Research Containing: Male

Modulation of Pleurodeles waltl DNA polymerase mu expression by extreme conditions encountered during spaceflight

by cfynanon 9 June 2015in Biology & Biotechnology No comment

DNA polymerase micro is involved in DNA repair, V(D)J recombination and likely somatic hypermutation of immunoglobulin genes. Our previous studies demonstrated that spaceflight conditions affect immunoglobulin gene expression and somatic hypermutation frequency. Consequently, we questioned whether Polmu expression could also be affected. To address this question, we characterized Polmu of the Iberian ribbed newt Pleurodeles waltl and exposed embryos of that species to spaceflight conditions or to environmental modifications corresponding to those encountered in the International Space Station. We noted a robust expression of Polmu mRNA during early ontogenesis and in the testis, suggesting that Polmu is involved in genomic stability. Full-length Polmu transcripts are 8-9 times more abundant in P. waltl than in humans and mice, thereby providing an explanation for the somatic hypermutation predilection of G and C bases in amphibians. Polmu transcription decreases after 10 days of development in space and radiation seem primarily involved in this down-regulation. However, space radiation, alone or in combination with a perturbation of the circadian rhythm, did not affect Polmu protein levels and did not induce protein oxidation, showing the limited impact of radiation encountered during a 10-day stay in the International Space Station.

Musculoskeletal injuries and minor trauma in space: incidence and injury mechanisms in U.S. astronauts

by cfynanon 9 June 2015in Biology & Biotechnology No comment

INTRODUCTION: Astronauts have sustained musculoskeletal injuries and minor trauma in space, but our knowledge of these injuries is based mainly on anecdotal reports. The purpose of our study was to catalog and analyze all in-flight musculoskeletal injuries occurring throughout the U.S. space program to date. METHODS: A database on in-flight musculoskeletal injuries among U.S. astronauts was generated from records at the Johnson Space Center. RESULTS: A total of 219 in-flight musculoskeletal injuries were identified, 198 occurring in men and 21 in women. Incidence over the course of the space program was 0.021 per flight day for men and 0.015 for women. Hand injuries represented the most common location of injuries, with abrasions and small lacerations representing common manifestations of these injuries. Crew activity in the spacecraft cabin such as translating between modules, aerobic and resistive exercise, and injuries caused by the extravehicular activity (EVA) suit components were the leading causes of musculoskeletal injuries. Exercise-related injuries accounted for an incidence of 0.003 per day and exercise is the most frequent source of injuries in astronauts living aboard the International Space Station (ISS). Interaction with EVA suit components accounted for an incidence of 0.26 injuries per EVA. DISCUSSION: Hand injuries were among the most common events occurring in U.S. astronauts during spaceflight. Identifying the incidence and mechanism of in-flight injuries will allow flight surgeons to quantify the amount of medical supplies needed in the design of next-generation spacecraft. Engineers can use in-flight injury data to further refine the EVA suit and vehicle components.

Simulation models of weightlessness in mammalian's developmental program

by cfynanon 9 June 2015in Biology & Biotechnology No comment

[Reproductive function of the male rat after a flight on the Kosmos-1129 biosatellite]

by cfynanon 9 June 2015in Biology & Biotechnology No comment

Male rats that were flown for 18.5 days on Cosmos-1129 were mated postflight with intact females. The mating 5 days postflight when the ejaculate consisted of spermatozoids that were exposed to zero-g effects in the mature stage yielded the litter which lagged behind the controls with respect to the growth and development during the first postnatal month. The mating 2.5-3 months postflight when the ejaculate consisted of spermatozoids that were exposed to zero-g effects at the stem cell stage yielded the litter which did not differ from the control.

Adaptation of mouse skeletal muscle to long-term microgravity in the MDS mission

by cfynanon 9 June 2015in Biology & Biotechnology No comment

The effect of microgravity on skeletal muscles has so far been examined in rat and mice only after short-term (5-20 day) spaceflights. The mice drawer system (MDS) program, sponsored by Italian Space Agency, for the first time aimed to investigate the consequences of long-term (91 days) exposure to microgravity in mice within the International Space Station. Muscle atrophy was present indistinctly in all fiber types of the slow-twitch soleus muscle, but was only slightly greater than that observed after 20 days of spaceflight. Myosin heavy chain analysis indicated a concomitant slow-to-fast transition of soleus. In addition, spaceflight induced translocation of sarcolemmal nitric oxide synthase-1 (NOS1) into the cytosol in soleus but not in the fast-twitch extensor digitorum longus (EDL) muscle. Most of the sarcolemmal ion channel subunits were up-regulated, more in soleus than EDL, whereas Ca(2+)-activated K(+) channels were down-regulated, consistent with the phenotype transition. Gene expression of the atrophy-related ubiquitin-ligases was up-regulated in both spaceflown soleus and EDL muscles, whereas autophagy genes were in the control range. Muscle-specific IGF-1 and interleukin-6 were down-regulated in soleus but up-regulated in EDL. Also, various stress-related genes were up-regulated in spaceflown EDL, not in soleus. Altogether, these results suggest that EDL muscle may resist to microgravity-induced atrophy by activating compensatory and protective pathways. Our study shows the extended sensitivity of antigravity soleus muscle after prolonged exposition to microgravity, suggests possible mechanisms accounting for the resistance of EDL, and individuates some molecular targets for the development of countermeasures.

Evaluation of gene, protein and neurotrophin expression in the brain of mice exposed to space environment for 91 days

by cfynanon 9 June 2015in Biology & Biotechnology No comment

Effects of 3-month exposure to microgravity environment on the expression of genes and proteins in mouse brain were studied. Moreover, responses of neurobiological parameters, nerve growth factor (NGF) and brain derived neurotrophic factor (BDNF), were also evaluated in the cerebellum, hippocampus, cortex, and adrenal glands. Spaceflight-related changes in gene and protein expression were observed. Biological processes of the up-regulated genes were related to the immune response, metabolic process, and/or inflammatory response. Changes of cellular components involving in microsome and vesicular fraction were also noted. Molecular function categories were related to various enzyme activities. The biological processes in the down-regulated genes were related to various metabolic and catabolic processes. Cellular components were related to cytoplasm and mitochondrion. The down-regulated molecular functions were related to catalytic and oxidoreductase activities. Up-regulation of 28 proteins was seen following spaceflight vs. those in ground control. These proteins were related to mitochondrial metabolism, synthesis and hydrolysis of ATP, calcium/calmodulin metabolism, nervous system, and transport of proteins and/or amino acids. Down-regulated proteins were related to mitochondrial metabolism. Expression of NGF in hippocampus, cortex, and adrenal gland of wild type animal tended to decrease following spaceflight. As for pleiotrophin transgenic mice, spaceflight-related reduction of NGF occurred only in adrenal gland. Consistent trends between various portions of brain and adrenal gland were not observed in the responses of BDNF to spaceflight. Although exposure to real microgravity influenced the expression of a number of genes and proteins in the brain that have been shown to be involved in a wide spectrum of biological function, it is still unclear how the functional properties of brain were influenced by 3-month exposure to microgravity.

Effects of spaceflight on the spermatogonial population of rat seminiferous epithelium

by cfynanon 9 June 2015in Biology & Biotechnology No comment

Testes from rats flown on Cosmos 1887 were compared with vivarium control and synchronous control samples. The mean weights of flight testes, normalized for weight per 100 g, were 6.4% less when compared with the vivarium controls. Counts of spermatogonia from tissue sections (seminiferous tubules in maturation stage 6) from five animals in each group revealed 4% fewer spermatogonia in flight testes compared with synchronous controls and 11% fewer spermatogonia in flight samples compared with vivarium controls.

Modeled microgravity and hindlimb unloading sensitize osteoclast precursors to RANKL-mediated osteoclastogenesis

by cfynanon 9 June 2015in Biology & Biotechnology No comment

Mechanical forces are essential to maintain skeletal integrity, and microgravity exposure leads to bone loss. The underlying molecular mechanisms leading to the changes in osteoblasts and osteoclast differentiation and function remain to be fully elucidated. Because of the infrequency of spaceflights and payload constraints, establishing in vitro and in vivo systems that mimic microgravity conditions becomes necessary. We have established a simulated microgravity (modeled microgravity, MMG) system to study the changes induced in osteoclast precursors. We observed that MMG, on its own, was unable to induce osteoclastogenesis of osteoclast precursors; however, 24 h of MMG activates osteoclastogenesis-related signaling molecules ERK, p38, PLC gamma 2, and NFATc1. Receptor activator of NFkB ligand (RANKL) (with or without M-CSF) stimulation for 3-4 days in gravity of cells that had been exposed to MMG for 24 h enhanced the formation of very large tartrate-resistant acid phosphatase (TRAP)-positive multinucleated (> 30 nuclei) osteoclasts accompanied by an upregulation of the osteoclast marker genes TRAP and cathepsin K. To validate the in vitro system, we studied the hindlimb unloading (HLU) system using BALB/c mice and observed a decrease in BMD of femurs and a loss of 3D microstructure of both cortical and trabecular bone as determined by micro-CT. There was a marked stimulation of osteoclastogenesis as determined by the total number of TRAP-positive multinucleated osteoclasts formed and also an increase in RANKL-stimulated osteoclastogenesis from precursors removed from the tibias of mice after 28 days of HLU. In contrast to earlier reported findings, we did not observe any histomorphometric changes in the bone formation parameters. Thus, the foregoing observations indicate that microgravity sensitizes osteoclast precursors for increased differentiation. The in vitro model system described here is potentially a valid system for testing drugs for preventing microgravity-induced bone loss by targeting the molecular events occurring in microgravity-induced enhanced osteoclastogenesis.

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Vital capacity, respiratory muscle strength, and pulmonary gas exchange during long-duration exposure to microgravity

by cfynanon 9 June 2015in Biology & Biotechnology No comment

Extended exposure to microgravity (μG) is known to reduce strength in weight-bearing muscles and was also reported to reduce respiratory muscle strength. Short- duration exposure to μG reduces vital capacity (VC), a surrogate measure for respiratory muscle strength, for the first few days, with little change in O2 uptake, ventilation, or end-tidal partial pressures. Accordingly we measured VC, maximum inspiratory and expiratory pressures, and indexes of pulmonary gas exchange in 10 normal subjects (9 men, 1 woman, 39–52 yr) who lived on the International Space Station for 130–196 days in a normoxic, normobaric atmosphere. Subjects were studied four times in the standing and supine postures preflight at sea level at 1 G, approximately monthly in μG, and multiple times postflight. VC in μG was essentially unchanged compared with preflight standing [5.28 ± 0.08 liters (mean ± SE), n = 187; 5.24 ± 0.09, n = 117, respectively; P = 0.03] and considerably greater than that measured supine in 1G (4.96 ± 0.10, n = 114, P < 0.001). There was a trend for VC to decrease after the first 2 mo of μG, but there were no changes postflight. Maximum respiratory pressures in μG were generally intermediate to those standing and supine in 1G, and importantly they showed no decrease with time spent in μG. O2 uptake and CO2 production were reduced (∼12%) in extended μG, but inhomogeneity in the lung was not different compared with short-duration exposure to μG. The results show that VC is essentially unchanged and respiratory muscle strength is maintained during extended exposure to μG, and metabolic rate is reduced.

Lung function is unchanged in the 1 G environment following 6-months exposure to microgravity

by cfynanon 9 June 2015in Biology & Biotechnology No comment

Many organ systems adapt in response to the removal of gravity, such as that occurring during spaceflight. Such adaptation occurs over varying time periods depending on the organ system being considered, but the effect is that upon a return to the normal 1 G environment, the organ system is ill-adapted to that environment. As a consequence, either countermeasures to the adaptive process in flight, or rehabilitation upon return to 1 G is required. To determine whether the lung changed in response to a long period without gravity, we studied numerous aspects of lung function on ten subjects (one female) before and after they were exposed to 4-6 months of microgravity (microG, weightlessness) in the normobaric normoxic environment of the International Space Station. With the exception of small (and likely physiologically inconsequential) changes in expiratory reserve volume, one index of peripheral gas mixing in the periphery of the lung, and a possible slight reduction in D(L)CO in the early postflight period despite an unchanged cardiac output, lung function was unaltered by 4-6 months in microG. These results suggest that unlike many other organ systems in the human body, lung function returns to normal after long term exposure to the removal of gravity. We conclude that that in a normoxic, normobaric environment, lung function is not a concern following long-duration future spaceflight exploration missions of up to 6 months.

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Research Containing: Male

Modulation of Pleurodeles waltl DNA polymerase mu expression by extreme conditions encountered during spaceflight

Musculoskeletal injuries and minor trauma in space: incidence and injury mechanisms in U.S. astronauts

Simulation models of weightlessness in mammalian's developmental program

[Reproductive function of the male rat after a flight on the Kosmos-1129 biosatellite]

Adaptation of mouse skeletal muscle to long-term microgravity in the MDS mission

Evaluation of gene, protein and neurotrophin expression in the brain of mice exposed to space environment for 91 days

Effects of spaceflight on the spermatogonial population of rat seminiferous epithelium

Modeled microgravity and hindlimb unloading sensitize osteoclast precursors to RANKL-mediated osteoclastogenesis

Vital capacity, respiratory muscle strength, and pulmonary gas exchange during long-duration exposure to microgravity

Lung function is unchanged in the 1 G environment following 6-months exposure to microgravity