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At least 73 records · Page 4

Analyses of plasma for metabolic and hormonal changes in rats flown aboard Cosmos 2044

Plasmas samples from rats flown aboard Cosmos 2044 were analyzed for the levels of key metabolites, electrolytes, enzymes, and hormones. The major differences between the flight group and the synchronous control were elevations in glucose, cholesterol, phosphate, creatinine, blood urea nitrogen, lactate dehydrogenase, and aspartate aminotransferase and decreased levels of thyroxine. Most of these differences were not mimicked by tail suspension of ground-based rats; however, both flight and suspended rats exhibited inhibited testosterone secretion. Corticosterone, immunoreactive growth hormone, and prolactin showed inconsistent differences from the various control groups, suggesting that the levels of these hormones were not due to actual or simulated microgravity.

Merrill, Alfred H., Jr.↗

Calcium-regulated nuclear enzymes: potential mediators of phytochrome-induced changes in nuclear metabolism?

Calcium ions have been proposed to serve as important regulatory elements in stimulus-response coupling for phytochrome responses. An important test of this hypothesis will be to identify specific targets of calcium action that are required for some growth or development process induced by the photoactivated form of phytochrome (Pfr). Initial studies have revealed that there are at least two enzymes in pea nuclei that are stimulated by Pfr in a Ca(2+)-dependent fashion, a calmodulin-regulated nucleoside triphosphatase and a calmodulin-independent but Ca(2+)-dependent protein kinase. The nucleoside triphosphatase appears to be associated with the nuclear envelope, while the protein kinase co-purifies with a nuclear fraction highly enriched for chromatin. This short review summarizes the latest findings on these enzymes and relates them to what is known about Pfr-regulated nuclear metabolism.

Non-NASA Center↗

Changes in Liver Metabolic Gene Expression from Radiation Exposure

Radiation exposure is one of the unique physiological challenges of human spaceflight that is not encountered on earth. While radiation exposure is known to impart physiological stresses and alter normal function, it is unclear how it specifically affects drug metabolism. A major concern is that the actions of medications used in spaceflight may deviate from the expectations formed from terrestrial use. This concern was investigated at the molecular level by analyzing how gamma radiation exposure affected gene expression in the livers of mice. Three different doses of radiation were administered and after various intervals of recovery time, gene expression was measured with RT-qPCR screening arrays for drug metabolism and DNA repair. After examining the results of 192 genes total from each of 72 mice, 65 genes were found to be significantly affected by at least one of the doses of radiation. In general, the genes affected are involved in the metabolism of drugs with lipid or steroid hormone-like structures, as well as the maintenance of redox homeostasis and repair of DNA damage.

Peters, C. P.↗

Changes in Liver Metabolic Gene Expression from Radiation Exposure

Increased exposure to radiation is one physiological stressor associated with spaceflight. While known to alter normal physiological function, how radiation affects metabolism of administered medications is unclear. Crew health could be affected if the actions of medications used in spaceflight deviated from expectations formed during terrestrial medication use. Three different doses of gamma radiation (50 mGy - 6.05 Gy) and a sham were administered to groups of 6 mice each, and after various intervals of recovery time, liver gene expression was measured with RT-qPCR arrays for drug metabolism and DNA repair enzymes. Results indicated approx.65 genes of the 190 tested were significantly affected by at least one of the radiation doses. Many of the affected genes are involved in the metabolism of drugs with hydrophobic or steroid-like structures, maintenance of redox homeostasis and repair of DNA damage. Most affected genes returned to near control expression levels by 7 days post-treatment. With 6 Gy exposure, metallothionein expression was 132-fold more than control at the 4 hr time point, and fell at each later time point (11-fold at 24 hrs, and 8-fold at 7 days). In contrast, Cyp17a1 showed a 4-fold elevation at 4 hrs after exposure and remained constant for 7 days.

Peters, C. P.↗

Urinary Acid Excretion Can Predict Changes in Bone Metabolism During Space Flight

Mitigating space flight-induced bone loss is critical for space exploration, and a dietary countermeasure would be ideal. We present here preliminary data from a study where we examined the role of dietary intake patterns as one factor that can influence bone mineral loss in astronauts during space flight. Crewmembers (n=5) were asked to consume a prescribed diet with either a low (0.3-0.6) or high (1.0-1.3) ratio of animal protein to potassium (APro:K) before and during space flight for 4-d periods. Diets were controlled for energy, total protein, calcium, and sodium. 24-h urine samples were collected on the last day of each of the 4-d controlled diet sessions. 24-h urinary acid excretion, which was predicted by dietary potential renal acid load, was correlated with urinary n-telopeptide (NTX, Pearson R = 0.99 and 0.80 for the high and low APro:K sessions, respectively, p<0.001). The amount of protein when expressed as the percentage of total energy (but not as total grams) was also correlated with urinary NTX (R = 0.66, p<0.01). These results, from healthy individuals in a unique environment, will be important to better understand diet and bone interrelationships during space flight as well as on Earth. The study was funded by the NASA Human Research Program.

Zwart, Sara R.↗

Changes in Liver Metabolic Gene Expression after Radiation Exposure

The health of the liver, especially the rate of its metabolic enzymes, determines the concentration of circulating drugs as well as the duration of their efficacy. Most pharmaceuticals are metabolized by the liver, and clinically-used medication doses are given with normal liver function in mind. A drug overdose can result in the case of a liver that is damaged and removing pharmaceuticals from the circulation at a rate slower than normal. Alternatively, if liver function is elevated and removing drugs from the system more quickly than usual, it would be as if too little drug had been given for effective treatment. Because of the importance of the liver in drug metabolism, we want to understand any effects of spaceflight on the enzymes of the liver. Exposure to cosmic radiation is one aspect of spaceflight that can be modeled in ground experiments.

Peters, C. P.↗

An Updated Look at the Pro K Experiment: Urinary Acid Excretion Can Predict Changes in Bone Metabolism During Space Flight

Mitigating space flight-induced bone loss is critical for space exploration, and diet can play a major role in this effort (1). Previous ground-based studies provide evidence that dietary composition can influence bone resorption during bed rest (2). In this study we examined the role of dietary intake patterns as one factor that can influence bone mineral loss in astronauts during space flight. Crew members were asked to consume, for 4 days at a time, prescribed menus with either a low (0.3-0.6 g/mEq) or high (1.0-1.3 g/mEq) ratio of animal protein to potassium (APro:K). Menus were developed for each crewmember, and were designed to meet both crew preferences and study constraints. Intakes of energy, total protein, calcium, and sodium were held relatively constant between the two diets. The order of the menus was randomized, and crews completed each set (low and high) once before and twice during space flight, for a total of 6 controlled diet sessions. One inflight session and three postflight sessions (R+30, R+180, R+365) monitored typical dietary intake. As of this writing, data are available from 14 crew members. Two subject's samples are awaiting return from ISS via Space-X, and the final subject has one more collection session planned in November 2014. On the last day of each of the 4-d controlled diet sessions, 24-h urine samples were collected, along with a fasting blood sample on the morning of the 5th day. Preliminary analyses will show the relationships between diet and flight on markers of bone metabolism. The results from this study, which represent healthy individuals in a unique environment, will be important to better understand diet and bone interrelationships during space flight as well as on Earth. These data will be important as nutritional requirements and food systems are developed for future exploration-class missions. This study was funded by the Human Health Countermeasures Element of NASA Human Research Program.

Zwart, Sara R.↗

Dietary and Urinary Sulfur can Predict Changes in Bone Metabolism During Space Flight

Mitigating space flight-induced bone loss is critical for space exploration, and diet can play a major role in this effort. Previous ground-based studies provide evidence that dietary composition can influence bone resorption during bed rest. In this study we examined the role of dietary intake patterns as one factor that can influence bone mineral loss in astronauts during space flight. Crew members were asked to consume, for 4 days at a time, prescribed menus with either a low (0.3-0.6 g/mEq) or high (1.0-1.3 g/mEq) ratio of animal protein to potassium (APro:K). Menus were developed for each crewmember, and were designed to meet both crew preferences and study constraints. Intakes of energy, total protein, calcium, and sodium were held relatively constant between the two diets. The order of the menus was randomized, and crews completed each set (low and high) once before and twice during space flight, for a total of 6 controlled diet sessions. One inflight session and three postflight sessions (R+30, R+180, R+365) monitored typical dietary intake. As of this writing, data are available from 14 crew members. The final three subjects' inflight samples are awaiting return from the International Space Station via Space-X. On the last day of each of the 4-d controlled diet sessions, 24-h urine samples were collected, along with a fasting blood sample on the morning of the 5th day. Preliminary analyses show that urinary excretion of sulfate (normalized to lean body mass) is a significant predictor of urinary n-telopeptide (NTX). Dietary sulfate (normalized to lean body mass) is also a significant predictor of urinary NTX. The results from this study, will be important to better understand diet and bone interrelationships during space flight as well as on Earth. This study was funded by the Human Health Countermeasures Element of the NASA Human Research Program.

Zwart, Sara R.↗

Mitochondria Dysfunction Central in Driving Health Risks Associated with Spaceflight

Background: Determining the biological impact of spaceflight through novel approaches is essential to reduce the health risks to astronauts for long-term space missions. The current established health risks due to spaceflight are only reflecting known symptomatic and physiologic responses and do not reflect early onset of other potential diseases. There are many unknown variables which still need to be identified to fully understand the health impacts due to the environmental factors in space. Materials and Methods: One method to uncover potential novel biological mechanisms responsible for health risks in astronauts is by utilizing NASA’s GeneLab platform (genelab.nasa.gov). GeneLab is public repository that hosts multiple omics datasets generated from space biology experiments that include experiments flown in space, simulated cosmic radiation experiments, and simulated microgravity experiments. This presentation will provide an example of analysis and novel hypothesis generation that is being produced with GeneLab datasets. A comprehensive multi-omics approach was implemented correlating transcriptomics, proteomics, metabolomics, and methylation analysis. Results: We found that cells have stronger overall biological response than the tissues to spaceflight, with mitochondrial activity and innate immunity pathways being heavily impacted. NASA Twin Study results are consistent with a specific alteration in mitochondrial ATP production. Our results indicate that the space environment can directly induce mitochondrial damage, with mitochondrial dysfunctions being a cause for chronic inflammation and both being involved in the development of metabolic disorders that cause changes in lipid metabolism. We also found biological changes occurring during spaceflight with cell cycle, circadian rhythm and olfactory activity pathways can also influence and be influenced by alterations on mitochondrial activity

Afshin Beheshti↗

BioSentinel ISS Control Experiment Final Investigation Summary Form

Each payload has 18 fluidic cards and each fluidic card has 16 microfluidic wells, for a total of 288 wells. Card activation occurs at different time points throughout the 6-month mission and following ground commands. At each timepoint, two fluidic cards are filled with growth medium containing nutrients and a metabolic indicator dye. In addition to card filling, the temperature of the cards increases from ~4°C (stasis mode) to 23°C to allow for cell growth. The metabolic dye changes color from blue to pink, then pink to clearin the presence of metabolically active yeast cells. The colorimetric changes and cell growth are monitored using a 3-light-emitting diode(LED)optical detection system. The optical data determines how fast the cells are able to recover after accumulating radiation damage over time.After ground command initiation, all the fluidics, thermal and optical detection steps in BioSentinel are fully automated.The biosensor response data is compared to physical dosimetry data collected onboard the same payload. This dosimeter or linear energy transfer (LET)spectrometer is based on TimePix chip technology. This chip measures the total ionizing radiation dose in addition to calculating the LET of each particle that traverses its sensor, thus allowing researchers to characterize the radiation environment around the payload.The biological response (and physical dosimetry) on ISS over time is compared to the deep space mission and to data obtained on the ground.This analysis provides insight on the biological effects of the space radiation exposure in preparation for future long-duration missions to space and inhabitation beyond low-Earth orbit (LEO).

BioSentinel↗

Modeling Calcium Loss from Bones During Space Flight

Calcium loss from bones during space flight creates a risk for astronauts who travel into space, and may prohibit space flights to other planets. The problem of calcium loss during space flight has been studied using animal models, bed rest (as a ground-based model), and humans in-flight. In-flight studies have typically documented bone loss by comparing bone mass before and after flight. To identify changes in metabolism leading to bone loss, we have performed kinetic studies using stable isotopes of calcium. Oral (Ca-43) and intravenous (Ca-46) tracers were administered to subjects (n=3), three-times before flight, once in-flight (after 110 days), and three times post-flight (on landing day, and 9 days and 3 months after flight). Samples of blood, saliva, urine, and feces were collected for up to 5 days after isotope administration, and were analyzed for tracer enrichment. Tracer data in tissues were analyzed using a compartmental model for calcium metabolism and the WinSAAM software. The model was used to: account for carryover of tracer between studies, fit data for all studies using the minimal number of changes between studies, and calculate calcium absorption, excretion, bone calcium deposition and bone calcium resorption. Results showed that fractional absorption decreased by 50% during flight and that bone resorption and urinary excretion increased by 50%. Results were supported by changes in biochemical markers of bone metabolism. Inflight bone loss of approximately 250 mg Ca/d resulted from decreased calcium absorption combined with increased bone resorption and excretion. Further studies will assess the time course of these changes during flight, and the effectiveness of countermeasures to mitigate flight-induced bone loss. The overall goal is to enable human travel beyond low-Earth orbit, and to allow for better understanding and treatment of bone diseases on Earth.

Wastney, Meryl E.↗

Mineral balance, experiment M071

Concern for the long term metabolic consequences of weightless flight was the basis for the conception of the Skylab medical experiment to measure mineral balance. Proper interpretation of obtained data that diminished atmospheric pressure has no appreciable effect, or at least no protective effect, on calcium metabolism. The absence of changes in calcium metabolism indicates that a stable baseline observation has been made for Skylab as far as the effects of atmosphere or calcium metabolism are concerned.

Whedon, G. D.↗

Prevention of disuse osteoporosis: Effect of sodium fluoride during five weeks of bed rest

An attempt was made to modify factors which promote disuse osteoporosis and thereby prevent it from occurring. Since fluoride is currently used to enhance bone formation in the treatment of low turnover osteoporosis, it was hypothesized that if the fluoride ion was available over a long period of time that it would slow the demonstrated loss of calcium by inhibiting bone resorption and enhancing bone formation. This study was used to determine whether oral medication with sodium F will modify or prevent 5 weeks of bed rest induced disuse osteoporosis, to determine the longitudinal effects of 5 weeks of bed rest on PTH, CT and calcitriol, to measure muscle volume changes and metabolic activity by magnetic resonance imaging and magnetic resonance spectroscopy during prolonged bed rest, to measure changes in peak muscle strength and fatigability, and to measure bone turnover in bone biopsies. Subjects were studied during 1 week of equilibration, 4 weeks of control ambulation, 5 weeks of bed rest, and 1 week of reambulation.

Schneider, Victor S.↗

The Role of Vitamin D in the Bone Changes Associated with Simulated Weightlessness

The role of vitamin D in the change in bone metabolism was examined. The serum concentrations in rats sacrificed after 2, 5, 7, 10, 12 and 15 days of suspension was measured. Between days 1 and 5 of suspension and then gradually decreased towards normal between days 5 and 15. The time course of the changes in the circulating concentrations of 1,25(OH)2D and 24,25(OH)2D mirror almost precisely the changes in bone metabolism. The relationship between the changes in vitamin D metabolism and bone metabolism is investigated. Whether the bone changes are due to the change in serum concentration of 1,25(OH)2D or the changes in bone formation causing a reduction in Ca flux out of the serum pool and thereby suppressing 1,25(OH)2D production is examined. It is found that suspension had no effect on hormone concentration in the 1,25(OH)2D infused animals. Nevertheless, both vehicle and 1,25(OH)2D infused suspended rats exhibited the same reduction in bone mineral, and uptake of (45)Ca. It is suggested that the transitory reduction in circulating 1,25(OH)2D during suspension is not likely to cause the abnormalities in bone metabolism but rather that the changes in bone metabolism are primary and cause the fall in serum 1,25(OH)2D concentration. This supports the hypothesis that the metabolic abnormalities in bone associated with simulated weightlessness are due to the direct effect of unweighting on the bone.

Halloran, B. P.↗

Investigating Biological Responses to Space-like Radiation using the yeast Saccharomyces cerevisiae

As we plan crewed missions to the Moon, Mars, and beyond, it is essential to understand how persistent exposure to space radiation affects biology. Unlike on the International Space Station, where crew support and sample return are possible, experiments for long-duration missions require autonomous systems with no sample return. Human cells would be ideal biosensors, but limitations in culture methods, extended prelaunch storage, and long flight durations make it very difficult to keep human cells alive. Unlike other model systems, yeast can survive the constraints of long-duration spaceflight. Despite a billion years of evolution separating yeast from humans, we share homology in hundreds of genes important for basic cell function, including responses to DNA damage. Thus, yeast are excellent biosensors for detecting types/extent of damage induced by space radiation. BioSentinel is NASA’s latest biological CubeSat, and first interplanetary space bioscience mission. BioSentinel is manifested on Artemis 1, the first test flight of NASA’s Space Launch System, in the coming year. The BioSensor payload within BioSentinel contains two yeast strains. The wild type serves as a control for health and “normal” DNA damage repair (DDR). The rad51 deletion mutant is defective for DDR and will undergo alterations to growth and metabolism as it accumulates radiation damage. Changes in growth and metabolic activity will be measured using a 3-color LED detection system and the metabolic redox dye alamarBlue®. Preliminary tests indicate a significant change in alamarBlue response to space-like, low-dose ionizing radiation. We will discuss these findings in four parts – Introduction to biological CubeSats and the BioSentinel mission (presented by Sergio Santa Maria), preliminary responses to space-like ionizing radiation (presented here), a deeper dive into tracking metabolic changes after exposure to ionizing radiation (presented by Diana Gentry), and a look into methods for correcting flight optical data (presented by Abbey Kim). This work is funded by NASA’s Advanced Exploration Systems.

CubeSat↗

Metabolism and biochemistry in hypogravity

The headward shift of body fluid and increase in stress-related hormones that occur in hypogravity bring about a number of changes in metabolism and biochemistry of the human body. Such alterations may have important effects on health during flight and during a recovery period after return to earth. Body fluid and electrolytes are lost, and blood levels of several hormones that control metabolism are altered during space flight. Increased serum calcium may lead to an increased risk of renal stone formation during flight, and altered drug metabolism could influence the efficacy of therapeutic agents. Orthostatic intolerance and an increased risk of fracturing weakened bones are concerns at landing. It is important to understand biochemistry and metabolism in hypogravity so that clinically important developments can be anticipated and prevented or ameliorated.

Leach, Carolyn S.↗