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At least 19 records

Computer simulations of postural change, water immersion and bedrest - An integrative approach for understanding the spaceflight response

Mathematical modeling techniques were used to simulate the fluid electrolyte (F-E) responses during gravity unloading. It is shown that the response to weightlessness can best be understood by separately examining the acute (hours to days) and chronic (days to weeks) phases, and assuming the presence of normal, although complex, feedback regulatory processes. Headward shifts of fluid are shown to be primarily responsible for acute body losses of extracellular F-E. Losses of body water are closely related to the volume of fluid shifts from the legs. A diuresis is predicted within the first several hours of hypogravity, and this may be obscured by a reduced F-E intake; on Skylab, early F-E losses occurred primarily by deficit intake.

Leonard, J. I.↗

Changes in monkey horizontal semicircular canal afferent responses after spaceflight

Extracellular responses from single horizontal semicircular canal afferents in two rhesus monkeys were studied after recovery from a 14-day biosatellite (Cosmos 2044) orbital spaceflight. On the 1st postflight day, the mean gain for 9 different horizontal canal afferents, tested using one or several different passive yaw rotation waveforms, was nearly twice that for 20 horizontal canal afferents similarly tested during preflight and postflight control studies. Adaptation of the afferent response to passive yaw rotation on the 1st postflight day was also greater. These results suggest that at least one component of the vestibular end organ (the semicircular canals) is transiently modified after exposure to 14 days of microgravity. It is unclear whether the changes are secondary to other effects of microgravity, such as calcium loss, or an adaptive response. If the response is adaptive, then this report is the first evidence that the response of the vestibular end organ may be modified (presumably by the central nervous system via efferent connections) after prolonged unusual vestibular stimulation. If this is the case, the sites of plasticity of vestibular responses may not be exclusively within central nervous system vestibular structures, as previously believed.

Correia, M. J.↗

Skeletal responses to spaceflight

The role of gravity in the determination of bone structure is elucidated by observations in adult humans and juvenile animals during spaceflight. The primary response of bone tissue to microgravity is at the interface of the mineral and matrix in the process of biomineralization. This response is manifested by demineralization or retarded growth in some regions of the skeleton and hypermineralization in others. The most pronounced effects are seen in the heelbone and skull, the most distally located bones relative to the heart. Ground based flight simulation models that focus on changes in bone structure at the molecular, organ, and whole body levels are described and compared to flight results. On Earth, the morphologic and compositional changes in the unloaded bones are very similar to changes during flight; however, the ground based changes appear to be more transient. In addition, a redistribution of bone mineral in gravity-dependent bones occurs both in space and during head down positioning on Earth. Longitudinal data provided considerable information on the influence of endocrine and muscular changes on bone structure after unloading.

Morey-Holton, Emily↗

Immunological and Hematopoietic Biotechnology Studies

The purpose of the work carried under this interchanges was to support the development of space flight biotechnology experiments in the areas of immunology and hematopoiesis to facilitate the commercial development of space. The studies involved the interaction and development of experiments with biotechnology companies for necessary ground-based studies to allow the development of flight studies. The thrust of the work was to develop experiments with the Chiron Corporation and Bioserve involving the use of interleukin-2 to modulate the effects of spaceflight on immune responses. Spaceflight has been shown to have multiple effects on immune responses (1). lnterleukin-2 is an immuno-regulator that could have potential to counter some of the alterations induced in immune responses by spaceflight (1). To test this possibility before flight, rats were suspended antiorthostatically (2) and treated with interleukin-2. Antiorthostatic suspension is a model for some of the effects of spaceflight on immune responses (2). The interleukin-2 was given to see if it could alter some of the effects of suspension. This was achieved. As a result of these studies, two flight experiments were developed and flown with the Chiron Corp. And Bioserve to determine if use of interleukin-2 could prevent or attenuate the effects of space flight on immune responses.

Fernandez-Botran, Rafael↗

Neuroendocrine and Immune System Responses with Spaceflights

Despite the fact that the first human was in space during 1961 and individuals have existed in a microgravity environment for more than a year, there are limited spaceflight data available on the responses of the neuroendocrine and immune systems. Because of mutual interactions between these respective integrative systems, it is inappropriate to assume that the responses of one have no impact on functions of the other. Blood and plasma volume consistently decrease with spaceflight; hence, blood endocrine and immune constituents will be modified by both gravitational and measurement influences. The majority of the in-flight data relates to endocrine responses that influence fluids and electrolytes during the first month in space. Adrenocorticotropin (ACTH), aldo-sterone. and anti-diuretic hormone (ADH) appear to be elevated with little change in the atrial natriuretic peptides (ANP). Flight results longer than 60 d show increased ADH variability with elevations in angiotensin and cortisol. Although post-flight results are influenced by reentry and recovery events, ACTH and ADH appear to be consistently elevated with variable results being reported for the other hormones. Limited in-flight data on insulin and growth hormone levels suggest they are not elevated to counteract the loss in muscle mass. Post-flight results from short- and long-term flights indicate that thyroxine and insulin are increased while growth hormone exhibits minimal change. In-flight parathyroid hormone (PTH) levels are variable for several weeks after which they remain elevated. Post-flight PTH was increased on missions that lasted either 7 or 237 d, whereas calcitonin concentrations were increased after 1 wk but decreased after longer flights. Leukocytes are elevated in flights of various durations because of an increase in neutrophils. The majority of post-flight data indicates immunoglobulin concentrations are not significantly changed from pre-flight measurements. However, the numbers of T-lymphocytes and natural killer cells are decreased with post-flight conditions. Of the lymphokines, interleukin-2 production, lymphocyte responsiveness, and the activity of natural killer cells are consistently reduced post-flight. Limited head-down tilt (HDT) data suggest it is an effective simulation model for microgravity investigations. Neuroendocrine and pharmacological countermeasures are virtually nonexistent arid should become high priority items for future research. Although exercise has the potential to be an effective countermeasure for various neuroen-docrine-immune responses in microgravity, this concept must be tested before flights to Mars are scheduled.

Tipton, Charles M.↗

The catecholamine response to spaceflight: role of diet and gender

Compared with men, women appear to have a decreased sympathetic nervous system (SNS) response to stress. The two manifestations where the sexual dimorphism has been the most pronounced involve the response of the SNS to fluid shifts and fuel metabolism during exercise. The objectives of this study were to investigate whether a similar sexual dimorphism was found in the response to spaceflight. To do so, we compared catecholamine excretion by male and female astronauts from two similar shuttle missions, Spacelab Life Sciences 1 (SLS1, 1991) and 2 (SLS2, 1993) for evidence of sexual dimorphism. To evaluate the variability of the catecholamine response in men, we compared catecholamine excretion from the two SLS missions against the 1996 Life and Microgravity Sciences Mission (LMS) and the 1973 Skylab missions. RESULTS: No gender- or mission-dependent changes were found with epinephrine. Separating out the SLS1/2 data by gender shows that norepinephrine excretion was essentially unchanged with spaceflight in women (98 +/- 10%; n = 3) and substantially decreased with the men (41 +/- 9%; n = 4, P < 0.05). Data are a percentage of mean preflight value +/- SE. Comparisons among males demonstrated significant mission effects on norepinephrine excretion. After flight, there was a transient increase in norepinephrine but no evidence of any gender-specific effects. We conclude that norepinephrine excretion during spaceflight is both mission and gender dependent. Men show the greater response, with at least three factors being involved, a response to microgravity, energy balance, and the ratio of carbohydrate to fat in the diet.

NASA Discipline Regulatory Physiology↗

Translational Line of Sight: a multi-omics longitudinal study of the murine retinal response to spaceflight hazard analogs

The space environment includes unique hazards like radiation and microgravity which adversely affect physiology and behavior of humans and rodent models. To better characterize the retinal response to spaceflight, we assessed a multi-omics NASA GeneLab dataset where 6-month-old female mice were gamma irradiated and/or hindlimb unloaded for 21 days followed by whole transcriptome shotgun sequencing (RNA-Seq) and reduced representation bisulfite sequencing (RRBS) of retina samples collected at 7 days, 1 month or 4 months post-exposure. We compared time-matched epigenomic and transcriptomic retinal profiles revealing a total of 4,178 differentially methylated loci or regions, and 457 differentially expressed genes. Highest correlation in methylation differences was seen across different conditions at the same time point (e.g., between radiation exposure and hindlimb unloaded at 7 days). Biological processes related to nucleotide metabolism were enriched in all groups with activation at 1 month and suppression at 7 days and 4 months. Genes and processes related to Notch and Wnt signaling showed alterations 4 months post-exposure. Interestingly, Notch3 and Lrg1 showed differential patterns in the NASA Twins Study in-flight samples and in response to stressors in the murine retina in the current study. A total of 23 genes were both differentially methylated and expressed, including genes involved in retinal disease or cataract development (Crybb3, Fgfr1, Pitpnm3, Sipa1l3, Sox9) and inflammatory response (B4galt6, Ppm1a, Sphk1). To our knowledge, the current multi-omics analysis is the first multi-omics study to interrogate the epigenomic and transcriptomic impacts of radiation and hindlimb unloading on the retina in isolation and in combination. The results provide an insight into the retinal response to individual spaceflight hazard analogs and their interplay at different post-exposure stages and contributes towards a mechanistic understanding of spaceflight-induced vision impairment using ground-based models.

Prachi Kothiyal↗

Proton Exchange Membrane Fuel Cell Transient Load Response

Spaceflight mission profiles may not be limited to constant power loads. It is necessary for the associated power system to support changes in load in addition to being energy dense. H2-O2 proton exchange membrane (PEM) fuel cells can accommodate such requirements without significant current smoothing or additional devices to provide transient power. This testing involved current load step changes to characterize non-flow-through PEM fuel cell response to increasing and decreasing load step changes over a range of 0 to 0.5 A/sq. cm. It was determined that fuel cell output voltage stabilizes within 4 ms with no noticeable steady-state performance degradation, following exposure of the fuel cell to transient loads of up to ~1.5 A/sq. cm. Faster stabilization generally occurred following larger step changes.

fuel cell↗

Reduced Gravity Contributes to Neutrophil to Lymphocyte Ratio Shifting and Promotion of the Oxidative Stress Response

Spaceflight can cause immune system dysfunction, such as elevated white blood cells (WBC) and polymorphonuclear neutrophils (PMN), along with unchanged or reduced lymphocyte counts. A high PMN to lymphocyte ratio (NLR) can acts as a poor prognosis in cancer and a biomarker for subclinical inflammation however, the NLR has not been identified as a predictor of astronaut health during spaceflight. CBC data collected on board the International Space Station (ISS) was repurposed to determine the granulocyte to lymphocyte ratio (GLR) in humans and the NLR in rodents. The results displayed a progressive increase in GLR and NLR during spaceflight and at landing. The mechanism for increased NLR was assessed in vitro using the microgravity-analog, rotating wall vessel (RWV), with human WBCs. The results indicated that simulated microgravity led to increased GLR and NLR profiles, and production of reactive oxygen species (ROS) and myeloperoxidase (MPO). Interestingly, simulated microgravity increased the number of matured PMNs that showed impaired phagocytic function, while treatment with tert-Butyl hydroperoxide (TBHP), also reduced PMN phagocytosis. In addition, 30-days of simulated microgravity (hindlimb unloading) in mice, indicated an increased NLR and MPO gene expression, which were mitigated in mitochondrial catalase overexpressing transgenic mice, suggesting ROS scavenging is essential for maintaining homeostatic immunity. Collectively, we propose that the health status of astronauts during future short- and long-term space missions can be monitored by their NLR profile, in addition to utilizing this measurement as a tool for oxidative stress response countermeasure development to restore homeostatic immunity.

Paul, Amber M.↗

The Human Sympathetic Nervous System Response to Spaceflight

The sympathetic nervous system is an important part of the autonomic (or automatic) nervous system. When an individual stands up, the sympathetic nervous system speeds the heart and constricts blood vessels to prevent a drop in blood pressure. A significant number of astronauts experience a drop in blood pressure when standing for prolonged periods after they return from spaceflight. Difficulty maintaining blood pressure with standing is also a daily problem for many patients. Indirect evidence available before the Neurolab mission suggested the problem in astronauts while in space might be due partially to reduced sympathetic nervous system activity. The purpose of this experiment was to identify whether sympathetic activity was reduced during spaceflight. Sympathetic nervous system activity can be determined in part by measuring heart rate, nerve activity going to blood vessels, and the release of the hormone norepinephrine into the blood. Norepinephrine is a neurotransmitter discharged from active sympathetic nerve terminals, so its rate of release can serve as a marker of sympathetic nervous system action. In addition to standard cardiovascular measurements (heart rate, blood pressure), we determined sympathetic nerve activity as well as norepinephrine release and clearance on four crewmembers on the Neurolab mission. Contrary to our expectation, the results demonstrated that the astronauts had mildly elevated resting sympathetic nervous system activity in space. Sympathetic nervous system responses to stresses that simulated the cardiovascular effects of standing (lower body negative pressure) were brisk both during and after spaceflight. We concluded that, in the astronauts tested, the activity and response of the sympathetic nervous system to cardiovascular stresses appeared intact and mildly elevated both during and after spaceflight. These changes returned to normal within a few days.

Ertl, Andrew C.↗

Altered skeletal pattern of gene expression in response to spaceflight and hindlimb elevation

Spaceflight leads to osteopenia, in part by inhibiting bone formation. Using an animal model (hindlimb elevation) that simulates the weightlessness of spaceflight, we and others showed a reversible inhibition of bone formation and bone mineralization. In this study, we have measured the mRNA levels of insulin-like growth factor I (IGF-I), IGF-I receptor (IGF-IR), alkaline phosphatase, and osteocalcin in the tibiae of rats flown aboard National Aeronautics and Space Administration Shuttle Flight STS-54 and compared the results with those obtained from their ground-based controls and from the bones of hindlimb-elevated animals. Spaceflight and hindlimb elevation transiently increase the mRNA levels for IGF-I, IGF-IR, and alkaline phosphatase but decrease the mRNA levels for osteocalcin. The changes in osteocalcin and alkaline phosphatase mRNA levels are consistent with a shift toward decreased maturation, whereas the rise in IGF-I and IGF-IR mRNA levels may indicate a compensatory response to the fall in bone formation. We conclude that skeletal unloading during spaceflight or hindlimb elevation resets the pattern of gene expression in the osteoblast, giving it a less mature profile.

NASA Discipline Musculoskeletal↗

NASA Headquarters Space Operations Center: Providing Situational Awareness for Spaceflight Contingency Response

This paper discusses the NASA Headquarters mishap response process for the Space Shuttle and International Space Station programs, and how the process has evolved based on lessons learned from the Space Shuttle Challenger and Columbia accidents. It also describes the NASA Headquarters Space Operations Center (SOC) and its special role in facilitating senior management's overall situational awareness of critical spaceflight operations, before, during, and after a mishap, to ensure a timely and effective contingency response.

Maxwell, Theresa G.↗

Effects and Responses to Spaceflight in the Mouse Retina

Several stress environmental factors are combined in a unique fashion during spaceflight, affecting living beings widely across their physiological systems. Recently, attention has been placed on vision changes in astronauts returning from long duration missions. Alterations include hyperoptic shift, globe flattening, choroidal folds and optic disc edema, which are probably associated with increased intracranial pressure. These observations justify a better characterization of the ocular health risks associated with spaceflight. This study investigates the impact of spaceflight on the biology of the mouse retina. Within a successful tissue sharing effort, eyes from albino Balb/cJ mice aboard STS-133 were collected for histological analysis and gene expression profiling of the retina at 1 and 7 days after landing. Both vivarium and AEM (Animal Enclosure Module) mice were used as ground controls. Oxidative stress-induced DNA damage was higher in the flight samples compared to controls on R+1, and decreased on R+7. A trend toward higher oxidative and cellular stress response gene expression was also observed on R+1 compared to AEM controls, and these levels decreased on R+7. Several genes coding for key antioxidant enzymes, namely, heme-oxygenase-1, peroxiredoxin, and catalase, were among those upregulated after flight. Likewise, NF B and TGFbeta1, were upregulated in one flight specimen that overall showed the most elevated oxidative stress markers on R+1. In addition, retinas from vivarium control mice evidenced higher oxidative stress markers, NF B and TGFbeta1, likely due to the more intense illumination in vivarium cages versus the AEM. These preliminary data suggest that spaceflight represents a source of environmental stress that translates into oxidative and cellular stress in the retina, which is partially reversible upon return to Earth. Further work is needed to dissect the contribution of the various spaceflight factors (microgravity, radiation) and to evaluate the impact of the stress response on retinal health.

Zanello, Susana B.↗

A Dominant Arabidopsis Thaliana ACTIN7 Mutant for Studies of Cytoskeletal-Mediated Root Gravity and Spaceflight Stress Responses

A forward genetic screen for Arabidopsis thaliana mutants that exhibited differential sensitivity to the actin-disrupting compound, latrunculin B (LatB), was conducted to uncover new players involved in actin-mediated root gravity responses. This to the isolation of a mutant that exhibited robust primary root growth at 100 nM LatB, which is a concentration that severely inhibits wild-type root elongation. Phenotypic analysis revealed that hypocotyl elongation in the dark and root hair tip growth in the mutant could tolerate LatB concentrations that impaired these processes in wild type. A cross between the mutant and wild type resulted in progeny resistance to LatB, which indicated that the mutant is dominant (hereafter referred to as LBR1 for LatB Resistant1). Filamentous-actin (F-actin) organization in LBR1 primary roots remained intact at 100 nM LatB, while that of wild type exhibited fragmented F-actin. Next generation sequencing revealed that LBR1 had a single nucleotide polymorphism (SNP) in the AT5G09810 gene that changed cytosine to a thiamine at the first exon. AT5G09810 encodes ACTIN7 (ACT7), which is one of three vegetative actin isoforms in A. thaliana. The SNP in the ACT7 gene led to a change in a single amino acid from proline at position 32 to a serine. Transgenic complementation of LBR1 plants with wild-type ACT7 under the control of the ACT7 promoter (pACT7:ACT7) and wild-type plants with LBR1, which contained the proline to serine mutation, also under the ACT7 promoter (pACT7:LBR1) confirmed that LBR1 is ACT7. The pACT7:LBR1 construct was also able to confer LatB resistance to the act7-5 and act2-3 vegetative ACT mutants. Moreover, LBR1 exhibited partial tolerance to salt and low phosphate, and enhanced root skewing on a clinostat, suggesting that site-directed engineering of vegetative ACT presents a strategy for generating stress-tolerant plants for spaceflight applications and studies of actin-mediated gravity responses.

Plant Space Biology↗

A Dominant Arabidopsis Thaliana ACTIN7 Mutant for Studies of Cytoskeletal-Mediated Root Gravity and Spaceflight Stress Responses

A forward genetic screen for Arabidopsis thaliana mutants that exhibited differential sensitivity to the actin-disrupting compound, latrunculin B (LatB), was conducted to uncover new players involved in actin-mediated root gravity responses. This led to the isolation of a mutant that exhibited robust primary root growth at 100 nM LatB, which is a concentration that severely inhibits wild-type root elongation. Phenotypic analysis revealed that hypocotyl elongation in the dark and root hair tip growth in the mutant could tolerate LatB concentrations that impaired these processes in wild type. A cross between the mutant and wild type resulted in progeny resistance to LatB, which indicated that the mutant is dominant (hereafter referred to as LBR1 for LatB Resistant1). Filamentous-actin (F-actin) organization in LBR1 primary roots remained intact at 100 nM LatB, while that of wild type exhibited fragmented F-actin. Next generation sequencing revealed that LBR1 had a single nucleotide polymorphism (SNP) in the AT5G09810 gene that changed cytosine to a thiamine at the first exon. AT5G09810 encodes ACTIN7 (ACT7), which is one of three vegetative actin isoforms in A. thaliana. The SNP in the ACT7 gene led to a change in a single amino acid from proline at position 32 to a serine. Transgenic complementation of LBR1 plants with wild-type ACT7 under the control of the ACT7 promoter (pACT7:ACT7) and wild-type plants with LBR1, which contained the proline to serine mutation, also under the ACT7 promoter (pACT7:LBR1) confirmed that LBR1 is ACT7. The pACT7:LBR1 construct was also able to confer LatB resistance to the act7-5 and act2-3 vegetative ACT mutants. Moreover, LBR1 exhibited partial tolerance to salt and low phosphate, and enhanced root skewing on a clinostat, suggesting that site-directed engineering of vegetative ACT presents a strategy for generating stress-tolerant plants for spaceflight applications and studies of actin-mediated gravity responses.

Plant Space Biology↗

Skeletal muscle response to spaceflight, whole body suspension, and recovery in rats

The effects of a 7-day spaceflight (SF), 7- and 14-day-long whole body suspension (WBS), and 7-day-long recovery on the muscle weight and the morphology of the soleus and the extensor digitorum longus (EDL) of rats were investigated. It was found that the effect of 7-day-long SF and WBS were highly comparable for both the soleus and the EDL, although the soleus muscle from SF rats showed greater cross-sectional area reduction than that from WBS rats. With a longer duration of WBS, there was a continued reduction in cross-sectional fast-twitch fiber area. Muscle plasticity, in terms of fiber and capillary responses, showed differences in responses of the two types of muscles, indicating that antigravity posture muscles are highly susceptible to unloading.

Musacchia, X. J.↗