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At least 289 records · Page 16

Advantage of Animal Models with Metabolic Flexibility for Space Research Beyond Low Earth Orbit

As the worlds space agencies and commercial entities continue to expand beyond Low Earth Orbit (LEO), novel approaches to carry out biomedical experiments with animals are required to address the challenge of adaptation to space flight and new planetary environments. The extended time and distance of space travel along with reduced involvement of Earth-based mission support increases the cumulative impact of the risks encountered in space. To respond to these challenges, it becomes increasingly important to develop the capability to manage an organisms self-regulatory control system, which would enable survival in extraterrestrial environments. To significantly reduce the risk to animals on future long duration space missions, we propose the use of metabolically flexible animal models as pathfinders, which are capable of tolerating the environmental extremes exhibited in spaceflight, including altered gravity, exposure to space radiation, chemically reactive planetary environments and temperature extremes.In this report we survey several of the pivotal metabolic flexibility studies and discuss the importance of utilizing animal models with metabolic flexibility with particular attention given to the ability to suppress the organism's metabolism in spaceflight experiments beyond LEO. The presented analysis demonstrates the adjuvant benefits of these factors to minimize damage caused by exposure to spaceflight and extreme planetary environments. Examples of microorganisms and animal models with dormancy capabilities suitable for space research are considered in the context of their survivability under hostile or deadly environments outside of Earth. Potential steps toward implementation of metabolic control technology in spaceflight architecture and its benefits for animal experiments and manned space exploration missions are discussed.

metabolic flexibility↗

Predicting cancer rates in astronauts from animal carcinogenesis studies and cellular markers

The radiation space environment includes particles such as protons and multiple species of heavy ions, with much of the exposure to these radiations occurring at extremely low average dose-rates. Limitations in databases needed to predict cancer hazards in human beings from such radiations are significant and currently do not provide confidence that such predictions are acceptably precise or accurate. In this article, we outline the need for animal carcinogenesis data based on a more sophisticated understanding of the dose-response relationship for induction of cancer and correlative cellular endpoints by representative space radiations. We stress the need for a model that can interrelate human and animal carcinogenesis data with cellular mechanisms. Using a broad model for dose-response patterns which we term the "subalpha-alpha-omega (SAO) model", we explore examples in the literature for radiation-induced cancer and for radiation-induced cellular events to illustrate the need for data that define the dose-response patterns more precisely over specific dose ranges, with special attention to low dose, low dose-rate exposure. We present data for multiple endpoints in cells, which vary in their radiosensitivity, that also support the proposed model. We have measured induction of complex chromosome aberrations in multiple cell types by two space radiations, Fe-ions and protons, and compared these to photons delivered at high dose-rate or low dose-rate. Our data demonstrate that at least three factors modulate the relative efficacy of Fe-ions compared to photons: (i) intrinsic radiosensitivity of irradiated cells; (ii) dose-rate; and (iii) another unspecified effect perhaps related to reparability of DNA lesions. These factors can produce respectively up to at least 7-, 6- and 3-fold variability. These data demonstrate the need to understand better the role of intrinsic radiosensitivity and dose-rate effects in mammalian cell response to ionizing radiation. Such understanding is critical in extrapolating databases between cellular response, animal carcinogenesis and human carcinogenesis, and we suggest that the SAO model is a useful tool for such extrapolation.

Non-NASA Center↗

Compression of echocardiographic scan line data using wavelet packet transform

An efficient compression strategy is indispensable for digital echocardiography. Previous work has suggested improved results utilizing wavelet transforms in the compression of 2D echocardiographic images. Set partitioning in hierarchical trees (SPIHT) was modified to compress echocardiographic scanline data based on the wavelet packet transform. A compression ratio of at least 94:1 resulted in preserved image quality.

Non-NASA Center↗

Investigation of electrolyte measurement in diluted whole blood using spectroscopic and chemometric methods

The feasibility of using near-infrared (NIR) spectroscopy in combination with partial least-squares (PLS) regression was explored to measure electrolyte concentration in whole blood samples. Spectra were collected from diluted blood samples containing randomized, clinically relevant concentrations of Na+, K+, and Ca2+. Sodium was also studied in lysed blood. Reference measurements were made from the same samples using a standard clinical chemistry instrument. Partial least squares (PLS) was used to develop calibration models for each ion with acceptable results (Na+, R2 = 0.86, CVSEP = 9.5 mmol/L; K+, R2 = 0.54, CVSEP = 1.4 mmol/L; Ca2+, R2 = 0.56, CVSEP = 0.18 mmol/L). Slightly improved results were obtained using a narrower wavelength region (470-925 nm) where hemoglobin, but not water, absorbed indicating that ionic interaction with hemoglobin is as effective as water in causing measurable spectral variation. Good models were also achieved for sodium in lysed blood, illustrating that cell swelling, which is correlated with sodium concentration, is not required for calibration model development.

Non-NASA Center↗

Is there a common mechanism underlying genomic instability, bystander effects and other nontargeted effects of exposure to ionizing radiation?

A number of nontargeted and delayed effects associated with radiation exposure have now been described. These include radiation-induced genomic instability, death-inducing and bystander effects, clastogenic factors and transgenerational effects. It is unlikely that these nontargeted effects are directly induced by cellular irradiation. Instead, it is proposed that some as yet to be identified secreted factor can be produced by irradiated cells that can stimulate effects in nonirradiated cells (death-inducing and bystander effects, clastogenic factors) and perpetuate genomic instability in the clonally expanded progeny of an irradiated cell. The proposed factor must be soluble and capable of being transported between cells by cell-to-cell gap junction communication channels. Furthermore, it must have the potential to stimulate cellular cytokines and/or reactive oxygen species. While it is difficult to imagine a role for such a secreted factor in contributing to transgenerational effects, the other nontargeted effects of radiation may all share a common mechanism.

Non-NASA Center↗

The psychology of isolated and confined environments. Understanding human behavior in Antarctica

Psychosocial adaptation to isolated and confined environments exhibits 4 distinct characteristics. First, it is seasonal: Variations in mood are associated with the altered diurnal cycle and psychological segmentation of the mission. Second, it is situational: Concurrent measures of personality, interpersonal needs, and coping styles are better predictors of mood and performance than are predeployment measures. Third, it is social: Members of expeditions with low social coherence report significantly more depression, anxiety, and anger than individuals belonging to expeditions with high social coherence. Fourth, it is salutogenic: Depressed mood is inversely associated with the severity of the physical environment of the station, and the winter-over experience is associated with reduced subsequent rates of hospital admissions, suggesting positive benefits for individuals seeking challenging experiences.

NASA Program Biomedical Research and Countermeasur↗

The human respiratory gate

Respiratory activity phasically alters membrane potentials of preganglionic vagal and sympathetic motoneurones and continuously modulates their responsiveness to stimulatory inputs. The most obvious manifestation of this 'respiratory gating' is respiratory sinus arrhythmia, the rhythmic fluctuations of electrocardiographic R-R intervals observed in healthy resting humans. Phasic autonomic motoneurone firing, reflecting the throughput of the system, depends importantly on the intensity of stimulatory inputs, such that when levels of stimulation are low (as with high arterial pressure and sympathetic activity, or low arterial pressure and vagal activity), respiratory fluctuations of sympathetic or vagal firing are also low. The respiratory gate has a finite capacity, and high levels of stimulation override the ability of respiration to gate autonomic responsiveness. Autonomic throughput also depends importantly on other factors, including especially, the frequency of breathing, the rate at which the gate opens and closes. Respiratory sinus arrhythmia is small at rapid, and large at slow breathing rates. The strong correlation between systolic pressure and R-R intervals at respiratory frequencies reflects the influence of respiration on these two measures, rather than arterial baroreflex physiology. A wide range of evidence suggests that respiratory activity gates the timing of autonomic motoneurone firing, but does not influence its tonic level. I propose that the most enduring significance of respiratory gating is its use as a precisely controlled experimental tool to tease out and better understand otherwise inaccessible human autonomic neurophysiological mechanisms.

Review↗

Nonlinear dynamics in cardiac conduction

Electrical conduction in the heart shows many phenomena familiar from nonlinear dynamics. Among these phenomena are multiple basins of attraction, phase locking, and perhaps period-doubling bifurcations and chaos. We describe a simple cellular-automation model of electrical conduction which simulates normal conduction patterns in the heart as well as a wide range of disturbances of heart rhythm. In addition, we review the application of percolation theory to the analysis of the development of complex, self-sustaining conduction patterns.

NASA Discipline Cardiopulmonary↗

Making it without losing it: Type A, achievement motivation, and scientific attainment revisited

In a study by Matthews, Helmreich, Beane, and Lucker (1980), responses by academic psychologists to the Jenkins Activity Survey for Health Prediction (JAS), a measure of the Type A construct, were found to be significantly, positively correlated with two measures of attainment, citations by others to published work and number of publications. In the present study, JAS responses from the Matthews et al. sample were subjected to a factor analysis with oblique rotation and two new subscales were developed on the basis of this analysis. The first, Achievement Strivings (AS) was found to be significantly correlated with both the publication and citation measures. The second scale, Impatience and Irritability (I/I), was uncorrelated with the achievement criteria. Data from other samples indicate that I/I is related to a number of health symptoms. The results suggest that the current formulation of the Type A construct may contain two components, one associated with positive achievement and the other with poor health.

NASA Discipline Space Human Factors↗

Regulation of RYR1 activity by Ca(2+) and calmodulin

The skeletal muscle calcium release channel (RYR1) is a Ca(2+)-binding protein that is regulated by another Ca(2+)-binding protein, calmodulin. The functional consequences of calmodulin's interaction with RYR1 are dependent on Ca(2+) concentration. At nanomolar Ca(2+) concentrations, calmodulin is an activator, but at micromolar Ca(2+) concentrations, calmodulin is an inhibitor of RYR1. This raises the question of whether the Ca(2+)-dependent effects of calmodulin on RYR1 function are due to Ca(2+) binding to calmodulin, RYR1, or both. To distinguish the effects of Ca(2+) binding to calmodulin from those of Ca(2+) binding to RYR1, a mutant calmodulin that cannot bind Ca(2+) was used to evaluate the effects of Ca(2+)-free calmodulin on Ca(2+)-bound RYR1. We demonstrate that Ca(2+)-free calmodulin enhances the affinity of RYR1 for Ca(2+) while Ca(2+) binding to calmodulin converts calmodulin from an activator to an inhibitor. Furthermore, Ca(2+) binding to RYR1 enhances its affinity for both Ca(2+)-free and Ca(2+)-bound calmodulin.

Non-NASA Center↗

New imaging technology: measurement of myocardial perfusion by contrast echocardiography

Myocardial perfusion imaging has long been a goal for the non-invasive echocardiographic assessment of the heart. However, many factors at play in perfusion imaging have made this goal elusive. Harmonic imaging and triggered imaging with newer contrast agents have made myocardial perfusion imaging potentially practical in the very near future. The application of indicator dilution theory to the coronary circulation and bubble contrast agents is fraught with complexities and sources of error. Therefore, quantification of myocardial perfusion by non-invasive echocardiographic imaging requires further investigation in order to make this technique clinically viable.

NASA Program Biomedical Research and Countermeasur↗

Horizontal vestibuloocular reflex evoked by high-acceleration rotations in the squirrel monkey. III. Responses after labyrinthectomy

The horizontal angular vestibuloocular reflex (VOR) evoked by high-frequency, high-acceleration rotations was studied in four squirrel monkeys after unilateral labyrinthectomy. Spontaneous nystagmus was measured at the beginning and end of each testing session. During the period that animals were kept in darkness (4 days), the nystagmus at each of these times measured approximately 20 degrees /s. Within 18-24 h after return to the light, the nystagmus (measured in darkness) decreased to 2.8 +/- 1.5 degrees /s (mean +/- SD) when recorded at the beginning but was 20.3 +/- 3.9 degrees /s at the end of the testing session. The latency of the VOR measured from responses to steps of acceleration (3,000 degrees /s(2) reaching a velocity of 150 degrees /s) was 8.4 +/- 0.3 ms for responses to ipsilesional rotations and 7.7 +/- 0.4 ms for contralesional rotations. During the period that animals were kept in darkness after the labyrinthectomy, the gain of the VOR measured during the steps of acceleration was 0.67 +/- 0.12 for contralesional rotations and 0.39 +/- 0.04 for ipsilesional rotations. Within 18-24 h after return to light, the VOR gain for contralesional rotations increased to 0.87 +/- 0.08, whereas there was only a slight increase for ipsilesional rotations to 0.41 +/- 0. 06. A symmetrical increase in the gain measured at the plateau of head velocity was noted after the animals were returned to light. The VOR evoked by sinusoidal rotations of 2-15 Hz, +/-20 degrees /s, showed a better recovery of gain at lower (2-4 Hz) than at higher (6-15 Hz) frequencies. At 0.5 Hz, gain decreased symmetrically when the peak amplitude was increased from 20 to 100 degrees /s. At 10 Hz, gain was decreased for ipsilesional half-cycles and increased for contralesional half-cycles when velocity was raised from 20 to 50 degrees /s. A model incorporating linear and nonlinear pathways was used to simulate the data. Selective increases in the gain for the linear pathway accounted for the recovery in VOR gain for responses at the velocity plateau of the steps of acceleration and for the sinusoidal rotations at lower peak velocities. The increase in gain for contralesional responses to steps of acceleration and sinusoidal rotations at higher frequencies and velocities was due to an increase in the contribution of the nonlinear pathway. This pathway was driven into cutoff and therefore did not affect responses for rotations toward the lesioned side.

NASA Discipline Neuroscience↗

The pressor response to water drinking in humans : a sympathetic reflex?

BACKGROUND: Water drinking increases blood pressure profoundly in patients with autonomic failure and substantially in older control subjects. The mechanism that mediates this response is not known. METHODS AND RESULTS: We studied the effect of drinking tap water on seated blood pressure in 47 patients with severe autonomic failure (28 multiple system atrophy [MSA], 19 pure autonomic failure patients [PAF]). Eleven older controls and 8 young controls served as control group. We also studied the mechanisms that could increase blood pressure with water drinking. Systolic blood pressure increased profoundly with water drinking, reaching a maximum of 33+/-5 mm Hg in MSA and 37+/-7 in PAF mm Hg after 30 to 35 minutes. The pressor response was greater in patients with more retained sympathetic function and was almost completely abolished by trimethaphan infusion. Systolic blood pressure increased by 11+/-2.4 mm Hg in elderly but not in young controls. Plasma norepinephrine increased in both groups. Plasma renin activity, vasopressin, and blood volume did not change in any group. CONCLUSIONS: Water drinking significantly and rapidly raises sympathetic activity. Indeed, it raises plasma norepinephrine as much as such classic sympathetic stimuli as caffeine and nicotine. This effect profoundly increases blood pressure in autonomic failure patients, and this effect can be exploited to improve symptoms due to orthostatic hypotension. Water drinking also acutely raises blood pressure in older normal subjects. The pressor effect of oral water is an important yet unrecognized confounding factor in clinical studies of pressor agents and antihypertensive medications.

Non-NASA Center↗

Inflight exercise affects stand test responses after space flight

PURPOSE: The purpose of this study was to determine whether exercise performed by Space Shuttle crew members during short-duration space flights (9-16 d) affects the heart rate (HR) and blood pressure (BP) responses to standing within 2-4 h of landing. METHODS: Thirty crew members performed self-selected inflight exercise and maintained exercise logs to monitor their exercise intensity and duration. Two subjects participated in this investigation during two different flights. A 10-min stand test, preceded by at least 6 min of quiet supine rest, was completed 10-15 d before launch (PRE) and within 4 h of landing (POST). Based upon their inflight exercise records, subjects were grouped as either high (HIex: > or = 3 times/week, HR > or = 70% HRmax, > or = 20 min/session, N = 11), medium (MEDex: > or = 3 times/week, HR < 70% HRmax, > or = 20 min/session, N = 10), or low (LOex: < or = 3 times/week, HR and duration variable, N = 11) exercisers. HR and BP responses to standing were compared between groups (ANOVA, P < or = 0.05). RESULTS: There were no PRE differences between the groups in supine or standing HR and BP. Although POST supine HR was similar to PRE, all groups had an increased standing HR compared with PRE. The increase in HR upon standing was significantly greater after flight in the LOex group (36 +/- 5 bpm) compared with HIex or MEDex groups (25 +/- 1 bpm; 22 +/- 2 bpm). Similarly, the decrease in pulse pressure (PP) from supine to standing was unchanged after space flight in the MEDex and HIex groups but was significantly greater in the LOex group (PRE: -9 +/- 3; POST: -19 +/- 4 mm Hg). CONCLUSIONS: Thus, moderate to high levels of inflight exercise attenuated HR and PP responses to standing after space flight.

manned↗

Interaction of genetic predisposition and environmental factors in the pathogenesis of idiopathic orthostatic intolerance

BACKGROUND: The hemodynamic and autonomic abnormalities in idiopathic orthostatic intolerance (IOI) have been studied extensively. However, the mechanisms underlying these abnormalities are not understood. If genetic predisposition were important in the pathogenesis of IOI, monozygotic twins of patients with IOI should have similar hemodynamic and autonomic abnormalities. METHODS: We studied two patients with IOI and their identical twins. Both siblings in the first twin pair had orthostatic symptoms, significant orthostatic tachycardia, increased plasma norepinephrine levels with standing, and a greater than normal decrease in systolic blood pressure with trimethaphan infusion. RESULTS: Both siblings had a normal response of plasma renin activity to upright posture. In the second twin pair, only one sibling had symptoms of orthostatic intolerance, an orthostatic tachycardia, and raised plasma catecholamines with standing. The affected sibling had inappropriately low plasma renin activity with standing and was 8-fold more sensitive to the pressor effect of phenylephrine than the unaffected sibling. CONCLUSIONS: We conclude that in some patients, IOI seems to be strongly influenced by genetic factors. In others, however, IOI may be mainly caused by nongenetic factors. These findings suggest that IOI is heterogenous, and that both genetic and environmental factors contribute individually or collectively to create the IOI phenotype.

NASA Discipline Regulatory Physiology↗

Horizontal vestibuloocular reflex evoked by high-acceleration rotations in the squirrel monkey. I. Normal responses

The horizontal angular vestibuloocular reflex (VOR) evoked by high-frequency, high-acceleration rotations was studied in five squirrel monkeys with intact vestibular function. The VOR evoked by steps of acceleration in darkness (3,000 degrees /s(2) reaching a velocity of 150 degrees /s) began after a latency of 7.3 +/- 1.5 ms (mean +/- SD). Gain of the reflex during the acceleration was 14.2 +/- 5.2% greater than that measured once the plateau head velocity had been reached. A polynomial regression was used to analyze the trajectory of the responses to steps of acceleration. A better representation of the data was obtained from a polynomial that included a cubic term in contrast to an exclusively linear fit. For sinusoidal rotations of 0.5-15 Hz with a peak velocity of 20 degrees /s, the VOR gain measured 0.83 +/- 0.06 and did not vary across frequencies or animals. The phase of these responses was close to compensatory except at 15 Hz where a lag of 5.0 +/- 0.9 degrees was noted. The VOR gain did not vary with head velocity at 0.5 Hz but increased with velocity for rotations at frequencies of >/=4 Hz (0. 85 +/- 0.04 at 4 Hz, 20 degrees /s; 1.01 +/- 0.05 at 100 degrees /s, P < 0.0001). No responses to these rotations were noted in two animals that had undergone bilateral labyrinthectomy indicating that inertia of the eye had a negligible effect for these stimuli. We developed a mathematical model of VOR dynamics to account for these findings. The inputs to the reflex come from linear and nonlinear pathways. The linear pathway is responsible for the constant gain across frequencies at peak head velocity of 20 degrees /s and also for the phase lag at higher frequencies being less than that expected based on the reflex delay. The frequency- and velocity-dependent nonlinearity in VOR gain is accounted for by the dynamics of the nonlinear pathway. A transfer function that increases the gain of this pathway with frequency and a term related to the third power of head velocity are used to represent the dynamics of this pathway. This model accounts for the experimental findings and provides a method for interpreting responses to these stimuli after vestibular lesions.

NASA Program Biomedical Research and Countermeasur↗

Materials processing in space: A survey of referred open literature publications

Over 190 reports published in the open literature by workers in the materials processing in space program are listed according to year as well as alphabetically by author. Thirty five reports submitted for publication are also cited. Supported either directly or indirectly by NASA, the research generally pertains to the influence (or lack of influence) of gravity on processes involved in crystal growth, solidification, fluid transport, containerless phenomena, and various separation techniques of interest to the biomedical community. Studies of the possibilities of using the high vacuum in the wake of orbiting vehicles for performing processes involving large heat loads and evolution of gases are also included.

Pentecost, E.↗

Role of genetic background in induced instability

Genomic instability is effectively induced by ionizing radiation. Recently, evidence has accumulated supporting a relationship between genetic background and the radiation-induced genomic instability phenotype. This is possibly due to alterations in proteins responsible for maintenance of genomic integrity or altered oxidative metabolism. Studies in human cell lines, human primary cells, and mouse models have been performed predominantly using high linear energy transfer (LET) radiation, or high doses of low LET radiation. The interplay between genetics, radiation response, and genomic instability has not been fully determined at low doses of low LET radiation. However, recent studies using low doses of low LET radiation suggest that the relationship between genetic background and radiation-induced genomic instability may be more complicated than these same relationships at high LET or high doses of low LET radiation. The complexity of this relationship at low doses of low LET radiation suggests that more of the population may be at risk than previously recognized and may have implications for radiation risk assessment.

NASA Discipline Radiation Health↗