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PubMed1994

Effects of altered gravity on plant cell processes: results of recent space and clinostatic experiments.

Space and clinostatic experiments revealed that plant cell structure and metabolism rearrangements depend on taxonomical position and physiological state of objects, growth phase and real or simulated microgravity influence duration. It was shown that clinostat conditions reproduce only a part of microgravity biological effects. It is established that various responses occur in microgravity: 1) rearrangements of cytoplasmic organelles ultrastructure and calcium balance; 2) physical-chemical properties of the plasmalemma are changed; 3) enzymes activity is often enhanced. These events provoke the acceleration of growth and differentiation of cells and their aging as a result; at the same time some responses can be considered as cell adaptation to microgravity.

Adaptation, Physiological↗
PubMed2000

Spaceflight induces changes in splenocyte subpopulations: effectiveness of ground-based models.

Spaceflight produces changes in the immune system. The mechanisms for the alterations in immune function after spaceflight remain unclear due in part to the difficulties associated with conducting spaceflight research. The purpose of the following studies, therefore, was to create a ground-based protocol that can reproduce the immunological changes found after spaceflight, i.e., changes in splenic lymphocyte populations. Rats were exposed to either flight aboard the Space Shuttle Endeavor (STS-77) or ground-based simulations of various components of the spaceflight experience. The ground-based mock spaceflight was comprised of exposure to launch and landing loads and unloading of the hindlimbs. In addition, each component of this ground-based mock spaceflight was tested separately. The results were that spaceflight reduced splenic CD4(+) T (helper/inducer) cells and CD11b(+) (neutrophils/macrophages) cells. The ground-based simulations of spaceflight did not reproduce the same pattern of splenocyte changes. In fact, exposure to landing loads alone increased splenic CD4(+) T (helper/inducer) cells. These findings support the conclusion that the ground models tested did not induce similar changes in the immune system as did spaceflight. It is possible, therefore, that stressors/factors unique to the spaceflight experience impact the immune system in ways that cannot be currently, fully modeled on the ground.

Animals↗
PubMed2003

Effects of simulated microgravity on closed-loop cardiovascular regulation and orthostatic intolerance: analysis by means of system identification.

Microgravity-induced orthostatic intolerance (OI) continues to be a primary concern for the human space program. To test the hypothesis that exposure to simulated microgravity significantly alters autonomic nervous control and, thus, contributes to increased incidence of OI, we employed the cardiovascular system identification (CSI) technique to evaluate quantitatively parasympathetic and sympathetic regulation of heart rate (HR). The CSI method analyzes second-to-second fluctuations in noninvasively measured HR, arterial blood pressure, and instantaneous lung volume. The coupling mechanisms between these signals are characterized by using a closed-loop model. Parameters reflecting parasympathetic and sympathetic responsiveness with regard to HR regulation can be extracted from the identified coupling mechanisms. We analyzed data collected from 29 human subjects before and after 16 days of head-down-tilt bed rest (simulated microgravity). Statistical analyses showed that parasympathetic and sympathetic responsiveness was impaired by bed rest. A lower sympathetic responsiveness and a higher parasympathetic responsiveness measured before bed rest identified individuals at greater risk of OI before and after bed rest. We propose an algorithm to predict OI after bed rest from measures obtained before bed rest.

Adult↗
PubMedDate not supplied

Activation of activator protein-1 in mouse brain regions exposed to simulated microgravity.

Microgravity induces stress, and the brain is one of the targets that is more influenced in this environment. Alteration in transcription factors can have enormous effect because of discrepancy in the signaling process of the cells. Activator protein-1 (AP-1) is a stress-regulated transcription factor and is involved in the regulation of physiological and pathological stimuli that include cytokines, growth factors, and stress signals. In the present study, an attempt has been made to observe the effect of a microgravity environment on the activation of AP-1 in the mouse brain. Our results show that AP-1 transcription factor is activated in simulated microgravity conditions in different regions of the brain. The activation of the AP-1 is dependent upon the increased kinase activity of c-Jun NH-terminal2 kinase-1. These results suggest that microgravity stress in the brain can elicit AP-1 activity.

Animals↗
PubMed2000

Mode of action of plasmolysed yeast on lymphocytes under microgravity stress.

A newly developed device to simulate microgravity for space biological investigations under laboratory conditions allowed us to apply a reproducible environmental stress on immunologically active cells. Cell proliferation, soluble IL-2 receptor in the culture supernatant, lymphocyte surface activation markers like CD25 (IL-2R), CD69 and HLA-Dr were the endpoints measured. Untreated donor lymphocyte reactions under microgravity were compared to the same cells treated with an immunomodulator from herbal plasmolysed yeast (Bio-Strath Food Supplement). The main finding is the enhancement of the proliferation inhibition under microgravitational stress by the herbal plasmolysed yeast.

Adjuvants, Immunologic↗
PubMed1998

Swimming kinematics and respiratory behaviour of Xenopus laevis larvae raised in altered gravity.

We examined the respiratory behaviours and swimming kinematics of Xenopus laevis tadpoles hatched in microgravity (Space Shuttle), simulated microgravity (clinostat) and hypergravity (3 g centrifuge). All observations were made in the normal 1 g environment. Previous research has shown that X. laevis raised in microgravity exhibit abnormalities in their lungs and vestibular system upon return to 1 g. The tadpoles raised in true microgravity exhibited a significantly lower tailbeat frequency than onboard 1 g centrifuge controls on the day of landing (day0), but this behaviour normalized within 9 days. The two groups did not differ significantly in buccal pumping rates. Altered buoyancy in the space-flight microgravity tadpoles was indicated by an increased swimming angle on the day after landing (day1). Tadpoles raised in simulated microgravity differed to a greater extent in swimming behaviours from their 1 g controls. The tadpoles raised in hypergravity showed no substantive effects on the development of swimming or respiratory behaviours, except swimming angle. Together, these results show that microgravity has a transient effect on the development of locomotion in X. laevis tadpoles, most notably on swimming angle, indicative of stunted lung development. On the basis of the behaviours we studied, there is no indication of neuromuscular retardation in amphibians associated with embryogenesis in microgravity.

Animals↗
PubMed2002

Simulated microgravity culture system for a 3-D carcinoma tissue model.

An in vitro organotypic culture model is needed to understand the complexities of carcinoma tissue consisting of carcinoma cells, stromal cells, and extracellular matrices. We developed a new in vitro model of carcinoma tissue using a rotary cell culture system with four disposable vessels (RCCS-4D) that provides a simulated microgravity condition. Solid collagen gels containing human pancreatic carcinoma NOR-P1 cells and fibroblasts or minced human pancreatic carcinoma tissue were cultured under a simulated microgravity condition or a static Ig condition for seven days. NOR-P1 cultures subjected to the simulated microgravity condition showed greater numbers of mitotic, cycling (Ki-67-positive), nuclear factor-kappa B-activating cells, and a lower number of apoptotic cells than were shown by cultures subjected to the static Ig condition. In addition, human pancreatic carcinoma specimens cultured under the simulated microgravity condition maintained the heterogeneous composition and cellular activity (determined by the cycling cell ratio and mitotic index) of the original carcinoma tissue better than static culture conditions. This new 3-D rotary cell culture system with four disposal vessels may be useful for in vitro studies of complex pancreatic carcinoma tissue.

Adenocarcinoma↗
PubMed2004

Automorphosis and auxin polar transport of etiolated pea seedlings under microgravity conditions.

On STS-95 space experiment, etiolated pea (Pisum sativum L. cv. Alaska) seedlings showed automorphosis and activities of auxin polar transport in epicotyls were substantially suppressed. These results together with the fact that inhibitors of auxin polar transport induced automorphosis-like growth and development strongly suggested that there are close relationships between automorphosis and auxin polar transport in etiolated pea seedlings. In order to know how gravistimuli control auxin polar transport at molecular levels, we isolated novel cDNAs of PsPIN2 and PsAUX1 encoding putative auxin efflux and influx carriers from etiolated pea seedlings. Significantly high levels in homology were found on nucleotide and deduced amino acid sequences among PsPIN2, PsPIN1 (accession no. AY222857) and AtPINs, and between PsAUX1 and AtAUX1. Exogenously applied auxin substantially enhanced the expression of PsAUX1 and PsPIN2 as well as PsPIN1. Simulated microgravity conditions on a 3-dimensional clinostat remarkably increased gene expression of PsPIN1 and PsAUX1 in the hook and the 1st internode of pea epicotyls, while the increase of expression of PsPIN2 in both organs was not so much. These results suggest that PsPINs and PsAUX1 are auxin-inducible genes, and the expression of PsPINs and PsAUX1 is under the control of gravistimulation. A possible role of these genes in regulating auxin transport relevant to automorphosis of etiolated pea seedlings is also discussed.

Biological Transport↗
PubMed1999

Growth of pea epicotyl in low magnetic field: implication for space research.

A magnetic field is an inescapable environmental factor for plants on the earth. However, its impact on plant growth is not well understood. In order to survey how magnetic fields affect plant, Alaska pea seedlings were incubated under low magnetic field (LMF) and also in the normal geo-magnetic environment. Two-day-old etiolated seedlings were incubated in a magnetic shield box and in a control box. Sedimentation of amyloplasts was examined in the epicotyls of seedlings grown under these two conditions. The elongation of epicotyls was promoted by LMF. Elongation was most prominent in the middle part of the epicotyls. Cell elongation and increased osmotic pressure of cell sap were found in the epidermal cells exposed to LMF. When the gravitational environment was 1G, the epicotyls incubated under both LMF and normal geomagnetic field grew straight upward and amyloplasts sedimented similarly. However, under simulated microgravity (clinostat), epicotyl and cell elongation was promoted. Furthermore, the epicotyls bent and amyloplasts were dispersed in the cells in simulated microgravity. The dispersion of amyloplasts may relate to the posture control in epicotyl growth under simulated microgravity generated by 3D clinorotation, since it was not observed under LMF in 1G. Since enhanced elongation of cells was commonly seen both at LMF and in simulated microgravity, all elongation on the 3D-clinostat could result from pseudo-low magnetic field, as a by-product of clinorotation. (i.e., clinostat results could be based on randomization of magnetic field together with randomization of gravity vector.) Our results point to the possible use of space for studies in magnetic biology. With space experiments, the effects of dominant environmental factors, such as gravity on plants, could be neutralized or controlled for to reveal magnetic effects more clearly.

Cell Wall↗
PubMed2003

Changes in gravitational force induce alterations in gene expression that can be monitored in the live, developing zebrafish heart.

Little is known about the effect of microgravity on gene expression, particularly in vivo during embryonic development. Using transgenic zebrafish that express the gfp gene under the influence of a beta-actin promoter, we examined the affect of simulated-microgravity on GFP expression in the heart. Zebrafish embryos, at the 18-20 somite-stage, were exposed to simulated-microgravity for 24 hours. The intensity of GFP fluorescence associated with the heart was then determined using fluorescence microscopy. Our measurements indicated that simulated-microgravity induced a 23.9% increase in GFP-associated fluorescence in the heart. In contrast, the caudal notochord showed a 17.5% increase and the embryo as a whole showed only an 8.5% increase in GFP-associated fluorescence. This suggests that there are specific effects on the heart causing the more dramatic increase. These studies indicate that microgravity can influence gene expression and demonstrate the usefulness of this in vivo model of 'reporter-gene' expression for studying the effects of microgravity.

Animals↗
PubMed1984

Influence of clinostat rotation on fertilized amphibian egg pattern specification.

Pattern specification in fertile Xenopus eggs rotated on horizontal clinostats was monitored with respect to primary embryonic axis formation, subsequent morphogenesis, and compartmentalization of the cytoplasm. At the speeds of 1 to 24 rpm (which are believed to simulate microgravity) a large percentage of eggs developed normal axial structures. Eggs clinostated at 12 rpm showed a randomization of dorsal/ventral polarity. The cytoplasmic compartments showed some clinostat effects but no abnormal mixing, disruption or dislocation of compartments. It is predicted that Xenopus eggs fertilized and allowed to develop in space will retain normal cytoplasmic density compartments, establish primary axes and undergo normal morphogenesis in space. Their dorsal/ventral polarity may not, however be determined by the sperm entrance site (as is the case for 1g eggs).

Animals↗
PubMed1999

An experimental study and mathematical simulation of adrenergic control of hindlimb vessels in rats after 3-week tail suspension.

Adrenoreactivity of rat hindlimb vessels was studied in experiments with constant-pressure saline perfusion. An original mathematical model was applied to evaluate the mechanism of changes in vascular tone regulation. A 3-week suspension resulted in decreased responses to sympathetic nerve stimulation, as well as to exogenous noradrenaline, the latter effect being registered when the pressure level was close to normal. Mathematical simulation indicated that long-term suspension induces both structural and functional changes in the vascular bed of the hind limbs, one of which is a disorder in the myogenic mechanisms of vascular tone regulation. In suspended rats, suppression of the myogenic response can be one of the reasons for decreased vessel reactivity to constrictor stimuli and, consequently, for disturbances in blood flow regulation in skeletal muscles of the hind limbs.

Animals↗
PubMedDate not supplied

Evaluation of bleomycin-induced chromosome aberrations under simulated microgravity conditions in human lymphocytes using "FISH" techniques.

In the present investigation we report the effects of simulated microgravity conditions (clinostat) on the induction of chromosomal aberrations in human lymphocytes in vitro by (R) Bleomycin. Chromosomal aberrations have been analysed by means of fluorescent in situ hybridisation (FISH) and chromosome-specific composite DNA probes (chromosome painting). The results obtained show that, under simulated microgravity conditions, the levels of both symmetrical and asymmetrical (dicentrics, rings), the number of cells bearing "complex" aberrations and hence the total numbers of aberrations were significantly elevated at any of the dose-levels assayed, compared to the parallel treatments performed as 1g control ("ground"). Furthermore, the ratio symmetrical:asymmetrical translocations was markedly elevated under simulated microgravity conditions, compared to the findings usually observed under "normal" 1g conditions. On these bases, we are much inclined to believe that simulated microgravity, rather than limiting the resealing of DNA double strand breaks (DSB's) induced by genotoxic agents is influencing in terms of enhancement the misrejoining of DSB's which is actually responsible for the fixation of the original lesions to DNA into chromosomal aberrations. In addition, the possible different misrepair processes leading to the formation of symmetrical and asymmetrical translocations might be differentially influenced by microgravity being the symmetrical translocations significantly more represented.

Antimetabolites, Antineoplastic↗
PubMed1995

Mineral distribution in rat skeletons after exposure to a microgravity model.

Exposure to space flight models induces changes in the distribution of bone mineral in the human skeleton that has the features of a gravitational gradient. Regional bone mineral measurements with dual energy x-ray absorptiometry (DEXA) in male adults exposed to head-down tilt bed rest for 30 days show non-significant decrements in the pelvis and legs with 10% increases in the head region. Horizontal bed rest for 17 weeks reveals losses of bone mineral ranging from 2.2 to 10.4% from the lumbar spine to the calcaneus and an increase of 3.4% in the skull. Investigation of this phenomena would be most definitively carried out in an animal model. One candidate is the flight simulation model in the rat which removes body weight from the hind limbs and induces a cephalad fluid shift by suspending the animal by the tail. Weanling rats exposed to this model showed bone mineral to be lower in the hind limbs and higher in the skull after 3 weeks. These findings are similar in older 200 g animals after 2 weeks tail suspension. The purpose of this study was to determine the effect of age on the distribution of skeletal mineral in this model.

Aging↗
PubMed2006

Inhibition of active lymph pump by simulated microgravity in rats.

During spaceflight the normal head-to-foot hydrostatic pressure gradients are eliminated and body fluids shift toward the head, resulting in a diminished fluid volume in the legs and an increased fluid volume in the head, neck, and upper extremities. Lymphatic function is important in the maintenance of normal tissue fluid volume, but it is not clear how microgravity influences lymphatic pumping. We performed a detailed evaluation of the influence of simulated microgravity on lymphatic diameter, wall thickness, elastance, tone, and other measures of phasic contractility in isolated lymphatics. Head-down tail suspension (HDT) rats were used to simulate the effects of microgravity. Animals were exposed to HDT for 2 wk, after which data were collected and compared with the control non-HDT group. Lymphatics from four regional lymphatic beds (thoracic duct, cervical, mesenteric, and femoral lymphatics) were isolated, cannulated, and pressurized. Input and output pressures were adjusted to apply a range of transmural pressures and flows to the lymphatics. Simulated microgravity caused a potent inhibition of pressure/stretch-stimulated pumping in all four groups of lymphatics. The greatest inhibition was found in cervical lymphatics. These findings presumably are correlated to the cephalic fluid shifts that occur in HDT rats as well as those observed during spaceflight. Flow-dependent pump inhibition was increased after HDT, especially in the thoracic duct. Mesenteric lymphatics were less strongly influenced by HDT, which may support the idea that lymph hydrodynamic conditions in the mesenteric lymphatic during HDT are not dramatically altered.

Animals↗
PubMed1999

Microgravity cultivation of cells and tissues.

In vitro studies of cells and tissues in microgravity, either simulated by cultivation conditions on earth or actual, during spaceflight, are expected to help identify mechanisms underlying gravity sensing and transduction in biological organisms. In this paper, we review rotating bioreactor studies of engineered skeletal and cardiovascular tissues carried out in unit gravity, a four month long cartilage tissue engineering study carried out aboard the Mir Space Station, and the ongoing laboratory development and testing of a system for cell and tissue cultivation aboard the International Space Station.

Animals↗
PubMed2000

Can daily centrifugation prevent the haematocrit increase elicited by 6-degree, head-down tilt?

A measure to counteract the effects of low or zero gravity is required for long-term space flight, such as the manned Mars mission scheduled by the National Aeronautics and Space administration (NASA) for 2014. We conducted a series of centrifugation experiments with humans, using a short-arm centrifuge (radius 1.8 m, made by First Medical Co., Tokyo, Japan). We employed 6-degree, head-down tilt (HDT) for 4 days to simulate space flight. Ten healthy male volunteers underwent 4-day HDT and a 2-G daily centrifuge load for 60 min in the +Gz direction and measurements, such as haematocrit, 24-h urine volume, body weight and electrocardiogram (ECG) were made. There was no significant increase in the haematocrit during the HDT period, although our previous studies had shown a significant increase during HDT. A 60-min daily load of +2 Gz appears to be effective in reversing the haematocrit increase due to 4-day HDT.

Adult↗
PubMedDate not supplied

Impact of simulated microgravity on cell cycle control and cytokine release by U937 cells.

Previous experiments from flight- and ground-based model systems indicate unexpected alterations of human leukocytes, leading to growth retardation and depression of mitogenic activation. The response of myelomonocytic U937 cells to simulated microgravity was therefore investigated. To this purpose, U937 cells were cultured in the NASA-developed bioreactor Rotating Wall Vessel (RWV) as a device to simulate microgravity on earth. No apoptosis was detected, in part because of the up-regulation of hsp70. In agreement with results obtained in space-flown U937 cells, the cells grew more slowly in the RWV than under normal conditions and this correlated with the down-modulation of cdc25B. Marked alterations of the cytokine secretion profile and, in particular, of inflammatory chemokines, as well as a decrease of the proteasome activity, were also observed in response to microgravity.

Actins↗