Below, explore peer-reviewed journal articles related to ISS National Lab investigations. For a more extensive list of spaceflight-related publications (not limited to ISS National Lab sponsorship), see the International Space Station Research Results Citations on the NASA website.
Altered immune function has been demonstrated in astronauts during spaceflights dating back to Apollo and Skylab; this could be a major barrier to long-term space exploration. We tested the hypothesis that spaceflight causes changes in microRNA (miRNA) expression. Human leukocytes were stimulated with mitogens on board the International Space Station using an onboard normal gravity control. Bioinformatics showed that miR-21 was significantly up-regulated 2-fold during early T-cell activation in normal gravity, and gene expression was suppressed under microgravity. This was confirmed using quantitative real-time PCR (n = 4). This is the first report that spaceflight regulates miRNA expression. Global microarray analysis showed significant (P < 0.05) suppression of 85 genes under microgravity conditions compared to normal gravity samples. EGR3, FASLG, BTG2, SPRY2, and TAGAP are biologically confirmed targets and are co-up-regulated with miR-21. These genes share common promoter regions with pre-mir-21; as the miR-21 matures and accumulates, it most likely will inhibit translation of its target genes and limit the immune response. These data suggest that gravity regulates T-cell activation not only by transcription promotion but also by blocking translation via noncoding RNA mechanisms. Moreover, this study suggests that T-cell activation itself may induce a sequence of gene expressions that is self-limited by miR-21.—Hughes-Fulford, M., Chang, T. T., Martinez, E. M., Li, C.-F. Spaceflight alters expression of microRNA during T-cell activation.
Spaceflight impacts cardiovascular function in astronauts; however, its impact on cardiac development and the stem cells that form the basis for cardiac repair is unknown. Accordingly, further research is needed to uncover the potential relevance of such changes to human health. Using simulated microgravity (SMG) generated by two-dimensional clinorotation and culture aboard the International Space Station (ISS), we assessed the effects of mechanical unloading on human neonatal cardiovascular progenitor cell (CPC) developmental properties and signaling. Following 6-7 days of SMG and 12 days of ISS culture, we analyzed changes in gene expression. Both environments induced the expression of genes that are typically associated with an earlier state of cardiovascular development. To understand the mechanism by which such changes occurred, we assessed the expression of mechanosensitive small RhoGTPases in SMG-cultured CPCs and observed decreased levels of RHOA and CDC42. Given the effect of these molecules on intracellular calcium levels, we evaluated changes in noncanonical Wnt/calcium signaling. After 6-7 days under SMG, CPCs exhibited elevated levels of WNT5A and PRKCA. Similarly, ISS-cultured CPCs exhibited elevated levels of calcium handling and signaling genes, which corresponded to protein kinase C alpha (PKCα), a calcium-dependent protein kinase, activation after 30 days. Akt was activated, whereas phosphorylated extracellular signal-regulated kinase levels were unchanged. To explore the effect of calcium induction in neonatal CPCs, we activated PKCα using hWnt5a treatment on Earth. Subsequently, early cardiovascular developmental marker levels were elevated. Transcripts induced by SMG and hWnt5a-treatment are expressed within the sinoatrial node, which may represent embryonic myocardium maintained in its primitive state. Calcium signaling is sensitive to mechanical unloading and directs CPC developmental properties. Further research both in space and on Earth may help refine the use of CPCs in stem cell-based therapies and highlight the molecular events of development.
Spaceflight affects numerous organ systems in the body, leading to metabolic dysfunction that may have long-term consequences. Microgravity-induced alterations in liver metabolism, particularly with respect to lipids, remain largely unexplored. Here we utilize a novel systems biology approach, combining metabolomics and transcriptomics with advanced Raman microscopy, to investigate altered hepatic lipid metabolism in mice following short duration spaceflight. Mice flown aboard Space Transportation System -135, the last Shuttle mission, lose weight but redistribute lipids, particularly to the liver. Intriguingly, spaceflight mice lose retinol from lipid droplets. Both mRNA and metabolite changes suggest the retinol loss is linked to activation of PPARα-mediated pathways and potentially to hepatic stellate cell activation, both of which may be coincident with increased bile acids and early signs of liver injury. Although the 13-day flight duration is too short for frank fibrosis to develop, the retinol loss plus changes in markers of extracellular matrix remodeling raise the concern that longer duration exposure to the space environment may result in progressive liver damage, increasing the risk for nonalcoholic fatty liver disease.
Mesodinium rubrum is a globally distributed nontoxic ciliate that is known to produce intense red-colored blooms using enslaved chloroplasts from its algal prey. Although frequent enough to have been observed by Darwin, blooms of M. rubrum are notoriously difficult to quantify because M. rubrum can aggregate into massive clouds of rusty-red water in a very short time due to its high growth rates and rapid swimming behavior and can disaggregate just as quickly by vertical or horizontal dispersion. A September 2012 hyperspectral image from the Hyperspectral Imager for the Coastal Ocean sensor aboard the International Space Station captured a dense red tide of M. rubrum (106 cells per liter) in surface waters of western Long Island Sound. Genetic data confirmed the identity of the chloroplast as a cryptophyte that was actively photosynthesizing. Microscopy indicated extremely high abundance of its yellow fluorescing signature pigment phycoerythrin. Spectral absorption and fluorescence features were related to ancillary photosynthetic pigments unique to this organism that cannot be observed with traditional satellites. Cell abundance was estimated at a resolution of 100 m using an algorithm based on the distinctive yellow fluorescence of phycoerythrin. Future development of hyperspectral satellites will allow for better enumeration of bloom-forming coastal plankton, the associated physical mechanisms, and contributions to marine productivity.
Solar selective coatings are envisioned for use on minisatellites, for applications where solar energy is to be used to power heat engines or to provide thermal energy for remote regions in the interior of the spacecraft. These coatings are designed to have the combined properties of high solar absorptance and low infrared emittance. The coatings must be durable at elevated temperatures. For thermal bus applications, the temperature during operation is likely to be near 100°C. For heat engine applications, the temperature is expected to be much greater. The objective of this work was to screen candidate solar selective coatings for their high temperature durability. Candidate solar selective coatings were composed of molecular mixtures of metal and dielectric, including: nickel and aluminum oxide, titanium and aluminum oxide, and platinum and aluminum oxide. To identify high temperature durability, the solar absorptance and infrared emittance of the candidate coatings were evaluated initially, and after heating to temperatures in the range of 0°C to 700°C. The titanium and aluminum oxide molecular mixture was found to be the most durable.
Microgravity exposure is associated with loss of muscle mass and strength. The E3 ubiquitin ligase MuRF1 plays an integral role in degrading the contractile apparatus of skeletal muscle; MuRF1 null (KO) mice have shown protection in ground-based models of muscle atrophy. In contrast, MuRF1 KO mice subjected to 21 days of microgravity on the International Space Station (ISS) were not protected from muscle atrophy. In a time course experiment microgravity-induced muscle loss on the ISS showed MuRF1 gene expression was not upregulated. A comparison of the soleus transcriptome profiles between spaceflight and a publicly available data set for hindlimb suspension, a claimed surrogate model of microgravity, showed only marginal commonalities between the models. These findings demonstrate spaceflight induced atrophy is unique, and that understanding of effects of space requires study situated beyond the Earth’s mesosphere.
Gravity has an important role in both the development and maintenance of bone mass. This is most evident in the rapid and intense bone loss observed in both humans and animals exposed to extended periods of microgravity in spaceflight. Here, cohabitating 9-week-old male C57BL/6 mice resided in spaceflight for ~4 weeks. A skeletal survey of these mice was compared to both habitat matched ground controls to determine the effects of microgravity and baseline samples in order to determine the effects of skeletal maturation on the resulting phenotype. We hypothesized that weight-bearing bones would experience an accelerated loss of bone mass compared to non-weight-bearing bones, and that spaceflight would also inhibit skeletal maturation in male mice. As expected, spaceflight had major negative effects on trabecular bone mass of the following weight-bearing bones: femur, tibia, and vertebrae. Interestingly, as opposed to the bone loss traditionally characterized for most weight-bearing skeletal compartments, the effects of spaceflight on the ribs and sternum resembled a failure to accumulate bone mass. Our study further adds to the insight that gravity has site-specific influences on the skeleton.
Microgravity-induced alterations in the autonomic nervous system (ANS) contribute to derangements in both the mechanical and electrophysiologic function of the cardiovascular system, leading to severe symptoms in humans following space travel. Because the ANS forms embryonically from neural crest progenitors (NCs), we hypothesized that microgravity can impair NC derived cardiac structures. Accordingly, we conducted in vitro simulated microgravity experiments employing NC genetic lineage-tracing in mice with cKitCreERT2/+, Isl1nLacZ and Wnt1-Cre reporter alleles. Inducible fate-mapping in adult mouse hearts and pluripotent stem cells (iPSCs) demonstrated reduced cKitCreERT2/+-mediated labeling of both NC-derived cardiomyocytes and autonomic neurons (p<0.0005 vs. controls). Whole-transcriptome analysis, suggested that this effect was associated with repressed cardiac NC- and upregulated mesoderm-related gene-expression profiles, coupled with abnormal BMP/TGF-? and Wnt/?-catenin signaling. To separate the manifestations of simulated microgravity on NC- vs. mesodermal-cardiac derivatives, we conducted Isl1nLacZ lineage analyses which indicated a ~3-fold expansion (p<0.05) in mesoderm-derived Isl-1+ pacemaker sinoatrial nodal cells; and a ~3-fold reduction (p<0.05) in cardiac NC-derived ANS cells, including sympathetic nerves and Isl-1+ cardiac ganglia. Finally, NC-specific fate-mapping with a Wnt1-Cre reporter iPSC model of murine NC development confirmed that simulated microgravity directly impacted the in vitro development of cardiac NC progenitors and their contribution to the sympathetic and parasympathetic innervation of the iPSC-derived myocardium. Together these findings reveal an important role for gravity in the development of NCs and their postnatal derivatives; and have important therapeutic implications for human space exploration, providing insights into cellular and molecular mechanisms of microgravity-induced cardiomyopathies/ channelopathies.
Microgravity has a profound effect on cardiovascular function, however, little is known about the impact of microgravity on progenitors that reside within the heart. We investigated the effect of simulated microgravity exposure on progenitors isolated from the neonatal and adult human heart by quantifying changes in functional parameters, gene expression and protein levels after 6-7 days of 2D clinorotation. Utilization of neonatal and adult cardiovascular progenitors in ground-based studies has provided novel insight into how microgravity may affect cells differently depending on age.
Efficient generation of cardiomyocytes from human pluripotent stem cells is critical for their regenerative applications. Microgravity and 3D culture can profoundly modulate cell proliferation and survival. Here, we engineered microscale progenitor cardiac spheres from human pluripotent stem cells and exposed the spheres to simulated microgravity using a random positioning machine for 3 days during their differentiation to cardiomyocytes. This process resulted in the production of highly enriched cardiomyocytes (99% purity) with high viability (90%) and expected functional properties, with a 1.5 to 4-fold higher yield of cardiomyocytes from each undifferentiated stem cell as compared with 3D-standard gravity culture. Increased induction, proliferation and viability of cardiac progenitors as well as up-regulation of genes associated with proliferation and survival at the early stage of differentiation were observed in the 3D culture under simulated microgravity. Therefore, a combination of 3D culture and simulated microgravity can be used to efficiently generate highly enriched cardiomyocytes.
Several small life sciences research modules were designed to accommodate both scientific research and K-12 educational objectives on the same spaceflight mission. The K-12 educational objectives are accomplished by participating students around the globe and complimented by ground experiments conducted in their own classrooms. The spaceflight research is analyzed by students through image analysis of downlinked video and still images. The science objectives of the mission often require sample return for more detailed sample analysis on ground. Integration of new modules as part of a CGBA Science Insert (CSI) into the CGBA incubator is facilitated through standardized interfaces. Engineering challenges, trades and system architecture designs are presented for the CGBA Incubator and the CSI life sciences habitats currently on board of ISS.
The Hyperspectral Imager for the Coastal Ocean (HICO) offers the coastal environmental monitoring community an unprecedented opportunity to observe changes in coastal and estuarine water quality across a range of spatial scales not feasible with traditional field-based monitoring or existing ocean colour satellites. HICO, an Office of Naval Research-sponsored programme, is the first space-based maritime hyperspectral imaging instrument designed specifically for the coastal ocean. HICO has been operating since September 2009 from the Japanese Experiment Module ? Exposed Facility on the International Space Station (ISS). The high pixel resolution (approximately 95 m at nadir) and hyperspectral imaging capability offer a unique opportunity for characterizing a wide range of water colour constituents that could be used to assess environmental condition. In this study, we transform atmospherically corrected ISS/HICO hyperspectral imagery and derive environmental response variables routinely used for evaluating the environmental condition of coastal ecosystem resources. Using atmospherically corrected HICO imagery and a comprehensive field validation programme, three regionally specific algorithms were developed to estimate basic water-quality properties traditionally measured by monitoring agencies. Results indicated that a three-band chlorophyll a algorithm performed best (R2 = 0.62) when compared with in situ measurement data collected 2?4 hours of HICO acquisitions. Coloured dissolved organic matter (CDOM) (R2 = 0.93) and turbidity (R2 = 0.67) were also highly correlated. The distributions of these water-quality indicators were mapped for four estuaries along the northwest coast of Florida from April 2010 to May 2012. However, before the HICO sensor can be transitioned from proof-of-concept to operational status and its data applied to benefit decisions made by coastal managers, problems with vicarious calibration of the sensor need to be resolved and standardized protocols are required for atmospheric correction. Ideally, the sensor should be placed on a polar orbiting platform for greater spatial and temporal coverage as well as for image synchronization with field validation efforts.
The ultimate survival of humanity is dependent upon colonization of other planetary bodies. Key challenges to such habitation are (patho)physiologic changes induced by known, and unknown, factors associated with long-duration and distance space exploration. However, we currently lack biological models for detecting and studying these changes. Here, we use a remote automated culture system to successfully grow an animal in low Earth orbit for six months. Our observations, over 12 generations, demonstrate that the multi-cellular soil worm Caenorhabditis elegans develops from egg to adulthood and produces progeny with identical timings in space as on the Earth. Additionally, these animals display normal rates of movement when fully fed, comparable declines in movement when starved, and appropriate growth arrest upon starvation and recovery upon re-feeding. These observations establish C. elegans as a biological model that can be used to detect changes in animal growth, development, reproduction and behaviour in response to environmental conditions during long-duration spaceflight. This experimental system is ready to be incorporated on future, unmanned interplanetary missions and could be used to study cost-effectively the effects of such missions on these biological processes and the efficacy of new life support systems and radiation shielding technologies.
Heart rate (HR) is a valuable and widespread measure for physical training programs, although its description of conditioning is limited to the cardiac response to exercise. More comprehensive measures of exercise adaptation include cardiac output (dot Q), stroke volume (SV) and oxygen uptake (dot VO2), but these physiological parameters can be measured only with cumbersome equipment installed in clinical settings. In this work, we explore the ability of pulse transit time (PTT) to represent a valuable pairing with HR for indirectly estimating dot Q, SV and dot VO2 non-invasively. PTT was measured as the time interval between the peak of the electrocardiographic (ECG) R-wave and the onset of the photoplethysmography (PPG) waveform at the periphery (i.e. fingertip) with a portable sensor. Fifteen healthy young subjects underwent a graded incremental cycling protocol after which HR and PTT were correlated with dot Q, SV and dot VO2 using linear mixed models. The addition of PTT significantly improved the modeling of dot Q, SV and dot VO2 at the individual level ($R_1^2 = 0.419$ for SV, 0.548 for dot Q, and 0.771 for dot VO2) compared to predictive models based solely on HR ($R_1^2 = 0.379$ for SV, 0.503 for dot Q, and 0.745 for dot VO2). While challenges in sensitivity and artifact rejection exist, combining PTT with HR holds potential for development of novel wearable sensors that provide exercise assessment largely superior to HR monitors.
We introduce a decentralized attitude control strategy that can dramatically reduce the usage of propellant, by taking full advantage of the physical coupling of the tether. Motivated by a controllability analysis, indicating that both array resizing and spin-up are fully controllable by the reaction wheels and the tether motor, we report the first propellant-free underactuated control results for tethered formation flying spacecraft. This paper also describes the hardware development and experimental validation of the proposed method using the Synchronized Position Hold, Engage, and Reorient Experimental Satellites test bed. In particular, a new relative sensing mechanism that uses sixdegree-of-freedom force-torque sensors and rate gyroscopes is introduced and validated in the closed-loop control experiments.
This is the second in a series of papers that exploit the physical coupling of tethered spacecraft to derive a propellant-free spin-up and attitude control strategy. We take a nonlinear control approach to underactuated tethered formation flying spacecraft, whose lack of full state feedback linearizability, along with their complex nonholonomic behavior, characterizes the difficult nonlinear control problem. We introduce several nonlinear control laws that are more efficient in tracking time-varying trajectories than linear control. We also extend our decentralized control approach to underactuated tethered systems, thereby eliminating the need for any intersatellite communication. To our knowledge, this work reports the first nonlinear control results for underactuated tethered formation flying spacecraft. This article further illustrates the potential of the proposed strategy by providing a new momentum dumping method that does not use torque-generating thrusters.
A precise measurement of the proton flux in primary cosmic rays with rigidity (momentum/charge) from 1 GV to 1.8 TV is presented based on 300 million events. Knowledge of the rigidity dependence of the proton flux is important in understanding the origin, acceleration, and propagation of cosmic rays. We present the detailed variation with rigidity of the flux spectral index for the first time. The spectral index progressively hardens at high rigidities.
Knowledge of the precise rigidity dependence of the helium flux is important in understanding the origin, acceleration, and propagation of cosmic rays. A precise measurement of the helium flux in primary cosmic rays with rigidity (momentum/charge) from 1.9 GV to 3 TV based on 50 million events is presented and compared to the proton flux. The detailed variation with rigidity of the helium flux spectral index is presented for the first time. The spectral index progressively hardens at rigidities larger than 100 GV. The rigidity dependence of the helium flux spectral index is similar to that of the proton spectral index though the magnitudes are different. Remarkably, the spectral index of the proton to helium flux ratio increases with rigidity up to 45 GV and then becomes constant; the flux ratio above 45 GV is well described by a single power law.
Knowledge of the rigidity dependence of the boron to carbon flux ratio (B/C) is important in understanding the propagation of cosmic rays. The precise measurement of the B/C ratio from 1.9 GV to 2.6 TV, based on 2.3 million boron and 8.3 million carbon nuclei collected by AMS during the first 5 years of operation, is presented. The detailed variation with rigidity of the B/C spectral index is reported for the first time. The B/C ratio does not show any significant structures in contrast to many cosmic ray models that require such structures at high rigidities. Remarkably, above 65 GV, the B/C ratio is well described by a single power law RΔ with index Δ=−0.333±0.014(fit)±0.005(syst), in good agreement with the Kolmogorov theory of turbulence which predicts Δ=−1/3 asymptotically.
We present a measurement of the cosmic ray (e++e−) flux in the range 0.5 GeV to 1 TeV based on the analysis of 10.6 million (e++e−) events collected by AMS. The statistics and the resolution of AMS provide a precision measurement of the flux. The flux is smooth and reveals new and distinct information. Above 30.2 GeV, the flux can be described by a single power law with a spectral index γ=−3.170±0.008(stat+syst)±0.008(energy scale).