Microbiology of human spaceflight: microbial responses to mechanical forces that impact health and habitat sustainability.

SUMMARYUnderstanding the dynamic adaptive plasticity of microorganisms has been advanced by studying their responses to extreme environments. Spaceflight research platforms provide a unique opportunity to study microbial characteristics in new extreme adaptational modes, including sustained exposure to reduced forces of gravity and associated low fluid shear force conditions. Under these conditions, unexpected microbial responses occur, including alterations in virulence, antibiotic and stress resistance, biofilm formation, metabolism, motility, and gene expression, which are not observed using conventional experimental approaches. Here, we review biological and physical mechanisms that regulate microbial responses to spaceflight and spaceflight analog environments from both the microbe and host-microbe perspective that are relevant to human health and habitat sustainability. We highlight instrumentation and technology used in spaceflight microbiology experiments, their limitations, and advances necessary to enable next-generation research. As spaceflight experiments are relatively rare, we discuss ground-based analogs that mimic aspects of microbial responses to reduced gravity in spaceflight, including those that reduce mechanical forces of fluid flow over cell surfaces which also simulate conditions encountered by microorganisms during their terrestrial lifecycles. As spaceflight mission durations increase with traditional astronauts and commercial space programs send civilian crews with underlying health conditions, microorganisms will continue to play increasingly critical roles in health and habitat sustainability, thus defining a new dimension of occupational health. The ability of microorganisms to adapt, survive, and evolve in the spaceflight environment is important for future human space endeavors and provides opportunities for innovative biological and technological advances to benefit life on Earth.

Blood flow restriction: The acute effects of body tilting and reduced gravity analogues on limb occlusion pressure.

Blood flow restriction (BFR) has been identified as a potential countermeasure to mitigate physiological deconditioning during spaceflight. Guidelines recommend that tourniquet pressure be prescribed relative to limb occlusion pressure (LOP); however, it is unclear whether body tilting or reduced gravity analogues influence LOP. We examined LOP at the leg and arm during supine bedrest and bodyweight suspension (BWS) at 6° head-down tilt (HDT), horizontal (0°), and 9.5° head-up tilt (HUT) positions. Twenty-seven adults (age, 26 ± 5 years; height, 1.75 ± 0.08 m; body mass, 73 ± 12 kg) completed all tilts during bedrest. A subgroup (n = 15) additionally completed the tilts during BWS. In each position, LOP was measured twice in the leg and arm using the Delfi Personalized Tourniquet System after 5 min of rest and again after a further 5 min. The LOP at the leg increased significantly from 6° HDT to 9.5° HUT in bedrest and BWS by 9-15 mmHg (Cohen's d = 0.7-1.0). Leg LOP was significantly higher during BWS at horizontal and 9.5° HUT postures relative to the same angles during bedrest by 8 mmHg (Cohen's d = 0.6). Arm LOP remained unchanged between body tilts and analogues. Intraclass correlation coefficients for LOP measurements taken after an initial and subsequent 5 min rest period in all conditions ranged between 0.91-0.95 (leg) and 0.83-0.96 (arm). It is advised that LOP be measured before the application of a vascular occlusion in the same body tilt/setting to which it is applied to minimize discrepancies between the actual and prescribed tourniquet pressure.

Intrinsic dynamics of emulsions: Experiments in microgravity on the International Space Station.

HYPOTHESIS: In order to understand the basic mechanisms affecting emulsion stability, the intrinsic dynamics of the drop population must be investigated. We hypothesize that transient ballistic motion can serve as a marker of interactions between drops. In 1G conditions, buoyancy-induced drop motion obscures these interactions. The microgravity condition onboard the International Space Station enable this investigation. EXPERIMENTS: We performed Diffusing Wave Spectroscopy (DWS) experiments in the ESA Soft Matter Dynamics (SMD) facility. We used Monte Carlo simulations of photon trajectory to support data analysis. The analysis framework was validated by ground-based characterizations of the initial drop size distribution (DSD) and the properties of the oil/water interface in the presence of surfactant. FINDINGS: We characterized the drop size distribution and found to be bi-disperse. Drop dynamics shows transient ballistic features at early times, reaching a stationary regime of primarily diffusion-dominated motion. This suggests different ageing mechanisms: immediately after emulsification, the main mechanism is coalescence or aggregation between small drops. However at later times, ageing proceeds via coalescence or aggregation of small with large drops in some emulsions. Our results elucidate new processes relevant to emulsion stability with potential impact on industrial processes on Earth, as well as enabling technologies for space exploration.

Gut matters in microgravity: potential link of gut microbiota and its metabolites to cardiovascular and musculoskeletal well-being.

The gut microbiota and its secreted metabolites play a significant role in cardiovascular and musculoskeletal health and diseases. The dysregulation of the intestinal microbiota poses a significant threat to cardiovascular and skeletal muscle well-being. Nonetheless, the precise molecular mechanisms underlying these changes remain unclear. Furthermore, microgravity presents several challenges to cardiovascular and musculoskeletal health compromising muscle strength, endothelial dysfunction, and metabolic changes. The purpose of this review is to critically examine the role of gut microbiota metabolites on cardiovascular and skeletal muscle functions and dysfunctions. It also explores the molecular mechanisms that drive microgravity-induced deconditioning in both cardiovascular and skeletal muscle. Key findings in this review highlight that several alterations in gut microbiota and secreted metabolites in microgravity mirror characteristics seen in cardiovascular and skeletal muscle diseases. Those alterations include increased levels of Firmicutes/Bacteroidetes (F/B) ratio, elevated lipopolysaccharide levels (LPS), increased in para-cresol (p-cresol) and secondary metabolites, along with reduction in bile acids and Akkermansia muciniphila bacteria. Highlighting the potential, modulating gut microbiota in microgravity conditions could play a significant role in mitigating cardiovascular and skeletal muscle diseases not only during space flight but also in prolonged bed rest scenarios here on Earth.

Response of Staphylococcus aureus physiology and Agr quorum sensing to low-shear modeled microgravity.

Staphylococcus aureus is commonly isolated from astronauts returning from spaceflight. Previous analysis of omics data from S. aureus low Earth orbit cultures indicated significantly increased expression of the Agr quorum sensing system and its downstream targets in spaceflight samples compared to ground controls. In this current study, the rotary cell culture system (RCCS) was used to investigate the effect of low-shear modeled microgravity (LSMMG) on S. aureus physiology and Agr activity. When cultured in the same growth medium and temperature as the previous spaceflight experiment, S. aureus LSMMG cultures exhibited decreased agr expression and altered growth compared to normal gravity control cultures, which are typically oriented with oxygenation membrane on the bottom of the high aspect rotating vessel (HARV). When S. aureus was grown in an inverted gravity control orientation (oxygenation membrane on top of the HARV), reduced Agr activity was observed relative to both traditional control and LSMMG cultures, signifying that oxygen availability may affect the observed differences in Agr activity. Metabolite assays revealed increased lactate and decreased acetate excretion in both LSMMG and inverted control cultures. Secretomics analysis of LSMMG, control, and inverted control HARV culture supernatants corroborated these results, with inverted and LSMMG cultures exhibiting a decreased abundance of Agr-regulated virulence factors and an increased abundance of proteins expressed in low-oxygen conditions. Collectively, these studies suggest that the orientation of the HARV oxygenation membrane can affect S. aureus physiology and Agr quorum sensing in the RCCS, a variable that should be considered when interpreting data using this ground-based microgravity model.IMPORTANCES. aureus is commonly isolated from astronauts returning from spaceflight and from surfaces within human-inhabited closed environments such as spacecraft. Astronaut health and immune function are significantly altered in spaceflight. Therefore, elucidating the effects of microgravity on S. aureus physiology is critical for assessing its pathogenic potential during long-term human space habitation. These results also highlight the necessity of eliminating potential confounding factors when comparing simulated microgravity model data with actual spaceflight experiments.

[Effect of Collagen Peptides on Function of Mouse T Lymphocytes under Simulated Microgravity].

OBJECTIVE: To understand the effect of collagen peptides on the function of mouse lymphocytes under simulated microgravity. METHODS: The splenocytes of mice were isolated, and the rotary cell culture system was used to simulate the microgravity. The T lymphocytes were stimulated with mitotic agents, concanavalin A (ConA), and the cells were treated with different concentrations of collagen peptides. The proliferation of lymphocytes and the levels of cytokines in the supernatant were detected. RESULTS: Simulated microgravity could inhibit the proliferation of spleen T lymphocytes and decrease the level of cytokines in the supernatant. Collagen peptides could promote the lymphocyte proliferation and cytokine production in cells cultured under simulated microgravity. CONCLUSION: Collagen peptides may attenuate the inhibitory effect of simulated microgravity on T lymphocytes by regulating the cell proliferation and the secretion of cytokines.

LLLT accelerates experimental wound healing under microgravity conditions via PI3K/AKT-CCR2 signal axis.

Background and Purpose: The risk of skin injuries in space is increasing with longer space missions and a growing astronaut population. This highlights the importance of understanding the adverse effects of weightlessness on wound healing. The objective of this research was to examine the therapeutic potential of Low-Level Light Therapy (LLLT) on skin healing processes under simulated microgravity (SMG) conditions and uncover the underlying molecular mechanisms, thus providing innovative solutions and a sound theoretical basis for space skin injuries. Methods: Hindlimb unloading (HU) mice models were used to simulate weightlessness conditions, with or without a complete management of LLLT for 14 days. A systematic testing consisting of HE, Masson and immunohistochemical staining was performed against the standardized mouse tissue specimens. In vitro assessment of cellular biological functions under SMG conditions was carried out in the rotation system of culture (RSOC) using HaCaT and NIH3T3 cell-lines. Results: Under SMG conditions, LLLT significantly reduced skin wound area in HU mice, especially on Days 10 (p < 0.001), accompanied by increased collagen deposition and elevated levels of Ki67 and CD31. Moreover, LLLT showed impressive anti-inflammatory effects represented by the reduced in pro-inflammatory markers including LY6G, F4/80 and CD86, as well as the decreased levels of IL-1ß, IL-6 and TNF-α. Conversely, an elevation in the anti-inflammatory marker CD206 was observed. By employing bioinformatics technology, we further found the PI3K/AKT signaling was prominent in the KEGG pathway analysis and CCR2 acted as a hub gene in the interaction network. Therefore, we demonstrated that LLLT could enhance the phosphorylation of PI3K/AKT and reduce CCR2 expression under SMG conditions, while CCR2 knockdown promoted the phosphorylation of PI3K/AKT, suggesting an important role of CCR2/PI3K/AKT signal axis in LLLT-accelerated wound healing under SMG conditions. Conclusion: LLLT induced activation of the PI3K/AKT signaling pathway through suppression of CCR2 expression, which significantly enhanced skin wound healing under SMG conditions.s.

Cultivation in long-term simulated microgravity is detrimental to pyocyanin production and subsequent biofilm formation ability of Pseudomonas aeruginosa.

Pseudomonas aeruginosa forms aggregates known as biofilms. Previous studies have shown that when P. aeruginosa is cultivated in space, thicker and structurally different biofilms are formed than from those grown on Earth. We investigated how microgravity, simulated in a laboratory setting, influenced the growth, colonization, and virulence potentials of a P. aeruginosa PA14 wild-type strain, as well as two surface attachment-defective (sad) mutants altered at crucial biofilm-forming steps: flgK and pelA. Using high-aspect ratio rotating-wall vessel (HARV) bioreactors, P. aeruginosa bacteria were grown to stationary phase under prolonged (6 days) exposure to simulated microgravity or normal gravity conditions. After the exposure, the capacity of the culture to form biofilms was measured. Additionally, pigment (pyocyanin) formed by each culture during the incubation was extracted and quantified. We demonstrate that the first prolonged exposure to low-shear modeled microgravity (LSMMG) and without nutrient replenishment significantly diminishes wild-type P. aeruginosa PA14 biofilm formation abilities after exposure and pyocyanin production during exposure, while the mutant strains exhibit differing outcomes for both properties. IMPORTANCE: Given plans for humans to engage in prolonged space travel, we investigated biofilm and pigment/virulence factor formation in Pseudomonas aeruginosa when cultivated in microgravity. These bacteria are opportunistic pathogens in immunocompromised individuals. Previous studies of space travelers have shown some immune system diminutions. Hence, our studies shed some light on how prolonged cultivation of bacteria in simulated microgravity conditions affect their growth characteristics.

In situ study on articular cartilage degeneration in simulated microgravity by HOF-ATR-FTIR spectroscopy.

Fourier transform infrared spectroscopy (FTIRS) can provide rich information on the composition and content of samples, enabling the detection of subtle changes in tissue composition and structure. This study represents the first application of FTIRS to investigate cartilage under microgravity. Simulated microgravity cartilage model was firstly established by tail-suspension (TS) for 7, 14 and 21 days, which would be compared to control samples. A self-developed hollow optical fiber attenuated total reflection (HOF-ATR) probe coupled with a FTIR spectrometer was used for the spectral acquisition of cartilage samples in situ, and one-way analysis of variance (ANOVA) was employed to analyze the changes in the contents of cartilage matrix at different stages. The results indicate that cartilage degenerates in microgravity, the collagen content gradually decreases with the TS time, and the structure of collagen fibers changes. The trends of proteoglycan content and collagen integrity show an initial decrease followed by an increase, ultimately significantly decreasing. The findings provide the basis for the cartilage degeneration in microgravity with TS time, which must be of real significance for space science and health detection.

The Case for Bisphosphonate Use in Astronauts Flying Long-Duration Missions.

Changes in the structure of bone can occur in space as an adaptive response to microgravity and on Earth due to the adaptive effects to exercise, to the aging of bone cells, or to prolonged disuse. Knowledge of cell-mediated bone remodeling on Earth informs our understanding of bone tissue changes in space and whether these skeletal changes might increase the risk for fractures or premature osteoporosis in astronauts. Comparisons of skeletal health between astronauts and aging humans, however, may be both informative and misleading. Astronauts are screened for a high level of physical fitness and health, are launched with high bone mineral densities, and perform exercise daily in space to combat skeletal atrophy as an adaptive response to reduced weight-bearing function, while the elderly display cellular and tissue pathology as a response to senescence and disuse. Current clinical testing for age-related bone change, applied to astronauts, may not be sufficient for fully understanding risks associated with rare and uniquely induced bone changes. This review aims to (i) highlight cellular analogies between spaceflight-induced and age-related bone loss, which could aid in predicting fractures, (ii) discuss why overreliance on terrestrial clinical approaches may miss potentially irreversible disruptions in trabecular bone microarchitecture induced by spaceflight, and (iii) detail how the cellular effects of the bisphosphonate class of drugs offer a prophylactic countermeasure for suppressing the elevated bone resorption characteristically observed during long-duration spaceflights. Thus the use of the bisphosphonate will help protect the bone from structural changes while in microgravity either along with exercise or alone when exercise is not performed, e.g. after an injury or illness.

Cardiovascular effects of long-duration space flight.

Introduction: Early studies exploring the physiological effects of space travel have indicated the body's capacity for reversible adaptation. However, the impact of long-duration spaceflight, exceeding 6 months, presents more intricate challenges. Effects on the Cardiovascular CV System: Extended exposure to microgravity and radiation profoundly affects the CV system. Notable phenomena include fluid shifts toward the head and modified arterial pressure. These changes disrupt blood pressure regulation and elevate cardiac output. Additionally, the loss of venous compression leads to a reduction in central venous pressure. Fluid and Plasma Volume Changes: The displacement of fluid from the vascular system to the interstitium, driven by baroreceptor stimulation, results in a 10%-15% decline in plasma volume. Cardiac Muscle and Hematocrit Variations: Intriguingly, despite potential increases in cardiac workload, cardiac muscle atrophy and perplexing variations in hematocrit levels have been observed. The mechanism underlying atrophy appears to involve a shift in protein synthesis from the endoplasmic reticulum to the mitochondria via mortalin-mediated mechanisms. Arrhythmias and QT Interval Prolongation: Instances of arrhythmias have been recurrently documented, although generally nonlethal, in both Russian and American space missions. Long-duration spaceflight has been associated with the prolongation of the QT interval, particularly in extended missions. Radiation Effects: Exposure of the heart to the proton and heavy ion radiation pervasive in deep space contributes to coronary artery degeneration, augmented aortic stiffness, and carotid intima thickening through collagen-mediated processes. Moreover, it accelerates the onset of atherosclerosis and triggers proinflammatory responses. Reentry and Postflight Challenges: Upon reentry, astronauts frequently experience orthostatic intolerance and altered sympathetic responses, which bear potential hazards in scenarios requiring rapid mobilization or evacuation. Conclusion: Consequently, careful monitoring of these cardiac risks is imperative for forthcoming missions. While early studies illuminate the adaptability of the body to space travel's challenges, the intricacies of long-duration missions and their effects on the CV system necessitate continued investigation and vigilance to ensure astronaut health and mission success.

A simulated microgravity-oriented AIE probe-ECM hydrogel-integrated chip for cell culture and superoxide anion radical detection.

Human space activities have been continuously increasing. Astronauts experiencing spaceflight are faced with health problems caused by special space environments such as microgravity, and the investigation of cell injury is fundamental. The development of a platform capable of cell culture and injury detection is the prerequisite for the investigation. Constructing a platform suitable for special conditions in space life science research is the key issue. The ground-based investigation is an indispensable part of the research. Accordingly, a simulated microgravity (SMG)-oriented integrated chip platform capable of 3D cell culture and in situ visual detection of superoxide anion radical (O2•-) is developed. SMG can cause oxidative stress in human cells, and O2•- is one of the signaling molecules. Thus, a O2•--responsive aggregation-induced emission (AIE) probe is designed, which shows high selectivity and sensitivity to O2•-. Moreover, the probe exhibits abilities of long-term and wash-free staining to cells due to the AIE behavior, which is precious for space cell imaging. Meanwhile, a chip with a high-aspect-ratio chamber for adequate medium storage for the lack of the perfusion system during the SMG experiment and a cell culture chamber which can integrate the extracellular matrix (ECM) hydrogel for the bioinspired 3D cell culture is fabricated. In addition, a porous membrane is introduced between the chambers to prevent the hydrogel from separating during the SMG experiment. The afforded AIE probe-ECM hydrogel-integrated chip can achieve 3D culturing of U87-MG cells and in situ fluorescent detection of endogenous O2•- in the cells after long-term staining under SMG. The chip provides a powerful and potential platform for ground-based investigation in space life science and biomedical research.

Optimizing healthcare in space: the role of ultrasound imaging in medical conditions.

In the context of long-distance space travel, managing medical conditions presents unique challenges due to communication delays. Consequently, onboard physicians must possess proficiency in diagnostic tools such as ultrasound, which has demonstrated its efficacy in the Space. However, there is a notable lack of comprehensive discussion regarding its effectiveness in handling medical scenarios in the Space. This bibliometric and systematic review aims to provide an updated analysis of the evidence supporting the role of ultrasound imaging in diagnosing medical conditions within microgravity environments.

Three-Dimensional Rotary Culture to Model Mycobacterial Biofilms in Low-Shear Detergent-Free Liquid Suspension.

In vitro biofilm models have allowed researchers to investigate the role biofilms play in the pathogenesis, virulence, and antimicrobial drug susceptibility of a wide range of bacterial pathogens. Rotary cell culture systems create three-dimensional cellular structures, primarily applied to eukaryotic organoids, that better capture characteristics of the cells in vivo. Here, we describe how to apply a low-shear, detergent-free rotary cell culture system to generate biofilms of Mycobacterium bovis BCG. The three-dimensional biofilm model forms mycobacterial cell aggregates in suspension as surface-detached biomass, without severe nutrient starvation or environmental stress, that can be harvested for downstream experiments. Mycobacterium bovis BCG derived from cell clusters display antimicrobial drug tolerance, presence of an extracellular matrix, and evidence of cell wall remodeling, all features of biofilm-associated bacteria that may be relevant to the treatment of tuberculosis.

Skeletal muscle-on-a-chip in microgravity as a platform for regeneration modeling and drug screening.

Microgravity has been shown to lead to both muscle atrophy and impaired muscle regeneration. The purpose was to study the efficacy of microgravity to model impaired muscle regeneration in an engineered muscle platform and then to demonstrate the feasibility of performing drug screening in this model. Engineered human muscle was launched to the International Space Station National Laboratory, where the effect of microgravity exposure for 7 days was examined by transcriptomics and proteomics approaches. Gene set enrichment analysis of engineered muscle cultured in microgravity, compared to normal gravity conditions, highlighted a metabolic shift toward lipid and fatty acid metabolism, along with increased apoptotic gene expression. The addition of pro-regenerative drugs, insulin-like growth factor-1 (IGF-1) and a 15-hydroxyprostaglandin dehydrogenase inhibitor (15-PGDH-i), partially inhibited the effects of microgravity. In summary, microgravity mimics aspects of impaired myogenesis, and the addition of these drugs could partially inhibit the effects induced by microgravity.

Inflammasome-Inhibiting Nanoligomers Are Neuroprotective against Space-Induced Pathology in Healthy and Diseased Three-Dimensional Human Motor and Prefrontal Cortex Brain Organoids.

The microgravity and space environment has been linked to deficits in neuromuscular and cognitive capabilities, hypothesized to occur due to accelerated aging and neurodegeneration in space. While the specific mechanisms are still being investigated, spaceflight-associated neuropathology is an important health risk to astronauts and space tourists and is being actively investigated for the development of appropriate countermeasures. However, such space-induced neuropathology offers an opportunity for accelerated screening of therapeutic targets and lead molecules for treating neurodegenerative diseases. Here, we show a proof-of-concept high-throughput target screening (on Earth), target validation, and mitigation of microgravity-induced neuropathology using our Nanoligomer platform, onboard the 43-day SpaceX CRS-29 mission to the International Space Station. First, comparing 3D healthy and diseased prefrontal cortex (PFC, for cognition) and motor neuron (MN, for neuromuscular function) organoids, we assessed space-induced pathology using biomarkers relevant to Alzheimer's disease (AD), frontotemporal dementia (FTD), and amyotrophic lateral sclerosis (ALS). Both healthy and diseased PFC and MN organoids showed significantly enhanced neurodegeneration in space, as measured through relevant disease biomarkers, when compared to their respective Earth controls. Second, we tested the top two lead molecules, NI112 that targeted NF-κB and NI113 that targeted IL-6. We observed that these Nanoligomers significantly mitigate the AD, FTD, and ALS relevant biomarkers like amyloid beta-42 (Aß42), phosphorylated tau (pTau), Kallikrein (KLK-6), Tar DNA-binding protein 43 (TDP-43), and others. Moreover, the 43-day Nanoligomer treatment of these brain organoids did not appear to cause any observable toxicity or safety issues in the target organoid tissue, suggesting good tolerability for these molecules in the brain at physiologically relevant doses. Together, these results show significant potential for both the development and translation of NI112 and NI113 molecules as potential neuroprotective countermeasures for safer space travel and demonstrate the usefulness of the space environment for rapid, high-throughput screening of targets and lead molecules for clinical translation. We assert that the use of microgravity in drug development and screening may ultimately benefit millions of patients suffering from debilitating neurodegenerative diseases on Earth.

Integrated analysis of miRNAome and transcriptome reveals that microgravity induces the alterations of critical functional gene modules via the regulation of miRNAs in short-term space-flown C. elegans.

Microgravity, as a unique hazardous factor encountered in space, can induce a series of harmful effects on living organisms. The impact of microgravity on the pivotal functional gene modules stemming from gene enrichment analysis via the regulation of miRNAs is not fully illustrated. To explore the microgravity-induced alterations in critical functional gene modules via the regulation of miRNAs, in the present study, we proposed a novel bioinformatics algorithm for the integrated analysis of miRNAome and transcriptome from short-term space-flown C. elegans. The samples of C. elegans were exposed to two space conditions, namely spaceflight (SF) and spaceflight control (SC) onboard the International Space Station for 4 days. Additionally, the samples of ground control (GC) were included for comparative analysis. Using the present algorithm, we constructed regulatory networks of functional gene modules annotated from differentially expressed genes (DEGs) and their associated regulatory differentially expressed miRNAs (DEmiRNAs). The results showed that functional gene modules of molting cycle, defense response, fatty acid metabolism, lysosome, and longevity regulating pathway were facilitated by 25 down-regulated DEmiRNAs (e.g., cel-miR-792, cel-miR-65, cel-miR-70, cel-lsy-6, cel-miR-796, etc.) in the SC vs. GC groups, whereas these modules were inhibited by 13 up-regulated DEmiRNAs (e.g., cel-miR-74, cel-miR-229, cel-miR-70, cel-miR-249, cel-miR-85, etc.) in the SF vs. GC groups. These findings indicated that microgravity could significantly alter gene expression patterns and their associated functional gene modules in short-term space-flown C. elegans. Additionally, we identified 34 miRNAs as post-transcriptional regulators that modulated these functional gene modules under microgravity conditions. Through the experimental verification, our results demonstrated that microgravity could induce the down-regulation of five critical functional gene modules (i.e., molting cycle, defense response, fatty acid metabolism, lysosome, and longevity regulating pathways) via the regulation of miRNAs in short-term space-flown C. elegans.

Imaging in spaceflight associated neuro-ocular syndrome (SANS): Current technology and future directions in modalities.

With plans for future long-duration crewed exploration, NASA has identified several high priority potential health risks to astronauts in space. One such risk is a collection of neurologic and ophthalmic findings termed spaceflight associated neuro-ocular syndrome (SANS). The findings of SANS include optic disc edema, globe flattening, retinal nerve fiber layer thickening, chorioretinal folds, hyperopic shifts, and cotton-wool spots. The cause of SANS was initially thought to be a cephalad fluid shift in microgravity leading to increased intracranial pressure, venous stasis and impaired CSF outflow, but the precise etiology of SANS remains ill defined. Recent studies have explored multiple possible pathogenic mechanisms for SANS including genetic and hormonal factors; a cephalad shift of fluid into the orbit and brain in microgravity; and disruption to the brain glymphatic system. Orbital, ocular, and cranial imaging, both on Earth and in space has been critical in the diagnosis and monitoring of SANS (e.g., fundus photography, optical coherence tomography (OCT), magnetic resonance imaging (MRI), and orbital/cranial ultrasound). In addition, we highlight near-infrared spectroscopy and diffusion tensor imaging, two newer modalities with potential use in future studies of SANS. In this manuscript we provide a review of these modalities, outline their current and potential use in space and on Earth, and review the reported major imaging findings in SANS.

Cardiovascular adaptations in microgravity conditions.

Gravity has had a significant impact on the evolution of life on Earth with organisms developing necessary biological adaptations over billions of years to counter this ever-existing force. There has been an exponential increase in experiments using real and simulated gravity environments in the recent years. Although an understanding followed by discovery of counter measures to negate diminished gravity in space had been the driving force of research initially, there has since been a phenomenal leap wherein a force unearthly as microgravity is beginning to show promising potential. The current review summarizes pathophysiological changes that occur in multiple aspects of the cardiovascular system when exposed to an altered gravity environment leading to cardiovascular deconditioning and orthostatic intolerance. Gravity influences not just the complex multicellular systems but even the survival of organisms at the molecular level by intervening fundamental cellular processes, directly affecting those linked to actin and microtubule organization via mechano-transduction pathways. The reach of gravity ranges from cytoskeletal rearrangement that regulates cell adhesion and migration to intracellular dynamics that dictate cell fate commitment and differentiation. An understanding that microgravity itself is not present on Earth propels the scope of simulated gravity conditions to be a unique and useful environment that could be explored for enhancing the potential of stem cells for a wide range of applications as has been highlighted here.