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Search indexed NASA NTRS and DOE OSTI research on propulsion, heat transfer, battery materials and energy systems. Follow report and document links to the original sources.

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At least 271 records · Page 15
All sourcesNASA NTRSDOE OSTI
NASA NTRS2002

Activation of c-Jun N-terminal kinase and apoptosis in endothelial cells mediated by endogenous generation of hydrogen peroxide

Reactive oxygen species have been implicated in the activation of signal transduction pathways. However, extracellular addition of oxidants such as hydrogen peroxide (H2O2) often requires concentrations that cannot be readily achieved under physiological conditions to activate biological responses such as apoptosis. Explanations for this discrepancy have included increased metabolism of H2O2 in the extracellular environment and compartmentalization within the cell. We have addressed this issue experimentally by examining the induction of apoptosis of endothelial cells induced by exogenous addition of H2O2 and by a redox cycling agent, 2,3-dimethoxy-1,4-naphthoquinone, that generates H2O2 in cells. Here we show that low nanomolar steady-state concentrations (0.1-0.5 nmol x min(-1) x 10(6) cells) of H2O2 generated intracellularly activate c-Jun N terminal kinase and initiate apoptosis in endothelial cells. A comparison with bolus hydrogen peroxide suggests that the low rate of intracellular formation of this reactive oxygen species results in a similar profile of activation for both c-Jun N terminal kinase and the initiation of apoptosis. However, a detailed analysis reveals important differences in both the duration and profile for activation of these signaling pathways.

Non-NASA Center↗
NASA NTRS1997

A down-to-earth model of gravisensing

The statolith hypothesis for gravity sensing is the most accepted model of gravity sensing in plants. However, the lukewarm acceptance of the statolith hypothesis among plant physiologists is most likely due to inertia and not due to any one experiment done over the past one hundred years that unambiguously pitted the statolith hypothesis against any of the competing hypotheses. Here we emphasize the weaknesses of the statolith hypothesis and suggest that the gravitational pressure hypothesis is superior in describing gravisensing in all plant cells.

Non-NASA Center↗
NASA NTRS1991

A non-invasive measure of minerals and electrolytes in tissue

A system for collecting epithelial cells from the oral mucosa for the determination of ion concentration is discussed with application to the study of man's adaptation to microgravity. A number of characteristics of these cells influenced the choice for clinical testing. They are non-cornified epithelial cells located on the inferior aspect of the tongue; therefore, they are well protected from trauma. They have the capability of reflecting relatively recent physiologic changes since they are renewed every three days and have aerobic metabolism. Most importantly, they are easily accessible and can be removed by a wooden applicator stick with minimum discomfort. Smears of cells removed in this manner show predominantly individual cells rather than sheets of contiuous cells. This facilitates the visual isolation of single cells with the electron microscope for analysis. NASA's principle effort in the development of a test to measure the ion concentration in sublingual cells has been research by the biomedical program carried out by scientists with expertise in skeletal metabolism. These efforts were directed toward determining the biological meaning and deviations in interacellular ions in nonhuman primates and in male volunteers for experiments in a model for weightlessness. A brief one page summary of the experiments and results are presented.

Arnaud, Sara B.↗
NASA NTRS1989

Age-related changes in human vestibulo-ocular reflexes: Sinusoidal rotation and caloric tests

The dynamic response properties of horizontal vestibulo-ocular reflex (VOR) were characterized in 216 human subjects ranging in age from 7 to 81 years. The object of this cross-sectional study was to determine the effects of aging on VOR dynamics, and to identify the distributions of parameters which describe VOR responses to caloric and to sinusoidal rotational stimuli in a putatively normal population. Caloric test parameters showed no consistent trend with age. Rotation test parameters showed declining response amplitude and slightly less compensatory response phase with increasing age. The magnitudes of these changes were not large relative to the variability within the population. The age-related trends in VOR were not consistent with the anatomic changes in the periphery reported by others which showed an increasing rate of peripheral hair cell and nerve fiber loss in subjects over 55 years. The poor correlation between physiological and anatomical data suggest that adaptive mechanisms in the central nervous system are important in maintaining the VOR.

Peterka, R. J.↗
NASA NTRS1992

Changes in renal function and fluid and electrolyte regulation in space flight

The cephalad fluid redistribution resulting from weightlessness has a number of physiologic consequences. Plasma volume is reduced soon after weightlessness is reached, and red blood cell mass reduction follows. Plasma atrial natriuretic peptide, which inhibits aldosterone secretion, was elevated during space flight while plasma aldosterone was below preflight levels. Serum sodium was also reduced and potassium was elevated. Antidiuretic hormone (ADH) was markedly elevated at almost all measurement times in the first eight days of flight, but plasma volume did not return to preflight levels.

Leach, C. S.↗
NASA NTRS1992

Normalization of cell responses in cat striate cortex

Simple cells in the striate cortex have been depicted as half-wave-rectified linear operators. Complex cells have been depicted as energy mechanisms, constructed from the squared sum of the outputs of quadrature pairs of linear operators. However, the linear/energy model falls short of a complete explanation of striate cell responses. In this paper, a modified version of the linear/energy model is presented in which striate cells mutually inhibit one another, effectively normalizing their responses with respect to stimulus contrast. This paper reviews experimental measurements of striate cell responses, and shows that the new model explains a significantly larger body of physiological data.

Heeger, D. J.↗
NASA NTRS1999

Development of a Whole Blood Staining Device for use During Space Shuttle Flights

Exposure to microgravity during space flight results in profound physiologic changes. Numerous studies have shown changes in circulating populations of peripheral blood immune cells immediately after space flight. It is currently unknown if these changes result from exposure to microgravity or are caused by the stress of reentry and readaptation to gravity. We have developed the whole blood staining device as a system for the staining of whole blood collected during space flight for subsequent flow cytometric analysis, This device contains all liquids to address safety issues concerned with space flight and also moves the cells through the staining, lyse/fixation and dilution steps.

Sams, Clarence F.↗
NASA NTRS1998

Simulated Microgravity Induced Cytoskeletal Rearrangements are Modulated by Protooncogenes

Microgravity is the environment living systems encounter during space flight and gravitational unloading is the effect of this environment on living systems. The cell, being a multiphasic chemical system, is a useful starting point to study the potential impact of gravity unloading on physiological function. In the absence of gravity, sedimentation of organelles including chromosomes, mitochondria, nuclei, the Golgi apparatus, vacuoles, and the endoplasmic reticulum may be affected. Most of these organelles, however, are somewhat held in place by cytoskeleton. Hansen and Igber suggest that intermediate filaments act to stabilize the nuleus against rotational movement, and integrate cell and nuclear structure. The tensegrity theory supports the idea that mechanical or physical forces alters the cytoskeletal structures of a cell resulting in the changes in cell: matrix interactions and receptor-signaling coupling. This type of stress to the cytoskeleton may be largely responsible regulating cell shape, growth, movement and metabolism. Mouse MC3T3 El cells under microgravity exhibited significant cytoskeletal changes and alterations in cell growth. The alterations in cytoskeleton architecture may be due to changes in the expression of actin related proteins or integrins. Philopott and coworkers reported on changes in the distribution of microtubule and cytoskeleton elements in the cells of heart tissue from space flight rats and those centrifuged at 1.7g. Other researchers have showed that microgravity reduced EGF-induced c-fos and c-jun expression compared to 1 g controls. Since c-fos and c-jun are known regulators of cell growth, it is likely that altered signal transduction involving protooncogenes may play a crucial role in the reduced growth and alterations in cytoskeletal arrangements found during space flight. It is clear that a microgravity environment induces a number of changes in cell shape, cell surface molecules, gene expression, and cytoskeletal reorganization. However the underlying mechanism for these cellular changes have not been clearly defined. We examined alterations in endothelial migration, and cytoskeleton architecture (microfilamentous f-actin and vimentin-rich- intermediate filaments) following wounding under simulated microgravity. We also examined the possibility that altered signal transduction pathways, involving protooncogenes, may play a crucial role in microgravity-induced retardation of cell migration and alterations in cytoskeletal organization. We hypothesize that, based on the tensegrity theory, cytoskeletal organization respond to gravitational unloading and through this response, cell behavior, function and gene expression are modified.

Melhado, C. D.↗
NASA NTRS1998

Immune responses in space flight

Space flight has been shown to have profound effects on immunological parameters of humans, monkeys and rodents. These studies have been carried out by a number of different laboratories. Among the parameters affected are leukocyte blastogenesis, natural killer cell activity, leukocyte subset distribution, cytokine production - including interferons and interleukins, and macrophage maturation and activity. These changes start to occur only after a few days space flight, and some changes continue throughout long-term space flight. Antibody responses have received only very limited study, and total antibody levels have been shown to be increased after long-term space flight. Several factors could be involved in inducing these changes. These factors could include microgravity, lack of load-bearing, stress, acceleration forces, and radiation. The mechanism(s) for space flight-induced changes in immune responses remain(s) to be established. Certainly, there can be direct effects of microgravity, or other factors, on cells that play a fundamental role in immune responses. However, it is now clear that there are interactions between the immune system and other physiological systems that could play a major role. For example, changes occurring in calcium use in the musculoskeletal system induced by microgravity or lack of use could have great impact on the immune system. Most of the changes in immune responses have been observed using samples taken immediately after return from space flight. However, there have been two recent studies that have used in-flight testing. Delayed-type hypersensitivity responses to common recall antigens of astronauts and cosmonauts have been shown to be decreased when tested during space flights. Additionally, natural killer cell and blastogenic activities are inhibited in samples taken from rats during space flight. Therefore, it is now clear that events occurring during space flight itself can affect immune responses. The biological significance of space flight-induced changes in immune parameters remains to be established; however, as duration of flights increases, the potential for difficulties due to impaired immune responses also increases.

manned↗
DOE OSTI2025

Host cell and viral protease targets of human SERPINs identified by in silico docking

Serine protease inhibitors (SERPINs) are involved in various physiological processes and diseases, such as inflammation, cancer metastasis, and neurodegeneration. Their role in viral infections is poorly understood, as their expression patterns during infection and the range of proteases they target have yet to be fully characterized. Here, we show widespread expression of human SERPINs in response to respiratory virus infections, both in bronchioalveolar lavages from COVID-19 patients and in polarized human airway epithelial cultures. Using in silico docking of 10 SERPINs to 48 host proteases, we confirm known targets and predict new interactions. Protease activity assays validated selected interactions, confirming the newly predicted host targets for PAI-1 (SERPINE1) and PAI-2 (SERPINB2). PAI-1 inhibits cathepsin L, essential for SARS-CoV-2 maturation, and suppresses multi-cycle replication of both ancestral SARS-CoV-2 WA-1 and its variant Omicron BA.1. In addition, we identify PAI-2 as an antiviral SERPIN that reduces infectivity of human adenovirus 5 by directly inhibiting the adenoviral protease. Our study leverages in silico docking using full-length 3D protein structures to uncover new SERPIN targets, offering a range of candidate targets for therapeutic interventions.

59 BASIC BIOLOGICAL SCIENCES↗
NASA NTRS2017

Physiological and Molecular Changes in Various Biological Organisms Cultured under Simulated Microgravity Conditions

Microgravity is one of the most import factors in space flight where its impact on living biological organisms is concerned. Many different ailments have been reported in astronauts such as spaceflight related osteopenia, cardiovascular concerns, and loss of eye sight. In order to understand why µg causes these issues we must understand what is happening at the most basic of biological structures, the cell. The work done in this report is a culmination of contributions made to a much larger project. The project seeks to understand how cellular physiology is changing in SMG conditions and use this knowledge to feed into a follow-up study on the genetic changes that are seen in SMG environments. Cells were imaged using confocal microscopy after 20hrs and 48hrs in a 3D clinostat called the Gravite. Lengths, widths, heights, and total cell areas were measured using an image analysis software package ImageJ. There were significant differences in lengths and widths of cell nuclei, and total area of cell coverage. The report then discusses some of the problems with the testing apparatus and how 3D printing technology may be used to create better sample holders for the 3D clinostat.

cell biology↗
NASA NTRS2017

The Integrated Impact of Diet On Human Immune Response, the Gut Microbiota, and Nutritional Status During Adaptation to a Spaceflight Analog

Spaceflight impacts human physiology, including well documented immune system dysregulation. Diet, immune function, and the microbiome are interlinked, but diet is the only one of these factors that we have the ability to easily, and significantly, alter on Earth or during flight. As we understand dietary impacts on physiology more thoroughly, we may then improve the spaceflight diet to improve crew health and potentially reduce flight-associated physiological alterations. It is expected that increasing the consumption of fruits and vegetables and bioactive compounds (e.g.,omega-3 fatty acids, lycopene, flavonoids) and therefore enhancing overall nutritional intake from the nominal shelf-stable, fully-processed space food system could serve as a countermeasure to improve human immunological profiles, the taxonomic profile of the gut microbiota, and nutritional status, especially where currently dysregulated during spaceflight. This interdisciplinary study will determine the effect of the current shelf-stable spaceflight diet compared to an "enhanced" shelf-stable spaceflight diet (25% more foods rich in omega-3 fatty acids, lycopene, flavonoids, fruits, and vegetables). The NASA Human Exploration Research Analog (HERA) 2017 missions, consisting of closed chamber confinement, realistic mission simulation, in a high-fidelity mock space vehicle, will serve as a platform to replicate mission stressors and the dysregulated physiology observed in astronauts. Biosampling of crew members will occur at selected intervals, with complete dietary tracking. Outcome measures will include immune markers (e.g., peripheral leukocyte distribution, inflammatory cytokine profiles, T cell function), the taxonomic and metatranscriptomic profile of the gut microbiome, and nutritional status biomarkers and metabolites. Data collection will also include complete dietary tracking. Statistical evaluations will determine physiological and biochemical shifts in relation to nutrient in take and study phase. Beneficial improvements will provide evidence of the impact of diet on crew health and adaptation to this spaceflight analog, and will aid in the design and development of more-efficient targeted dietary interventions.

Douglas, G. L.↗
DOE OSTI2025

Redox poise in R. rubrum phototrophic growth drives large-scale changes in macromolecular pathways

During photoheterotrophic growth on organic substrates, purple nonsulfur photosynthetic bacteria like Rhodospirillum rubrum can acquire electrons by multiple means, including oxidation of organic substrates, oxidation of inorganic electron donors (e.g., H 2 ), and by reverse electron flow from the photosynthetic electron transport chain. These electrons are stored as reduced electron-carrying cofactors (e.g., NAD(P)H and ferredoxin). The overall ratio of oxidized to reduced cofactors (e.g., NAD(P)+:NAD(P)H), or ’redox poise’, is difficult to understand or predict, as are the cellular processes for dissipating these reducing equivalents. Using physics-based models that capture mass action kinetics consistent with the thermodynamics of reactions and pathways, a range of redox conditions for heterophototrophic growth are evaluated, from conditions in which the NADP+/NADPH levels approach thermodynamic equilibrium to conditions in which the NADP+/NADPH ratio is far above the typical physiological values. Modeling predictions together with experimental measurements indicate that the redox poise of the cell results in large-scale changes in the activity of biosynthetic pathways and, thus, changes in cell macromolecule levels (DNA, RNA, proteins, and fatty acids). Furthermore, modeling predictions indicate that during phototrophic growth, reverse electron flow from the quinone pool is a minor contributor to the production of reduced cofactors (e.g., NAD(P)H) compared to other oxidative processes (H 2 and carbon substrate oxidation). Instead, the quinone pool primarily operates to aid ATP production. The high level of ATP, in turn, drives reduction processes even when NADPH levels are relatively low compared to NADP+ by coupling ATP hydrolysis to the reductive processes. The model, in agreement with experimental measurements of macromolecule ratios of cells growing on different carbon substrates, indicates that the dynamics of nucleotide versus lipid and protein production is likely a significant mechanism of balancing oxidation and reduction in the cell.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2025

Redox Poise during Rhodospirillum rubrum Phototrophic Growth Drives Large-scale Changes in Macromolecular Synthesis Pathways

During photoheterotrophic growth on organic substrates, purple nonsulfur photosynthetic bacteria like Rhodospirillum rubrum can acquire electrons by multiple means, including oxidation of organic substrates, oxidation of inorganic electron donors (e.g., H2), and by reverse electron flow from the photosynthetic electron transport chain. These electrons are stored as reduced electron-carrying cofactors (e.g., NAD(P)H and ferredoxin). The overall ratio of oxidized to reduced cofactors (e.g., NAD(P)+:NAD(P)H), or ’redox poise’, is difficult to understand or predict, as are the cellular processes for dissipating these reducing equivalents. Using physics-based models that capture mass action kinetics consistent with the thermodynamics of reactions and pathways, a range of redox conditions for heterophototrophic growth are evaluated, from conditions in which the NADP+/NADPH levels approach thermodynamic equilibrium to conditions in which the NADP+/NADPH ratio is far above the typical physiological values. Modeling predictions together with experimental measurements indicate that the redox poise of the cell results in large-scale changes in the activity of biosynthetic pathways and, thus, changes in cell macromolecule levels (DNA, RNA, proteins, and fatty acids). Furthermore, modeling predictions indicate that during phototrophic growth, reverse electron flow from the quinone pool is a minor contributor to the production of reduced cofactors (e.g., NAD(P)H) compared to other oxidative processes (H2 and carbon substrate oxidation). Instead, the quinone pool primarily operates to aid ATP production. The high level of ATP, in turn, drives reduction processes even when NADPH levels are relatively low compared to NADP+ by coupling ATP hydrolysis to the reductive processes. The model, in agreement with experimental measurements of macromolecule ratios of cells growing on different carbon substrates, indicates that the dynamics of nucleotide versus lipid and protein production is likely a significant mechanism of balancing oxidation and reduction in the cell.

59 BASIC BIOLOGICAL SCIENCES↗
NASA NTRS1975

Study of toxicological evaluation of fire suppressants and extinguishers

The application of fluorocarbons as possible candidates for fire extinguishers and/or suppressants in confined spaces (such as spacecraft, aircraft, or submarines) was investigated, with special emphasis on their safety to man since they would be inhaled on an almost continuous basis. Short-term exposure experiments, using various animal species, were devised to look at specific parameters in order to determine which of the candidate compounds were sufficiently non-toxic to warrant long-term investigations. The following physiologic criteria were examined; tissue distribution, fluoride concentration, effect on mitochondria, microsomes, liposomes, and liver cell nuclei, erythrocyte fragility, clinical chemistry values, hematology, pathology, cardiac sensitization, behavioral effects. Various rodent species were used for initial investigations, with non-human primate exposures for Freon 116 which was warranted for negative results on rodents. Various types of exposure chambers were used, including closed dynamic chambers allowing for a recirculating atmosphere.

Source record↗