Research Containing: Space Flight

Some of the aspects of comparative analysis of the hemodynamic reactions to LBNP in cosmonauts of different age groups

by cfynanon 9 June 2015in Biology & Biotechnology No comment

This was the first study of age-related differences of the cardiovascular system functioning and reactions to the LBNP test in career cosmonauts. Results of 174 LBNP tests performed within the standard medical monitoring program using Gamma-01 (orbital station Mir) and Gamma-lM (ISS) were subjected to comparative analysis. Thirty eight cosmonauts–members of 25 long-duration Mir and ISS missions were divided into two age groups, i.e. 30-39 y.o. (mean 36 & 0.7, 39% of all subjects) and 40-55 y.o. (mean 46 & 0.8, 61% of all subjects). The testing was performed before launch and in flight (typically on FD-120). Age-specifc changes in the hemodynamic status were recorded in resting cosmonauts pre-flight and in spaceflight microgravity; relative dynamics of the CV parameters in response to standing posture imitation was on one and the same patterns and yet demonstrated unequal intensity before and in flight. Test results implicate that analysis and interpretation of cosmonauts' medical monitoring data should take into account individual age, which is of particular practical importance when dealing with the LBNP test data obtained in different periods of space flight.

Dependence of the circulation system functioning on cosmonaut age according to the results of physical loading tests on a veloergometer

by cfynanon 9 June 2015in Biology & Biotechnology No comment

Age-related hemodynamic reactions to the standard incremental physical loading tests on a cycle ergometer were assessed in cosmonauts before and during extended space missions. Analysis of the data from 353 tests performed with 63 cosmonauts differentiated into three age groups (30–39, 40–49, and 50–55 years old) showed changes in adaptive-compensatory hemodynamic responses to microgravity and physical loading depending on age. The consistent gradual degradation of the heart chronotropic function with age can be interpreted as a symptom of declining cardiovascular reactivity. In orbit, the cardiac output volume depended mainly on heart rate and blood pressure (i.e., vascular tone).

The effects of space flight and microgravity on the growth and differentiation of PICM-19 pig liver stem cells

by cfynanon 9 June 2015in Biology & Biotechnology No comment

The PICM-19 pig liver stem cell line was cultured in space for nearly 16 d on the STS-126 mission to assess the effects of spaceflight on the liver's parenchymal cells-PICM-19 cells to differentiate into either monolayers of fetal hepatocytes or 3-dimensional bile ductules (cholangiocytes). Semi-quantitative data included light microscopic assessments of final cell density, cell morphology, and response to glucagon stimulation and electron microscopic assessment of the cells' ultrastructural features and cell-to-cell connections and physical relationships. Quantitative assessments included assays of hepatocyte detoxification functions, i.e., inducible P450 activities and urea production and quantitation of the mRNA levels of several liver-related genes. Three post-passage age groups were included: 4-d-, 10-d-, and 14-d-old cultures. In comparing flight vs. ground-control cultures 17 h after the space shuttle's return to earth, no differences were found between the cultures with the exception being that some genes were differentially expressed. By light microscopy both young and older cultures, flight and ground, had grown and differentiated normally in the Opticell culture vessels. The PICM-19 cells had grown to approximately 75% confluency, had few signs of apoptosis or necrosis, and had either differentiated into monolayer patches of hepatocytes with biliary canaliculi visible between the cells or into 3-dimensional bile ductules with well-defined lumens. Ultrastructural features between flight and ground were similar with the PICM-19 cells displaying numerous mitochondria, Golgi apparatus, smooth and rough endoplasmic reticulum, vesicular bodies, and occasional lipid vacuoles. Cell-to-cell arrangements were typical in both flight and ground-control samples; biliary canaliculi were well-formed between the PICM-19 cells, and the cells were sandwiched between the STO feeder cells. PICM-19 cells displayed inducible P450 activities. They produced urea in a glutamine-free medium and produced more urea in response to ammonia. The experiment's aim to gather preliminary data on the PICM-19 cell line's suitability as an in vitro model for assessments of liver function in microgravity was demonstrated, and differences between flight and ground-control cultures were minor.

Microgravity during spaceflight directly affects in vitro osteoclastogenesis and bone resorption

by cfynanon 9 June 2015in Biology & Biotechnology No comment

During space flight, severe losses of bone mass are observed. Both bone formation and resorption are probably involved, but their relative importance remains unclear. The purpose of this research is to understand the role of osteoclasts and their precursors in microgravity-induced bone loss. Three experiments on isolated osteoclasts (OCs) and on their precursors, OSTEO, OCLAST, and PITS, were launched in the FOTON-M3 mission. The OSTEO experiment was conducted for 10 d in microgravity within bioreactors with a perfusion system, where the differentiation of precursors, cultured on a synthetic 3-dimensional bonelike biomaterial, skelite, toward mature OCs was assessed. In OCLAST and in PITS experiments, differentiated OCs were cultured on devitalized bovine bone slices for 4 d in microgravity. All of the experiments were replicated on ground in the same bioreactors, and OCLAST also had an inflight centrifuge as a control. Gene expression in microgravity, compared with ground controls, demonstrated a severalfold increase in genes involved in osteoclast maturation and activity. Increased bone resorption, proved by an increased amount of collagen telopeptides released VS ground and centrifuge control, was also found. These results indicate for the first time osteoclasts and their precursors as direct targets for microgravity and mechanical forces.

Fertilization of sea urchin eggs and sperm motility are negatively impacted under low hypergravitational forces significant to space flight

by cfynanon 9 June 2015in Biology & Biotechnology No comment

Sperm and other flagellates swim faster in microgravity (microG) than in 1 G, raising the question of whether fertilization is altered under conditions of space travel. Such alterations have implications for reproduction of plant and animal food and for long-term space habitation by man. We previously demonstrated that microG accelerates protein phosphorylation during initiation of sperm motility but delays the sperm response to the egg chemotactic factor, speract. Thus sperm are sensitive to changes in gravitational force. New experiments using the NiZeMi centrifugal microscope examined whether low hypergravity (hyperG) causes effects opposite to microG on sperm motility, signal transduction, and fertilization. Sperm % motility and straight-line velocity were significantly inhibited by as little as 1.3 G. The phosphorylation states of FP130, an axonemal phosphoprotein, and FP160, a cAMP-dependent salt-extractable flagellar protein, both coupled to motility activation, showed a more rapid decline in hyperG. Most critically, hyperG caused an approximately 50% reduction in both the rate of sperm-egg binding and fertilization. The similar extent of inhibition of both fertilization parameters in hyperG suggests that the primary effect is on sperm rather than eggs. These results not only support our earlier microG data demonstrating that sperm are sensitive to small changes in gravitational forces but more importantly now show that this sensitivity affects the ability of sperm to fertilize eggs. Thus, more detailed studies on the impact of space flight on development should include studies of sperm function and fertilization.

Bone turnover in wild type and pleiotrophin-transgenic mice housed for three months in the International Space Station (ISS)

by cfynanon 9 June 2015in Biology & Biotechnology No comment

Bone is a complex dynamic tissue undergoing a continuous remodeling process. Gravity is a physical force playing a role in the remodeling and contributing to the maintenance of bone integrity. This article reports an investigation on the alterations of the bone microarchitecture that occurred in wild type (Wt) and pleiotrophin-transgenic (PTN-Tg) mice exposed to a near-zero gravity on the International Space Station (ISS) during the Mice Drawer System (MDS) mission, to date, the longest mice permanence (91 days) in space. The transgenic mouse strain over-expressing pleiotrophin (PTN) in bone was selected because of the PTN positive effects on bone turnover. Wt and PTN-Tg control animals were maintained on Earth either in a MDS payload or in a standard vivarium cage. This study revealed a bone loss during spaceflight in the weight-bearing bones of both strains. For both Tg and Wt a decrease of the trabecular number as well as an increase of the mean trabecular separation was observed after flight, whereas trabecular thickness did not show any significant change. Non weight-bearing bones were not affected. The PTN-Tg mice exposed to normal gravity presented a poorer trabecular organization than Wt mice, but interestingly, the expression of the PTN transgene during the flight resulted in some protection against microgravity's negative effects. Moreover, osteocytes of the Wt mice, but not of Tg mice, acquired a round shape, thus showing for the first time osteocyte space-related morphological alterations in vivo. The analysis of specific bone formation and resorption marker expression suggested that the microgravity-induced bone loss was due to both an increased bone resorption and a decreased bone deposition. Apparently, the PTN transgene protection was the result of a higher osteoblast activity in the flight mice.

Spaceflight-induced alterations in cerebral artery vasoconstrictor, mechanical, and structural properties: implications for elevated cerebral perfusion and intracranial pressure

by cfynanon 9 June 2015in Biology & Biotechnology No comment

Evidence indicates that cerebral blood flow is both increased and diminished in astronauts on return to Earth. Data from ground-based animal models simulating the effects of microgravity have shown that decrements in cerebral perfusion are associated with enhanced vasoconstriction and structural remodeling of cerebral arteries. Based on these results, the purpose of this study was to test the hypothesis that 13 d of spaceflight [Space Transportation System (STS)-135 shuttle mission] enhances myogenic vasoconstriction, increases medial wall thickness, and elicits no change in the mechanical properties of mouse cerebral arteries. Basilar and posterior communicating arteries (PCAs) were isolated from 9-wk-old female C57BL/6 mice for in vitro vascular and mechanical testing. Contrary to that hypothesized, myogenic vasoconstrictor responses were lower and vascular distensibility greater in arteries from spaceflight group (SF) mice (n=7) relative to ground-based control group (GC) mice (n=12). Basilar artery maximal diameter was greater in SF mice (SF: 236+/-9 mum and GC: 215+/-5 mum) with no difference in medial wall thickness (SF: 12.4+/-1.6 mum; GC: 12.2+/-1.2 mum). Stiffness of the PCA, as characterized via nanoindentation, was lower in SF mice (SF: 3.4+/-0.3 N/m; GC: 5.4+/-0.8 N/m). Collectively, spaceflight-induced reductions in myogenic vasoconstriction and stiffness and increases in maximal diameter of cerebral arteries signify that elevations in brain blood flow may occur during spaceflight. Such changes in cerebral vascular control of perfusion could contribute to increases in intracranial pressure and an associated impairment of visual acuity in astronauts during spaceflight.

Toll mediated infection response is altered by gravity and spaceflight in Drosophila

by cfynanon 9 June 2015in Biology & Biotechnology No comment

Space travel presents unlimited opportunities for exploration and discovery, but requires better understanding of the biological consequences of long-term exposure to spaceflight. Immune function in particular is relevant for space travel. Human immune responses are weakened in space, with increased vulnerability to opportunistic infections and immune-related conditions. In addition, microorganisms can become more virulent in space, causing further challenges to health. To understand these issues better and to contribute to design of effective countermeasures, we used the Drosophila model of innate immunity to study immune responses in both hypergravity and spaceflight. Focusing on infections mediated through the conserved Toll and Imd signaling pathways, we found that hypergravity improves resistance to Toll-mediated fungal infections except in a known gravitaxis mutant of the yuri gagarin gene. These results led to the first spaceflight project on Drosophila immunity, in which flies that developed to adulthood in microgravity were assessed for immune responses by transcription profiling on return to Earth. Spaceflight alone altered transcription, producing activation of the heat shock stress system. Space flies subsequently infected by fungus failed to activate the Toll pathway. In contrast, bacterial infection produced normal activation of the Imd pathway. We speculate on possible linkage between functional Toll signaling and the heat shock chaperone system. Our major findings are that hypergravity and spaceflight have opposing effects, and that spaceflight produces stress-related transcriptional responses and results in a specific inability to mount a Toll-mediated infection response.

Biomedical analysis of rat body hair after hindlimb suspension for 14 days

by cfynanon 9 June 2015in Biology & Biotechnology No comment

The levels of 26 minerals in rat body hair were analyzed in control and hindlimb-suspended Wistar Hannover rats (n=5 each). We quantified the levels of 22 minerals in this experiment. However, we were unable to measure the levels of 4 minerals (Be, V, Cd, and Hg) quantitatively because they were below the limit of detection. Of the 22 quantified, the levels of 19 minerals were not significantly different between control and hindlimb-suspended groups. The levels of 3 minerals (Pb, Cr, and Al) tended to be higher in the hindlimb-suspended group than in the control group; however, this difference was not significant. The concentrations of 3 other minerals (I, K, and Mg) were significantly different between the 2 groups. The iodine (I) level was 58.2% higher in the hindlimb-suspended group than in the control group (P<0.05). Potassium (K) and magnesium (Mg) levels were 55.2% and 20.4% lower, respectively, in the experimental group (0.05 in both cases). These results indicate that a physiological change in mineral metabolism resulting from physical or mental stress, such as hindlimb suspension, is reflected in body hair. The Japan Aerospace Exploration Agency (JAXA) has initiated a human research study to investigate the effects of long-term space flight on gene expression and mineral metabolism by analyzing hair samples of astronauts who stayed in the International Space Station (ISS) for 6 months. We believe that hindlimb suspension for 14 days can simulate the effects of an extremely severe environment, such as space flight, because the hindlimb suspension model elicits a rapid physiological change in skeletal muscle, bone, and fluid shift even in the short term. These results also suggest that we can detect various effects on the body by analyzing the human scalp hair shaft.

Amphibian development in the virtual absence of gravity

by cfynanon 9 June 2015in Biology & Biotechnology No comment

To test whether gravity is required for normal amphibian development, Xenopus laevis females were induced to ovulate aboard the orbiting Space Shuttle. Eggs were fertilized in vitro, and although early embryonic stages showed some abnormalities, the embryos were able to regulate and produce nearly normal larvae. These results demonstrate that a vertebrate can ovulate in the virtual absence of gravity and that the eggs can develop to a free-living stage.

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Research Containing: Space Flight

Some of the aspects of comparative analysis of the hemodynamic reactions to LBNP in cosmonauts of different age groups

The effects of space flight and microgravity on the growth and differentiation of PICM-19 pig liver stem cells

Microgravity during spaceflight directly affects in vitro osteoclastogenesis and bone resorption

Fertilization of sea urchin eggs and sperm motility are negatively impacted under low hypergravitational forces significant to space flight

Bone turnover in wild type and pleiotrophin-transgenic mice housed for three months in the International Space Station (ISS)

Spaceflight-induced alterations in cerebral artery vasoconstrictor, mechanical, and structural properties: implications for elevated cerebral perfusion and intracranial pressure

Toll mediated infection response is altered by gravity and spaceflight in Drosophila

Biomedical analysis of rat body hair after hindlimb suspension for 14 days

Amphibian development in the virtual absence of gravity