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NASA NTRS1994

US experiments flown on the Soviet biosatellite Cosmos 2044. Volume 1: Mission description, experiments K-7-01 - K-7-15

Cosmos 2044 was launched on September 15, 1989, containing radiation dosimetry experiments and a biological payload including two young male rhesus monkeys, ten adult male Wistar rats, insects, amphibians, protozoa, cell cultures, worms, plants and fish. The biosatellite was launched from the Plesetsk Cosmodrome in the Soviet Union for a mission duration of 14 days, as planned. The major research objectives were: (1) Study adaptive response mechanisms of mammals during flight; (2) Study physiological mechanisms underlying vestibular, motor system and brain function in primates during early and later adaptation phases; (3) Study the tissue regeneration processes of mammals; (4) Study the development of single-celled organisms, cell cultures and embryos in microgravity; (5) Study radiation characteristics during the mission and investigate doses, fluxes and spectra of cosmic radiation for various types of shielding. American and Soviet specialists jointly conducted 29 experiments on this mission including extensive preflight and post flight studies with rhesus monkeys, and tissue processing and cell culturing post flight. Biosamples and data were subsequently transferred to the United States. The U.S. responsibilities for this flight included development of flight and ground-based hardware, the preparation of rat tissue sample procedures, the verification testing of hardware and experiment procedures, and the post flight analysis of biospecimens and data for the joint experiments. The U.S. investigations included four primate experiments, 24 rat experiments, and one radiation dosimetry experiment. Three scientists investigated tissue repair during flight for a subgroup of rats injured preflight by surgical intervention. A description of the Cosmos 2044 mission is presented in this report including preflight, on-orbit and post flight activities. The flight and ground-based bioinstrumentation which was developed by the U.S. and U.S.S.R. is also described, along with the associated preflight testing of the U.S. hardware.

Connolly, James P.↗
NASA NTRS1994

Microgravity Flight - Accommodating Non-Human Primates

Spacelab Life Sciences-3 (SLS-3) was scheduled to be the first United States man-tended microgravity flight containing Rhesus monkeys. The goal of this flight as in the five untended Russian COSMOS Bion flights and an earlier American Biosatellite flight, was to understand the biomedical and biological effects of a microgravity environment using the non-human primate as human surrogate. The SLS-3/Rhesus Project and COSMOS Primate-BIOS flights all utilized the rhesus monkey, Macaca mulatta. The ultimate objective of all flights with an animal surrogate has been to evaluate and understand biological mechanisms at both the system and cellular level, thus enabling rational effective countermeasures for future long duration human activity under microgravity conditions and enabling technical application to correction of common human physiological problems within earth's gravity, e.g., muscle strength and reloading, osteoporosis, immune deficiency diseases. Hardware developed for the SLS-3/Rhesus Project was the result of a joint effort with the French Centre National d'Etudes Spatiales (CNES) and the United States National Aeronautics and Space Administration (NASA) extending over the last decade. The flight hardware design and development required implementation of sufficient automation to insure flight crew and animal bio-isolation and maintenance with minimal impact to crew activities. A variety of hardware of varying functional capabilities was developed to support the scientific objectives of the original 22 combined French and American experiments, along with 5 Russian co-investigations, including musculoskeletal, metabolic, and behavioral studies. Unique elements of the Rhesus Research Facility (RRF) included separation of waste for daily delivery of urine and fecal samples for metabolic studies and a psychomotor test system for behavioral studies along with monitored food measurement. As in untended flights, telemetry measurements would allow monitoring of thermoregulation, muscular, and cardiac responses to weightlessness. In contrast, the five completed Cosmos/Bion flights, lacked the metabolic samples and behavioral task monitoring, but did facilitate studies of the neurovestibular system during several of the flights.

Dalton, Bonnie P.↗
NASA NTRS1997

Final Science Reports of the US Experiments Flown on the Russian Biosatellite Cosmos 2229

Cosmos 2229 was launched on December 29, 1992, containing a biological payload including two young male rhesus monkeys, insects, amphibians, and cell cultures. The biosatellite was launched from the Plesetsk Cosmodrome in Russia for a mission duration of 11.5 days. The major research objectives were: (1) Study of adaptive response mechanisms of mammals during flight; and (2) Study of physiological mechanisms underlying vestibular, motor system and brain function in primates during early and later adaptation phases. American scientists and their Russian collaborators conducted 11 experiments on this mission which included extensive preflight and postflight studies with rhesus monkeys. Biosamples and data were subsequently transferred to the United States. The U.S. responsibilities for this flight included the development of experiment protocols, the fabrication of some flight instrumentation and experiment-specific ground-based hardware, the conducting of preflight and postflight testing and the analysis of biospecimens and data for the U.S. experiments. A description of the Cosmos 2229 mission is presented in this report including preflight, on-orbit and postflight activities. The flight and ground-based bioinstrumentation which was developed by the U.S. and Russia is also described, along with the associated preflight testing ot the U.S. hardware. Final Science Reports for the experiments are also included.

Connolly, James P.↗
NASA NTRS1997

Light and Gravity Effects on Circadian Rhythms of Rhesus Macaques

Temporal integration of a biological organism's physiological, behavioral and biochemical systems depends upon its circadian timing system. The endogenous period of this timing system is typically synchronized to the 24- hour day by environmental cues. The daily alternation of light and dark has long been known as one of the most potent environmental synchronizers influencing the circadian timing system. Alterations in the lighting environment (length or intensity of light exposure) can also affect the homeostatic state of the organism. A series of experiments was performed using rhesus monkeys with the objective of defining the fundamental properties of the circadian rhythm of body temperature. Three major experiments were performed in addition to several preliminary studies. These experiments explored 1.) the response of the rhesus body temperature rhythm to varying day length and light intensity; 2.) the response of the body temperature rhythm to light exposure as a function of time of day; and 3.) the characteristics of the metabolic heat production rhythm which is responsible for the daily cycle in body temperature. Results of these three completed experiments will be reported here. In addition, preliminary experiments were also performed in social entrainment of rhesus circadian rhythms and the properties of rhesus body temperature rhythms in constant conditions, where no external time cues were provided. Four adult male rhesus monkeys served as subjects in all experiments. All experiments were performed at the California Regional Primate Research Center. Each animal was implanted with a biotelemetry unit that measured deep body temperature. All surgeries were performed by a board certified veterinary surgeon under sterile conditions. The biotelemetry implants also provided an index of activity level in each animal. For metabolic heat production measurements, oxygen consumption and carbon dioxide production were measured and the caloric equivalent of these was calculated. Specific methodologies are described in detail.

Fuller, Charles↗
NASA NTRS1999

An Evaluation of Collagen Metabolism in Non Human Primates Associated with the Bion 11 Space Program-Markers of Urinary Collagen Turnover and Muscle Connective Tissue

Patients exhibiting changes in connective tissue and bone metabolism also show changes in urinary by-products of tissue metabolism. Furthermore, the changes in urinary connective tissue and bone metabolites precede alterations at the tissue macromolecular level. Astronauts and Cosmonauts have also shown suggestive increases in urinary by-products of mineralized and non-mineralized tissue degradation. Thus, the idea of assessing connective tissue and bone response in spaceflight monkeys by measurement of biomarkers in urine has merit. Other investigations of bone and connective histology, cytology and chemistry in the Bion 11 monkeys will allow for further validation of the relationship of urinary biomarkers and tissue response. In future flights the non-invasive procedure of urinary analysis may be useful in early detection of changes in these tissues. Purpose: The purpose of this grant investigation was to evaluate mineralized and non-mineralized connective tissue responses of non-human primates to microgravity by the non-invasive analysis of urinary biomarkers. Secondly, we also wanted to assess muscle connective tissue adaptive changes in three weight-bearing skeletal muscles: the soleus, medial gastrocnemius and tibialis anterior by obtaining pre-flight and post-flight small biopsy specimens in collaboration with Dr. V. Reggie Edgerton's laboratory at the University of California at Los Angeles.

Vailas, Arthur C.↗
NASA NTRS1999

An Evaluation of Collagen Metabolism in Non Human Primates Associated with the Bion 11 Space Program-Markers of Urinary Collagen Turnover and Muscle Connective Tissue

Patients exhibiting changes in connective tissue and bone metabolism also show changes in urinary by-products of tissue metabolism. Furthermore, the changes in urinary connective tissue and bone metabolites precede alterations at the tissue macromolecular level. Astronauts and Cosmonauts have also shown suggestive increases in urinary by-products of mineralized and non-mineralized tissue degradation. Thus, the idea of assessing connective tissue and bone response in spaceflight monkeys by measurement of biomarkers in urine has merit. Other investigations of bone and connective histology, cytology and chemistry in the Bion 11 monkeys will allow for further validation of the relationship of urinary biomarkers and tissue response. In future flights the non-invasive procedure of urinary analysis may be useful in early detection of changes in these tissues. The purpose of this grant investigation was to evaluate mineralized and non-mineralized connective tissue responses of non-human primates to microgravity by the non-invasive analysis of urinary biomarkers. Secondly, we also wanted to assess muscle connective tissue adaptive changes in three weight-bearing skeletal muscles: the soleus, media] gastrocnemius and tibialis anterior by obtaining pre-flight and post-flight small biopsy specimens in collaboration with Dr. V. Reggie Edgerton's laboratory at the University of California at Los Angeles.

Vailas, Arthur C.↗
NASA NTRS1999

The Effects of Gravity on the Circadian Timing System

All vertebrates have a physiological control system that regulates the timing of the rhythms of their daily life. Dysfunction of this system, the circadian timing system (CTS), adversely affects an organism's ability to respond to environmental challenges and has been linked to physiological and psychological disorders. Exposure to altered gravitational environments (the microgravity of space and hyperdynamic environments produced via centrifugation) produces changes in both the functioning of the CTS and the rhythmic variables it controls. The earliest record of primate rhythms in a spaceflight environment come from Biosatellite III. The subject, a pig-tailed macaque, showed a loss of synchronization of the body temperature rhythm and a fragmented sleep-wake cycle. Alterations in the rhythm of body temperature were also seen in rhesus macaques flown on COSMOS 1514. Squirrel monkeys exposed to chronic centrifugation showed an initial decrease in the amplitude and mean of their body temperature and activity rhythms. In a microgravity environment, Squirrel monkeys on Spacelab-3 showed a reduction in the mean and amplitude of their feeding rhythms. Since 1992 we have had the opportunity to participate on three US/Russian sponsored biosatellite missions on which a total of six juvenile male rhesus macaques were flown. These animals uniformly exhibited delays in the phasing of their temperature rhythms, but not their heart rate or activity rhythms during spaceflight. There was also a tendency for changes in waveform mean and amplitude. These data suggest that the spaceflight environment may have a differential effect on the different oscillators controlling different rhythmic variables. Ongoing studies are examining the effects of +G on the CTS. The long-term presence of humans in space highlights the need for effective countermeasures to gravitational effects on the CTS.

Fuller, Charles A.↗
NASA NTRS2003

Neural Dynamics Underlying Event-Related Potentials

There are two opposing hypotheses about the brain mechanisms underlying sensory event-related potentials (ERPs). One holds that sensory ERPs are generated by phase resetting of ongoing electroencephalographic (EEG) activity, and the other that they result from signal averaging of stimulus-evoked neural responses. We tested several contrasting predictions of these hypotheses by direct intracortical analysis of neural activity in monkeys. Our findings clearly demonstrate evoked response contributions to the sensory ERP in the monkey, and they suggest the likelihood that a mixed (Evoked/Phase Resetting) model may account for the generation of scalp ERPs in humans.

Shah, Ankoor S.↗
NASA NTRS2003

Accuracy of saccades to remembered targets as a function of body orientation in space

A vertical asymmetry in memory-guided saccadic eye movements has been previously demonstrated in humans and in rhesus monkeys. In the upright orientation, saccades generally land several degrees above the target. The origin of this asymmetry has remained unknown. In this study, we investigated whether the asymmetry in memory saccades is dependent on body orientation in space. Thus animals performed memory saccades in four different body orientations: upright, left-side-down (LSD), right-side-down (RSD), and supine. Data in all three rhesus monkeys confirm previous observations regarding a significant upward vertical asymmetry. Saccade errors made from LSD and RSD postures were partitioned into components made along the axis of gravity and along the vertical body axis. Up/down asymmetry persisted only in body coordinates but not in gravity coordinates. However, this asymmetry was generally reduced in tilted positions. Therefore the upward bias seen in memory saccades is egocentric although orientation in space might play a modulatory role.

NASA Discipline Neuroscience↗
NASA NTRS2002

Techniques for measurement of thoracoabdominal asynchrony

Respiratory motion measured by respiratory inductance plethysmography often deviates from the sinusoidal pattern assumed in the traditional Lissajous figure (loop) analysis used to determine thoraco-abdominal asynchrony, or phase angle phi. We investigated six different time-domain methods of measuring phi, using simulated data with sinusoidal and triangular waveforms, phase shifts of 0-135 degrees, and 10% noise. The techniques were then used on data from 11 lightly anesthetized rhesus monkeys (Macaca mulatta; 7.6 +/- 0.8 kg; 5.7 +/- 0.5 years old), instrumented with a respiratory inductive plethysmograph, and subjected to increasing levels of inspiratory resistive loading ranging from 5-1,000 cmH(2)O. L(-1). sec(-1).The best results were obtained from cross-correlation and maximum linear correlation, with errors less than approximately 5 degrees from the actual phase angle in the simulated data. The worst performance was produced by the loop analysis, which in some cases was in error by more than 30 degrees. Compared to correlation, other analysis techniques performed at an intermediate level. Maximum linear correlation and cross-correlation produced similar results on the data collected from monkeys (SD of the difference, 4.1 degrees ) but all other techniques had a high SD of the difference compared to the correlation techniques.We conclude that phase angles are best measured using cross-correlation or maximum linear correlation, techniques that are independent of waveform shape, and robust in the presence of noise. Copyright 2002 Wiley-Liss, Inc.

Non-NASA Center↗
NASA NTRS2001

Size and myonuclear domains in Rhesus soleus muscle fibers: short-term spaceflight

The cross-sectional area (CSA), myonuclear number per mm of fiber length, and myonuclear domain (cytoplasmic volume/myonucleus) of mechanically isolated single fibers from biopsies of the soleus muscle of 5 vivarium control, 3 flight simulation and 2 flight (BION 11) Rhesus monkeys (Macaca [correction of Macacca] mulatta) were determined using confocal microscopy before and after a 14-day experimental period. Simulation monkeys were confined in chairs placed in capsules identical to those used during the flight. Fibers were classified as type I, type II or hybrid (containing both types I and II) based on myosin heavy chain (MHC) gel electrophoresis. A majority of the fibers sampled contained only type I MHC, i.e. 89, 62 and 68% for the control, simulation and flight groups, respectively. Most of the remaining fibers were hybrids, i.e. 8, 36 and 32% for the same groups. There were no significant pre-post differences in the fiber type composition for any of the experimental groups. There also were no significant pre-post differences in fiber CSA, myonuclear number or myonuclear domain. There was, however, a tendency for the fibers in the post-flight biopsies to have a smaller mean CSA and myonuclear domain (approximately 10%, p=0.07) than the fibers in the pre-flight biopsy. The combined mean cytoplasmic volume/myonucleus for all muscle fiber phenotypes in the Rhesus soleus muscle was approximately 25,000 micrometers3 and there were no differences in pre-post samples for the control and simulated groups. The cytoplasmic domains tended to be lower (p=0.08) after than before flight. No phenotype differences in cytoplasmic domains were observed. These data suggest that after a relatively short period of actual spaceflight, modest fiber atrophy occurs in the soleus muscle fibers without a concomitant change in myonuclear number.

NASA Experiment Number 8808A05↗
NASA NTRS1997

The heuristic and motivational value of video reinforcement

Four rhesus monkeys (Macaca mulatta) were tested on joystick-based computer tasks in which they could choose to be reinforced either with pellets-only or with pellets + video. A variety of videotapes were used to reinforce task performance. The monkeys significantly preferred to be rewarded with a pellet and 10 s of a blank screen than a pellet plus 10 s of videotape. When they did choose to see videotaped images, however, they were significantly more likely to view video of themselves than video of their roommate or of unfamiliar conspecifics. These data support earlier findings of individual differences in preference for video reinforcement, and have clear implications for the study of face-recognition and self-recognition by nonhuman primates.

NASA Discipline Space Human Factors↗
NASA NTRS1992

The Language Research Center's Computerized Test System for environmental enrichment and psychological assessment

In the spring of 1987, we undertook to provide environmental enrichment to nonhuman primate subjects in ways that would complement and even contribute to the bio-behaviorial science that justified the monkeys' captivity. Of course, the psychological well-being of captive primates--and indeed all research species-- has been an area of intense research activity since the 1985 amendment of the Animal Welfare Act. This mandate for researchers to ensure the psychological, as well as physical, fitness of experimental animals catalyzed the humane and scientific interests of the research community. The contemporary literature is replete with proposed means both of assaying and of providing enrichment and well-being. Notwithstanding, consensus on either assessment or intervention has yet to be reached. The paradigm we employed was modelled after successful efforts with chimpanzees. An automated test system was constructed in which subjects responded to computer tasks by manipulating a joystick. The tasks, interactive game-like versions of many of the classic testing paradigms of cognitive and comparative psychology, permitted the controlled presentation of stimuli and demands without the required presence of a human experimenter. Despite significant barriers to the success, rhesus monkeys (Macaca mulatta) and a variety of other primate species (including, of course, humans) have mastered the skills necessary for testing in this paradigm. Previous experiments have illustrated the utility of the test system for addressing questions of learning, memory, attention, perception, and motivation. Additional data have been reported to support the contention that the Language Research Center's Computerized Test System (LRC-CTS) serves its other raison d'etre--providing environmental enrichment and assessing psychological well-being. This paper is designed to augment previous descriptions of the technology and the paradigm for scientists and caretakers interested in environmental enrichment and performance assessment with primates.

Non-NASA Center↗
NASA NTRS1999

Contribution of the cerebellar flocculus to gaze control during active head movements

The flocculus and ventral paraflocculus are adjacent regions of the cerebellar cortex that are essential for controlling smooth pursuit eye movements and for altering the performance of the vestibulo-ocular reflex (VOR). The question addressed in this study is whether these regions of the cerebellum are more globally involved in controlling gaze, regardless of whether eye or active head movements are used to pursue moving visual targets. Single-unit recordings were obtained from Purkinje (Pk) cells in the floccular region of squirrel monkeys that were trained to fixate and pursue small visual targets. Cell firing rate was recorded during smooth pursuit eye movements, cancellation of the VOR, combined eye-head pursuit, and spontaneous gaze shifts in the absence of targets. Pk cells were found to be much less sensitive to gaze velocity during combined eye-head pursuit than during ocular pursuit. They were not sensitive to gaze or head velocity during gaze saccades. Temporary inactivation of the floccular region by muscimol injection compromised ocular pursuit but had little effect on the ability of monkeys to pursue visual targets with head movements or to cancel the VOR during active head movements. Thus the signals produced by Pk cells in the floccular region are necessary for controlling smooth pursuit eye movements but not for coordinating gaze during active head movements. The results imply that individual functional modules in the cerebellar cortex are less involved in the global organization and coordination of movements than with parametric control of movements produced by a specific part of the body.

NASA Discipline Neuroscience↗
NASA NTRS1998

Evidence for increased cardiac compliance during exposure to simulated microgravity

We measured hemodynamic responses during 4 days of head-down tilt (HDT) and during graded lower body negative pressure (LBNP) in invasively instrumented rhesus monkeys to test the hypotheses that exposure to simulated microgravity increases cardiac compliance and that decreased stroke volume, cardiac output, and orthostatic tolerance are associated with reduced left ventricular peak dP/dt. Six monkeys underwent two 4-day (96 h) experimental conditions separated by 9 days of ambulatory activities in a crossover counterbalance design: 1) continuous exposure to 10 degrees HDT and 2) approximately 12-14 h per day of 80 degrees head-up tilt and 10-12 h supine (control condition). Each animal underwent measurements of central venous pressure (CVP), left ventricular and aortic pressures, stroke volume, esophageal pressure (EsP), plasma volume, alpha1- and beta1-adrenergic responsiveness, and tolerance to LBNP. HDT induced a hypovolemic and hypoadrenergic state with reduced LBNP tolerance compared with the control condition. Decreased LBNP tolerance with HDT was associated with reduced stroke volume, cardiac output, and peak dP/dt. Compared with the control condition, a 34% reduction in CVP (P = 0.010) and no change in left ventricular end-diastolic area during HDT was associated with increased ventricular compliance (P = 0.0053). Increased cardiac compliance could not be explained by reduced intrathoracic pressure since EsP was unaltered by HDT. Our data provide the first direct evidence that increased cardiac compliance was associated with headward fluid shifts similar to those induced by exposure to spaceflight and that reduced orthostatic tolerance was associated with lower cardiac contractility.

Non-NASA Center↗
NASA NTRS1994

Spaceflight and protein metabolism, with special reference to humans

Human space missions have shown that human spaceflight is associated with a loss of body protein. Specific changes include a loss of lean body mass, decreased muscle mass in the calves, decreased muscle strength, and changes in plasma proteins and amino acids. The major muscle loss is believed to be associated with the antigravity (postural) muscle. The most significant loss of protein appears to occur during the first month of flight. The etiology is believed to be multifactorial with contributions from disuse atrophy, undernutrition, and a stress type of response. This article reviews the results of American and Russian space missions to investigate this problem in humans, monkeys, and rats. The relationship of the flight results with ground-based models including bedrest for humans and hindlimb unweighting for rats is also discussed. The results suggest that humans adapt to spaceflight much better than either monkeys or rats.

Review↗
NASA NTRS1992

The representation of the spatial vertical in human optokinetic nystagmus

With our stimulus conditions we were unable to record more than 2-3 beats of OKAN; therefore direct comparison to the data recorded from monkeys is not possible. We did, however, see cross-coupling in OKN. In monkeys, cross-coupling predominates in OKAN, indicating that velocity storage underlies this phenomenon. We consistently saw the axis of response shift towards the spatial vertical. This implies that although OKAN was weak, velocity storage contributed a representation of the spatial vertical to OKN that is dependent on the axis of the head or body with respect to gravity.

Non-NASA Center↗