Human space travel and exploration are of interest to both the industrial and scientific community. However, there are many adverse effects of spaceflight on human physiology. In particular, there is ...a lack of understanding of the extent to which microgravity affects the immune system. T cells, key players of the adaptive immune system and long-term immunity, are present not only in blood circulation but also reside within the tissue. As of yet, studies investigating the effects of microgravity on T cells are limited to peripheral blood or traditional 2D cell culture that recapitulates circulating blood. To better mimic interstitial tissue, 3D cell culture has been well established for physiologically and pathologically relevant models. In this work, we utilize 2D cell culture and 3D collagen matrices to gain an understanding of how simulated microgravity, using a random positioning machine, affects both circulating and tissue-resident T cells. T cells were studied in both resting and activated stages. We found that 3D cell culture attenuates the effects of simulated microgravity on the T cells transcriptome and nuclear irregularities compared to 2D cell culture. Interestingly, simulated microgravity appears to have less effect on activated T cells compared to those in the resting stage. Overall, our work provides novel insights into the effects of simulated microgravity on circulating and tissue-resident T cells which could provide benefits for the health of space travellers.
Root system architecture affects the efficient uptake of water and nutrients in plants. The root growth angle, which is a critical component in determining root system architecture, is affected by ...root gravitropism; however, the mechanism of root gravitropism in rice remains largely unknown. In this study, we conducted a time-course transcriptome analysis of rice roots under conditions of simulated microgravity using a three-dimensional clinostat and following gravistimulation to detect candidate genes associated with the gravitropic response. We found that
(
) genes, which are involved in the regulation of auxin transport, were preferentially up-regulated during simulated microgravity conditions and rapidly down-regulated by gravistimulation. We also found that the transcription factor
A2s (
s) and
s, showed the similar expression patterns with the
s. A co-expression network analysis and an in silico motif search within the upstream regions of the co-expressed genes revealed possible transcriptional control of
s by HSFs. Because HSFA2s are transcriptional activators, whereas HSFB2s are transcriptional repressors, the results suggest that the gene regulatory networks governed by HSFs modulate the gravitropic response through transcriptional control of
s in rice roots.
Background Long-term space missions will necessarily require producing viable seeds to be used for plant cultivation over time under altered gravity conditions. Pollen is known to play a key role in ...determining seed and fruit production over seed-to-seed cycles, but very few studies have evaluated pollen functionality under altered gravity. Methods We performed ground-based experiments to test how simulated microgravity can affect the directional growth of pollen tubes as a potential bottleneck in seed and fruit sets. The effect of clinorotation was assessed in the pollen of Solanum lycopersicum L. cv. ‘Micro-Tom’ and Brassica rapa L. var. silvestris , both eligible for cultivation in space. Pollen tube length and tortuosity were compared under 1 g and simulated microgravity with a uniaxial clinostat. Results The main results highlighted that simulated microgravity significantly increased pollen tube length and tortuosity compared to 1 g conditions. Further, clinorotation prompted a differential effect on pollen germination between S. lycopersicum and B. rapa . A more in-depth analysis evaluating the effect of gravity on the directional growth of pollen tubes excluded gravitropic responses as responsible for the tube tip position reached after germination. Discussion This research provides new insights into how altered gravity can interfere with plant reproduction and, in particular, microgametophyte functionality. Our findings represent a basis for further studies aimed at understanding the effect of real microgravity on plant reproduction and developing countermeasures to ensure seed-to-seed cultivation in long-term space missions and achieve self-sufficiency in food supplies from Earth.
Circadian rhythms are regular oscillations of an organism's physiology with a period of approximately 24 h. In the model plant Arabidopsis thaliana, circadian rhythms regulate a suite of ...physiological processes, including transcription, photosynthesis, growth, and flowering. The circadian clock and external rhythmic factors have extensive control of the underlying biochemistry and physiology. Therefore, it is critical to consider the time of day when performing gravitropism experiments, even if the circadian clock is not a focus of study. We describe the critical factors and methods to be considered and methods to investigate the possible circadian regulation of gravitropic responses.
Earth's gravity is essential for maintaining skeletal muscle mass and function in the body. The role of gravity in the myogenic mechanism has been studied with animal experiments in the International ...Space Station. Recently, gravity-control devices allow to study the effects of gravity on cultured cells on the ground. This study demonstrated that simulated microgravity accelerated aging of human skeletal muscle myoblasts in an in-vitro culture. The microgravity culture induced a significant decrease in cell proliferation and an enlargement of the cytoskeleton and nucleus of cells. Similar changes are often observed in aged myoblasts following several passages. In fact, by the microgravity culture the expression of senescence associated β-Gal was significantly enhanced, and some muscle-specific proteins decreased in the enlarged cells. Importantly, these microgravity effects remained with the cells even after a return to normal gravity conditions. Consequently, the microgravity-affected myoblasts demonstrated a reduced capability of differentiation into myotubes. In the body, it is difficult to interpret the disability of microgravity-affected myoblasts, since muscle regeneration is linked to the supply of new myogenic cells. Therefore, our in-vitro cell culture study will be advantageous to better understand the role of each type of myogenic cell in human muscle without gravitational stress at the single cell level.
•Gravity-control device for understanding effects of gravity on human muscle cells.•A decrease in proliferation of human myoblasts induced by simulated microgravity.•Aging including enlargement and senescence accelerated by simulated microgravity.•A reduced capability to differentiate into myotubes from the “aged” cells.•Understanding specific roles of myoblasts at the single cell level in microgravity.
Skin and its cell components continuously subject to extrinsic and intrinsic mechanical forces and are mechanical sensitive. Disturbed mechanical homeostasis may lead to changes in skin functions. ...Gravity is the integral mechanical force on the earth, however, how gravity contributes to the maintenance of skin function and how microgravity in space affects the wound healing are poorly understood. Here, using microgravity analogs, we show that simulated microgravity (SMG) inhibits the healing of cutaneous wound and the accumulation of dermal fibroblasts in the wound bed. In vitro, SMG inhibits the migration of human foreskin fibroblast cells (HFF‐1), and decreases the F‐actin polymerization and YAP (yes‐associated protein) activity. The SMG‐inhibited migration can be recovered by activating YAP or F‐actin polymerization using lysophosphatidic acid (LPA) or jasplakinolide (Jasp), suggesting the involvement of F‐actin/YAP signaling pathway in this process. In SMG rats, LPA treatment improves the cutaneous healing with increased dermal fibroblasts in the wound bed. Together, our results demonstrate that SMG attenuates the cutaneous wound healing by inhibiting dermal fibroblast migration, and propose the crucial role of F‐actin/YAP mechano‐transduction in the maintenance of skin homeostasis under normal gravity, and YAP as a possible therapeutic target for the skin care of astronauts in space.
Studies of the function of the female reproductive system in zero gravity are urgent for the future exploration of deep space. Female reproductive cells, oocytes, are rich in mitochondria, which ...allow oocytes to produce embryos. The rate of cellular respiration was determined to assess the functional state of the mitochondrial apparatus in Drosophila melanogaster ovaries in which the full cycle of oogenesis took place under simulated microgravity. Since cellular respiration depends on the state of the cytoskeleton, the contents of the main cytoskeletal proteins were determined by Western blotting. To modulate the structure of the cytoskeleton, essential phospholipids were administered per os at a dosage of 500 mg/kg in medium. The results of this study show that after a full cycle of oogenesis under simulated microgravity, the rate of cellular respiration in the fruit fly ovaries increases, apparently due to complex II of the respiratory chain. At the same time, we did not find any changes in the area of oocytes or in the content of proteins in the respiratory chain. However, changes were found in the relative contents of proteins of the actin cytoskeleton. There were no changes of essential phospholipids and no increase in the rate of cellular respiration of the ovaries after exposure to simulated microgravity. However, in the control, the administration of essential phospholipids led to a decrease in the efficiency of oxygen consumption in the flies’ ovaries due to complexes IV–V.
To study processes related to weightlessness in ground-based cell biological research, a theoretically assumed microgravity environment is typically simulated using a clinostat – a small laboratory ...device that rotates cell culture vessels with the aim of averaging out the vector of gravitational forces. Here, we report that the rotational movement during fast clinorotation induces complex fluid motions in the cell culture vessel, which can trigger unintended cellular responses. Specifically, we demonstrate that suppression of myotube formation by 2D-clinorotation at 60 rpm is not an effect of the assumed microgravity but instead is a consequence of fluid motion. Therefore, cell biological results from fast clinorotation cannot be attributed to microgravity unless alternative explanations have been rigorously tested and ruled out. We consider two control experiments mandatory, i) a static, non-rotating control, and ii) a control for fluid motion. These control experiments are also highly recommended for other rotation speed settings and experimental conditions. Finally, we discuss strategies to minimize fluid motion in clinorotation experiments.
•Clinostats rotate cell cultures to average-out the vector of gravitational forces.•Rotational movements induce complex fluid motions in cell culture vessels.•Suppression of myotube formation during clino-rotation is due to fluid motion.•Cell biological results from clino-rotation may not be attributed to microgravity.•Additional control experiments to determine fluid motion effects are mandatory.
•Examining if autophagy can regulate cognitive functions in HU mice.•Two-week HU treatment induced anxious emotions and LTP deficits.•HU decreased hippocampal autophagy level in HU mice.•NR2A/2B, SOD ...and MDA were involved in improving impairments induced by HU.•Rapamycin mitigated anxiety and enhanced LTP via upregulating autophagy in HU mice.
This study examined whether increasing autophagy could improve cognitive deficits in hindlimb unloaded (HU) mice, which was used as an animal model of synaptic plasticity impairment. Male C57BL/6 mice were randomly divided into three groups: control, HU and HU + rapamycin groups. Hindlimb unloading treatment was used to establish the animal model for 2 weeks. Rapamycin was intraperitoneally injected at a dose of 0.5 mg/kg/day along with hindlimb unloading procedure. The open field test and the elevated plus maze test showed that rapamycin considerably prevented the level of anxiety and increased exploratory behaviour in HU mice. Afterwards, long-term potentiation (LTP) recorded in the hippocampal dentate gyrus (DG) region was effectively reduced by rapamycin, which was significantly inhibited by HU procedure. In addition, rapamycin further increased the autophagy level, which was already elevated in HU mice. Meanwhile, the expression of NMDA receptor 2A and 2 B was modified by rapamycin in HU mice. Moreover, rapamycin noticeably increased the total superoxide dismutase (T-SOD) activity and reduced the malondialdehyde (MDA) as well as the level of carbonylated proteins in HU mice’s hippocampus. The results show that increasing autophagy may pacificate the anxious emotion, and partly alleviate the hippocampal synaptic plasticity deficits.
Caenorhabditis elegans is a useful animal model to determine the underlying mechanism for the response to simulated microgravity. In this study, we employed C. elegans as an animal model to ...investigate the role of lipid metabolic sensors in regulating the response to simulated microgravity. Among the lipid metabolic sensors, simulated microgravity treatment could increase the expressions of sbp-1 and mdt-15. RNAi knockdown of sbp-1 or mdt-15 induced a susceptibility to toxicity of simulated microgravity, suggesting the alteration in SBP-1 and MDT-1 mediated a protective response to simulated microgravity. Tissue-specific activity analysis demonstrated that both MDT-15 and SBP-1 could act in the intestine to regulate the response to simulated microgravity. Genetic interaction analysis further indicated that intestinal MDT-15 acted upstream of SBP-1 to regulate the response to simulated microgravity. During the control of response to simulated microgravity, fatty acyl CoA desaturase FAT-6 was identified as the downstream target of intestinal SBP-1. Therefore, the identified signaling cascade of MDT-15-SBP-1-FAT-6 suggested the important function of lipid metabolic sensors in mediating a novel intestinal signaling pathway to regulate the response to simulated microgravity in nematodes.
•MDT-15 and SBP-1 were involved in the regulation of microgravity response.•MDT-15-SBP-1 acted in the intestine to regulate the microgravity response.•FAT-6 was identified as target of SBP-1 in controlling the microgravity response.•We identified a novel intestinal signaling pathway in controlling microgravity response.
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