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At least 199 records · Page 11

Heat Shock Protein 40 and Immune Function in Altered Gravity

In space, astronauts are more susceptible to pathogens, viral reactivation and immunosuppression, which poses limits to their health and the mission. Interestingly, during space flight, stress-inducible heat shock proteins (HSP) are robustly induced, and the overexpression of HSPs have been implicated in immune dysregulation, therefore HSPs may be critically involved in regulating immune homeostasis. HSP40/DNAJ1 plays a major role in proper protein translation and folding. Its loss of function has been implicated in susceptibility to microbial infection, while its overexpression has been implicated in autoimmunity, collectively suggesting its complicated, but necessary, role in maintaining immunological function. To determine the role of HSP40 during stress-induced altered gravity conditions, wild-type and Hsp40 mutant Drosophila melanogaster were exposed to ground-based chronic hypergravity conditions, followed by quantitative PCR (qPCR) analysis of immune gene expression. In addition, larval hemocytes were collected to determine the functional output in response to E. coli bioparticle phagocytosis. Preliminary data indicates a required role for Hsp40 in strengthening immune function during stress-induced spaceflight in flies. In short, a critical need to evaluate the relationship between HSPs and immune suppression during space flight is necessary. Since space travel may become available to the general public in the not too distant future, and for the possibility of long-term space missions, a more comprehensive evaluation of the molecules responsible for immune dysfunction observed during space flight is required.

hypergravity↗

Exploration of Circadian Rhythms in Patients with Bilateral Vestibular Loss

Background New insights have expanded the influence of the vestibular system to the regulation of circadian rhythmicity. Indeed, hypergravity or bilateral vestibular loss (BVL) in rodents causes a disruption in their daily rhythmicity for several days. The vestibular system thus influences hypothalamic regulation of circadian rhythms on Earth, which raises the question of whether daily rhythms might be altered due to vestibular pathology in humans. The aim of this study was to evaluate human circadian rhythmicity in people presenting a total bilateral vestibular loss (BVL) in comparison with control participants. Methodology and Principal Findings Nine patients presenting a total idiopathic BVL and 8 healthy participants were compared. Their rest-activity cycle was recorded by actigraphy at home over 2 weeks. The daily rhythm of temperature was continuously recorded using a telemetric device and salivary cortisol was recorded every 3 hours from 6:00AM to 9:00PM over 24 hours. BVL patients displayed a similar rest activity cycle during the day to control participants but had higher nocturnal actigraphy, mainly during weekdays. Sleep efficiency was reduced in patients compared to control participants. Patients had a marked temperature rhythm but with a significant phase advance (73 min) and a higher variability of the acrophase (from 2:24 PM to 9:25 PM) with no correlation to rest-activity cycle, contrary to healthy participants. Salivary cortisol levels were higher in patients compared to healthy people at any time of day. Conclusion We observed a marked circadian rhythmicity of temperature in patients with BVL, probably due to the influence of the light dark cycle. However, the lack of synchronization between the temperature and rest-activity cycle supports the hypothesis that the vestibular inputs are salient input to the circadian clock that enhance the stabilization and precision of both external and internal entrainment.

59 BASIC BIOLOGICAL SCIENCES↗

Effects of continuous exposure to high gravity on gravity preference in rats.

Rats were chronically centrifuged in excess of 2.0 g for 6 or 12 mo. They were given four 24-hr gravity-preference tests in a spiral centrifuge in which they could adjust the gravity level imposed by locomoting inward or outward radially along a track. Chronically centrifuged rats (Group CC) spent as much time at 2.0 g as at 1.0 g while normally raised controls (Group NC) selecdonly 1.0 g. Group CC initially selected 2.0 g and a preference for 1.0 g developed over the four test sessions. These results suggest that hypergravity is not necessarily an aversive stimulus and that gravity preference may depend initially upon the reference level involved. The ultimate selection of 1.0 g by chronically centrifuged animals suggests that a preference for a familiar gravity environment is replaced by a preference for low-gravity stimuli.

Mccoy, D. F.↗

Effect of altered gravity on temperature regulation in mammals: Investigation of gravity effect on temperature regulation in mammals

Male, Long-Evans hooded rats were instrumented for monitoring core and hypothalamic temperatures as well as shivering and nonshivering thermogenesis in response to decreased ambient temperature in order to characterize the nature of the neural controller of temperature in rats at 1G and evaluate chronic implantation techniques for the monitoring of appropriate parameters at hypergravic fields. The thermoregulatory responses of cold-exposed rats at 2G were compared to those at 1G. A computer model was developed to simulate the thermoregulatory system in the rat. Observations at 1 and 2G were extended to acceleration fields of 1.5, 3.0 and 4.0G and the computer model was modified for application to altered gravity conditions. Changes in the acceleration field resulted in inadequate heat generation rather than increased heat loss. Acceleration appears to impair the ability of the neurocontroller to appropriately integrate input signals for body temperature maintenance.

Horwitz, B. A.↗

Effects of chronic centrifugation on skeletal muscle fibers in young developing rats

Three groups of 30-d old male and female rats were centrifuged for 2, 4, 8, and 16 weeks, after which their soleus and plantaris muscles were analysed for changes in proportions of muscle fiber types. The groups were: earth control, maintained at earth gravity without rotation; rotation control, subjected to a gravitational force of 1.05 G and 28 rpm; and rotation experimental, subjected to a gravitational force of 2 G and 28 rpm. Muscle fibers were classified into four fiber types on the basis of actomyosin ATPase activity as slow oxidative, fast oxidative glycolytic and either fast glycolytic (plantaris) or intermediate (soleus). Hypergravity resulted in an increase in slow oxidative fibers in soleus relative to the earth control, but not of females treated similarly. The relationship of body weight to the changes in proportion of slow oxidative fibers is discussed.

Martin, W. D.↗

Temperature and behavioral responses of squirrel monkeys to 2Gz acceleration

This study examines the responses of squirrel monkeys to acute +2Gz exposure. Body temperature responses of loosely restrained animals were recorded via a thermistor in the colon. Behavioral responses were recorded by video monitoring. After baseline recording at 1G, monkeys were exposed to 2G for 60 min. The body temperature started to fall within 10 min of the onset of centrifugation and declined an average of 1.4 C in 60 min. This is in contrast to a stable body temperature during the control period. Further, after a few minutes at 2G, the animals became drowsy and appeared to fall asleep. During the control period, however, they were alert and continually shifting their gaze about the cage. Thus, primates are susceptible to hypergravic fields in the +Gz orientation. The depression in primate body temperature was consistent and significant. Further, the observed drowsiness in this study has significant ramifications regarding alertness and performance in man.

Fuller, C. A.↗

Effects of simulated increased gravity on the rate of aging of rats - Implications for the rate of living theory of aging

It was found that the rate of aging of 17 month old rats which had been exposed to 3.14 times normal gravity in an animal centrifuge for 8 months was larger than that of the controls as determined by the apparently elevated lipofuscin content in heart and kidney, reduced numbers and increased size of mitochondria of heart tissue, and inferior liver mitochondria respiration. Steady-state food intake per day per kg body weight, which is presumably proportional to rate of living or specific basal metabolic expenditure, was found to be about 18 percent higher than in the controls after an initial 2 month adaptation period. Although half of the centrifuged animals lived only a little shorter than the controls (average about 343 vs. 364 days on the average, statistically nonsignificant), the remaining half (longest survivors) lived on the centrifuge an average of 520 days (range 483-572) compared to an average of 574 days (range 502-615) for the controls, computed from the onset of centrifugation, or 11 percent shorter. These findings indicate that a moderate increase of the level of basal metabolism of young adult rats adapted to hypergravity compared to controls in normal gravity is accompanied by a roughly similar increase in the rate of organ aging and reduction of survival, in agreement with Pearl's (1928) rate of living theory of aging, previously experimentally demonstrated only in poikilotherms.

Economos, A. C.↗

Effects of deceleration on the humoral antibody response in rats

Effects of hypergravity, simulated by chronic centrifugation, followed by a return to normal G (deceleration) on the immune system of rats were investigated. Two groups of male rats (28 days at 2.1 G, and 3.1 G) were compared to the control group (1.0 G). The animals were immunized by i.p. injections of sheep red blood cells on days 29, 42, and 57, and bled on days 36, 47, and 62. While the centrifuged rats ate and gainedsignificantly less than the control rats, the antibody titers and the organ/body mass ratios for the adrenal glands, kidneys, lungs, heart, and thymus were unaffected by gravity exposures, as were the values of the hematocrit and the white blood cell counts. It is concluded that deceleration does not adversely affect these particular aspects of the immune system.

Barone, R. P.↗

Amphibian egg cytoplasm response to altered g-forces and gravity orientation

Elucidation of dorsal/ventral polarity and primary embryonic axis development in amphibian embryos requires an understanding of cytoplasmic rearrangements in fertile eggs at the biophysical, physiological, and biochemical levels. Evidence is presented that amphibian egg cytoplasmic components are compartmentalized. The effects of altered orientation to the gravitational vector (i.e., egg inversion) and alterations in gravity force ranging from hypergravity (centrifugation) to simulated microgravity (i.e., horizontal clinostat rotation) on cytoplasmic compartment rearrangements are reviewed. The behavior of yolk compartments as well as a newly defined (with monoclonal antibody) nonyolk cytoplasmic compartment, in inverted eggs and in eggs rotated on horizontal clinostats at their buoyant density, is discussed.

Neff, A. W.↗

Instability of ocular torsion in zero gravity - Possible implications for space motion sickness

It is proposed that study of the eye torsion reflex and its behavior under novel gravitational states may possibly provide the basis for a long-sought test to predict space motion sickness (SMS). Measures of eye torsion such as ocular counterrolling and spontaneous eye torsion, were examined during hypo- and hypergravity in parabolic flight on the NASA KC-135 aircraft. Ten subjects, including two astronauts, one who had experienced SMS and one who had not, were ranked according to scores of torsional inability at 0 G and divided into two equal groups of high and low susceptibility to SMS. At 1.8 G the groups were significantly different in both the instability measure and the measure of torsional ability. No differences were detected in eye torsion in either 0 G or 1.8 G and none of the tests were significantly different in 1 G. Results suggest that tests of eye torsion on the KC-135 might differentiate those who would experience SMS from those who would not, although it is noted that this is not yet proven.

Diamond, Shirley G.↗

Space Station Centrifuge: A Requirement for Life Science Research

A centrifuge with the largest diameter that can be accommodated on Space Station Freedom is required to conduct life science research in the microgravity environment of space. (This was one of the findings of a group of life scientists convened at the University of California, Davis, by Ames Research Center.) The centrifuge will be used as a research tool to understand how gravity affects biological processes; to provide an on-orbit one-g control; and to assess the efficacy of using artificial gravity to counteract the deleterious biological effect of space flight. The rationale for the recommendation and examples of using ground-based centrifugation for animal and plant acceleration studies are presented. Included are four appendixes and an extensive bibliography of hypergravity studies.

Smith, Arthur H.↗

The Biological Flight Research Facility

NASA Ames Research Center is building a research facility, the Biological Flight Research Facility (BFRF), to meet the needs of life scientists to study the long-term effects of variable gravity on living systems. The facility will be housed on Space Station Freedom and is anticipated to operate for the lifetime of the station, approximately 30 years. It will allow plant and animal biologists to study the role of gravity, or its absence, at varying gravity intensities for varying periods of time and with various organisms. The principal difference between current Spacelab missions and those on Space Station Freedom, other than length of mission, will be the capability to perform on-orbit science procedures and the capability to simulate earth gravity. Initially, the facility will house plants and rodents in habitats which can be maintained at microgravity or can be placed on a 2.5-m diam centrifuge. However, the facility is also being designed to accommodate future habitats for small primates, avian, and aquatic specimens. The centrifuge will provide 1 g for controls and will also be able to provide gravity from 0.01 to 2.0 g for threshold gravity studies as well as hypergravity studies. The BFRF will provide the means to conduct basic experiments to gain an understanding of the effects of microgravity on the structure and function of plants and animals, as well as investigate the role of gravity as a potential countermeasure for the physiological changes observed in microgravity.

Johnson, Catherine C.↗

Understanding the organization of the amphibian egg cytoplasm - Gravitational force as a probe

A combination of hypergravity (centrifugation) and hypogravity (clinostat) studies have been carried out on amphibian (frog, Xenopus) eggs. The results reveal that the twinning caused by centrifugation exhibits substantial spawning to spawning variation. That variation can be attributed to the apparent viscosity of the egg's internal cytoplasm. Simulated hypogravity results in a relocation of the egg's third (horizontal) cleavage furrow, toward the equator. Substantial egg-to-egg variation is also observed in this 'cleavage effect'. For interpreting spaceflight data and for using G-forces as probes for understanding the egg's architecture the egg variation documented herein should be considered.

Neff, Anton W.↗

An overview of gravitational physiology

The focus of this review is on the response of humans and animals to the effects of the near weightless condition occurring aboard orbiting spacecraft. Gravity is an omnipresent force that has been a constant part of our lives and of the evolution of all living species. Emphasis is placed on the general mechanisms of adaptation to altered gravitational fields and vectors, i.e., both hypo- and hypergravity. A broad literature review of gravitational biology was conducted and the general state of our knowledge in this area is discussed. The review is specifically targeted at newcomers to the exciting and relatively new area of space and gravitational biology.

Miquel, Jaime↗

Acute hemodynamic response to weightlessness during parabolic flight

The effect of a short exposure to weightlessness on hemodynamic parameters of humans was investigated in seven subjects flown aboard the KC-135 aircraft. Particular attention is given to the relationships among various hemodynamic responses to hypergravic and hypogravic states, observed for four different postures: semisupine, supine, standing, and sitting. Results are presented on changes in the thoracic fluid index, heart rate, cardiac index, and the coefficient of variation of the R-R intervals. High values of the coefficient of variation were found at the onset of 0-G, suggesting that vagal cardiac neural activity increases in all positions except supine (where a small decrease was registered).

Mukai, Chiaki N.↗

Central circulatory hemodynamics as a function of gravitational stress

This study focuses on an evaluation of the central hemodynamics in a nonhuman primate model to variations in gravitational states. The baboon, phylogenectically close to man, was chosen as the human surrogate. The study environments selected are head-down and head-up tilt in the physiology laboratory, centrifugation to test hypergravic stress, and parabolic flights to test transient acute responses to microgravity.

Latham, Rick D.↗

Gravity as a probe for understanding pattern specification

Amphibian eggs from Xenopus laevis were employed as a model system. Xenopus embryos were demonstrated to be sensitive to novel force fields. Under clinostat-simulated weightlessness the location of the third cleavage furrow was shifted towards the equator; the dorsal lip was shifted closer to the vegetal pole; and head and eye dimensions of hatching tadpoles were enlarged. Effects of centrifuge-simulated hypergravity were the opposite of those of simulated weightlessness. Those morphological alterations had their own force-sensitive period, and a substantial spawning-to-spawning variation in sensitivity was observed. Despite those dramatic differences in embryogenesis, tadpoles at the feeding stage were largely indistinguishable from controls.

Malacinski, George M.↗

Monoclonal antibodies directed against surface molecules of multicell spheroids

The objective of this project is to generate a library of monoclonal antibodies (MAbs) directed against surface molecules of tumor and transformed cells grown as multicell spheroids (MCS). These MCS are highly organized, 3-dimensional multicellular structures which exhibit many characteristics of in vivo organized tissues not found in conventional monolayer or suspension culture. Therefore MCS make better in vitro model systems to study the interactions of mammalian cells, and provide a functional assay for surface adhesion molecules. This project also involves investigations of cell-cell interactions in a gravity-based environment. It will provide a base of scientific information necessary to expand the focus of the project in future years to microgravity and hypergravity-based environments. This project also has the potential to yield important materials (e.g., cellular products) which may prove useful in the diagnosis and/or treatment of certain human diseases. Moreover, this project supports the training of both undergraduate and graduate students; thus, it will assist in developing a pool of future scientists with research experience in an area (gravitational biology) of interest to NASA.

Martinez, Andrew O.↗