Simulated Microgravity Environment Research Articles

Mitophagy Regulates the Circadian Rhythms by Degrading NR1D1 in Simulated Microgravity and Isolation Environments.

Long-term spaceflight is known to induce disruptions in circadian rhythms, which are driven by a central pacemaker located in the suprachiasmatic nucleus (SCN) of the hypothalamus, but the underlying molecular mechanisms remain unclear. Here, we developed a rat model that simulated microgravity and isolation environments through tail suspension and isolation (TSI). We found that the TSI environment imposed circadian disruptions to the core body temperature, heart rate, and locomotor-activity rhythms of rats, especially in the amplitude of these rhythms. In TSI model rats' SCNs, the core circadian gene NR1D1 showed higher protein but not mRNA levels along with decreased BMAL1 levels, which indicated that NR1D1 could be regulated through post-translational regulation. The autophagosome marker LC3 could directly bind to NR1D1 via the LC3-interacting region (LIR) motifs and induce the degradation of NR1D1 in a mitophagy-dependent manner. Defects in mitophagy led to the reversal of NR1D1 degradation, thereby suppressing the expression of BMAL1. Mitophagy deficiency and subsequent mitochondrial dysfunction were observed in the SCN of TSI models. Urolithin A (UA), a mitophagy activator, demonstrated an ability to enhance the amplitude of core body temperature, heart rate, and locomotor-activity rhythms by prompting mitophagy induction to degrade NR1D1. Cumulatively, our results demonstrate that mitophagy exerts circadian control by regulating NR1D1 degradation, revealing mitophagy as a potential target for long-term spaceflight as well as diseases with SCN circadian disruption.

Impact of modeled microgravity stress on innate immunity in a beneficial animal-microbe symbiosis

The innate immune response is the first line of defense for all animals to not only detect invading microbes and toxins but also sense and interface with the environment. One such environment that can significantly affect innate immunity is spaceflight. In this study, we explored the impact of microgravity stress on key elements of the NFκB innate immune pathway. The symbiosis between the bobtail squid Euprymna scolopes and its beneficial symbiont Vibrio fischeri was used as a model system under a simulated microgravity environment. The expression of genes associated with the NFκB pathway was monitored over time as the symbiosis progressed. Results revealed that although the onset of the symbiosis was the major driver in the differential expression of NFκB signaling, the stress of simulated low-shear microgravity also caused a dysregulation of expression. Several genes were expressed at earlier time points suggesting that elements of the E. scolopes NFκB pathway are stress-inducible, whereas expression of other pathway components was delayed. The results provide new insights into the role of NFκB signaling in the squid-vibrio symbiosis, and how the stress of microgravity negatively impacts the host immune response. Together, these results provide a foundation to develop mitigation strategies to maintain host-microbe homeostasis during spaceflight.

Construction of microgravity biological knowledge graph and its applications in anti-osteoporosis drug prediction

Microgravity in the space environment can potentially have various negative effects on the human body, one of which is bone loss. Given the increasing frequency of human space activities, there is an urgent need to identify effective anti-osteoporosis drugs for the microgravity environment. Traditional microgravity experiments conducted in space suffer from limitations such as time-consuming procedures, high costs, and small sample sizes. In recent years, the in-silico drug discovery method has emerged as a promising strategy due to the advancements in bioinformatics and computer technology. In this study, we first collected a total of 184,915 literature articles related to microgravity and bone loss. We employed a combination of dependency path extraction and clustering techniques to extract data from the text. Afterwards, we conducted data cleaning and standardization to integrate data from several sources, including The Global Network of Biomedical Relationships (GNBR), Curated Drug–Drug Interactions Database (DDInter), Search Tool for Interacting Chemicals (STITCH), DrugBank, and Traditional Chinese Medicines Integrated Database (TCMID). Through this integration process, we constructed the Microgravity Biology Knowledge Graph (MBKG) consisting of 134,796 biological entities and 3,395,273 triplets. Subsequently, the TransE model was utilized to perform knowledge graph embedding. By calculating the distances between entities in the model space, the model successfully predicted potential drugs for treating osteoporosis and microgravity-induced bone loss. The results indicate that out of the top 10 ranked western medicines, 7 have been approved for the treatment of osteoporosis. Additionally, among the top 10 ranked traditional Chinese medicines, 5 have scientific literature supporting their effectiveness in treating bone loss. Among the top 20 predicted medicines for microgravity-induced bone loss, 15 have been studied in microgravity or simulated microgravity environments, while the remaining 5 are also applicable for treating osteoporosis. This research highlights the potential application of MBKG in the field of space drug discovery.

Effect of 15 days -6° head-down bed rest on microbial communities of supragingival plaque in young men.

The microgravity environment astronauts experience during spaceflight can lead to an increased risk of oral diseases and possible changes in oral microecology. In this study, we aimed to assess changes in the microbial community of supragingival plaques to explore the effects of spaceflight microgravity environment on oral microecology. Sixteen healthy male volunteers were recruited, and supragingival plaque samples were collected under -6° head-down bed rest (HDBR) at five-time points: day 1 before HDBR; days 5, 10, and 15 of HDBR; and day 6 of recovery. Bacterial genomic DNA was sequenced using gene sequencing technology with 16S ribosomal ribonucleic acid V3-V4 hypervariable region amplification and the obtained data were analyzed bioinformatically. Alpha diversity analysis showed a significant increase in species richness in supragingival plaque samples on day 15 of HDBR compared with that at pre-HDBR. Beta diversity analysis revealed that the community composition differed among the groups. Species distribution showed that, compared with those at pre-HDBR, the relative abundances of Corynebacterium and Aggregatibacter increased significantly during HDBR, while those of Veillonella, Streptococcus, and Lautropia decreased significantly. Moreover, compared with those at pre-HDBR, the relative abundance of Leptotrichia increased significantly on day 6 of recovery, whereas the relative abundances of Porphyromonas and Streptococcus decreased significantly. Network analysis showed that the interaction relationship between the dominant genera became simpler during HDBR, and the positive and negative correlations between them showed dynamic changes. Phylogenetic investigation of communities by reconstruction of unobserved states analysis showed that the amino acid metabolism function of plaque microorganisms was more enriched during HDBR. In summary, in a 15-day simulated microgravity environment, the diversity, species distribution, interaction relationship, and metabolic function of the supragingival plaque microbial community changed, which suggests that microgravity may affect the oral microecosystem by changing the balance of supragingival plaque microbial communities and further leading to the occurrence and development of oral diseases.

Enhancing cell-scale performance via sustained release of the varicella-zoster virus antigen from a microneedle patch under simulated microgravity.

The immune system of astronauts might become weakened in the microgravity environment in space, and the dormant varicella-zoster virus (VZV) in the body might be reactivated, seriously affecting their work and safety. For working in orbit for the long term, there is currently no efficient and durable delivery system of general vaccines in a microgravity environment. Accordingly, based on the previous foundation, we designed, modified, and synthesized a biodegradable and biocompatible copolymer, polyethylene glycol-polysulfamethazine carbonate urethane (PEG-PSCU) that could be mainly adopted to fabricate a novel sustained-release microneedle (S-R MN) patch. Compared with conventional biodegradable microneedles, this S-R MN patch could not only efficiently encapsulate protein vaccines (varicella-zoster virus glycoprotein E, VZV gE) but also further prolong the release time of VZV gE in a simulated microgravity (SMG) environment. Eventually, we verified the activation of dendritic cells by VZV gE released from the S-R MN patch in an SMG environment and the positive bioeffect of activated dendritic cells on lymphocytes using an in vitro lymph node model. This study is of great significance for the exploration of long-term specific immune responses to the VZV in an SMG environment.

X-Ray Imaging in the Simulated Microgravity Environment of Parabolic Flight.

INTRODUCTION: The advancement of human spaceflight has made urgent the need to develop medical imaging technology to ensure a high level of in-flight care. To date, only ultrasound has been used in spaceflight. Radiography has multiple advantages over ultrasound, including lower operator dependence, more rapid acquisition, typically higher spatial resolution, and characterization of tissue with acoustic impedance precluding ultrasound. This proof-of-concept work demonstrates for the first time the feasibility of performing human radiographs in microgravity.METHODS: Radiographs of a phantom and human subject's hand, knee, chest, cervical spine, and pelvis were obtained aboard a parabolic flight in microgravity and simulated lunar gravity with various subject and operator positions. Control radiographs were acquired with the same system on the ground. These radiographs were performed with a Food and Drug Administration-approved ultra-portable, wireless, battery-powered, digital x-ray system.RESULTS: The radiographs of the phantom acquired in reduced gravity were qualitatively and quantitatively compared to the ground controls and found to exhibit similar diagnostic adequacy. There was no statistically significant difference in contrast resolution or spatial resolution with a spatial resolution across all imaging environments up to the Nyquist frequency of 3.6 line-pairs/mm and an average contrast-to-noise ratio of 2.44.DISCUSSION: As mass, power, and volume limitations lessen over the coming decades and the miniaturization of imaging equipment continues, in-flight implementation of nonsonographic modalities will become practical. Given the demonstrated ease of use and satisfactory image quality, portable radiography is ready to be the new frontier of space medical imaging.Lerner D, Pohlen M, Wang A, Walter J, Cairnie M, Gifford S. X-ray imaging in the simulated microgravity environment of parabolic flight. Aerosp Med Hum Perform. 2023; 94(10):786-791.

SIMULATED MICROGRAVITY CHANGES THE NUMBER OF MECHANICALLY GATED AND MECHANOSENSITIVE ION CHANNELS GENES TRANSCRIPTS IN RAT VENTRICULAR CARDIOMYOCYTES

The mechanoelectrical feedback in the heart is based on the work of mechanically gated (MGCs) and mechanosensitive (MSCs) channels. Since microgravity alters the heart’s morphological and physiological properties, we hypothesized that the expression of both MGCs and MSCs would be affected. We employed RNA transcriptome sequencing to investigate changes in the gene transcript levels of MGCs and MSCs in isolated rat ventricular cardiomyocytes under control conditions and in a simulated microgravity environment. For the first time, our findings demonstrated that simulated microgravity induces alterations in the gene transcript levels of specific MGCs, such as TRPM7, TRPV2, TRPP1, TRPP2, Piezo1, TMEM63A, TMEM36B, and known MSCs, including K2P2.1, K2P3.1, Kir6.1, Kir6.2, NaV1.5, CaV1.2, KV7.1. However, other voltage-gated channels and channels lacking a voltage sensor remained unaffected. These findings suggest that the altered expression of MGCs and MSCs could lead to changes in the net currents across the membrane, ultimately impacting the heart’s function.

Effects of short-term exposure to simulated microgravity on the physiology of Bacillus subtilis and multiomic analysis.

In our study, Bacillus subtiliswas disposed to a simulated microgravity (SMG) environment in high-aspect ratio rotating-wall vessel bioreactors for 14 days, while the control group was disposed to the same bioreactors in a normal gravity (NG) environment for 14 days. The B. subtilisstrain exposed to the SMG (labeled BSS) showed an enhanced growth ability, increased biofilm formation ability, increased sensitivity to ampicillin sulbactam and cefotaxime, and some metabolic alterations compared with theB. subtilisstrain under NG conditions (labeled BSN) and the original strain ofB. subtilis(labeled BSO). The differentially expressed proteins (DEPs) associated with an increased growth rate, such as DNA strand exchange activity, oxidoreductase activity, proton-transporting ATP synthase complex, and biosynthetic process, were significantly upregulated in BSS. The enhanced biofilm formation ability may be related with the DEPs of spore germination and protein processing in BSS, and differentially expressed genes involved in protein localization and peptide secretion were also significantly enriched. The results revealed that SMG may increase the level of related functional proteins by upregulating or downregulating affiliated genes to change physiological characteristics and modulate growth ability, biofilm formation ability (epsB, epsC, epsN), antibiotic sensitivity (penP) and metabolism. Our experiment may gives new ideas for the study of space microbiology.

Effects of short-term -30° HDT on contrast sensitivity.

Potential cognitive and physiological alterations due to space environments have been investigated in long-term space flight and various microgravity-like conditions, for example, head-down tilt (HDT), confinement, isolation, and immobilization. However, little is known about the influence of simulated microgravity environments on visual function. Contrast sensitivity (CS), which indicates how much contrast a person requires to see a target, is a fundamental feature of human vision. Here, we investigated how the CS changed by 1-h -30° HDT and determined the corresponding mechanisms with a perceptual template model. A quick contrast sensitivity function procedure was used to assess the CS at ten spatial frequencies and three external noise levels. We found that (1) relative to the  + 30° head-up tilt (HUT) position, 1-h -30° HDT significantly deteriorated the CS at intermediate frequencies when external noise was present; (2) CS loss was not detected in zero- or high-noise conditions; (3) HDT-induced CS loss was characterized by impaired perceptual template; and (4) self-reported questionnaires indicated that subjects felt less pleasure and more excitement, less comfort and more fatigued by screen light, less comfort in the area around the eye, and serious symptoms such as piercing pain, blur acid, strain, eye burning, and dizziness after HDT. These findings improve our understanding of the negative effects of simulated microgravity on visual function and elucidate the potential risks of astronauts during space flight.

Influence of gonadectomy on muscle health in micro- and partial-gravity environments in rats.

Gonadal hormones, such as testosterone and estradiol, modulate muscle size and strength in males and females. However, the influence of sex hormones on muscle strength in micro- and partial-gravity environments (e.g., the Moon or Mars) is not fully understood. The purpose of this study was to determine the influence of gonadectomy (castration/ovariectomy) on progression of muscle atrophy in both micro- and partial-gravity environments in male and female rats. Male and female Fischer rats (n = 120) underwent castration/ovariectomy (CAST/OVX) or sham surgery (SHAM) at 11 wk of age. After 2 wk of recovery, rats were exposed to hindlimb unloading (0 g), partial weight bearing at 40% of normal loading (0.4 g, Martian gravity), or normal loading (1.0 g) for 28 days. In males, CAST did not exacerbate body weight loss or other metrics of musculoskeletal health. In females, OVX animals tended to have greater body weight loss and greater gastrocnemius loss. Within 7 days of exposure to either microgravity or partial gravity, females had detectable changes to estrous cycle, with greater time spent in low-estradiol phases diestrus and metestrus (∼47% in 1 g vs. 58% in 0 g and 72% in 0.4 g animals, P = 0.005). We conclude that in males testosterone deficiency at the initiation of unloading has little effect on the trajectory of muscle loss. In females, initial low estradiol status may result in greater musculoskeletal losses.NEW & NOTEWORTHY We find that removal of gonadal hormones does not exacerbate muscle loss in males or females during exposure to either simulated microgravity or partial-gravity environments. However, simulated micro- and partial gravity did affect females' estrous cycles, with more time spent in low-estrogen phases. Our findings provide important data on the influence of gonadal hormones on the trajectory of muscle loss during unloading and will help inform NASA for future crewed missions to space and other planets.

Mesenchymal Stem Cell Behavior under Microgravity: From Stress Response to a Premature Senescence.

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.

TiO2 nanostructured implant surface-mediated M2c polarization of inflammatory monocyte requiring intact cytoskeleton rearrangement

BackgroundMicrogravity directly disturbs the reorganization of the cytoskeleton, exerting profound effects on the physiological process of macrophages. Although it has been established that macrophage M1/M2 polarization could be manipulated by the surface nanostructure of biomaterial in our previous study under normal gravity, how will inflammatory monocytes (iMos)-derived macrophages respond to diverse nanostructured Ti surfaces under normal gravity or microgravity remains unrevealed.ResultsIn this study, Cytochalasin D, a cytoskeleton relaxant, was employed to establish the simulated microgravity (SMG) environment. Our results showed that human iMos polarized into M2c macrophages on NT5 surface but M1 type on NT20 surface with divergent inflammatory phenotypes according to the profile of macrophage polarization featured molecules under normal gravity. However, such manipulative effects of NTs surfaces on iMos-derived macrophages were strikingly weakened by SMG, characterized by the altered macrophage morphology, changed cytokine secretion profile, and decreased cell polarization capacity.ConclusionsTo our knowledge, this is the first metallic implantable material study focusing on the functions of specific monocyte subsets and its crucial role of the cytoskeleton in materials-mediated host immune response, which enriches our mechanism knowledge about the crosstalk between immunocytes and biomaterials. The results obtained in the present study may also provide potential targets and strategies for biomaterial development and clinical treatment via precise immune-regulation under normal gravity and microgravity.Graphic

МОЛЕКУЛЯРНЫЕ МЕХАНИЗМЫ ГРАВИЧУВСТВИТЕЛЬНОСТИ: ОТ КЛЕТОК К ВНЕКЛЕТОЧНОМУ МАТРИКСУ

Gravity deprivation is one of the major risk factors in spaceflight. Medical and biological studies show that as a result of prolonged exposure to weightlessness, astronauts and cosmonauts experience unfavorable changes in many physiological systems (loss of bone mass, muscle atrophy, cardiovascular insufficiency, sensorimotor coordination disorders, etc.). Physiological and pathophysiological mechanisms of response to microgravity exposure at different levels of organization (molecular, cellular, tissue, organismal) and subsequent adaptation are actively studied. Under the conditions of the constantly acting terrestrial gravitational field, multicellular organisms have formed a multicomponent mechanoreceptor apparatus including cellular (nucleo- and cytoskeletal skeleton) and extracellular (connective tissue matrix) mechanosensitive elements. The coordination of these compartments is carried out by specialized protein complexes, forming a mechanoreceptor unit. When the Earth's gravity is removed, this unit will be the basis for adaptation processes, acting as a kind of complex gravity receptor. Ground-based simulations are particularly important to elucidate the mechanisms that provide the response to microgravity, as flight limitations do not allow large-scale studies in space. In this review, we analyze the current understanding of the molecular mechanisms of gravity sensiing and the cellular response to microgravity under both real and simulated microgravity environments and discuss the directions for further research in this area.

Detrimental effects of simulated microgravity on mast cell homeostasis and function.

Exposure to microgravity causes significant alterations in astronauts' immune systems during spaceflight; however, it is unknown whether microgravity affects mast cell homeostasis and activation. Here we show that microgravity negatively regulates the survival and effector function of mast cells. Murine bone marrow-derived mast cells (BMMCs) were cultured with IL-3 in a rotary cell culture system (RCCS) that generates a simulated microgravity (SMG) environment. BMMCs exposed to SMG showed enhanced apoptosis along with the downregulation of Bcl-2, and reduced proliferation compared to Earth's gravity (1G) controls. The reduction in survival and proliferation caused by SMG exposure was recovered by stem cell factor. In addition, SMG impaired mast cell degranulation and cytokine secretion. BMMCs pre-exposed to SMG showed decreased release of β-hexosaminidase, interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) upon stimulation with phorbol 12-myristate-13-acetate (PMA) plus calcium ionophore ionomycin, which correlated with decreased calcium influx. These findings provide new insights into microgravity-mediated alterations of mast cell phenotypes, contributing to the understanding of immune system dysfunction for further space medicine research.

Are head-down tilt bedrest studies capturing the true nature of spaceflight-induced cognitive changes? A review.

Although a number of studies have examined cognitive functions in space, the reasons behind the observed changes described by space research and anecdotal reports have not yet been elucidated. A potential source of cognitive changes is the cephalad fluid shift in the body caused by the lack of hydrostatic pressure under microgravity. These alterations can be modeled under terrestrial conditions using ground-based studies, such as head-down tilt bedrest (HDBR). In this review, we compare the results of the space and HDBR cognitive research. Results for baseline and in-flight/in-HDBR comparisons, and for baseline and post-flight/post-HDBR comparisons are detailed regarding sensorimotor skills, time estimation, attention, psychomotor speed, memory, executive functions, reasoning, mathematical processing, and cognitive processing of emotional stimuli. Beyond behavioral performance, results regarding brain electrical activity during simulated and real microgravity environments are also discussed. Finally, we highlight the research gaps and suggest future directions.

Striated Muscle Evaluation Based on Velocity and Amortization Ratio of Mechanical Impulse Propagation in Simulated Microgravity Environment.

Long-duration space flight missions impose extreme physiological stress and/or changes, such as musculoskeletal function degradation, on the crew due to the microgravity exposure. A great deal of research studies have been conducted in order to understand these physiological stress influences and to provide countermeasures to minimize the observed negative effects of weightlessness exposure on musculoskeletal function. Among others, studies and experiments have been conducted in DI analogue Earth-based facilities in order to reproduce the weightlessness negative effects on the human body. This paper presents a complex muscular analysis of mechanical wave propagation in striated muscle, using MusTone, a device developed in-house at the Institute of Space Science, Romania. The data were collected during a 21-day DI campaign in order to investigate muscle fibers' behavior in longitudinal direction, after applying a mechanical impulse, taking into account two particular parameters, namely propagation velocity and amortization ratio. The parameters were determined based on the wave-propagation data collected from five points (one impact point, two distal direction points, and two proximal direction points) along the muscle fiber. By statistically analyzing propagation velocity and amortization ratio parameters, the study revealed that muscle deconditioning is time dependent, the amortization ratio is more significant in the distal direction, and the lower fibers are affected the most.

Effect of Microgravity on the Gut Microbiota Bacterial Composition in a Hindlimb Unloading Model.

We utilised a ground-based microgravity hindlimb unloading (HU) mouse model to elucidate the gut microbiota bacterial changes in mice under a simulated microgravity environment. Four-month-old, male C57/Bl6 mice were randomly divided into ground-based controls and the HU groups and kept under controlled environmental conditions. For the microgravity environment, the mice were suspended in special cages individually for 20 days. At the end of the suspension, the mice were sacrificed; gut dissections were performed, followed by a metagenomic analysis of bacterial species, which was carried out by extracting DNA and 16S rRNA analysis. The results revealed that the gut bacterial communities of mice under gravity and microgravity were different. Notably, our findings revealed differences in the bacterial community structure. Around 449 bacterial OTUs were specific to mice kept under normal gravity versus 443 bacterial OTUs under microgravity conditions. In contrast, 694 bacterial OTUs were common to both groups. When the relative abundance of taxa was analyzed, Bacteroidetes dominated the gut (64.7%) of normal mice. Conversely, mice in the microgravity environment were dominated by Firmicutes (42.7%), and the relative abundance of Bacteroidetes differed significantly between the two groups (p < 0.05). The distribution of Muribaculaceae between normal mice versus microgravity mice was significantly different, at 62% and 36.4%, respectively (p < 0.05). Furthermore, a significant decrease in 11 bacteria was observed in mice under simulated microgravity, including Akkermansia muciniphila, Eubacterium coprostanoligenes, Bacteroides acidifaciens, Clostridium leptum, Methylorubrum extorquens, Comamonas testosterone, Desulfovibrio fairfieldensis, Bacteroides coprocola, Aerococcus urinaeequi, Helicobacter hepaticus, and Burkholderiales. Further studies are needed to elucidate gut bacterial metabolites of these identified bacterial species in microgravity conditions and normal environment. Notably, the influence of these metabolites on obesity, neuroprotection, musculoskeletal and cardiovascular dysfunction, longevity, inflammation, health, and disease in astronauts ought to be investigated and will be important in developing procedures against adverse effects in astronauts following space travel.

A multisite and anti-cross-contamination brief touch sampler for asteroid sample return mission☆

Asteroids are the “time capsules” of the solar system, storing the origin and evolution of the protoplanetary disk. In addition, they are the remaining “building blocks” of the Earth and terrestrial planets, preserving the initial materials of the latter. To study the first 10 million years history of the solar system, a multisite and anti-cross-contamination brief touch sampler (BTS) was designed for the asteroid sample return (ASR) mission of the Chinese Academy of Sciences (CAS). The sampler provides a pair of counterrotating brush wheels to balance the angular momentum during the sampling processes. A combination of brushes with different shapes and stiffnesses are used to maximize the success of the sample acquisition and guide the sample into the sample canister through the anti-impact guide cover. The sample canister is designed with three sample storage containers with independently sealed doors. The canister can accommodate samples from three different sites without cross contamination to conveniently study the substance distribution of asteroids. Because asteroids have typical microgravity characteristics, prototype verification in a simulated microgravity environment was also conducted. The experimental results show that the sample acquisition processes are effective and that a minimum of 2 g of simulated regolith particles can be sampled within 3 s.

The Role of 4-Phenylbutyric Acid in Gut Microbial Dysbiosis in a Mouse Model of Simulated Microgravity

The altered gut microbes of astronauts during space travel may contribute to health issues after their return to Earth. Previously, an association between the elevated endoplasmic reticulum (ER) stress and gut microbial dysbiosis has been described. Herein, we induced gut microbial changes in mice under a simulated microgravity environment in an established model of hindlimb unloaded (HU) mice. The intestinal metabolomic profiles under microgravity conditions using the HU model were examined, along with the potential role of 4-phenylbutyric acid (4-PBA), a potent ER stress inhibitor. For a microgravity environment, the mice were suspended in special cages individually for three weeks. Mice were sacrificed, and gut dissections were performed, followed by amplicon sequencing analysis of bacterial species via DNA extraction and 16S rRNA analysis. The results indicate that the gut bacterial communities of mice differed under gravity and microgravity conditions. Principal component analyses revealed differences in the bacterial community structure in all groups. Around 434 operational taxonomic units (OTUs) were specific to mice seen in controls, while 620 OTUs were specific to HU mice. Additionally, 321 bacterial OTUs were specific to HU mice treated with 4-PBA. When the relative abundance of taxa was analyzed, Bacteroidetes dominated the gut of control and HU mice treated with 4-PBA.. In contrast, the untreated HU mice were dominated by Firmicutes. At the genus level, a reduction in beneficial species of Akkermansia and Lactobacillus was observed in HU but not the unloaded–treated and control mice. Furthermore, an increase in the relative abundance of Lachnospiraceae and Enterorhabdus, associated with inflammation, was observed in HUmice but not in controls and unloaded-treated mice. Following treatment with 4-PBA, the ratio of Firmicutes to Bacteroidetes was restored in unloaded–treated mice, comparable to controls. Of note, beneficial microbes such as Akkermansia and Lactobacillus were observed in unloaded–treated mice but not or in lesser relative abundance in HU mice. Nonetheless, microbial diversity was reduced in unloaded–treated mice compared to controls, and future studies are needed to mitigate this finding. These may comprise the addition of pre-/pro- and postbiotic species in the diet to increase microbial diversity. Overall, the findings suggest that 4-PBA, a potent ER stress inhibitor, may have therapeutic value in treating patients on prolonged bed rest or astronauts during spaceflight.

Comprehensive Understanding of Inactivity-induced Gait Alteration in Rodents.

It is well known that disuse affects neural systems and that joint motions become altered; however, which outcomes properly exhibit these characteristics is still unclear. The present study describes a motion analysis approach that utilizes three-dimensional (3D) reconstruction from video captures. Using this technology, disuse-evoked alterations of walking performances were observed in rodents exposed to a simulated microgravity environment by unloading their hindlimb by their tail. After 2 weeks of unloading, the rats walked on a treadmill, and their gait motions were captured with four charge-coupled device (CCD) cameras. 3D motion profiles were reconstructed and compared to those of control subjects using the image processing software. The reconstructed outcome measures successfully portrayed distinct aspects of distorted gait motion: hyperextension of the knee and ankle joints and higher position of the hip joints during the stance phase. Motion analysis is useful for several reasons. First, it enables quantitative behavioral evaluations instead of subjective observations (e.g., pass/fail in certain tasks). Second, multiple parameters can be extracted to fit specific needs once the fundamental datasets are obtained. Despite hurdles for broader application, the disadvantages of this method, including labor intensity and cost, may be alleviated by determining comprehensive measurements and experimental procedures.