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Pala, Renzo, Sara Cruciani, Alessia Manca, et al. "Mesenchymal Stem Cell Behavior under Microgravity: From Stress Response to a Premature Senescence." International Journal of Molecular Sciences 24, no. 9 (2023): 7753. http://dx.doi.org/10.3390/ijms24097753.
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Mesenchymal stem cells are undifferentiated cells able to acquire different phenotypes under specific stimuli. Wharton’s jelly is a tissue in the umbilical cord that contains mesenchymal stromal cells (MSCs) with a high plasticity and differentiation potential. Their regeneration capability is compromised by cell damage and aging. The main cause of cell damage is oxidative stress coming from an imbalance between oxidant and antioxidant species. Microgravity represents a stressing condition able to induce ROS production, ultimately leading to different subcellular compartment damages. Here, we analyzed molecular programs of stemness (Oct-4; SOX2; Nanog), cell senescence, p19, p21 (WAF1/CIP1), p53, and stress response in WJ-MSCs exposed to microgravity. From our results, we can infer that a simulated microgravity environment is able to influence WJ-MSC behavior by modulating the expression of stress and stemness-related genes, cell proliferation regulators, and both proapoptotic and antiapoptotic genes. Our results suggest a cellular adaptation addressed to survival occurring during the first hours of simulated microgravity, followed by a loss of stemness and proliferation capability, probably related to the appearance of a molecular program of senescence.
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Pietronigro, Frank. "Research Project Number 33: Investigating the Creative Process in a Microgravity Environment." Leonardo 33, no. 3 (2000): 169–77. http://dx.doi.org/10.1162/002409400552469.
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The author, an interdiscipli-nary artist, discusses his creation of art in a microgravity environ-ment as part of the 1998 NASA Student Reduced Gravity Flight Program. He discusses his three-dimensional “drift paintings” which floated in the air along with his body in microgravity. The au-thor posits that the transcendent quality of the creative process can help keep the human spirit alive during long-term space missions.
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Kicza, Mary E., and Robert C. Rhome. "Long-range national and international planning for the National Aeronautics and Space Administration's Microgravity Science and Applications Program." Advances in Space Research 13, no. 7 (1993): 5–12. http://dx.doi.org/10.1016/0273-1177(93)90349-g.
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CACCIAPUOTI, LUIGI, and OLIVIER MINSTER. "FUNDAMENTAL PHYSICS ACTIVITIES IN THE HME DIRECTORATE OF THE EUROPEAN SPACE AGENCY." International Journal of Modern Physics D 16, no. 12a (2007): 1957–66. http://dx.doi.org/10.1142/s0218271807011255.
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The Human Spaceflight, Microgravity, and Exploration (HME) Directorate of the European Space Agency is strongly involved in fundamental physics research. One of the major activities in this field is represented by the ACES (Atomic Clock Ensemble in Space) mission. ACES will demonstrate the high performances of a new generation of atomic clocks in the microgravity environment of the International Space Station (ISS). Following ACES, a vigorous research program has been recently approved to develop a second generation of atomic quantum sensors for space applications: atomic clocks in the optical domain, aiming at fractional frequency stability and accuracy in the low 10-18 regime; inertial sensors based on matter-wave interferometry for the detection of tiny accelerations and rotations; a facility to study degenerate Bose gases in space. Tests of quantum physics on large distance scales represent another important issue addressed in the HME program. A quantum communication optical terminal has been proposed to perform a test of Bell's inequalities on pairs of entangled photons emitted by a source located on the ISS and detected by two ground stations. In this paper, present activities and future plans will be described and discussed.
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Izzo, Luigi Gennaro, and Giovanna Aronne. "Root Tropisms: New Insights Leading the Growth Direction of the Hidden Half." Plants 10, no. 2 (2021): 220. http://dx.doi.org/10.3390/plants10020220.
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Tropisms are essential responses of plants, orienting growth according to a wide range of stimuli. Recently, considerable attention has been paid to root tropisms, not only to improve cultivation systems, such as those developed for plant-based life support systems for future space programs, but also to increase the efficiency of root apparatus in water and nutrient uptake in crops on Earth. To date, the Cholodny–Went theory of differential auxin distribution remains the principal tropistic mechanism, but recent findings suggest that it is not generally applicable to all root tropisms, and new molecular pathways are under discussion. Therefore, an in-depth understanding of the mechanisms and functions underlying root tropisms is needed. Contributions to this special issue aimed to embrace reviews and research articles that deepen molecular, physiological, and anatomical processes orchestrating root tropisms from perception of the stimulus to bending. The new insights will help in elucidating plant–environment interactions, providing potential applications to improve plant growth on Earth and in space where microgravity diminishes or nullifies the gravitropism dominance.
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Komarova, Margarita Y., Sergey V. Rozhkov, Oksana A. Ivanova, et al. "Cultured Myoblasts Derived from Rat Soleus Muscle Show Altered Regulation of Proliferation and Myogenesis during the Course of Mechanical Unloading." International Journal of Molecular Sciences 23, no. 16 (2022): 9150. http://dx.doi.org/10.3390/ijms23169150.
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The structure and function of soleus muscle fibers undergo substantial remodeling under real or simulated microgravity conditions. However, unloading-induced changes in the functional activity of skeletal muscle primary myoblasts remain poorly studied. The purpose of our study was to investigate how short-term and long-term mechanical unloading would affect cultured myoblasts derived from rat soleus muscle. Mechanical unloading was simulated by rat hindlimb suspension model (HS). Myoblasts were purified from rat soleus at basal conditions and after 1, 3, 7, and 14 days of HS. Myoblasts were expanded in vitro, and the myogenic nature was confirmed by their ability to differentiate as well as by immunostaining/mRNA expression of myogenic markers. The proliferation activity at different time points after HS was analyzed, and transcriptome analysis was performed. We have shown that soleus-derived myoblasts differently respond to an early and later stage of HS. At the early stage of HS, the proliferative activity of myoblasts was slightly decreased, and processes related to myogenesis activation were downregulated. At the later stage of HS, we observed a decrease in myoblast proliferative potential and spontaneous upregulation of the pro-myogenic program.
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Hunter, Steve L., Charles Dischinger, and Samantha Estes. "Three-Dimensional Simulation: Microgravity Environments and Applications." Journal of Spacecraft and Rockets 39, no. 2 (2002): 194–97. http://dx.doi.org/10.2514/2.3819.
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Diaz Palacios, Fabio, Guillermo Sahonero Alvarez, Gabriel Rojas, Miguel Clavijo, Jhon Ordoñez, and Khalil Nallar. "Exploring Microgravity Liquid Printing Based on Resin Solidification for Outer Space Applications." Key Engineering Materials 956 (September 29, 2023): 195–202. http://dx.doi.org/10.4028/p-xtb4yz.
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Space traveling, extra-planetary exploration and even colonization requires to replicate our capabilities of manufacturing under non-entirely known environments and conditions. With the recent, yet always present, interest on colonizing spaces like the Moon or even Mars, space-based Additive Manufacturing (AM) has been considered for enabling space inhabitants to build their own tools. However, the same manufacturing techniques that are commonly used on Earth are not entirely applicable in space, especially during the considerably long traveling stage. Thus, several works have reported the study of how AM could be used in microgravity or near-zero g conditions by using the International Space Station as a laboratory. Unfortunately, the costs for doing such experiments are prohibitive, which is why experimentation in microgravity conditions on Earth is promising. In this paper, we explore the possibility of applying light-sensitive resin under Microgravity conditions using a Drop Tower facility and we propose a microgravity liquid printing technique. Our preliminary experiments focused on studying movement and extrusion velocities, extrusion nozzle diameter, UV light power, extrusion, and solidification times. The experimental runs (one catapult launch and four drops) let us find promising, although not entirely conclusive, data and practices to be considered in future works using this methodology. As expected, there is a similarity to liquid extrusion on Earth given that the initial shape and speed of extrusion influences the liquid material. Our findings also suggest that an initial contact point would help to increase the contact force due to surface tension and that the extrusion and solidification times are less than 5 seconds, which implies faster printing processes than in earth gravity conditions because the microgravity provides us less layer mixing during extrusion. The hardware, material and Microgravity drop tests used confirm the feasibility of this technique and they become an initial step for this printing process and liquid materials.
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Sabbatini, Maurizio, Valentina Bonetto, Valeria Magnelli, Candida Lorusso, Francesco Dondero, and Maria Angela Masini. "Microgravity as an Anti-Metastatic Agent in an In Vitro Glioma Model." Biophysica 3, no. 4 (2023): 636–50. http://dx.doi.org/10.3390/biophysica3040043.
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Gravity is a primary physical force that has a profound influence on the stability of the cell cytoskeleton. In our research, we investigated the influence of microgravity on altering the cytoskeletal pathways of glioblastoma cells. The highly infiltrative behavior of glioblastoma is supported by cytoskeletal dynamics and surface proteins that allow glioblastoma cells to avoid stable connections with the tissue environment and other cells. Glioblastoma cell line C6 was exposed to a microgravity environment for 24, 48, and 72 h by 3D-RPM, a laboratory instrument recognized to reproduce the effect of microgravity in cell cultures. The immunofluorescence for GFAP, vinculin, and Connexin-43 was investigated as signals related to cytoskeleton dynamics. The polymerization of GFAP and the expression of focal contact structured by vinculin were found to be altered, especially after 48 and 72 h of microgravity. Connexin-43, involved in several intracellular pathways that critically promote cell motility and invasion of glioma cells, was found to be largely reduced following microgravity exposure. In conclusion, microgravity, by reducing the expression of Connexin-43, alters the architecture of specific cytoskeletal elements such as GFAP and increases the focal contact, which can induce a reduction in glioma cell mobility, thereby inhibiting their aggressive metastatic behavior.
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Wilson, William W., and Lawrence J. DeLucas. "Applications of the second virial coefficient: protein crystallization and solubility." Acta Crystallographica Section F Structural Biology Communications 70, no. 5 (2014): 543–54. http://dx.doi.org/10.1107/s2053230x1400867x.
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This article begins by highlighting some of the ground-based studies emanating from NASA's Microgravity Protein Crystal Growth (PCG) program. This is followed by a more detailed discussion of the history of and the progress made in one of the NASA-funded PCG investigations involving the use of measured second virial coefficients (Bvalues) as a diagnostic indicator of solution conditions conducive to protein crystallization. A second application of measuredBvalues involves the determination of solution conditions that improve or maximize the solubility of aqueous and membrane proteins. These two important applications have led to several technological improvements that simplify the experimental expertise required, enable the measurement of membrane proteins and improve the diagnostic capability and measurement throughput.
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Eppelbaum, Lev V. "Review of Environmental and Geological Microgravity Applications and Feasibility of Its Employment at Archaeological Sites in Israel." International Journal of Geophysics 2011 (2011): 1–9. http://dx.doi.org/10.1155/2011/927080.
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Microgravity investigations are widely applied at present for solving various environmental and geological problems. Unfortunately, microgravity survey is comparatively rarely used for searching for hidden ancient targets. It is caused mainly by small geometric size of the desired archaeological objects and various types of noise complicating the observed useful signal. At the same time, development of modern generation of field gravimetric equipment allows to register promptly and digitally microGal (10-8 m/s2) anomalies that offer a new challenge in this direction. An advanced methodology of gravity anomalies analysis and modern 3D modeling, intended for ancient targets delineation, is briefly presented. It is supposed to apply in archaeological microgravity the developed original methods for the surrounding terrain relief computing. Calculating second and third derivatives of gravity potential are useful for revealing some closed peculiarities of the different Physical-Archaeological Models (PAMs). It is underlined that physical measurement of vertical gravity derivatives in archaeological studying has a significant importance and cannot be replaced by any transformation methods. Archaeological targets in Israel have been ranged by their density/geometrical characteristics in several groups. The performed model computations indicate that microgravity investigations might be successfully applied at least in 20–25% of archaeological sites in Israel.
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Lee, Mark C., and John F. Newcomb. "Applying the Kano Methodology to Meet Customer Requirements: NASA's Microgravity Science Program." Quality Management Journal 4, no. 3 (1997): 95–106. http://dx.doi.org/10.1080/10686967.1997.11918805.
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Grodsinsky, Carlos M., and Mark S. Whorton. "Survey of Active Vibration Isolation Systems for Microgravity Applications." Journal of Spacecraft and Rockets 37, no. 5 (2000): 586–96. http://dx.doi.org/10.2514/2.3631.
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Ross, Byron, Oemer Akay, Alvia Mohammad-Yousuf, et al. "Synergistic Microfluidic and Optical Performance Enhancements of Photoelectrodes for Space Applications." ECS Meeting Abstracts MA2023-01, no. 30 (2023): 1801. http://dx.doi.org/10.1149/ma2023-01301801mtgabs.
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The realisation of long-term space missions as well as lunar habitats require reliable and efficient oxygen and chemical producing devices e.g., for life support, fuel generation and in-situ resource utilisation (ISRU). We have recently demonstrated that integrated semiconductor-electrocatalyst systems can be operated in microgravity environments generated for 9.2 s at the Bremen Drop Tower (Center of Applied Space Technology and Microgravity, ZARM) at terrestrial efficiencies, thus opening the possibility of utilising these photoelectrochemical (PEC) devices for chemical synthesis in space. 1,2 , 3 Our findings reveal that by altering the electrocatalyst surface morphology through nanostructuring, we can introduce catalytic hot-spots on the photoelectrode which - through their hydrophilic nature - can also enhance gas bubble detachment in microgravity and thus circumvent the near-absence of buoyancy.1,3 We have found that the surface hydrophilicity and electrocatalyst loading require however careful balancing as the most effective nanostructures for gas bubble desorption can also result in less catalyst material on the photoelectrode surface, which in turn leads to a non-optimal PEC device performance. Here, we present a combined theoretical and experimental microfluidic, optical and photoelectrocatalytic performance analysis of photoelectrodes with integrated, nanostructured electrocatalysts, aiming at providing a guideline for an optimal design for microgravity applications. Focusing on the hydrogen evolution reaction (HER) and a well-investigated photoabsorber for this reaction, p-type InP, we firstly built an optoelectronic model in COMSOL Multiphysics in pursuit of quantifying the optical performance enhancements of Rh and Pt electrocatalyst nanostructures such as nanopyramids, nanowires and sub-wavelength aperture holes.4 We then developed a microfluidic model using the same nanostructure geometries to predict the hydrophilicity of the device surface and subsequently, the gas bubble contact angle. The best-performing nanostructured photoelectrodes predicted in our models where then manufactured, photoelectrochemically tested and fully optically and spectroscopically characterised. Predicted local electric field enhancements through catalytic hotspot formation were moreover experimentally validated using scanning electrochemical cell microscopy (SECCM). Our findings indicate that our developed optoelectronic and microfluidic models can be utilised to design a theoretical framework for identifying ideal electrocatalyst nanostructures for microgravity applications. References Brinkert K, et al. Efficient solar hydrogen generation in microgravity environment. Nature Communications 9, (2018). Brinkert K, Mandin P. Fundamentals and future applications of electrochemical energy conversion in space. npj Microgravity 8, (2022). Akay Ö, et al. Releasing the Bubbles: Nanotopographical Electrocatalyst Design for Efficient Photoelectrochemical Hydrogen Production in Microgravity Environment. Advanced Science 9, 2105380 (2022). Tembhurne S, Haussener S. Integrated Photo-Electrochemical Solar Fuel Generators under Concentrated Irradiation. Journal of The Electrochemical Society 163, H988 (2016). Pan Y, Huang S, Li F, Zhao X, Wang W. Coexistence of superhydrophilicity and superoleophobicity: theory, experiments and applications in oil/water separation. Journal of Materials Chemistry A 6, 15057-15063 (2018).
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Gillies, Donald C. "Microscopy & Microanalytical Support for NASA's Microgravity Materials Science Programs." Microscopy Today 12, no. 5 (2004): 8–11. http://dx.doi.org/10.1017/s1551929500056236.
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The Materials Science Program of NASA's Office of Biological and Physical Research (OB PR) has attacked futidamental problems of materials science as defined by an external advisory group, known as the Discipline Working Group (DWG). These have been:•Nucleation and Metastable States•Prediction and Gontrol of Micrestructures•Crystal Growth and Detect Generation•Phase Separation and Interfacial Phenomena•Thermophysical Properties and Process Modeling.While the program's primary objectives are science-based and despite the fact that 90% of these programs concentrate on pre-cursor and theoretical research on the ground, NASA demands that there be a microgravity rationale driving the research.
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Winkelmaier, Garrett, Kosar Jabbari, Lung-Chang Chien, Peter Grabham, Bahram Parvin, and Janice Pluth. "Influence of Simulated Microgravity on Mammary Epithelial Cells Grown as 2D and 3D Cultures." International Journal of Molecular Sciences 24, no. 8 (2023): 7615. http://dx.doi.org/10.3390/ijms24087615.
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During space travel, astronauts will experience a unique environment that includes continuous exposure to microgravity and stressful living conditions. Physiological adaptation to this is a challenge and the effect of microgravity on organ development, architecture, and function is not well understood. How microgravity may impact the growth and development of an organ is an important issue, especially as space flight becomes more commonplace. In this work, we sought to address fundamental questions regarding microgravity using mouse mammary epithelial cells in 2D and 3D tissue cultures exposed to simulated microgravity. Mouse mammary HC11 cells contain a higher proportion of stem cells and were also used to investigate how simulated microgravity may impact mammary stem cell populations. In these studies, we exposed mouse mammary epithelial cells to simulated microgravity in 2D and then assayed for changes in cellular characteristics and damage levels. The microgravity treated cells were also cultured in 3D to form acini structures to define if simulated microgravity affects the cells’ ability to organize correctly, a quality that is of key importance for mammary organ development. These studies identify changes occurring during exposure to microgravity that impact cellular characteristics such as cell size, cell cycle profiles, and levels of DNA damage. In addition, changes in the percentage of cells revealing various stem cell profiles were observed following simulated microgravity exposure. In summary, this work suggests microgravity may cause aberrant changes in mammary epithelial cells that lead to an increase in cancer risk.
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Yuan, Mengqin, Haizhou Liu, Shunheng Zhou, et al. "Integrative Analysis of Regulatory Module Reveals Associations of Microgravity with Dysfunctions of Multi-body Systems and Tumorigenesis." International Journal of Molecular Sciences 21, no. 20 (2020): 7585. http://dx.doi.org/10.3390/ijms21207585.
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Previous studies have demonstrated that microgravity could lead to health risks. The investigation of the molecular mechanisms from the aspect of systems biology has not been performed yet. Here, we integratively analyzed transcriptional and post-transcriptional regulations based on gene and miRNA expression profiles in human peripheral blood lymphocytes cultured in modeled microgravity. Two hundred and thirty dysregulated TF-miRNA (transcription factor and microRNA) feed-forward loops (FFLs) were identified in microgravity. The immune, cardiovascular, endocrine, nervous and skeletal system subnetworks were constructed according to the functions of dysregulated FFLs. Taking the skeletal system as an example, most of genes and miRNAs in the subnetwork were involved in bone loss. In addition, several drugs have been predicted to have potential to reduce bone loss, such as traditional Chinese medicines Emodin and Ginsenoside Rh2. Furthermore, we investigated the relationships between microgravity and 20 cancer types, and found that most of cancers might be promoted by microgravity. For example, rectum adenocarcinoma (READ) might be induced by microgravity through reducing antigen presentation and suppressing IgA-antibody-secreting cells’ migration. Collectively, TF-miRNA FFL might provide a novel mechanism to elucidate the changes induced by microgravity, serve as drug targets to relieve microgravity effects, and give new insights to explore the relationships between microgravity and cancers.
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Fairlie, R., and J. F. Griffiths. "Oscillatory combustion in closed vessels under microgravity." Mathematical and Computer Modelling 36, no. 3 (2002): 245–57. http://dx.doi.org/10.1016/s0895-7177(02)00123-1.
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Wilfinger, William W., Carol S. Baker, Elaine L. Kunze, Allen T. Phillips, and Roy H. Hammerstedt. "Versatile Fluid-Mixing Device for Cell and Tissue Microgravity Research Applications." Journal of Spacecraft and Rockets 33, no. 1 (1996): 126–30. http://dx.doi.org/10.2514/3.55717.
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Neelam, Srujana, Brian Richardson, Richard Barker, et al. "Changes in Nuclear Shape and Gene Expression in Response to Simulated Microgravity Are LINC Complex-Dependent." International Journal of Molecular Sciences 21, no. 18 (2020): 6762. http://dx.doi.org/10.3390/ijms21186762.
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Microgravity is known to affect the organization of the cytoskeleton, cell and nuclear morphology and to elicit differential expression of genes associated with the cytoskeleton, focal adhesions and the extracellular matrix. Although the nucleus is mechanically connected to the cytoskeleton through the Linker of Nucleoskeleton and Cytoskeleton (LINC) complex, the role of this group of proteins in these responses to microgravity has yet to be defined. In our study, we used a simulated microgravity device, a 3-D clinostat (Gravite), to investigate whether the LINC complex mediates cellular responses to the simulated microgravity environment. We show that nuclear shape and differential gene expression are both responsive to simulated microgravity in a LINC-dependent manner and that this response changes with the duration of exposure to simulated microgravity. These LINC-dependent genes likely represent elements normally regulated by the mechanical forces imposed by gravity on Earth.
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Chen, Zhihao, Yan Zhang, Fan Zhao та ін. "Recombinant Irisin Prevents the Reduction of Osteoblast Differentiation Induced by Stimulated Microgravity through Increasing β-Catenin Expression". International Journal of Molecular Sciences 21, № 4 (2020): 1259. http://dx.doi.org/10.3390/ijms21041259.
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Background: Irisin, a novel exercise-induced myokine, was shown to mediate beneficial effects of exercise in osteoporosis. Microgravity is a major threat to bone homeostasis of astronauts during long-term spaceflight, which results in decreased bone formation. Methods: The hind-limb unloading mice model and a random position machine are respectively used to simulate microgravity in vivo and in vitro. Results: We demonstrate that not only are bone formation and osteoblast differentiation decreased, but the expression of fibronectin type III domain-containing 5 (Fdnc5; irisin precursor) is also downregulated under simulated microgravity. Moreover, a lower dose of recombinant irisin (r-irisin) (1 nM) promotes osteogenic marker gene (alkaline phosphatase (Alp), collagen type 1 alpha-1(ColIα1)) expressions, ALP activity, and calcium deposition in primary osteoblasts, with no significant effect on osteoblast proliferation. Furthermore, r-irisin could recover the decrease in osteoblast differentiation induced by simulated microgravity. We also find that r-irisin increases β-catenin expression and partly neutralizes the decrease in β-catenin expression induced by simulated microgravity. In addition, β-catenin overexpression could also in part attenuate osteoblast differentiation reduction induced by simulated microgravity. Conclusions: The present study is the first to show that r-irisin positively regulates osteoblast differentiation under simulated microgravity through increasing β-catenin expression, which may reveal a novel mechanism, and it provides a prevention strategy for bone loss and muscle atrophy induced by microgravity.
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Morabito, Caterina, Simone Guarnieri, Alessandra Cucina, Mariano Bizzarri, and Maria A. Mariggiò. "Antioxidant Strategy to Prevent Simulated Microgravity-Induced Effects on Bone Osteoblasts." International Journal of Molecular Sciences 21, no. 10 (2020): 3638. http://dx.doi.org/10.3390/ijms21103638.
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The effects induced by microgravity on human body functions have been widely described, in particular those on skeletal muscle and bone tissues. This study aims to implement information on the possible countermeasures necessary to neutralize the oxidative imbalance induced by microgravity on osteoblastic cells. Using the model of murine MC3T3-E1 osteoblast cells, cellular morphology, proliferation, and metabolism were investigated during exposure to simulated microgravity on a random positioning machine in the absence or presence of an antioxidant—the 6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid (Trolox). Our results confirm that simulated microgravity-induced morphological and metabolic alterations characterized by increased levels of reactive oxygen species and a slowdown of the proliferative rate. Interestingly, the use of Trolox inhibited the simulated microgravity-induced effects. Indeed, the antioxidant-neutralizing oxidants preserved cell cytoskeletal architecture and restored cell proliferation rate and metabolism. The use of appropriate antioxidant countermeasures could prevent the modifications and damage induced by microgravity on osteoblastic cells and consequently on bone homeostasis.
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Grimm, Daniela. "Microgravity and Space Medicine." International Journal of Molecular Sciences 22, no. 13 (2021): 6697. http://dx.doi.org/10.3390/ijms22136697.
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Bauer, Johann. "Microgravity and Cell Adherence." International Journal of Molecular Sciences 21, no. 6 (2020): 2214. http://dx.doi.org/10.3390/ijms21062214.
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Yim, Jaewoo, Sung Won Cho, Beomhee Kim, Sungwoo Park, Yong Hee Han, and Sang Woo Seo. "Transcriptional Profiling of the Probiotic Escherichia coli Nissle 1917 Strain under Simulated Microgravity." International Journal of Molecular Sciences 21, no. 8 (2020): 2666. http://dx.doi.org/10.3390/ijms21082666.
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Long-term space missions affect the gut microbiome of astronauts, especially the viability of some pathogens. Probiotics may be an effective solution for the management of gut microbiomes, but there is a lack of studies regarding the physiology of probiotics in microgravity. Here, we investigated the effects of microgravity on the probiotic Escherichia coli Nissle 1917 (EcN) by comparing transcriptomic data during exponential and stationary growth phases under simulated microgravity and normal gravity. Microgravity conditions affected several physiological features of EcN, including its growth profile, biofilm formation, stress responses, metal ion transport/utilization, and response to carbon starvation. We found that some changes, such as decreased adhesion ability and acid resistance, may be disadvantageous to EcN relative to gut pathogens under microgravity, indicating the need to develop probiotics optimized for space flight.
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Li, Wang, Xinyu Shu, Xiaoyu Zhang, et al. "Potential Roles of YAP/TAZ Mechanotransduction in Spaceflight-Induced Liver Dysfunction." International Journal of Molecular Sciences 24, no. 3 (2023): 2197. http://dx.doi.org/10.3390/ijms24032197.
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Microgravity exposure during spaceflight causes the disordered regulation of liver function, presenting a specialized mechano-biological coupling process. While YAP/TAZ serves as a typical mechanosensitive pathway involved in hepatocyte metabolism, it remains unclear whether and how it is correlated with microgravity-induced liver dysfunction. Here, we discussed liver function alterations induced by spaceflight or simulated effects of microgravity on Earth. The roles of YAP/TAZ serving as a potential bridge in connecting liver metabolism with microgravity were specifically summarized. Existing evidence indicated that YAP/TAZ target gene expressions were affected by mechanotransductive pathways and phase separation, reasonably speculating that microgravity might regulate YAP/TAZ activation by disrupting these pathways via cytoskeletal remodeling or nuclear deformation, or disturbing condensates formation via diffusion limit, and then breaking liver homeostasis.
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Cazzaniga, Alessandra, Fabian Ille, Simon Wuest, et al. "Scalable Microgravity Simulator Used for Long-Term Musculoskeletal Cells and Tissue Engineering." International Journal of Molecular Sciences 21, no. 23 (2020): 8908. http://dx.doi.org/10.3390/ijms21238908.
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We introduce a new benchtop microgravity simulator (MGS) that is scalable and easy to use. Its working principle is similar to that of random positioning machines (RPM), commonly used in research laboratories and regarded as one of the gold standards for simulating microgravity. The improvement of the MGS concerns mainly the algorithms controlling the movements of the samples and the design that, for the first time, guarantees equal treatment of all the culture flasks undergoing simulated microgravity. Qualification and validation tests of the new device were conducted with human bone marrow stem cells (bMSC) and mouse skeletal muscle myoblasts (C2C12). bMSC were cultured for 4 days on the MGS and the RPM in parallel. In the presence of osteogenic medium, an overexpression of osteogenic markers was detected in the samples from both devices. Similarly, C2C12 cells were maintained for 4 days on the MGS and the rotating wall vessel (RWV) device, another widely used microgravity simulator. Significant downregulation of myogenesis markers was observed in gravitationally unloaded cells. Therefore, similar results can be obtained regardless of the used simulated microgravity devices, namely MGS, RPM, or RWV. The newly developed MGS device thus offers easy and reliable long-term cell culture possibilities under simulated microgravity conditions. Currently, upgrades are in progress to allow real-time monitoring of the culture media and liquids exchange while running. This is of particular interest for long-term cultivation, needed for tissue engineering applications. Tissue grown under real or simulated microgravity has specific features, such as growth in three-dimensions (3D). Growth in weightlessness conditions fosters mechanical, structural, and chemical interactions between cells and the extracellular matrix in any direction.
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Simon, Ágota, Adriana Smarandache, Vicentiu Iancu, and Mihail Lucian Pascu. "Stability of Antimicrobial Drug Molecules in Different Gravitational and Radiation Conditions in View of Applications during Outer Space Missions." Molecules 26, no. 8 (2021): 2221. http://dx.doi.org/10.3390/molecules26082221.
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The evolution of different antimicrobial drugs in terrestrial, microgravity and hypergravity conditions is presented within this review, in connection with their implementation during human space exploration. Drug stability is of utmost importance for applications in outer space. Instabilities may be radiation-induced or micro-/hypergravity produced. The antimicrobial agents used in space may have diminished effects not only due to the microgravity-induced weakened immune response of astronauts, but also due to the gravity and radiation-altered pathogens. In this context, the paper provides schemes and procedures to find reliable ways of fighting multiple drug resistance acquired by microorganisms. It shows that the role of multipurpose medicines modified at the molecular scale by optical methods in long-term space missions should be considered in more detail. Solutions to maintain drug stability, even in extreme environmental conditions, are also discussed, such as those that would be encountered during long-duration space exploratory missions. While the microgravity conditions may not be avoided in space, the suggested approaches deal with the radiation-induced modifications in humans, bacteria and medicines onboard, which may be fought by novel pharmaceutical formulation strategies along with radioprotective packaging and storage.
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Dietz, Carlo, Manfred Infanger, Alexander Romswinkel, Florian Strube, and Armin Kraus. "Apoptosis Induction and Alteration of Cell Adherence in Human Lung Cancer Cells under Simulated Microgravity." International Journal of Molecular Sciences 20, no. 14 (2019): 3601. http://dx.doi.org/10.3390/ijms20143601.
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Background: Lung cancer cells are known to change proliferation and migration under simulated microgravity. In this study, we sought to evaluate cell adherence, apoptosis, cytoskeleton arrangement, and gene expression under simulated microgravity. Methods: Human lung cancer cells were exposed to simulated microgravity in a random-positioning machine (RPM). Cell morphology and adherence were observed under phase-contrast microscopy, cytoskeleton staining was performed, apoptosis rate was determined, and changes in gene and protein expression were detected by real-time PCR with western blot confirmation. Results: Three-dimensional (3D)-spheroid formation was observed under simulated microgravity. Cell viability was not impaired. Actin filaments showed a shift in alignment from longitudinal to spherical. Apoptosis rate was significantly increased in the spheroids compared to the control. TP53, CDKN2A, PTEN, and RB1 gene expression was significantly upregulated in the adherent cells under simulated microgravity with an increase in corresponding protein production for p14 and RB1. SOX2 expression was significantly upregulated in the adherent cells, but protein was not. Gene expressions of AKT3, PIK3CA, and NFE2L2 remained unaltered. Conclusion: Simulated microgravity induces alteration in cell adherence, increases apoptosis rate, and leads to upregulation of tumor suppressor genes in human lung cancer cells.
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Thiel, Cora S., Christian Vahlensieck, Timothy Bradley, Svantje Tauber, Martin Lehmann, and Oliver Ullrich. "Metabolic Dynamics in Short- and Long-Term Microgravity in Human Primary Macrophages." International Journal of Molecular Sciences 22, no. 13 (2021): 6752. http://dx.doi.org/10.3390/ijms22136752.
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Microgravity acts on cellular systems on several levels. Cells of the immune system especially react rapidly to changes in gravity. In this study, we performed a correlative metabolomics analysis on short-term and long-term microgravity effects on primary human macrophages. We could detect an increased amino acid concentration after five minutes of altered gravity, that was inverted after 11 days of microgravity. The amino acids that reacted the most to changes in gravity were tightly clustered. The observed effects indicated protein degradation processes in microgravity. Further, glucogenic and ketogenic amino acids were further degraded to Glucose and Ketoleucine. The latter is robustly accumulated in short-term and long-term microgravity but not in hypergravity. We detected highly dynamic and also robust adaptative metabolic changes in altered gravity. Metabolomic studies could contribute significantly to the understanding of gravity-induced integrative effects in human cells.
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Zhao, Zanyan, Xiangpu Wang, Yu Ma, and Xiaohong Duan. "Atp6v1h Deficiency Blocks Bone Loss in Simulated Microgravity Mice through the Fos-Jun-Src-Integrin Pathway." International Journal of Molecular Sciences 25, no. 1 (2024): 637. http://dx.doi.org/10.3390/ijms25010637.
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The microgravity conditions in outer space are widely acknowledged to induce significant bone loss. Recent studies have implicated the close relationship between Atp6v1h gene and bone loss. Despite this, the role of Atp6v1h in bone remodeling and its molecular mechanisms in microgravity have not been fully elucidated. To address this, we used a mouse tail suspension model to simulate microgravity. We categorized both wild-type and Atp6v1h knockout (Atp6v1h+/-) mice into two groups: regular feeding and tail-suspension feeding, ensuring uniform feeding conditions across all cohorts. Analysis via micro-CT scanning, hematoxylin-eosin staining, and tartrate-resistant acid phosphatase assays indicated that wild-type mice underwent bone loss under simulated microgravity. Atp6v1h+/- mice exhibited bone loss due to Atp6v1h deficiency but did not present aggravated bone loss under the same simulated microgravity. Transcriptomic sequencing revealed the upregulation of genes, such as Fos, Src, Jun, and various integrin subunits in the context of simulated microgravity and Atp6v1h knockout. Real-time quantitative polymerase chain reaction (RT-qPCR) further validated the modulation of downstream osteoclast-related genes in response to interactions with ATP6V1H overexpression cell lines. Co-immunoprecipitation indicated potential interactions between ATP6V1H and integrin beta 1, beta 3, beta 5, alpha 2b, and alpha 5. Our results indicate that Atp6v1h level influences bone loss in simulated microgravity by modulating the Fos-Jun-Src-Integrin pathway, which, in turn, affects osteoclast activity and bone resorption, with implications for osteoporosis. Therefore, modulating Atp6v1h expression could mitigate bone loss in microgravity conditions. This study elucidates the molecular mechanism of Atp6v1h’s role in osteoporosis and positions it as a potential therapeutic target against environmental bone loss. These findings open new possibilities for the treatment of multifactorial osteoporosis.
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Johnson, Ian R. D., Catherine T. Nguyen, Petra Wise, and Daniela Grimm. "Implications of Altered Endosome and Lysosome Biology in Space Environments." International Journal of Molecular Sciences 21, no. 21 (2020): 8205. http://dx.doi.org/10.3390/ijms21218205.
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Space exploration poses multiple challenges for mankind, not only on a technical level but also to the entire physiology of the space traveller. The human system must adapt to several environmental stressors, microgravity being one of them. Lysosomes are ubiquitous to every cell and essential for their homeostasis, playing significant roles in the regulation of autophagy, immunity, and adaptation of the organism to changes in their environment, to name a few. Dysfunction of the lysosomal system leads to age-related diseases, for example bone loss, reduced immune response or cancer. As these conditions have been shown to be accelerated following exposure to microgravity, this review elucidates the lysosomal response to real and simulated microgravity. Microgravity activates the endo-lysosomal system, with resulting impacts on bone loss, muscle atrophy and stem cell differentiation. The investigation of lysosomal adaptation to microgravity can be beneficial in the search for new biomarkers or therapeutic approaches to several disease pathologies on earth as well as the potential to mitigate pathophysiology during spaceflight.
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Calcagno, Gaetano, Jeremy Jeandel, Jean-Pol Frippiat та Sandra Kaminski. "Simulated Microgravity Disrupts Nuclear Factor κB Signaling and Impairs Murine Dendritic Cell Phenotype and Function". International Journal of Molecular Sciences 24, № 2 (2023): 1720. http://dx.doi.org/10.3390/ijms24021720.
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During spaceflights, astronauts face different forms of stress (e.g., socio-environmental and gravity stresses) that impact physiological functions and particularly the immune system. In this context, little is known about the effect of such stress on dendritic cells (DCs). First, we showed that hypergravity, but not chronic ultra-mild stress, a socio-environmental stress, induced a less mature phenotype characterized by a decreased expression of MHCII and co-stimulatory molecules. Next, using the random positioning machine (RPM), we studied the direct effects of simulated microgravity on either splenic DCs or Flt-3L-differentiated bone marrow dendritic cells (BMDCs). Simulated microgravity was found to reduce the BM-conventional DC (cDC) and splenic cDC activation/maturation phenotype. Consistent with this, BMDCs displayed a decreased production of pro-inflammatory cytokines when exposed to microgravity compared to the normogravity condition. The induction of a more immature phenotype in microgravity than in control DCs correlated with an alteration of the NFκB signaling pathway. Since the DC phenotype is closely linked to their function, we studied the effects of microgravity on DCs and found that microgravity impaired their ability to induce naïve CD4 T cell survival, proliferation, and polarization. Thus, a deregulation of DC function is likely to induce immune deregulation, which could explain the reduced efficiency of astronauts’ immune response.
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PYLYPENKO, O. V., D. E. SMOLENSKYY, O. D. NIKOLAYEV, and I. D. BASHLIY. "The approach to numerical simulation of the spatial movement of fluid with forming free gas inclusions in propellant tank at space flight conditions." Kosmìčna nauka ì tehnologìâ 28, no. 5 (2022): 03–14. http://dx.doi.org/10.15407/knit2022.05.003.
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The space propulsion systems ensure se veral start-ups and shutdowns of main liquid-propellant rocket engines under microgravity conditions for the spacecraft program movements and reorientation control. During the passive flight of the space stage (after its main engine shutdown), the liquid propellant in the tanks continues to move by inertia in microgravity away from the propellant management device as much as possible. In this case, the pressurization gas is displaced to the propellant management device, which creates the potential danger of gas entering the engine inlet in quantities unacceptable for the reliable engine restart. In this regard, determining the parameters of fluid movement in propellant tanks in microgravity conditions is an urgent problem that needs to be solved in the design period of liquid propulsion systems. We have developed an approach to the theoretical computation of the parameters of the motion of the ‘gas — fluid’ system in the propellant tanks of modern space stages in microgravity conditions. The approach is based on the use of the finite element method, the Volume of Fluid method and modern computer tools for finite-element analysis (Computer Aided Engineering — CAE systems). For the passive leg of the launch vehicle space flight, we performed mathematical modeling of the spatial movement of liquid propellant and forming free gas inclusions and determined the parameters of movement and shape of the free surface of the liquid in the tank as well as the location of gas inclusions. The numerical simulation of the fluid movement in an experimental sample of a spherical shape tank was performed with regard to the movement conditions in the SE Yuzhnoye Design Bureau ‘Drop tower’ for studying space object s in microgravity. The motion parameters of the ‘gas — fluid’ interface obtained as a result of mathematical modeling are in satisfactory agreement with the experimental data obtained. The use of the developed approach will significantly reduce the amount of experimental testing of the designed space stages.
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Herrera-Jordan, Katherinne, Pamela Pennington, and Luis Zea. "Reduced Pseudomonas aeruginosa Cell Size Observed on Planktonic Cultures Grown in the International Space Station." Microorganisms 12, no. 2 (2024): 393. http://dx.doi.org/10.3390/microorganisms12020393.
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Bacterial growth and behavior have been studied in microgravity in the past, but little focus has been directed to cell size despite its impact on a myriad of processes, including biofilm formation, which is impactful regarding crew health. To interrogate this characteristic, supernatant aliquots of P. aeruginosa cultured on different materials and media on board the International Space Station (ISS) as part of the Space Biofilms Project were analyzed. For that experiment, P. aeruginosa was grown in microgravity—with matching Earth controls—in modified artificial urine medium (mAUMg-high Pi) or LB Lennox supplemented with KNO3, and its formation of biofilms on six different materials was assessed. After one, two, and three days of incubation, the ISS crew terminated subsets of the experiment by fixation in paraformaldehyde, and aliquots of the supernatant were used for the planktonic cell size study presented here. The measurements were obtained post-flight through the use of phase contrast microscopy under oil immersion, a Moticam 10+ digital camera, and the FIJI image analysis program. Statistical comparisons were conducted to identify which treatments caused significant differences in cell dimensions using the Kruskal–Wallis and Dunn tests. There were statistically significant differences as a function of material present in the culture in both LBK and mAUMg-high Pi. Along with this, the data were also grouped by gravitational condition, media, and days of incubation. Comparison of planktonic cells cultured in microgravity showed reduced cell length (from 4% to 10% depending on the material) and diameter (from 1% to 10% depending on the material) with respect to their matching Earth controls, with the caveat that the cultures may have been at different points in their growth curve at a given time. In conclusion, smaller cells were observed on the cultures grown in microgravity, and cell size changed as a function of incubation time and the material upon which the culture grew. We describe these changes here and possible implications for human space travel in terms of crew health and potential applications.
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Ullrich, Oliver, Christian Paul Casal, Natalie Dové, et al. "Swiss Parabolic Flights: Development of a Non-Governmental Parabolic Flight Program in Switzerland Based on the Airbus A310 ZERO-G." Aerospace 10, no. 10 (2023): 860. http://dx.doi.org/10.3390/aerospace10100860.
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Parabolic flights are one of the most important pillars for research, development, and applications in space. Accordingly, we developed the world’s first non-governmental parabolic flight program using Novespace’s Airbus A310 ZERO-G. Through the flexible combination of academic research with industrial experiments, as well as with the support of private persons and low administrative efforts, we achieved a highly cost-efficient small-scale campaign concept, which is located at the Air Base Dübendorf in Switzerland. The program was very successful, and it resulted in 31 experiments and tests conducted by Universities and organizations in the industry in microgravity, culminating in many scientific publications and in larger subsequent projects for all users. We describe here how we designed, developed, tested, and built up this program. We also discuss the difficulties, problems, and success factors of a project that—for the first time—was successfully built from the “bottom-up”, and which was a large-scale flight research platform by scientists for scientists on a voluntary, non-governmental, and non-commercial basis.
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Manis, Cristina, Alessia Manca, Antonio Murgia, et al. "Understanding the Behaviour of Human Cell Types under Simulated Microgravity Conditions: The Case of Erythrocytes." International Journal of Molecular Sciences 23, no. 12 (2022): 6876. http://dx.doi.org/10.3390/ijms23126876.
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Erythrocytes are highly specialized cells in human body, and their main function is to ensure the gas exchanges, O2 and CO2, within the body. The exposure to microgravity environment leads to several health risks such as those affecting red blood cells. In this work, we investigated the changes that occur in the structure and function of red blood cells under simulated microgravity, compared to terrestrial conditions, at different time points using biochemical and biophysical techniques. Erythrocytes exposed to simulated microgravity showed morphological changes, a constant increase in reactive oxygen species (ROS), a significant reduction in total antioxidant capacity (TAC), a remarkable and constant decrease in total glutathione (GSH) concentration, and an augmentation in malondialdehyde (MDA) at increasing times. Moreover, experiments were performed to evaluate the lipid profile of erythrocyte membranes which showed an upregulation in the following membrane phosphocholines (PC): PC16:0_16:0, PC 33:5, PC18:2_18:2, PC 15:1_20:4 and SM d42:1. Thus, remarkable changes in erythrocyte cytoskeletal architecture and membrane stiffness due to oxidative damage have been found under microgravity conditions, in addition to factors that contribute to the plasticity of the red blood cells (RBCs) including shape, size, cell viscosity and membrane rigidity. This study represents our first investigation into the effects of microgravity on erythrocytes and will be followed by other experiments towards understanding the behaviour of different human cell types in microgravity.
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Sokolovskaya, Alisa, Ekaterina Korneeva, Danila Zaichenko, et al. "Changes in the Surface Expression of Intercellular Adhesion Molecule 3, the Induction of Apoptosis, and the Inhibition of Cell-Cycle Progression of Human Multidrug-Resistant Jurkat/A4 Cells Exposed to a Random Positioning Machine." International Journal of Molecular Sciences 21, no. 3 (2020): 855. http://dx.doi.org/10.3390/ijms21030855.
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Experiments from flight- and ground-based model systems suggest that unexpected alterations of the human lymphoblastoid cell line Jurkat, as well as effects on cell growth, metabolism, and apoptosis, can occur in altered gravity conditions. Using a desktop random positioning machine (RPM), we investigated the effects of simulated microgravity on Jurkat cells and their multidrug-resistant subline, Jurkat/A4 cells. The viability of Jurkat/A4 cells decreased after simulated microgravity in contrast with the Jurkat cells. At the same time, the viability between the experimental Jurkat cells and control Jurkat cells was not significantly different. Of note, Jurkat cells appeared as less susceptible to apoptosis than their multidrug-resistant clone Jurkat/A4 cells, whereas cell-cycle analysis showed that the percentage of Jurkat/A4 cells in the S-phase was increased after 72 and 96 h of RPM-simulated microgravity relative to their static counterparts. The differences in Jurkat cells at all phases between static and simulated microgravity were not significant. The surface expression of the intercellular adhesion molecule 3 (ICAM-3)—also known as cluster of differentiation (CD)50—protein was changed for Jurkat/A4 cells following exposure to the RPM. Changes in cell morphology were observed in the Jurkat/A4 cells after 96 h of RPM-simulated microgravity. Thus, we concluded that Jurkat/A4 cells are more sensitive to RPM-simulated microgravity as compared with the parental Jurkat cell line. We also suggest that intercellular adhesion molecule 3 may be an important adhesion molecule involved in the induction of leukocyte apoptosis. The Jurkat/A4 cells with an acquired multidrug resistance phenotype could be a useful model for studying the effects of simulated microgravity and testing anticancer drugs.
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Krakos (Podwin), Agnieszka, Patrycja Śniadek, Marta Jurga, et al. "Lab-on-Chip Culturing System for Fungi—Towards Nanosatellite Missions." Applied Sciences 12, no. 20 (2022): 10627. http://dx.doi.org/10.3390/app122010627.
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In this paper, a lab-on-chip system dedicated to fungi cultivation in Earth’s gravity and simulated microgravity, being a solution that could be used in future nanosatellite missions, is shown. For the first time, a fully glass lab-on-chip structure enabling the proper environment for cultivation of fungi species—Fusarium culmorum—is presented. Apart from the biological validation of the fungi cultures with the use of the lab-on-chip system, tests were carried out under induced microgravity utilising a Rotary Wall Vessel. Correct functioning of the lab-on-chip system was obtained, enabling the growth of fungi spores both in ground and in simulated microgravity conditions. Interestingly, culturing tests have shown that microgravity stimulates the growth of fungi notably, compared to the ground-based experimentation performed simultaneously. The findings of this study can provide substantial new knowledge on microscopic fungi cultivation in lab-on-chip devices, other soil organisms, as well as a potential behavior of these species in microgravity conditions. Culturing system shown in this work can help mycologists to provide better understanding of microscopic fungi nature and their development mechanisms at a single spore level. This opens the way towards regular usage of microfluidic tools in agriculture and horticulture fields and more importantly, in future research on microscopic fungi in space, e.g., as a part of nanosatellite missions.
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Moreno-Villanueva, Maria, Alan Feiveson, Stephanie Krieger, et al. "Synergistic Effects of Weightlessness, Isoproterenol, and Radiation on DNA Damage Response and Cytokine Production in Immune Cells." International Journal of Molecular Sciences 19, no. 11 (2018): 3689. http://dx.doi.org/10.3390/ijms19113689.
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The implementation of rotating-wall vessels (RWVs) for studying the effect of lack of gravity has attracted attention, especially in the fields of stem cells, tissue regeneration, and cancer research. Immune cells incubated in RWVs exhibit several features of immunosuppression including impaired leukocyte proliferation, cytokine responses, and antibody production. Interestingly, stress hormones influence cellular immune pathways affected by microgravity, such as cell proliferation, apoptosis, DNA repair, and T cell activation. These pathways are crucial defense mechanisms that protect the cell from toxins, pathogens, and radiation. Despite the importance of the adrenergic receptor in regulating the immune system, the effect of microgravity on the adrenergic system has been poorly studied. Thus, we elected to investigate the synergistic effects of isoproterenol (a sympathomimetic drug), radiation, and microgravity in nonstimulated immune cells. Peripheral blood mononuclear cells were treated with the sympathomimetic drug isoproterenol, exposed to 0.8 or 2 Gy γ-radiation, and incubated in RWVs. Mixed model regression analyses showed significant synergistic effects on the expression of the β2-adrenergic receptor gene (ADRB2). Radiation alone increased ADRB2 expression, and cells incubated in microgravity had more DNA strand breaks than cells incubated in normal gravity. We observed radiation-induced cytokine production only in microgravity. Prior treatment with isoproterenol clearly prevents most of the microgravity-mediated effects. RWVs may be a useful tool to provide insight into novel regulatory pathways, providing benefit not only to astronauts but also to patients suffering from immune disorders or undergoing radiotherapy.
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Sun, Yulong, Yuanyuan Kuang, and Zhuo Zuo. "The Emerging Role of Macrophages in Immune System Dysfunction under Real and Simulated Microgravity Conditions." International Journal of Molecular Sciences 22, no. 5 (2021): 2333. http://dx.doi.org/10.3390/ijms22052333.
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In the process of exploring space, the astronaut’s body undergoes a series of physiological changes. At the level of cellular behavior, microgravity causes significant alterations, including bone loss, muscle atrophy, and cardiovascular deconditioning. At the level of gene expression, microgravity changes the expression of cytokines in many physiological processes, such as cell immunity, proliferation, and differentiation. At the level of signaling pathways, the mitogen-activated protein kinase (MAPK) signaling pathway participates in microgravity-induced immune malfunction. However, the mechanisms of these changes have not been fully elucidated. Recent studies suggest that the malfunction of macrophages is an important breakthrough for immune disorders in microgravity. As the first line of immune defense, macrophages play an essential role in maintaining homeostasis. They activate specific immune responses and participate in large numbers of physiological activities by presenting antigen and secreting cytokines. The purpose of this review is to summarize recent advances on the dysfunction of macrophages arisen from microgravity and to discuss the mechanisms of these abnormal responses. Hopefully, our work will contribute not only to the future exploration on the immune system in space, but also to the development of preventive and therapeutic drugs against the physiological consequences of spaceflight.
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Grimm, Daniela. "Microgravity and Space Medicine 2.0." International Journal of Molecular Sciences 23, no. 8 (2022): 4456. http://dx.doi.org/10.3390/ijms23084456.
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Prasad, Binod, Daniela Grimm, Sebastian M. Strauch, et al. "Influence of Microgravity on Apoptosis in Cells, Tissues, and Other Systems In Vivo and In Vitro." International Journal of Molecular Sciences 21, no. 24 (2020): 9373. http://dx.doi.org/10.3390/ijms21249373.
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All life forms have evolved under the constant force of gravity on Earth and developed ways to counterbalance acceleration load. In space, shear forces, buoyance-driven convection, and hydrostatic pressure are nullified or strongly reduced. When subjected to microgravity in space, the equilibrium between cell architecture and the external force is disturbed, resulting in changes at the cellular and sub-cellular levels (e.g., cytoskeleton, signal transduction, membrane permeability, etc.). Cosmic radiation also poses great health risks to astronauts because it has high linear energy transfer values that evoke complex DNA and other cellular damage. Space environmental conditions have been shown to influence apoptosis in various cell types. Apoptosis has important functions in morphogenesis, organ development, and wound healing. This review provides an overview of microgravity research platforms and apoptosis. The sections summarize the current knowledge of the impact of microgravity and cosmic radiation on cells with respect to apoptosis. Apoptosis-related microgravity experiments conducted with different mammalian model systems are presented. Recent findings in cells of the immune system, cardiovascular system, brain, eyes, cartilage, bone, gastrointestinal tract, liver, and pancreas, as well as cancer cells investigated under real and simulated microgravity conditions, are discussed. This comprehensive review indicates the potential of the space environment in biomedical research.
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ElGindi, Mei, Ibrahim Hamed Ibrahim, Jiranuwat Sapudom, Anna Garcia-Sabate, and Jeremy C. M. Teo. "Engineered Microvessel for Cell Culture in Simulated Microgravity." International Journal of Molecular Sciences 22, no. 12 (2021): 6331. http://dx.doi.org/10.3390/ijms22126331.
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As the number of manned space flights increase, studies on the effects of microgravity on the human body are becoming more important. Due to the high expense and complexity of sending samples into space, simulated microgravity platforms have become a popular way to study these effects on earth. In addition, simulated microgravity has recently drawn the attention of regenerative medicine by increasing cell differentiation capability. These platforms come with many advantages as well as limitations. A main limitation for usage of these platforms is the lack of high-throughput capability due to the use of large cell culture vessels. Therefore, there is a requirement for microvessels for microgravity platforms that limit waste and increase throughput. In this work, a microvessel for commercial cell culture plates was designed. Four 3D printable (polycarbonate (PC), polylactic acid (PLA) and resin) and castable (polydimethylsiloxane (PDMS)) materials were assessed for biocompatibility with adherent and suspension cell types. PDMS was found to be the most suitable material for microvessel fabrication, long-term cell viability and proliferation. It also allows for efficient gas exchange, has no effect on cell culture media pH and does not induce hypoxic conditions. Overall, the designed microvessel can be used on simulated microgravity platforms as a method for long-term high-throughput biomedical studies.
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Fedeli, Valeria, Alessandra Cucina, Simona Dinicola, et al. "Microgravity Modifies the Phenotype of Fibroblast and Promotes Remodeling of the Fibroblast–Keratinocyte Interaction in a 3D Co-Culture Model." International Journal of Molecular Sciences 23, no. 4 (2022): 2163. http://dx.doi.org/10.3390/ijms23042163.
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Microgravity impairs tissue organization and critical pathways involved in the cell–microenvironment interplay, where fibroblasts have a critical role. We exposed dermal fibroblasts to simulated microgravity by means of a Random Positioning Machine (RPM), a device that reproduces conditions of weightlessness. Molecular and structural changes were analyzed and compared to control samples growing in a normal gravity field. Simulated microgravity impairs fibroblast conversion into myofibroblast and inhibits their migratory properties. Consequently, the normal interplay between fibroblasts and keratinocytes were remarkably altered in 3D co-culture experiments, giving rise to several ultra-structural abnormalities. Such phenotypic changes are associated with down-regulation of α-SMA that translocate in the nucleoplasm, altogether with the concomitant modification of the actin-vinculin apparatus. Noticeably, the stress associated with weightlessness induced oxidative damage, which seemed to concur with such modifications. These findings disclose new opportunities to establish antioxidant strategies that counteract the microgravity-induced disruptive effects on fibroblasts and tissue organization.
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Markina, Elena, Ekaterina Tyrina, Andrey Ratushnyy, Elena Andreeva, and Ludmila Buravkova. "Heterotypic Cell Culture from Mouse Bone Marrow under Simulated Microgravity: Lessons for Stromal Lineage Functions." International Journal of Molecular Sciences 24, no. 18 (2023): 13746. http://dx.doi.org/10.3390/ijms241813746.
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Muscle and skeleton structures are considered most susceptible to negative factors of spaceflights, namely microgravity. Three-dimensional clinorotation is a ground-based simulation of microgravity. It provides an opportunity to elucidate the effects of microgravity at the cellular level. The extracellular matrix (ECM) content, transcriptional profiles of genes encoding ECM and remodelling molecules, and secretory profiles were investigated in a heterotypic primary culture of bone marrow cells after 14 days of 3D clinorotation. Simulated microgravity negatively affected stromal lineage cells, responsible for bone tissue formation. This was evidenced by the reduced ECM volume and stromal cell numbers, including multipotent mesenchymal stromal cells (MSCs). ECM genes encoding proteins responsible for matrix stiffness and cell-ECM contacts were downregulated. In a heterotypic population of bone marrow cells, the upregulation of genes encoding ECM degrading molecules and the formation of a paracrine profile that can stimulate ECM degradation, may be mechanisms of osteodegenerative events that develop in real spaceflight.
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Kim, Ban-seok, Alfredo V. Alcantara, Je-Hyun Moon, et al. "Comparative Analysis of Muscle Atrophy During Spaceflight, Nutritional Deficiency and Disuse in the Nematode Caenorhabditis elegans." International Journal of Molecular Sciences 24, no. 16 (2023): 12640. http://dx.doi.org/10.3390/ijms241612640.
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While spaceflight is becoming more common than before, the hazards spaceflight and space microgravity pose to the human body remain relatively unexplored. Astronauts experience muscle atrophy after spaceflight, but the exact reasons for this and solutions are unknown. Here, we take advantage of the nematode C. elegans to understand the effects of space microgravity on worm body wall muscle. We found that space microgravity induces muscle atrophy in C. elegans from two independent spaceflight missions. As a comparison to spaceflight-induced muscle atrophy, we assessed the effects of acute nutritional deprivation and muscle disuse on C. elegans muscle cells. We found that these two factors also induce muscle atrophy in the nematode. Finally, we identified clp-4, which encodes a calpain protease that promotes muscle atrophy. Mutants of clp-4 suppress starvation-induced muscle atrophy. Such comparative analyses of different factors causing muscle atrophy in C. elegans could provide a way to identify novel genetic factors regulating space microgravity-induced muscle atrophy.
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Degan, Paolo, Katia Cortese, Alessandra Pulliero, et al. "Simulated Microgravity Effects on Human Adenocarcinoma Alveolar Epithelial Cells: Characterization of Morphological, Functional, and Epigenetic Parameters." International Journal of Molecular Sciences 22, no. 13 (2021): 6951. http://dx.doi.org/10.3390/ijms22136951.
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Background: In space, the reduction or loss of the gravity vector greatly affects the interaction between cells. Since the beginning of the space age, microgravity has been identified as an informative tool in biomedicine, including cancer research. The A549 cell line is a hypotriploid human alveolar basal epithelial cell line widely used as a model for lung adenocarcinoma. Microgravity has been reported to interfere with mitochondrial activity, energy metabolism, cell vitality and proliferation, chemosensitivity, invasion and morphology of cells and organelles in various biological systems. Concerning lung cancer, several studies have reported the ability of microgravity to modulate the carcinogenic and metastatic process. To investigate these processes, A549 cells were exposed to simulated microgravity (µG) for different time points. Methods: We performed cell cycle and proliferation assays, ultrastructural analysis of mitochondria architecture, as well as a global analysis of miRNA modulated under µG conditions. Results: The exposure of A549 cells to microgravity is accompanied by the generation of polynucleated cells, cell cycle imbalance, growth inhibition, and gross morphological abnormalities, the most evident are highly damaged mitochondria. Global miRNA analysis defined a pool of miRNAs associated with µG solicitation mainly involved in cell cycle regulation, apoptosis, and stress response. To our knowledge, this is the first global miRNA analysis of A549 exposed to microgravity reported. Despite these results, it is not possible to draw any conclusion concerning the ability of µG to interfere with the cancerogenic or the metastatic processes in A549 cells. Conclusions: Our results provide evidence that mitochondria are strongly sensitive to µG. We suggest that mitochondria damage might in turn trigger miRNA modulation related to cell cycle imbalance.
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Mezzina, Lidia, Angelo Nicosia, Fabiana Vento, Guido De Guidi, and Placido Giuseppe Mineo. "Photosensitized Thermoplastic Nano-Photocatalysts Active in the Visible Light Range for Potential Applications Inside Extraterrestrial Facilities." Nanomaterials 12, no. 6 (2022): 996. http://dx.doi.org/10.3390/nano12060996.
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Among different depollution methods, photocatalysis activated by solar light is promising for terrestrial outdoor applications. However, its use in underground structures and/or microgravity environments (e.g., extraterrestrial structures) is forbidden. In these cases, there are issues related to the energy emitted from the indoor lighting system because it is not high enough to promote the photocatalytic mechanism. Moreover, microgravity does not allow the recovery of the photocatalytic slurry from the depolluted solution. In this work, the synthesis of a filmable nanocomposite based on semiconductor nanoparticles supported by photosensitized copolyacrylates was performed through a bulk in situ radical copolymerization involving a photosensitizer macromonomer. The macromonomer and the nanocomposites were characterized through UV-Vis, fluorescence and NMR spectroscopies, gel permeation chromatography and thermogravimetric analysis. The photocatalytic activity of the sensitized nanocomposites was studied through photodegradation tests of common dyes and recalcitrant xenobiotic pollutants, employing UV-Vis and visible range (λ > 390 nm) light radiations. The sensitized nanocomposite photocatalytic performances increased about two times that of the unsensitized nanocomposite and that of visible range light radiation alone (>390 nm). The experimental data have shown that these new systems, applied as thin films, have the potential for use in indoor deep underground and extraterrestrial structures.
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Thiel, Cora Sandra, Svantje Tauber, Beatrice Lauber, et al. "Rapid Morphological and Cytoskeletal Response to Microgravity in Human Primary Macrophages." International Journal of Molecular Sciences 20, no. 10 (2019): 2402. http://dx.doi.org/10.3390/ijms20102402.
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The FLUMIAS (Fluorescence-Microscopic Analyses System for Life-Cell-Imaging in Space) confocal laser spinning disk fluorescence microscope represents a new imaging capability for live cell imaging experiments on suborbital ballistic rocket missions. During the second pioneer mission of this microscope system on the TEXUS-54 suborbital rocket flight, we developed and performed a live imaging experiment with primary human macrophages. We simultaneously imaged four different cellular structures (nucleus, cytoplasm, lysosomes, actin cytoskeleton) by using four different live cell dyes (Nuclear Violet, Calcein, LysoBrite, SiR-actin) and laser wavelengths (405, 488, 561, and 642 nm), and investigated the cellular morphology in microgravity (10−4 to 10−5 g) over a period of about six minutes compared to 1 g controls. For live imaging of the cytoskeleton during spaceflight, we combined confocal laser microscopy with the SiR-actin probe, a fluorogenic silicon-rhodamine (SiR) conjugated jasplakinolide probe that binds to F-actin and displays minimal toxicity. We determined changes in 3D cell volume and surface, nuclear volume and in the actin cytoskeleton, which responded rapidly to the microgravity environment with a significant reduction of SiR-actin fluorescence after 4–19 s microgravity, and adapted subsequently until 126–151 s microgravity. We conclude that microgravity induces geometric cellular changes and rapid response and adaptation of the potential gravity-transducing cytoskeleton in primary human macrophages.