Space Microgravity Research Articles

Loss of Parafollicular Cells during Gravitational Changes (Microgravity, Hypergravity) and the Secret Effect of Pleiotrophin

It is generally known that bone loss is one of the most important complications for astronauts who are exposed to long-term microgravity in space. Changes in blood flow, systemic hormones, and locally produced factors were indicated as important elements contributing to the response of osteoblastic cells to loading, but research in this field still has many questions. Here, the possible biological involvement of thyroid C cells is being investigated. The paper is a comparison between a case of a wild type single mouse and a over-expressing pleiotrophin single mouse exposed to hypogravity conditions during the first animal experiment of long stay in International Space Station (91 days) and three similar mice exposed to hypergravity (2Gs) conditions. We provide evidence that both microgravity and hypergravity induce similar loss of C cells with reduction of calcitonin production. Pleiotrophin over-expression result in some protection against negative effects of gravity change. Potential implication of the gravity mechanic forces in the regulation of bone homeostasis via thyroid equilibrium is discussed.

Ground-Based Facilities for Simulation of Microgravity: Organism-Specific Recommendations for Their Use, and Recommended Terminology

Research in microgravity is indispensable to disclose the impact of gravity on biological processes and organisms. However, research in the near-Earth orbit is severely constrained by the limited number of flight opportunities. Ground-based simulators of microgravity are valuable tools for preparing spaceflight experiments, but they also facilitate stand-alone studies and thus provide additional and cost-efficient platforms for gravitational research. The various microgravity simulators that are frequently used by gravitational biologists are based on different physical principles. This comparative study gives an overview of the most frequently used microgravity simulators and demonstrates their individual capacities and limitations. The range of applicability of the various ground-based microgravity simulators for biological specimens was carefully evaluated by using organisms that have been studied extensively under the conditions of real microgravity in space. In addition, current heterogeneous terminology is discussed critically, and recommendations are given for appropriate selection of adequate simulators and consistent use of nomenclature.

Infection Prevention and Control During Prolonged Human Space Travel

Prolonged human spaceflight to another planet or an asteroid will introduce unique challenges of mitigating the risk of infection. During space travel, exposure to microgravity, radiation, and stress alter human immunoregulatory responses, which can in turn impact an astronaut's ability to prevent acquisition of infectious agents or reactivation of latent infection. In addition, microgravity affects virulence, growth kinetics, and biofilm formation of potential microbial pathogens. These interactions occur in a confined space in microgravity, providing ample opportunity for heavy microbial contamination of the environment. In addition, there is the persistence of aerosolized, microbe-containing particles. Any mission involving prolonged human spaceflight must be carefully planned to minimize vulnerabilities and maximize the likelihood of success.

Synergistic Effects of Incubation in Rotating Bioreactors and Cumulative Low Dose 60Co γ-ray Irradiation on Human Immortal Lymphoblastoid Cells

The complex space environments can influence cell structure and function. The research results on space biology have shown that the major mutagenic factors in space are microgravity and ionizing radiation. In addition, possible synergistic effects of radiation and microgravity on human cells are not well understood. In this study, human immortal lymphoblastoid cells were established from human peripheral blood lymphocytes and the cells were treated with low dose (0.1, 0.15 and 0.2 Gy) cumulative 60Co γ-irradiation and simulated weightlessness [obtained by culturing cells in the Rotating Cell Culture System (RCCS)]. The commonly used indexes of cell damage such as micronucleus rate, cell cycle and mitotic index were studied. Previous work has proved that Gadd45 (growth arrest and DNA-damage-inducible protein 45) gene increases with a dose-effect relationship, and will possibly be a new biological dosimeter to show irradiation damage. So Gadd45 expression is also detected in this study. The micronucleus rate and the expression of Gadd45α gene increased with irradiation dose and were much higher after incubation in the rotating bioreactor than that in the static irradiation group, while the cell proliferation after incubation in the rotating bioreactor decreased at the same time. These results indicate synergetic effects of simulated weightlessness and low dose irradiation in human cells. The cell damage inflicted by γ-irradiation increased under simulated weightlessness. Our results suggest that during medium- and long-term flight, the human body can be damaged by cumulative low dose radiation, and the damage will even be increased by microgravity in space.

High performance satellite dynamics and control simulation for multi-purpose application

In a collaborative research effort between the German Aerospace Center and the Center of Applied Space Technology and Microgravity, University of Bremen, the high performance satellite dynamics simulator (HPS) is being developed. The simulator is assembled as a library of simulation modules, functions and utilities, thematically grouped into sub-libraries. The single sub-libraries contain modules for dynamics, environmental models for the calculation of gravity, atmosphere, magnetic field, solar pressure, eclipse, ephemerides, and preprocessing tools for the pre-calculation of surface forces and torques. A transformation library including date and coordinate transformations and several mathematical functions are also provided. Furthermore, a basic set of simple actuator and sensor models is being developed. All modules can be used in MiL (model-in-the-loop) and SiL (software-in-the-loop) applications, and several modules are ready for use in HiL (hardware-in-the-loop) environments. The simulator project has emerged from the desire to avoid re-development, benefit from tools that are already in use and have been validated for recurring problem statements, and build up upon existing knowledge for new challenges. This paper describes the simulator library content in detail and exemplifies application for selected use cases.

Regulation of eIF2α phosphorylation in hindlimb-unloaded and STS-135 space-flown mice

Various environmental stresses elevate the phosphorylation level of eukaryotic translation initiation factor 2 alpha (eIF2α) and induce transcriptional activation of a set of stress responsive genes such as activating transcription factors 3 and 6 (ATF3 and ATF6), CCAAT/enhancer-binding protein homologous protein (CHOP), and Xbp1 (X-box binding protein 1). These stress sources include radiation, oxidation, and stress to the endoplasmic reticulum, and it is recently reported that unloading by hindlimb unloading is such a stress source. No studies, however, have examined the phosphorylation level of eIF2α (eIF2α-p) using skeletal samples that have experienced microgravity in space. In this study we addressed a question: Does a mouse tibia flown in space show altered levels of eIF2α-p? To address this question, we obtained STS-135 flown samples that were harvested 4–7h after landing. The tibia and femur isolated from hindlimb unloaded mice were employed as non-flight controls. The effects of loading were also investigated in non- flight controls. Results indicate that the level of eIF2α-p of the non-flight controls was elevated during hindlimb unloading and reduced after being released from unloading. Second, the eIF2α-p level of space-flown samples was decreased, and mechanical loading to the tibia caused the reduction of the eIF2α-p level. Third, the mRNA levels of ATF3, ATF6, and CHOP were lowered in space-flown samples as well as in the non-flight samples 4–7h after being released from unloading. Collectively, the results herein indicated that a release from hindlimb unloading and a return to normal weight environment from space provided a suppressive effect to eIF2α-linked stress responses and that a period of 2–4h is sufficient to induce this suppressive outcome.

Introduction to aerospace medicine

Recent reports show that over 2 billion people are travelling via air every year, and the number of countries involved in space exploration is growing. Aerospace medicine, one of the specialty areas in preventive medicine, focuses on the clinical care, research, and operational support of the health, safety, and performance of crewmembers and passengers of air and space vehicles. Flight surgeons are military medical officers who play an important role in these tasks. The civilian equivalent of the flight surgeon is the aviation medical examiner (AME). Among the challenges that we encounter at high altitudes are a change in pressure, noise, spa-tial disorientation, and acceleration. We should also overcome microgravity and radiation in space. The common in-flight medical emergencies are abdominal pain, diarrhea, chest pain, coll-apse, asthma, diabetes, and allergic reactions. There is only one aerospace medical institute, the Aerospace Medical Center, in the Republic of Korea. The Aerospace Medical Association of Korea, established in 1989, continues to grow. In the near future, aerospace medicine will be an important part of preventive medicine in the Republic of Korea.

Fault-tolerant sliding mode control for the interferometer system under the unanticipated faults

The important precision control of the interferometer suffers from various faults in the complex space environment. However, the studies for the fault-tolerant control (FTC) in the interferometer are few. This paper first presents an active FTC scheme for the interferometer system in the presence of micro-gravity, micro-vibration and thermal disturbances in space. Kinds of unanticipated faults are quickly detected by the residue detection. Neural network is used to estimate the unanticipated faults online. The sliding mode control with a reaching law is designed for the normal control with a fixed upper bound and for the FTC with an adaptive upper bound adjusted by the neural network to recover the system performance under the faults. Stability analysis is performed by the Lyapunov theorem. Numerical simulations are used to verify the significant improved performance of the proposed FTC scheme.

Expression of p53-Regulated Proteins in Human Cultured Lymphoblastoid TSCE5 and WTK1 Cell Lines during Spaceflight

The aim of this study was to determine the biological effects of space radiations, microgravity, and the interaction of them on the expression of p53-regulated proteins. Space experiments were performed with two human cultured lymphoblastoid cell lines: one line (TSCE5) bears a wild-type p53 gene status, and another line (WTK1) bears a mutated p53 gene status. Under 1 gravity or microgravity conditions, the cells were grown in the cell biology experimental facility (CBEF) of the International Space Station for 8 days without experiencing the stress during launching and landing because the cells were frozen during these periods. Ground control samples were simultaneously cultured for 8 days in the CBEF on the ground for 8 days. After spaceflight, protein expression was analyzed using a Panorama(TM) Ab MicroArray protein chips. It was found that p53-dependent up-regulated proteins in response to space radiations and space environment were MeCP2 (methyl CpG binding protein 2), and Notch1 (Notch homolog 1), respectively. On the other hand, p53-dependent down-regulated proteins were TGF-β, TWEAKR (tumor necrosis factor-like weak inducer of apoptosis receptor), phosho-Pyk2 (Proline-rich tyrosine kinase 2), and 14-3-3θ/τ which were affected by microgravity, and DR4 (death receptor 4), PRMT1 (protein arginine methyltransferase 1) and ROCK-2 (Rho-associated, coiled-coil containing protein kinase 2) in response to space radiations. ROCK-2 was also suppressed in response to the space environment. The data provides the p53-dependent regulated proteins by exposure to space radiations and/or microgravity during spaceflight. Our expression data revealed proteins that might help to advance the basic space radiation biology.

Al2O3 nanoparticle reinforced Fe-based alloys synthesized by thermite reaction

It is very difficult to manufacture oxide nanoparticle strengthened alloys through the conventional casting in the gravity field or even in the space microgravity environment. A thermite reaction process was used to produce molten metal that was then solidified in a graphite mold in super gravity field caused by centrifugal force; we were able to obtain Al2O3 nanoparticle reinforced Fe-based alloys. The formation of Al2O3 nanoparticles was related to the addition of TiO2 xerogel to the thermite mixture, and their uniform distribution in the alloy can be explained by their assembly in (Ni, Fe)Al intermetallics during solidification owing to the low interfacial energy between them.

Effect of Simulated Microgravity on Salivary and Serum Oxidants, Antioxidants, and Periodontal Status

Microgravity is associated with an increase in peroxidative damage. The effect is more pronounced after long-duration space flights and can even last for several weeks after landing. The objective of the study is to determine the influence of simulated microgravity on the periodontal status and salivary and serum oxidant/antioxidant status of the body in simulated microgravity (-6° head-down-tilt [HDT) bed rest). Twenty healthy male volunteers were studied before and after 60 days of simulated microgravity (-6° HDT bed rest). We measured salivary and serum oxidative markers, such as malondialdehyde (MDA), 8-oxo-7,8 dihydro-2 deoxyguanosine (8-OHdG), and vitamins C and E, and clinical periodontal parameters (probing depth [PD] and clinical attachment level [CAL]). Serum and salivary vitamin C and E concentrations were significantly decreased, whereas MDA and 8-OHdG levels were significantly increased after 60 days of simulated microgravity. Serum and salivary markers showed a strong and significant correlation. CAL and PD were higher but not statistically significant in simulated microgravity. This study suggests that oxidative stress in the microgravity environment was increased but did not significantly influence periodontal parameters after 2 months. Also, this study indicates the possibility that the findings may have a broader clinical relevance to patients on bed rest or who are physically inactive. Studies on larger patient samples and follow-up for a longer time are required to verify the relationship between antioxidant status in the space microgravity condition and periodontal health.

Effects of Simulated Microgravity on Expression Profile of MicroRNA in Human Lymphoblastoid Cells

This study explores the changes in expression of microRNA (miRNA) and related genes under simulated microgravity conditions. In comparison with static 1 × g, microgravity has been shown to alter global gene expression patterns and protein levels in cultured cells or animals. miRNA has recently emerged as an important regulator of gene expression, possibly regulating as many as one-third of all human genes. However, very little is known about the effect of altered gravity on miRNA expression. To test the hypothesis that the miRNA expression profile would be altered in zero gravity resulting in altered regulation of gene expression leading to metabolic or functional changes in cells, we cultured TK6 human lymphoblastoid cells in a high aspect ratio vessel (bioreactor) for 72 h either in the rotating condition to model microgravity in space or in the static condition as a control. Expression of several miRNAs was changed significantly in the simulated microgravity condition including miR-150, miR-34a, miR-423-5p, miR-22, miR-141, miR-618, and miR-222. To confirm whether this altered miRNA expression correlates with gene expression and functional changes of the cells, we performed DNA microarray and validated the related genes using quantitative RT-PCR. Expression of several transcription factors including EGR2, ETS1, and c-REL was altered in simulated microgravity conditions. Taken together, the results reported here indicate that simulated microgravity alters the expression of miRNAs and genes in TK6 cells. To our knowledge, this study is the first to report the effects of simulated microgravity on the expression of miRNA and related genes.

Effect of microgravity on primordial germ cells (PGCs) in silk chicken offspring ( Gallus gallus domesticus)

Primordial germ cells (PGCs), precursors of germline cells, display a variety of antigens during their migration to target gonads. Here, we used silk chicken offspring ( Gallus gallus domesticus) embryos subjected to space microgravity to investigate the influence of microgravity on PGCs. The ShenZhou-3 unmanned spaceship carried nine fertilized silk chicken eggs, named the flight group, returned to Earth after 7 days space flight. And the control group has the same clan with the flight group. PGCs from flight and control group silk chicken offspring embryos were examined during migration by using two antibodies (2C9 and anti-SSEA-1), in combination with the horseradish peroxidase detection system, and using periodic acid-Schiff’s solution (PAS) reaction. After incubation for about 30 h, SSEA-1 and 2C9 positive cells were detected in the germinal crescent of flight and control group silk chicken offspring embryos. After incubation of eggs for 2–2.5 days, SSEA-1 and 2C9 positive cells were detected in embryonic blood vessels of flight and control group silk chicken offspring embryos. After incubation of eggs for 5.5 days, PGCs in the dorsal mesentery and gonad could also be identified in flight and control group silk chicken offspring embryos by using SSEA-1 and 2C9 antibodies. Based on location and PAS staining, these cells were identified as PGCs. Meanwhile, at the stage of PGCs migration and then becoming established in the germinal ridges, no difference in SSEA-1 or 2C9 staining was detected between female and male PGCs in flight and control group silk chicken offspring embryos. Although there were differences in the profiles of PGC concentration between male and female embryos during the special circulating stage, changing profile of PGCs concentration was similar in same sex between flight and control group offspring embryos. We concluded that there is little effect on PGCs in offspring embryos of microgravity-treated chicken and that PGC development appears to be normal.

Responses of Haloarchaea to Simulated Microgravity

Various effects of microgravity on prokaryotes have been recognized in recent years, with the focus on studies of pathogenic bacteria. No archaea have been investigated yet with respect to their responses to microgravity. For exposure experiments on spacecrafts or on the International Space Station, halophilic archaea (haloarchaea) are usually embedded in halite, where they accumulate in fluid inclusions. In a liquid environment, these cells will experience microgravity in space, which might influence their viability and survival. Two haloarchaeal strains, Haloferax mediterranei and Halococcus dombrowskii, were grown in simulated microgravity (SMG) with the rotary cell culture system (RCCS, Synthecon). Initially, salt precipitation and detachment of the porous aeration membranes in the RCCS were observed, but they were avoided in the remainder of the experiment by using disposable instead of reusable vessels. Several effects were detected, which were ascribed to growth in SMG: Hfx. mediterranei's resistance to the antibiotics bacitracin, erythromycin, and rifampicin increased markedly; differences in pigmentation and whole cell protein composition (proteome) of both strains were noted; cell aggregation of Hcc. dombrowskii was notably reduced. The results suggest profound effects of SMG on haloarchaeal physiology and cellular processes, some of which were easily observable and measurable. This is the first report of archaeal responses to SMG. The molecular mechanisms of the effects induced by SMG on prokaryotes are largely unknown; haloarchaea could be used as nonpathogenic model systems for their elucidation and in addition could provide information about survival during lithopanspermia (interplanetary transport of microbes inside meteorites).

Sympathetic neural influence on bone metabolism in microgravity (Review)

Bone loss is one of the most important complications for astronauts who are exposed to long-term microgravity in space and also for bedridden elderly people. Recent studies have indicated that the sympathetic nervous system plays a role in bone metabolism. This paper reviews findings concerning with sympathetic influences on bone metabolism to hypothesize the mechanism how sympathetic neural functions are related to bone loss in microgravity. Animal studies have suggested that leptin stimulates hypothalamus increasing sympathetic outflow to bone and enhances bone resorption through noradrenaline and β-adrenoreceptors in bone. In humans, even though there have been some controversial findings, use of β-adrenoblockers has been reported to be beneficial for prevention of osteoporosis and bone fracture. On the other hand, microneurographically-recorded sympathetic nerve activity was enhanced by exposure to microgravity in space as well as dry immersion or long-term bed rest to simulate microgravity. The same sympathetic activity became higher in elderly people whose bone mass becomes generally reduced. Our recent findings indicated a significant correlation between muscle sympathetic nerve activity and urinary deoxypyridinoline as a specific marker measuring bone resorption. Based on these findings we would like to propose a following hypothesis concerning the sympathetic involvement in the mechanism of bone loss in microgravity: An exposure to prolonged microgravity may enhance sympathetic neural traffic not only to muscle but also to bone. This sympathetic enhancement increases plasma noradrenaline level and inhibits osteogenesis and facilitates bone resorption through β-adrenoreceptors in bone to facilitate bone resorption to reduce bone mass. The use of β-adrenoblockers to prevent bone loss in microgravity may be reasonable.

Anti–oxidation actions of curcumin in two forms of bed rest: oxidative stress serum and salivary markers

Objective To determine the preventive effects of curcumin on peroxidative damage under two bed rest conditions. Methods 20 healthy male (10 with curcumin and 10 without curcumin) volunteers were selected. They were studied before, during, and just on bed rest conditions at −6° head-down-tilt (HDT) bed rest and bed rest position (BD) for 10 days. We measured the salivary and serum oxidative markers such as Malonaldehyde, 8-hydroxydeoxyguanosine, vitamin C and E just before HDT & BD, during HDT & BD experiment, and in course time of recovery with curcumin and without curcumin groups. Results The values of serum and salivary vitamin C & E showed statistically significant decrease in both bed rest conditions as compared to those of the conditions before and during the recovery stage. However, these levels were not significantly lowered in curcumin groups in contrast to the groups without curcumin (P>0.05). MDA and 8-OHdG levels showed significant increase in simulating microgravity and zero gravity conditions as compared to those before and in the recovery stage. However, these levels were lower in curcumin groups in contrast to the groups without curcumin(P<0.05). Serum and salivary correlation analysis revealed a strong and highly significant correlation for MDA, vitamin C & E and 8 dihydro-2 deoxyguanosine (8-OHdG) in the conditions before, during and in the recovery periods in both bed rest conditions. Since saliva collection is easy and non-invasive, measurements of salivary marker levels may prove to be useful in the space research. Conclusions Curcumin prevents peroxidative damage in both bed rest conditions. Further study is required on antioxidation actions of curcumin in space microgravity conditions.

Hydrodynamic Modeling of Dense Gas-Particle Turbulence Flows Under Microgravity Space Environments

An Euler–Euler two-fluid model based on the second-order-moment closure approach and the granular kinetic theory of dense gas-particle flows was presented. Anisotropy of gas-solid two-phase stress and the interaction between two-phase stresses are fully considered by two-phase Reynolds stress model and the transport equation of two-phase stress correlation. Under the microgravity space environments, hydrodynamic characters and particle dispersion behaviors of dense gas-particle turbulence flows are numerically simulated. Simulation results of particle concentration and particle velocity are in good agreement with measurement data under earth gravity environment. Decreased gravity can decrease the particle dispersion and can weaken the particle–particle collision as well as it is in favor of producing isotropic flow structures. Moreover, axial–axial fluctuation velocity correlation of gas and particle in earth gravity is approximately 3.0 times greater than those of microgravity and it is smaller than axial particle velocity fluctuation due to larger particle inertia and the larger particle turbulence diffusions.

Microarray analysis of spaceflown murine thymus tissue reveals changes in gene expression regulating stress and glucocorticoid receptors

The detrimental effects of spaceflight and simulated microgravity on the immune system have been extensively documented. We report here microarray gene expression analysis, in concert with quantitative RT-PCR, in young adult C57BL/6NTac mice at 8 weeks of age after exposure to spaceflight aboard the space shuttle (STS-118) for a period of 13 days. Upon conclusion of the mission, thymus lobes were extracted from space flown mice (FLT) as well as age- and sex-matched ground control mice similarly housed in animal enclosure modules (AEM). mRNA was extracted and an automated array analysis for gene expression was performed. Examination of the microarray data revealed 970 individual probes that had a 1.5-fold or greater change. When these data were averaged (n = 4), we identified 12 genes that were significantly up- or down-regulated by at least 1.5-fold after spaceflight (P < or = 0.05). The genes that significantly differed from the AEM controls and that were also confirmed via QRT-PCR were as follows: Rbm3 (up-regulated) and Hsph110, Hsp90aa1, Cxcl10, Stip1, Fkbp4 (down-regulated). QRT-PCR confirmed the microarray results and demonstrated additional gene expression alteration in other T cell related genes, including: Ctla-4, IFN-alpha2a (up-regulated) and CD44 (down-regulated). Together, these data demonstrate that spaceflight induces significant changes in the thymic mRNA expression of genes that regulate stress, glucocorticoid receptor metabolism, and T cell signaling activity. These data explain, in part, the reported systemic compromise of the immune system after exposure to the microgravity of space.

Space experimental studies of microgravity fluid science in China

Microgravity fluid physics is an important part of microgravity sciences, which consists of simple fluids of many new systems, gas-liquid two-phase flow and heat transfer, and complex fluid mechanics. In addition to the importance of itself in sciences and applications, microgravity fluid physics closely relates to microgravity combustion, space biotechnology and space materials science, and promotes the developments of interdisciplinary fields. Many space microgravity experiments have been performed on board the recoverable satellites and space ships of China and pushed the rapid development of microgravity sciences in China. In the present paper, space experimental studies and the main results of the microgravity fluid science in China in the last 10 years or so are introduced briefly.

Dynamic Model of an Astronaut Equipped with a Manned Maneuvering Unit in Virtual Reality

A virtual reality simulation system for a manned maneuvering unit (MMU) and a training system for an astronaut space walk is introduced. The system can simulate an astronaut’s outer space walk by means of manipulating the MMU, and it also can be used as a training environment by taking advantage of virtual reality properties of imagination, interaction, and immersion. As in microgravity space, an astronaut’s moving limbs cause changes in the MMU posture; these changes result in great offsets to correct direction and have a great effect on the MMU’s manipulation performance. A multibody astronaut model is developed by using relative coordinates according to the motion characteristics of an astronaut equipped with MMU. Motion information on the user’s limbs are captured by means of a motion capture subsystem and are mapped to an astronaut in virtual environment to simulate the astronaut’s limb motions while the astronaut is navigating in outer space. It is an open-chain system for an astronaut multibody mod...