Volume 4 (2016): Issue 1 (July 2016)

Recently, the increase in incidence of cardiovascular degeneration associated with weightlessness has drawn much attention to the detrimental effects of space travel on cardiovascular health. Particularly, the regulatory role of the endothelium in cardiovascular degeneration has been studied extensively. The goal of this study was to understand the effects of simulated microgravity on the proliferative, secretory, and anti-thrombogenic functions of endothelial cells differentiated from human blood-derived progenitor cells. Exposure to simulated microgravity enhanced proliferation, as well as the release of soluble nitric oxide while downregulating the release of pro-inflammatory cytokines, such as interleukin-6 (IL-6). Interestingly, the cells also upregulated gene expression of heat shock protein 70 (hsp70), which may be a potential adaptation mechanism of the cells to altered gravity conditions. However, the secretory and proliferative functions had no effect on the anti-thrombogenic functions of these cells. Their anti-coagulative and anti-thrombogenic abilities, as assessed by both upregulation of tissue plasminogen activator (tPA) and their ability to delay plasma clotting, were impaired on exposure to simulated microgravity. These results collectively provide a useful insight into various mechanisms involved in regulating anti-thrombogenic ability of the endothelium, as well as cardiovascular health in altered gravity conditions.

We studied isotropic-nematic (I-N) phase separation via gravity sedimentation in suspensions of plate-like colloidal particles of identical thickness but different lateral sizes (diameters). It is well-known that I-N phase transition occurs at a higher concentration for particles with larger aspect ratio (thickness/diameter) than for particles with smaller aspect ratio. Here we report that for the larger aspect ratios of nanoplates, gravity-driven I-N phase separation is faster. In a homogenously mixed I-N biphasic suspension of nanoplates, nematic tactoids nucleate, grow, and then undergo sedimentation in gravity, leading to the formation of a clear horizontal interface between the I and N phase. For I-N coexistent suspension of nanoplates with different aspect ratios but the same amount of nematic fractions, the larger the aspect ratio, the faster the formation of nematic tactoids and interface between isotropic liquid and nematic liquid crystal phase. The tactoid formation rate is governed by the rotational and translational diffusion rates, which are faster at larger aspect ratios. The time required for I-N separation (t*, seconds) varies inversely with the mean aspect ratio (< ξ >) of nanoplates and follows the relation, t^* = α < ξ >ⁿ, where α = 0.97 ± 1.30 s and n = −2.1 ± 0.2. The phase separation kinetics studied in our experiments offers guidance for the selection of aspect ratio of nanoplates for samples to be studied at the International Space Station (ISS).

Giant yeast colonies develop a low redox potential, which mimics the electrophilic milieu of both the mitochondrial drug metabolizing compartment and the hypoxic core of many tumors. The major metabolic mediators of low redox potential include: ATP, glutathione, NAD+/NADH, and NADP+/NADPH. Ammonia signaling is the critical mechanism that induces stratification of the giant yeast colonies to allow a low redox potential. A comparison of two powerful investigative models for drug pathways using Saccharomyces cerevisiae have been compounded by the use of different growth media and stimuli to the system. Chemogenetic profiling, which uses a pool of yeast deletion mutants to determine survival changes, is heavily slanted to the use of rich media. Giant yeast colonies studies are heavily slanted to the use of poor media. The current study answers the question “what is the difference over time in redox potential, and its major metabolic mediators, between giant yeast colonies grown on rich and poor media?” Using gene deletion tools, we show that cell death in giant yeast colonies is ammonia-dependent. In poor nutrient, ammonia-depleted (Sok2 deletion mutants) giant yeast cultures, rotation can allow manipulation of reactive oxygen species, providing a model to compare high and low redox states without chemical administration. Mechanistically, these changes are not due to detectable NAD/NAPH or NADP/NADPH changes, but are related in changes in glutathione and ATP concentration.

To evaluate effects of microgravity on virulence, we studied the ability of four common clinical pathogens—Klebsiella, Streptococcus, Proteus, and Pseudomonas—to kill wild type Caenorhabditis elegans (C. elegans) nematodes at the larval and adult stages. Simultaneous studies were performed utilizing spaceflight, rotation in a 2D clinorotation device, and static ground controls. Nematodes, microbes, and growth media were separated until exposed to true or modeled microgravity, then mixed and grown for 48 hours. Experiments were terminated by paraformaldehyde fixation, and optical density measurements were used to assay residual microorganisms. Spaceflight was associated with reduced virulence for Klebsiella and Streptococcus, but had negligible effect on Enterococcus and Pseudomonas. Clinorotation generated very different results with all four organisms showing significantly reduced virulence. We conclude that clinorotation is not a consistent model of the changes that actually occur under microgravity conditions. Further, bacteria virulence is unchanged or reduced, not increased during spaceflight.

To assess the comparative similarity of squat data collected as they wore a robotic exoskeleton, female athletes (n=14) did two exercise bouts spaced 14 days apart. Data from their exoskeleton workout was compared to a session they did with free weights. Each squat workout entailed a four-set, four-repetition paradigm with 60-second rest periods. Sets for each workout involved progressively heavier (22.5, 34, 45.5, 57 kg) loads. The same physiological, perceptual, and exercise performance dependent variables were measured and collected from both workouts. Per dependent variable, Pearson correlation coefficients, t-tests, and Cohen's d effect size compared the degree of similarity between values obtained from the exoskeleton and free weight workouts. Results show peak O₂, heart rate, and peak force data produced the least variability. In contrast, far more inter-workout variability was noted for peak velocity, peak power, and electromyography (EMG) values. Overall, an insufficient amount of comparative similarity exists for data collected from both workouts. Due to the limited data similarity, the exoskeleton does not exhibit an acceptable degree of validity. Likely the cause for the limited similarity was due to the brief amount of familiarization subjects had to the exoskeleton prior to actual data collection. A familiarization session that accustomed subjects to squats done with the exoskeleton prior to actual data collection may have considerably improved the validity of data obtained from that device.

The deleterious effects of spaceflight encompass numerous physiological effects that undermine long-term goals of manned round-trip missions to Mars. Among the greater losses are to the human musculoskeletal system due to limited mechanical/load-bearing activity. In-flight exercise and nutritional countermeasures seek to reduce physiological losses. Restoration of mechanical/load-bearing activity in microgravity is achieved with flywheel-based exercise hardware. Research with spaceflight analogs showed exercise done with flywheel-based devices abated muscle mass and strength losses with modest increases in net energy costs. This led to the installment of flywheel-based hardware on The International Space Station (ISS). To date, exercise with flywheel-based hardware has reduced musculoskeletal losses, with more success achieved for muscle-, versus bone-based, outcomes. In-flight exercise may better address bone losses with hardware that imparts high rates of impulse loading to the engaged musculoskeleton.