hypothesis by determining the accuracy of spatial localization of memorized visual targets in a perturbed gravitoinertial force field. As head orientation is involved in localization tasks and carrying relevant sensory systems (visual, vestibular and neck muscle proprioceptive), we also tested the effect of head posture on the accuracy of localization. Subjects (n=10) were seated off-axis on a rotating platform (120 degrees s(-1)) in complete darkness with the head fixed (head-fixed session) or free to move (head-free session). They were required to report verbally the egocentric spatial localization of visual memorized targets. They gave the perceived target location in direction (i.e. left or right) and in amplitude (in centimeters) relative to the direction they thought to be straight ahead. Results showed that the accuracy of visual localization decreased when subjects were exposed to inertial forces. Moreover, subjects localized the memorized visual targets more to the right than their actual position, that was in the direction of the inertial forces. With further analysis, it appeared that this shift of localization was concomitant with a shift of the visual straight ahead (VSA) in the opposite direction. Thus, the modified gravitoinertial force field led to a modification in the orientation of the egocentric reference frame. Furthermore, this shift of localization increased when the head was free to move while the head was tilted in roll toward the center of rotation of the platform and turned in yaw in the same direction. It is concluded that the orientation of the egocentric reference frame was influenced by the gravitoinertial vector.

Adolescent↗

Gramicidin S production by Bacillus brevis in simulated microgravity.

In a continuing study of microbial secondary metabolism in simulated microgravity, we have examined gramicidin S (GS) production by Bacillus brevis strain Nagano in NASA High Aspect Rotating Vessels (HARVs), which are designed to simulate some aspects of microgravity. Growth and GS production were found to occur under simulated microgravity. When performance under simulated microgravity was compared with that under normal gravity conditions in the bioreactors, GS production was found to be unaffected by simulated microgravity. The repressive effect of glycerol in flask fermentations was not observed in the HARV. Thus the negative effect of glycerol on specific GS formation is dependent on shear and/or vessel geometry, not gravity.

Anti-Bacterial Agents↗

Spectral characteristics of heart rate fluctuations during parabolic flight.

Parabolic flight is used to create short successive periods of changing gravity in a range between 0 and 1.8 Gz (1 Gz: 9.81 m/s(2)). The purpose of the present study was to evaluate whether cyclic variations in heart rate during +/-20 s periods of stable gravity in parabolic flight reflect autonomic modulation of cardiac chronotropy. During the 29th and 32nd ESA parabolic flight campaign ECG and respiration were recorded in 13 healthy volunteers in both standing and supine postures. We developed and validated a spectral algorithm especially adapted to study frequency components of heart rate among ultrashort (+/-20 s) stable gravity periods of parabolic flight. A low frequency (LF) component, starting from the lowest measurable frequency (+/-0.05 Hz) up to 0.15 Hz was distinguished from a high frequency (HF) component, ranging from 0.16 Hz up to 0.4 Hz. Powers were calculated by integration between corresponding limits and represented in normalized units (nu). With our method, we were able to reproduce normal findings in the upright posture at 1 Gz, i.e., less power in the HF component compared to supine (HFnu: 0.18+/-0.09 vs. 0.40+/-0.16). These postural related differences are shown to be eliminated at 0 Gz (HFnu: 0.30+/-0.12 vs. 0.32+/-0.13) and amplified at 1.8 Gz phases (HFnu: 0.15+/-0.10 vs. 0.39+/-0.16) of parabolic flight. In the supine position no coherent differences were shown in the measured variables among different gravity phases. Our observations strongly indicate that spectral characteristics of heart rate fluctuations among stable gravity periods of parabolic flight reflect parasympathetic nervous system control of cardiac chronotropy. At 1 Gz, there is a normal upright situation with less parasympathetic modulation of heart rate compared to supine. This effect is augmented during 1.8 Gz-conditions due to a suppressed parasympathetic control of heart rate in the upright posture. Alternatively, at 0 Gz, increased parasympathetic control in standing position eliminates differences in cardiac chronotropy compared to supine.

Adult↗

Biological investigations aboard biosatellite Cosmos-782.

The Cosmos-782 flight from 25 November to 15 December 1975, carried biological experiments designed to study the effects of weightlessness on insects and fish and on gravitropism and growth in several seed varieties. Investigations carried out on Drosophila melanogaster measured the frequency of recessive lethal mutations and the change in genetic distances in the sex chromosome. The study of Fundulus heteroclitus eggs and fry compared the effects of weightlessness and artificial gravity. Plants experiments studied spatial orientation of over and underground organs of Pinus silvestris and Crepis capillaris seeds. Other investigations used Phycomyces blakesleanus to compare spatial orientation and growth and development in weightlessness and artificial gravity.

Animals↗

Study of physiological effects of weightlessness and artificial gravity in the flight of the biosatellite Cosmos-936.

In the 18.5-day flight of the Soviet biosatellite Cosmos-936 (3-22, August 1977) com-parative investigations of the physiological effects of prolonged weightlessness (20 rats) and artificial gravity of 1 g (10 rats) were carried out. Throughout the flight artificial gravity was generated by means of animal rotation in two centrifuges with a radius of 320mm. Postflight examination of animals and treatment of the flight data were performed by Soviet scientists in collaboration with the specialists from Bulgaria, Czechoslovakia, the German Democratic Republic, Hungary, Poland, Rumania, France and the U.S.A. During the flight the total motor activity of the weightless rats was higher and their body temperature was lower than those of the centrifuged animals. Postflight examination of the weightless rats showed a greater percentage of errors during maze an increase in water intake and a decrease in diuresis; a fall of the resistance of peripheral red cells; an increase in the conditionally pathogenic microflora in the mouth; a decrease of oxygen consumption, carbon dioxide production and energy expenditures; a drop in the static physical endurance; a decline in the capacity to keep balance on the rail; an increase in the latent period of the lifting reflex, etc. The centrifugal animals displayed lesser or no change of the above type. These findings together with the biochemical and morphological data give evidence that during and after flight adaptive processes in the centrifuged rats developed better.

Adaptation, Physiological↗

Biomedical aspects of artificial gravity.

Artificial gravitv generated by spacecraft rotation may prove a universal countermeasure against adverse effects of weightlessness in the future. The paper summarizes the results of ground-based biomedical investigations of artificial gravity and flight experiments aboard Soviet biosatellites Cosmos-782 and Cosmos-936. It is believed that at the present stage the major goal of such investigations is to determine the minimum efficient value of artificial gravity in long-term flights which may eliminate adverse effects of prolonged weightlessness. In ground-bound studies the highest priority should be given to the development of methods on increasing human tolerance to the rotating environment.

Adaptation, Physiological↗

Artificial gravity in Space: vestibular tolerance assessed by human centrifuge spinning on Earth.

Artificial gravity created by the astronauts themselves, without any external power supply, by pedalling on coupled counterrotating bicycles along the inner wall of the space module (Twin Bikes System, TBS), was previously suggested (Antonutto et al., 1991) to prevent musculo-skeletal decay and cardiovascular deconditioning during long term space flights. To investigate whether this unusual rotating environment would determine abnormal stimulations of the vestibular system due to Coriolis cross coupled accelerations, thus leading to acute motion sickness (AMS), the conditions of a rotating environment were reproduced in a human centrifuge. A cycloergometer was fixed to the arm of the centrifuge, the rotation speed of which was equal to that yielding 1 g at the feet level in the TBS (i.e. ranging from 19 to 21 RPM). The ergometer position was such that the combination of the horizontal and gravitational acceleration vectors was 1.414 at the inner ear level and was aligned along the head to feet axis. Three subjects, pedalling at 50 W on a cycloergometer during centrifuge's spinning, were asked to move the head following an AMS' provocation protocol. None of them developed any AMS symptoms. This supports the look of the TBS as tool for avoiding musculo-skeletal and cardiovascular deconditioning during long term space flights.

Adult↗

Effects of unilateral selective hypergravity stimulation on gait.

The purpose of this work is to analyse the neural mechanisms of human motor perturbations induced by dynamic changes in gravity. A unilateral selective hypergravity stimulation (USHS) was produced by stretching an elastic band between the right shoulder and foot. The consequences of the extensor muscle tone change due to the positioning (increased muscular loading) and to its removal (decreased muscular loading) by the elastic band were observed on motor gait skill. Gait spatio-temporal parameters (horizontal displacement of both feet) and lower limb functional length variations (efficiency of flexion and extension movements of the lower limbs) were measured. The latter measure was performed using a device specially designed for that purpose. The main results were: (1) during and after USHS, gait perturbations appeared on the left--the body side not directly stimulated, (2) just after the end of USHS, perturbations were present on the right (homolateral) side evidencing a post treatment effect which caused a decrease in functional shortening of the lower limb during extension and an increase of functional shortening of the lower limb during stance (opposite in sense to the modification observed during swing). Such results afford evidence that, in addition to vestibular receptors, the mechanoreceptors of extensor muscles are involved in determining the changes in motor skills observed at the beginning and at the end of space flights.

Adaptation, Physiological↗

The role of artificial gravity in the exploration of space.

Terrestrial animals including the human require regular periodic gravitational (g) stimulation to maintain normal physiologic functions on earth or in space. Identical g stimulations can be produced in space with inertial forces (G) using a centrifuge. These stimulations may be made more efficient in preventing physiologic deconditioning by increasing G levels above 1 G. The effective operational use of the centrifuge in space to prevent physiologic deconditioning from microgravity exposures will require ground-based studies using weightless simulation such as bedrest or dry immersion with laboratories that have human-use centrifuges. The use of periodic, increased-G exposures in space may offer a practical inexpensive solution in preventing physiologic deconditioning.

Aerospace Medicine↗