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Research Containing: Spaceflight

Transient gene and microRNA expression profile changes of confluent human fibroblast cells in spaceflight

by on 22 August 2016in Biology & Biotechnology No comment

Microgravity, or an altered gravity environment different from the 1 g of the Earth, has been shown to influence global gene expression patterns and protein levels in cultured cells. However, most of the reported studies that have been conducted in space or by using simulated microgravity on the ground have focused on the growth or differentiation of these cells. It has not been specifically addressed whether nonproliferating cultured cells will sense the presence of microgravity in space. In an experiment conducted onboard the International Space Station, confluent human fibroblast cells were fixed after being cultured in space for 3 and 14 d, respectively, to investigate changes in gene and microRNA (miRNA) expression profiles in these cells. Results of the experiment showed that on d 3, both the flown and ground cells were still proliferating slowly, as measured by the percentage of Ki-67(+) cells. Gene and miRNA expression data indicated activation of NF-kappaB and other growth-related pathways that involve hepatocyte growth factor and VEGF as well as the down-regulation of the Let-7 miRNA family. On d 14, when the cells were mostly nonproliferating, the gene and miRNA expression profile of the flight sample was indistinguishable from that of the ground sample. Comparison of gene and miRNA expressions in the d 3 samples, with respect to d 14, revealed that most of the changes observed on d 3 were related to cell growth for both the flown and ground cells. Analysis of cytoskeletal changes via immunohistochemistry staining of the cells with antibodies for alpha-tubulin and fibronectin showed no difference between the flown and ground samples. Taken together, our study suggests that in true nondividing human fibroblast cells in culture, microgravity experienced in space has little effect on gene and miRNA expression profiles.-Zhang, Y., Lu, T., Wong, M., Wang, X., Stodieck, L., Karouia, F., Story, M., Wu, H. Transient gene and microRNA expression profile changes of confluent human fibroblast cells in spaceflight.

Related URLs:
http://www.ncbi.nlm.nih.gov/pubmed/26917741

Medication use by U.S. crewmembers on the International Space Station

by on 22 August 2016in Biology & Biotechnology No comment

The environment on the International Space Station (ISS) includes a variety of potential physiologic stressors, including low gravity, elevated exposure to radiation, confined living and working quarters, a heavy workload, and high public visibility. This retrospective study examined medication use during long-duration spaceflights (>30 d). Medication records from 24 crewmembers on 20 missions longer than 30 d over a 10 yr period were examined for trends in usage rates, efficacy, and indication, as well as adverse event quality, frequency, and severity. Results were compared with those from crewmembers on shorter space shuttle missions (>16 d) and other reports of medication use by healthy adults. The most frequently used medications on the ISS were for sleep problems, pain, congestion, or allergy. Medication use during spaceflight missions was similar to that noted on the Space Shuttle and in adult ambulatory medicine, except that usage of sleep aids was about 10 times higher during spaceflight missions. There were also 2 apparent treatment failures in cases of skin rash, raising questions about the efficacy or suitability of the treatments used. Many spaceflight-related medication uses (at least 10%) were linked to extravehicular activities, exercise protocols, or equipment and operationally driven schedule changes. It seems likely that alterations in spaceflight mission operations (schedule-shifting and lighting) or hardware (extravehicular activity suits and exercise equipment) could reduce the need for a sizable fraction of medication uses.

Related URLs:
http://www.ncbi.nlm.nih.gov/pubmed/26187345

Chemical Potency and Degradation Products of Medications Stored Over 550 Earth Days at the International Space Station

by on 22 August 2016in Biology & Biotechnology, Physical Sciences

Medications degrade over time, and degradation is hastened by extreme storage conditions. Current procedures ensure that medications aboard the International Space Station (ISS) are restocked before their expiration dates, but resupply may not be possible on future long-duration exploration missions. For this reason, medications stored on the ISS were returned to Earth for analysis. This was an opportunistic, observational pilot-scale investigation to test the hypothesis that ISS-aging does not cause unusual degradation. Nine medications were analyzed for active pharmaceutical ingredient (API) content and degradant amounts; results were compared to 2012 United States Pharmacopeia (USP) requirements. The medications were two sleep aids, two antihistamines/decongestants, three pain relievers, an antidiarrheal, and an alertness medication. Because the samples were obtained opportunistically from unused medical supplies, each medication was available at only 1 time point and no control samples (samples aged for a similar period on Earth) were available. One medication met USP requirements 5 months after its expiration date. Four of the nine (44% of those tested) medications tested met USP requirements 8 months post expiration. Another three medications (33%) met USP guidelines 2-3 months before expiration. One compound, a dietary supplement used as a sleep aid, failed to meet USP requirements at 11 months post expiration. No unusual degradation products were identified. Limited, evidence-based extension of medication shelf-lives may be possible and would be useful in preparation for lengthy exploration missions. Only analysis of flight-aged samples compared to appropriately matched ground controls will permit determination of the spaceflight environment on medication stability.

Related URLs:
http://www.ncbi.nlm.nih.gov/pubmed/26546565

Evolution of Russian Microgravity Countermeasures

by on 22 August 2016in Biology & Biotechnology No comment

INTRODUCTION: Countermeasures to prevent or partially offset the negative physiologic changes that are caused by the effects of microgravity play an important role in supporting the performance of crewmembers in flight and their safe return to Earth. Research conducted in Russia on the orbital stations Salyut and Mir, as well as simulation experiments on the ground, have demonstrated that changes that occur during extended spaceflight in various physiologic systems can be prevented or significantly decreased by using countermeasures. Hardware and techniques used on the ISS have been substantially improved to reflect the experience of previous extended missions on Russian orbital stations. Countermeasures used during early ISS missions consisted of the U.S. treadmill (TVIS), cycle ergometer (capital VE, Cyrilliccapital BE, Cyrillic-3), a set of resistance bands, a postural muscle loading suit (Penguin-3), electrical stimulator (Tonus-3), compression thigh cuffs (Braslet-capital EM, Cyrillic), a lower body negative pressure (LBNP) suit (Chibis), a lower body g-loading suit (Kentavr), and water/salt supplements. These countermeasures are described in this article.

Related URLs:
http://www.ncbi.nlm.nih.gov/pubmed/26630193

Guidelines for Dual Energy X-Ray Absorptiometry Analysis of Trabecular Bone-Rich Regions in Mice: Improved Precision, Accuracy, and Sensitivity for Assessing Longitudinal Bone Changes

by on 22 August 2016in Biology & Biotechnology No comment

Trabecular bone is frequently studied in osteoporosis research because changes in trabecular bone are the most common cause of osteoporotic fractures. Dual energy X-ray absorptiometry (DXA) analysis specific to trabecular bone-rich regions is crucial to longitudinal osteoporosis research. The purpose of this study is to define a novel method for accurately analyzing trabecular bone-rich regions in mice via DXA. This method will be utilized to analyze scans obtained from the International Space Station in an upcoming study of microgravity-induced bone loss. Thirty 12-week-old BALB/c mice were studied. The novel method was developed by preanalyzing trabecular bone-rich sites in the distal femur, proximal tibia, and lumbar vertebrae via high-resolution X-ray imaging followed by DXA and micro-computed tomography (micro-CT) analyses. The key DXA steps described by the novel method were (1) proper mouse positioning, (2) region of interest (ROI) sizing, and (3) ROI positioning. The precision of the new method was assessed by reliability tests and a 14-week longitudinal study. The bone mineral content (BMC) data from DXA was then compared to the BMC data from micro-CT to assess accuracy. Bone mineral density (BMD) intra-class correlation coefficients of the new method ranging from 0.743 to 0.945 and Levene’s test showing that there was significantly lower variances of data generated by new method both verified its consistency. By new method, a Bland-Altman plot displayed good agreement between DXA BMC and micro-CT BMC for all sites and they were strongly correlated at the distal femur and proximal tibia (r=0.846, p<0.01; r=0.879, p<0.01, respectively). The results suggest that the novel method for site-specific analysis of trabecular bone-rich regions in mice via DXA yields more precise, accurate, and repeatable BMD measurements than the conventional method. Related URLs:
http://www.ncbi.nlm.nih.gov/pubmed/26956416

Bone metabolism and renal stone risk during International Space Station missions

by on 22 August 2016in Biology & Biotechnology No comment

Bone loss and renal stone risk are longstanding concerns for astronauts. Bone resorption brought on by spaceflight elevates urinary calcium and the risk of renal stone formation. Loss of bone calcium leads to concerns about fracture risk and increased long-term risk of osteoporosis. Bone metabolism involves many factors and is interconnected with muscle metabolism and diet. We report here bone biochemistry and renal stone risk data from astronauts on 4- to 6-month International Space Station missions. All had access to a type of resistive exercise countermeasure hardware, either the Advanced Resistance Exercise Device (ARED) or the Interim Resistance Exercise Device (iRED). A subset of the ARED group also tested the bisphosphonate alendronate as a potential anti-resorptive countermeasure (Bis+ARED). While some of the basic bone marker data have been published, we provide here a more comprehensive evaluation of bone biochemistry with a larger group of astronauts. Regardless of exercise, the risk of renal stone formation increased during spaceflight. A key factor in this increase was urine volume, which was lower during flight in all groups at all time points. Thus, the easiest way to mitigate renal stone risk is to increase fluid consumption. ARED use increased bone formation without changing bone resorption, and mitigated a drop in parathyroid hormone in iRED astronauts. Sclerostin, an osteocyte-derived negative regulator of bone formation, increased 10-15% in both groups of astronauts who used the ARED (p<0.06). IGF-1, which regulates bone growth and formation, increased during flight in all 3 groups (p<0.001). Our results are consistent with the growing body of literature showing that the hyper-resorptive state of bone that is brought on by spaceflight can be countered pharmacologically or mitigated through an exercise-induced increase in bone formation, with nutritional support. Key questions remain about the effect of exercise-induced alterations in bone metabolism on bone strength and fracture risk. Related URLs:
http://www.ncbi.nlm.nih.gov/pubmed/26456109

Magnesium and Space Flight

by on 22 August 2016in Biology & Biotechnology No comment

Magnesium is an essential nutrient for muscle, cardiovascular, and bone health on Earth, and during space flight. We sought to evaluate magnesium status in 43 astronauts (34 male, 9 female; 47 +/- 5 years old, mean +/- SD) before, during, and after 4-6-month space missions. We also studied individuals participating in a ground analog of space flight (head-down-tilt bed rest; n = 27 (17 male, 10 female), 35 +/- 7 years old). We evaluated serum concentration and 24-h urinary excretion of magnesium, along with estimates of tissue magnesium status from sublingual cells. Serum magnesium increased late in flight, while urinary magnesium excretion was higher over the course of 180-day space missions. Urinary magnesium increased during flight but decreased significantly at landing. Neither serum nor urinary magnesium changed during bed rest. For flight and bed rest, significant correlations existed between the area under the curve of serum and urinary magnesium and the change in total body bone mineral content. Tissue magnesium concentration was unchanged after flight and bed rest. Increased excretion of magnesium is likely partially from bone and partially from diet, but importantly, it does not come at the expense of muscle tissue stores. While further study is needed to better understand the implications of these findings for longer space exploration missions, magnesium homeostasis and tissue status seem well maintained during 4-6-month space missions.

Related URLs:
http://www.ncbi.nlm.nih.gov/pubmed/26670248

Expression of p53-Regulated Proteins in Human Cultured Lymphoblastoid TSCE5 and WTK1 Cell Lines during Spaceflight

by on 22 August 2016in Biology & Biotechnology No comment

The aim of this study was to determine the biological effects of space radiations, microgravity, and the interaction of them on the expression of p53-regulated proteins. Space experiments were performed with two human cultured lymphoblastoid cell lines: one line (TSCE5) bears a wild-type p53 gene status, and another line (WTK1) bears a mutated p53 gene status. Under 1 gravity or microgravity conditions, the cells were grown in the cell biology experimental facility (CBEF) of the International Space Station for 8 days without experiencing the stress during launching and landing because the cells were frozen during these periods. Ground control samples were simultaneously cultured for 8 days in the CBEF on the ground for 8 days. After spaceflight, protein expression was analyzed using a PanoramaTM Ab MicroArray protein chips. It was found that p53-dependent up-regulated proteins in response to space radiations and space environment were MeCP2 (methyl CpG binding protein 2), and Notch1 (Notch homolog 1), respectively. On the other hand, p53-dependent down-regulated proteins were TGF-β, TWEAKR (tumor necrosis fac- tor-like weak inducer of apoptosis receptor), phosho-Pyk2 (Proline-rich tyrosine kinase 2), and 14-3-3θ/τ which were affected by microgravity, and DR4 (death receptor 4), PRMT1 (protein arginine methyltrans- ferase 1) and ROCK-2 (Rho-associated, coiled-coil containing protein kinase 2) in response to space radi- ations. ROCK-2 was also suppressed in response to the space environment. The data provides the p53- dependent regulated proteins by exposure to space radiations and/or microgravity during spaceflight. Our expression data revealed proteins that might help to advance the basic space radiation biology.

Related URLs:
http://www.ncbi.nlm.nih.gov/pubmed/22374402

Rapid Access:Dream Chaser® Space Traffic Management and Operations to Enable Near-Immediate Payload Access for Responsive Mission and Payload Support

by on 22 August 2016in Technology Development & Demonstration No comment

As research institutions all over the world are placing a higher value on space-based science, the need for rapid access to vehicles returning from space carrying experiments grows more important. One of the challenges of enhanced science utilization is rapid access to space vehicles post-flight, which is significantly enabled by effective space traffic management and integration of space operations into a mature commercial aviation system to achieve radically improved orbit to researcher timelines. Sierra Nevada Corporation’s (SNC) Space Systems’ Dream Chaser® reusable spacecraft is designed for multiple applications including cargo and/or crew resupply to the International Space Station and independent long duration science missions. The Dream Chaser is an optionally-piloted, reusable lifting-body spacecraft that lands horizontally on a runway, similar to the Space Shuttle. Unlike the Space Shuttle, the Dream Chaser design supports the unique capability of being able to land at many domestic and international commercial and public-use airports, and offers access to cargo and/or crew almost immediately thereafter. Though this capability presents a unique opportunity for researchers in the field of microgravity science, there are challenges when considering the current landscape of regulation, public risk, and autonomous flight. The potential opportunities associated with landing the Dream Chaser at public-use airports to enable globally convenient and rapid access to crew, cargo, and time critical microgravity experiments post-flight are identified and addressed in this paper.

Related URLs:
http://arc.aiaa.org/doi/abs/10.2514/6.2015-4582

Characteristics of local human skeleton responses to microgravity and drug treatment for osteoporosis in clinic

by on 22 August 2016in Biology & Biotechnology No comment

Analysis of the results of long term investigations of bones in cosmonauts on board Mir orbital sta tion(OS) and International Space Station (ISS) (n = 80) was performed. Theoretically predicted (evolution ary predefined) change in mass of different skeleton bones was found to be correlated (r = 0.904) with the position relative to Earth’s gravity vector. Vector dependence of bone loss results from local specificity of expression of bone metabolism genes, which reflects mechanical prehistory of skeleton structures in the evo lution of Homo erectus. Genetic polymorphism is accountable for high individual variability of bone loss, which is attested by the dependence of bone loss rate on polymorphism of certain genetic markers of bone metabolism. The type of the orbital vehicle did not affect the individual specific stability of the bone loss ratio in different segments of the skeleton. This fact is considered as a phenotype fingerprint of local metabolism in the form of a locus specific spatial structure of distribution of non collagen proteins responsible for posi tion regulation of endosteal metabolism. Drug treatment of osteoporosis (n = 107) evidences that recovery rate depends on bone location; the most likely reason is different effectiveness of local osteotropic interven tion into areas of bustling resorption.

Related URLs:
http://link.springer.com/article/10.1134/S0362119714070184