Radioprotective effects of induced astronaut torpor and advanced propulsion systems during deep space travel.

BACKGROUND: Human metabolic suppression is not a new concept, with 1950s scientific literature and movies demonstrating its potential use for deep space travel (Hock, 1960). An artificially induced state of metabolic suppression in the form of torpor would improve the amount of supplies required and therefore lessen weight and fuel required for missions to Mars and beyond (Choukèr et al., 2019). Transfer habitats for human stasis to Mars have been conceived (Bradford et al., 2018). Evidence suggests that animals, when hibernating, demonstrate relative radioprotection compared to their awake state. Experiments have also demonstrated relative radioprotection in conditions of hypothermia as well as during sleep (Bellesi et al., 2016 and Andersen et al., 2009). Circadian rhythm disrupted cells also appear to be more susceptible to radiation damage compared to those that are under a rhythmic control (Dakup et al., 2018). An induced torpor state for astronauts on deep space missions may provide a biological radioprotective state due to a decreased metabolism and hypothermic conditions. A regular enforced circadian rhythm might further limit DNA damage from radiation. The As Low As Reasonably Achievable (A.L.A.R.A.) radiation protection concept defines time, distance and shielding as ways to decrease radiation exposure. Whilst distance cannot be altered in space and shielding either passively or actively may be beneficial, time of exposure may be drastically decreased with improved propulsion systems. Whilst chemical propulsion systems have superior thrust to other systems, they lack high changes in velocity and fuel efficiency which can be achieved with nuclear or electric based propulsion systems. Radiation toxicity could be limited by reduced transit times, combined with the radioprotective effects of enforced circadian rhythms during a state of torpor or hibernation. OBJECTIVES: 1. Investigate how the circadian clock and body temperature may contribute to radioprotection during human torpor on deep space missions. 2. Estimate radiation dose received by astronauts during a transit to Mars with varying propulsion systems. METHODS: We simulated three types of conditions to investigate the potential radioprotective effect of the circadian clock and decreased temperature on cells being exposed to radiation such that may be the case during astronaut torpor. These conditions were: - Circadian clock strength: strong vs weak. - Light exposure: dark-dark vs light-dark cycle - Body temperature: 37C vs hypothermia vs torpor. We estimated transit times for a mission to Mars from Earth utilizing chemical, nuclear and electrical propulsion systems. Transit times were generated using the General Mission Analysis Tool (GMAT) and Matlab. These times were then input into the National Aeronautics and Space Administration (NASA) Online Tool for the Assessment of Radiation In Space (OLTARIS) computer simulator to estimate doses received by an astronaut for the three propulsion methods. RESULTS: Our simulation demonstrated an increase in radioprotection with decreasing temperature. The greatest degree of radioprotection was shown in cells that maintained a strong circadian clock during torpor. This was in contrast to relatively lower radioprotection in cells with a weak clock during normothermia. We were also able to demonstrate that if torpor weakened the circadian clock, a protective effect could be partially restored by an external drive such as lighting schedules to aid entrainment i.e.: Blue light exposure for periods of awake and no light for rest times For the propulsion simulation, estimated transit times from Earth to Mars were 258 days for chemical propulsion with 165.9mSv received, 209 days for nuclear propulsion with 134.4mSv received and 80 days for electrical propulsion with 51.4mSv received. CONCLUSION: A state of torpor for astronauts on deep space missions may not only improve weight, fuel and storage requirements but also provide a potential biological radiation protection strategy. Moreover, maintaining a controlled circadian rhythm during torpor conditions may aid radioprotection. In the not too distant future, propulsion techniques will be improved to limit transit time and hence decrease radiation dose to astronauts. Limiting exposure time and enhancing physiological radioprotection during transit could provide superior radioprotection benefits compared with active and passive radiation shielding strategies alone.

Endogenous plastic composite material in the Alzheimer's brain.

Accumulation of amyloid beta (Abeta) peptide in brain is the hallmark of Alzheimer's disease (AD). The resulting plaques though fibrous in nature may also consist of additional structures currently poorly defined. We hypothesize that plastic composite material contributes to plaque formation. This material is organized by polymers of acrolein, which is an oxidized lipid fragment found in AD. Acrolein, a 3-carbon compound, contains a carbonyl and a vinyl group that participate in polymerization via fundamental latex chemistry. The redox and surfactant properties of Abeta allow it to catalyze the polymerization of acrolein. We previously reported observations of thin plastic fragments of Abeta-polyacrolein. The current paper outlines the proposed steps in forming these plastic fragments. Endogenous plastic composite material may significantly contribute to the pathogenesis of AD.

Expression of a chimeric retroviral-lipase mRNA confers enhanced lipolysis in a hibernating mammal.

Hibernating mammals can survive several months without feeding by limiting their carbohydrate catabolism and using triacylglycerols stored in white adipose tissue (WAT) as their primary source of fuel. Here we show that a lipolytic enzyme normally found in the gut, pancreatic triacylglycerol lipase (PTL), is expressed in WAT of hibernating 13-lined ground squirrels (Spermophilus tridecemlineatus). PTL expressed in WAT is encoded by an unusual chimeric retroviral-PTL mRNA approximately 500 bases longer than the predominant PTL message found in other ground squirrel tissues. Seasonal measurements detect the chimeric mRNA and PTL enzymatic activity in WAT before and during hibernation, with both showing their lowest observed levels 1 wk after hibernation concludes in mid-March. PTL is expressed in addition to hormone-sensitive lipase, the enzyme typically responsible for hydrolysis of triacylglycerols in WAT. Because of the distinct catalytic and regulatory properties of both enzymes, this dual-triacylglycerol lipase system provides a means by which the fuel requirements of hibernating 13-lined ground squirrels can be met without interruption.

Microsatellite variation and fine-scale population structure in the wood frog (Rana sylvatica).

We investigated genetic population structure in wood frogs (Rana sylvatica) from a series of Prairie Pothole wetlands in the northern Great Plains. Amphibians are often thought to exist in demographic metapopulations, which require some movement between populations, yet genetic studies have revealed strong subdivision among populations, even at relatively fine scales (several km). Wood frogs are highly philopatric and studies of dispersal suggest that they may exhibit subdivision on a scale of approximately 1-2 km. We used microsatellites to examine population structure among 11 breeding assemblages separated by as little as 50 m up to approximately 5.5 km, plus one population separated from the others by 20 km. We found evidence for differentiation at the largest distances we examined and among a few neighbouring ponds, but most populations were strikingly similar in allele frequencies, suggesting high gene flow among all but the most distant populations. We hypothesize that the few significant differences among neighbouring populations at the finest scale may be a transient effect of extinction-recolonization founder events, driven by periodic drying of wetlands in this hydrologically dynamic landscape.

Low-temperature carbon utilization is regulated by novel gene activity in the heart of a hibernating mammal.

Hibernation is a physiological adaptation characterized by dramatic decreases in heart rate, body temperature, and metabolism, resulting in long-term dormancy. Hibernating mammals survive for periods up to 6 mo in the absence of food by minimizing carbohydrate catabolism and using triglyceride stores as their primary source of fuel. The cellular and molecular mechanisms underlying the changes from a state of activity to the hibernating state are poorly understood; however, the selective expression of genes offers one level of control. To address this problem, we used a differential gene expression screen to identify genes that are responsible for the physiological characteristics of hibernation in the heart of the thirteen-lined ground squirrel (Spermophilus tridecemlineatus). Here, we report that genes for pancreatic lipase and pyruvate dehydrogenase kinase isozyme 4 are up-regulated in the heart during hibernation. Pancreatic lipase is normally expressed exclusively in the pancreas, but when expressed in the hibernating heart it liberates fatty acids from triglycerides at temperatures as low as 0 degreesC. Pyruvate dehydrogenase kinase isozyme 4 inhibits carbohydrate oxidation and depresses metabolism by preventing the conversion of pyruvate to Ac-CoA. The resulting anaerobic glycolysis and low-temperature lipid catabolism provide evidence that adaptive changes in cardiac physiology are controlled by the differential expression of genes during hibernation.