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At least 19 records

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NASA NTRS1995

Evaluation of Flow Biosensor Technology in a Chronically-Instrumented Non-Human Primate Model

The Physiology Research Branch of Brooks AFB conducts both human and non-human primate experiments to determine the effects of microgravity and hypergravity on the cardiovascular system and to indentify the particular mechanisms that invoke these responses. Primary investigative research efforts in a non-human primate model require the calculation of total peripheral resistance (TPR), systemic arterial compliance (SAC), and pressure-volume loop characteristics. These calculations require beat-to-beat measurement of aortic flow. We have evaluated commercially available electromagnetic (EMF) and transit-time flow measurement techniques. In vivo and in vitro experiments demonstrated that the average error of these techniques is less than 25 percent for EMF and less than 10 percent for transit-time.

SC Koenig↗

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. The RRF accommodated two adult 8-11 kg rhesus monkeys, while the Russian experiments and hardware were configured for a younger animal in the 44 kg range. Both the American and Russian hardware maintained a controlled environmental system, specifically temperature, humidity, a timed lighting cycle, and had means for providing food and fluids to the animal(s). Crew availability during a Shuttle mission was to be an optimal condition for retrieval and refrigeration of the animal urine samples along with a manual calcein injection which could lead to greater understanding of bone calcium incorporation. A special portable bioisolation glove box was under development to support this aspect of the experiment profile along with the capability of any contingency human intervention. As a result of recent U.S./Russian negotiations, funding for Space Station, and a series of other events, the SLS-3 mission was cancelled and applicable Rhesus Project experiments incorporated into the Russian Bion 11 and 12 missions. A presentation of the RRF and COSMOS/Bion rhesus hardware is presented along with current plans for the hardware.

Dalton, Bonnie P.↗

NASA NTRS1995

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. The RRF accommodated two adult 8-11 kg rhesus monkeys, while the Russian experiments and hardware were configured for a younger animal in the 44 kg range. Both the American and Russian hardware maintained a controlled environmental system, specifically temperature, humidity, a timed lighting cycle, and had means for providing food and fluids to the animal(s). Crew availability during a Shuttle mission was to be an optimal condition for retrieval and refrigeration of the animal urine samples along with a manual calcein injection which could lead to greater understanding of bone calcium incorporation. A special portable bioisolation glove box was under development to support this aspect of the experiment profile along with the capability of any contingency human intervention. As a result of recent U.S./Russian negotiations, funding for Space Station, and a series of other events, the SLS-3 mission was cancelled and applicable Rhesus Project experiments incorporated into the Russian Bion 11 and 12 missions. A presentation of the RRF and COSMOS/Bion rhesus hardware is presented along with current plans for the hardware.

Dalton, Bonnie P.↗

NASA NTRS1994

Microgravity Flight - Accommodating Non-Human Primates

Dalton, Bonnie P.↗

DOE OSTI2025

Multidrug-resistant Shigella flexneri outbreak affecting humans and non-human primates in New Mexico, USA

Shigellosis is a gastrointestinal infection caused by species of Shigella . A large outbreak of Shigella flexneri serotype 2a occurred in Albuquerque, New Mexico between May 2021 and November 2023 that involved humans and non-human primates (NHP) from a local zoo. We analyzed the genomes of 202 New Mexican isolates as well as 15 closely related isolates from other states, and four from NHP. The outbreak was initially detected within men who have sex with men but then predominantly affected people experiencing homelessness. Nearly 70% of cases were hospitalized and there was one human death. The outbreak extended into Albuquerque’s BioPark Zoo, causing high morbidity and six deaths in NHPs. All isolates were multidrug-resistant, including towards fluoroquinolones, a first line treatment option which led to treatment failures in human and NHP populations. We show the circulation of the same S. flexneri strain in humans and NHPs, causing fatalities in both populations. This study demonstrates the threat of antimicrobial resistant organisms to vulnerable human and NHP populations and emphasizes the value of genomic surveillance within a One Health framework.

59 BASIC BIOLOGICAL SCIENCES↗

NASA NTRS1993

The Future for Non-Human Primate Models in Space

Explore the source record for details and available documents.

Freedom CNES NASA↗

NASA NTRS1994

Space Flight Effects on Intracellular Ions in Sublingual Cells of Non-Human Primates

We have used a novel technique that quantifies minerals and electrolytes from smears of sublingual cells by x-ray microanalysis to monitor metabolic changes in bed rest subjects. Increases in intracellular calcium (Ca), phosphorus (P), and potassium (K) were characteristic of subjects whose exercise regimen was inadequate to maintain calcium metabolism. To test the effects of space flight on intracellular ions, we analyzed cells from 2-4 kg Rhesus monkeys before and after 2 weeks in space or chair restraint (CR). There were increases in sublingual cell Ca, P and K after space flight which paralleled the clinical estimates of metabolic status of the animals and exceeded the levels found during CR on R+11. Increases after 2 weeks CR were 26% in Ca, 6% in P and 29% in K. Species similarity ill responses of intracellular ions to inactivity imposed by bed rest, restraint or microgravity suggest that this innovative non-invasive technique would be a useful in-flight monitor of exercise countermeasures directed toward maintaining calcium balance.

Arnaud, Sara B.↗

NASA NTRS1996

Squirrel Monkey Requirements for Chronic Acceleration

This study examined: (1) the ability of a small non-human primate to tolerate chronic centrifugation on a centrifuge with a radius of 0.9 m, and (2) the influence of centrifuge radius on the response of primates to hyperdynamic fields. Eight adult male squirrel monkeys were exposed to 1.5 g via centrifugation at two different radii (0.9 m and 3.0 m). Body temperature, activity, feeding and drinking were monitored. These primates did tolerate and adapt to 1.5G via centrifugation on either radius centrifuge. The results show, however, that centrifuge radius does have an effect on the responses of the primate to the hyperdynamic environment. Adaptation to the hyperdynamic environment occurred more quickly on the larger centrifuge. This study demonstrates that a small, non-human primate model, such as the squirrel monkey, could be used on a 0.9 m radius centrifuge such as is being considered by the NASA Space Station Program.

Fuller, Charles A.↗

NASA NTRS1985

Homeostasis in Primates in the Hyperdynamic Environment

The influence of chronic centrifugation upon the homestatic regulation of the circadian timekeeping system was examined. The interactions of body temperature regulation and the behavioral state of arousal were studied by evaluating the influence of cephalic fluid shifts induced by lower body positive air pressure (LBPP), upon these systems. The small diurnal squirrel monkey (Saimiri sciureus) was used as the non-human primate model. Results show that the circadian timekeeping system of these primates is functional in the hyperdynamic environment, however, some of its components appear to be regulated at different homeostatic levels. The LBPP resulted in an approximate 0.7 C decrease in DBT (p 0.01). However, although on video some animals appeared drowsy during LBPP, sleep recording revealed no significant changes in state of arousal. Thus, the physiological mechanisms underlying this lowering of body temperature can be independent of the arousal state.

Fuller, C. A.↗

NASA NTRS1995

Functional and cellular adaptation to weightlessness in primates

Considerable data has been collected on the response of hindlimb muscles to unloading due to both spaceflight and hindlimb suspension. One generalized response to a reduction in load is muscle fiber atrophy, although not all muscles respond the same. Our understanding of how muscles respond to microgravity, however, has come primarily from the examination of hindlimb muscles in the unrestrained rate in space. The non-human primate spaceflight paradigm differs considerably from the rodent paradigm in that the monkeys are restrained, usually in a sitting position, while in space. Recently, we examined the effects of microgravity on muscles of the Rhesus monkey by taking biopsies of selected hindlimb muscles prior to and following spaceflights of 14 and 12 day durations (Cosmos 2044 and 2229). Our results revealed that the monkey's response to microgravity differs from that of the rat. The apparent differences in the atrophic response of the hindlimb muscles of the monkey and rat to spaceflight may be attributed to the following: (1) a species difference; (2) a difference in the manner in which the animals were maintained during the flight (i.e., chair restraint or 'free-floating'); and/or (3) an ability of the monkeys to counteract the effects of spaceflight with resistive exercise.

Bodine-Fowler, Sue C.↗

NASA NTRS1996

Noninvasive markers of bone metabolism in the rhesus monkey: normal effects of age and gender

Measurement of bone turnover in conditions such as osteoporosis has been limited by the need for invasive iliac bone biopsy to reliably determine parameters of bone metabolism. Recent advances in the area of serum and urinary markers of bone metabolism have raised the possibility for noninvasive measurements; however, little nonhuman primate data exist for these parameters. The purpose of this experiment was to define the normal range and variability of several of the newer noninvasive bone markers which are currently under investigation in humans. The primary intent was to determine age and gender variability, as well as provide some normative data for future experiments in nonhuman primates. Twenty-four rhesus macaques were divided into equal groups of male and female according to the following age groupings: 3 years, 5-10 years, 15-20 years, and > 25 years. Urine was collected three times daily for a four-day period and measured for several markers of bone turnoverm including pyridinoline (PYD), deoxypyrodinoline (DPD), hydroxyproline, and creatinine. Bone mineral density measurements of the lumbar spine were performed at the beginning and end of the study period. Serum was also obtained at the time of bone densitometry for measurement of osteocalcin levels by radioimmunoassay. There were no significant differences in bone mineral density, urine PYD, or urine DPD based on gender. Bone density was lowest in the youngest animals, peaked in the 15-20-year group, but again decreased in the oldest animals. The osteocalcin, PYD, and DPD levels followed an inversely related pattern to bone density. The most important result was the relative age insensitivity of the ratio of PYD:DPD in monkeys up to age 20 years. Since bone density changes take months or years to become measurable and iliac biopsies are invasive, the PYD/DPD marker ratio may have important implications for rapid noninvasive measurement of the effects of potential treatments for osteoporosis in the non-human primate model.

NASA Discipline Musculoskeletal↗

DOE OSTI2025

A Pentavalent HIV-1 Subtype C Vaccine Containing Computationally Selected gp120 Strains Improves the Breadth of V1V2 Region Responses

Background: HIV-1 envelope (Env) variable loops 1 and 2 (V1V2) directed non-neutralizing antibodies were a correlate of decreased transmission risk in the RV144 vaccine trial. Thus, the elicitation and breadth of antibody responses against the V1V2 of HIV-1 Env are important considerations for HIV-1 vaccine candidates. The V1V2 region’s highly variable nature and the extensive diversity of subtype C HIV-1 Envelopes (Envs) make the V1V2 response breadth a high priority for HIV-1 vaccine regimens aiming for V1V2-mediated protection in Southern Africa. Here, we determined whether the breadth of the anti-V1V2 vaccine response can be broadened by including HIV-1 Env strains computationally designed to enhance the coverage of subtype C V1V2 sequence diversity. Methods: Three subtype C Env strains were selected to maximize antibody binding coverage while complementing subtype C vaccine gp120s that were given in human clinical trials in South Africa, as well as to improve epitope accessibility. Humoral immunogenicity of a novel trivalent gp120 vaccine immunogen, a bivalent gp120 boost already in clinical trials (1086C and TV1), and a pentavalent (all five gp120s combined) were evaluated in a preclinical immunization study in guinea pigs. The pentavalent combination was further evaluated with alum versus glucopyranosyl lipid adjuvants formulated in squalene-in-water emulsion (GLA-SE) adjuvants in non-human primates. The breadth of the anti-V1V2 response was assessed using an array of cross-subtype variable loops 1&2 (V1V2) scaffold proteins and linear V2 peptides. Results: The breadth of the IgG response against V1V2 antigens of the trivalent and pentavalent groups was comparable, and both were greater than the breadth of the bivalent group. Linear epitope mapping showed that two linear epitopes in V2 were targeted by the vaccinated animals: the V2 hotspot focused at 169K that potentially correlated with decreased HIV-1 risk in RV144 and the V2.2 site (179LDV/I181) that is part of the integrin α4β7 binding site. The bivalent vaccine elicited a significantly higher magnitude of binding to the V2 hotspot compared to the trivalent vaccine whereas the trivalent vaccine elicited significantly higher binding to the V2.2 epitope compared to the bivalent vaccine, while the pentavalent recognized both regions. Conclusions: These results demonstrate that the three new computationally selected subtype C Envs successfully complemented 1086C and TV1 for broader V1V2 antibody responses, and, in concert with adjuvants that stimulate V1V2 responses, can be considered as part of a rationale immunogen design to improve V1V2 IgG coverage in future vaccine trials in South Africa.

Immunology↗

DOE OSTI2025

Computationally Selected Multivalent HIV-1 Subtype C Vaccine Protects Against Heterologous SHIV Challenge

Background: The RV144 trial in Thailand is the only HIV-1 vaccine efficacy trial to date to demonstrate any efficacy. Genetic signatures suggested that antibodies targeting the variable loop 2 (V2) of the HIV-1 envelope played an important protective role. The ALVAC prime and protein boost follow-up trial in southern Africa (HVTN702) failed to show any efficacy. One hypothesis for this is the greater diversity of subtype C viruses in southern Africa relative to CRF01_AE in Thailand. Methods: Here, we determined whether an ALVAC prime with computationally selected gp120 boost immunogens maximizing coverage of diversity of subtype C viruses in the variable V1 and V2 regions (V1V2) improved the protection of non-human primates (NHPs) from a heterologous subtype C SHIV challenge compared to more traditional regimens. Results: An ALVAC prime with Trivalent subtype C gp120 boosts resulted in statistically significant protection from repeated intrarectal SHIV challenges compared to the control. Evaluation of the immunogenicity of each vaccine regimen at the time of challenge demonstrated that different gp120 combination boosts elicited similar high magnitudes of gp120 and breadth of V1V2-binding antibodies, as well as strong Fc-mediated immune responses. Low-to-no neutralization of the challenge virus was detected. A Cox proportional hazard analysis of five pre-selected immune parameters at the time of challenge identified ADCC against the challenge envelope as a correlate of protection. Systems serology analysis revealed that immune responses elicited by the different vaccine regimens were distinct and identified further correlates of resistance to infection. Conclusions: Computationally designed vaccines with maximized subtype C V1V2 coverage mediated protection of NHPs from a heterologous Tier-2 subtype C SHIV challenge.

Immunology↗

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↗

NASA NTRS1995

Acute exposure to 2G phase shifts the rat circadian timing system

The circadian timing system (CTS) provides internal and external temporal coordination of an animal's physiology and behavior. In mammals, the generation and coordination of these circadian rhythms is controlled by a neural pacemaker, the suprachiasmatic nucleus (SCN), located within the hypothalamus. The pacemaker is synchronized to the 24 hour day by time cures (zeitgebers) such as the light/dark cycle. When an animal is exposed to an environment without time cues, the circadian rhythms maintain internal temporal coordination, but exhibit a 'free-running' condition in which the period length is determined by the internal pacemaker. Maintenance of internal and external temporal coordination are critical for normal physiological and psychological function in human and non-human primates. Exposure to altered gravitational environments has been shown to affect the amplitude, mean, and timing of circadian rhythms in species ranging from unicellular organisms to man. However, it has not been determined whether altered gravitational fields have a direct effect on the neural pacemaker, or affect peripheral parameters. In previous studies, the ability of a stimulus to phase shift circadian rhythms was used to determine whether a stimulus has a direct effect on the neural pacemaker. The present experiment was performed in order to determine whether acute exposure to a hyperdynamic field could phase shift circadian rhythms.

Hoban-Higgins, T. M.↗

NASA NTRS1996

The Role of Linear Acceleration in Visual-Vestibular Interactions and Implications in Aircraft Operations

While considerable attention has been given to visual-vestibular interaction (VVI) during angular motion of the head as might occur during an aircraft spin, much less attention has been given to VVI during linear motion of the head. Such interaction might occur, for example, while viewing a stationary or moving display during vertical take-off and landing operations Research into linear VVI, particularly during prolonged periods of linear acceleration, has been hampered by the unavailability of a programmable translator capable of large excursions We collaborated with Otis Elevator Co. and used their research tower and elevator, whose motion could be digitally programmed, to vertically translate human subjects over a distance of 92.3 meters with a peak linear acceleration of 2 meters/sec(exp 2) During pulsatile or sinusoidal translation, the subjects viewed moving stripes (optokinetic stimulus) or a fixed point source (light emitting diode, led, display), respectively and it was generally found that. The direction of linear acceleration relative to the cardinal head axes and the direction of the slow component of optokinetic nystagmus (OKN) determined the extent of VVI during concomitant stripe motion and linear acceleration. Acceleration along the z head axis (A(sub z)) produced the largest VVI, particularly when the slow component of OKN was in the same direction as eye movements produced by the linear acceleration and Eye movements produced by linear acceleration are suppressed by viewing a fixed target at frequencies below 10 Hz But, above this frequency the suppression produced by VVI is removed. Finally, as demonstrated in non-human primates, vergence of the eyes appears to modulate the vertical eye movement response to linear acceleration in humans.

Correia, Manning J.↗

NASA NTRS1996

Computerized mappings of the cerebral cortex: a multiresolution flattening method and a surface-based coordinate system

We present a new method for generating two-dimensional maps of the cerebral cortex. Our computerized, two-stage flattening method takes as its input any well-defined representation of a surface within the three-dimensional cortex. The first stage rapidly converts this surface to a topologically correct two-dimensional map, without regard for the amount of distortion introduced. The second stage reduces distortions using a multiresolution strategy that makes gross shape changes on a coarsely sampled map and further shape refinements on progressively finer resolution maps. We demonstrate the utility of this approach by creating flat maps of the entire cerebral cortex in the macaque monkey and by displaying various types of experimental data on such maps. We also introduce a surface-based coordinate system that has advantages over conventional stereotaxic coordinates and is relevant to studies of cortical organization in humans as well as non-human primates. Together, these methods provide an improved basis for quantitative studies of individual variability in cortical organization.

Non-NASA Center↗

NASA NTRS1990

Centrifuge Facility Conceptual System Study. Volume 1: Facility overview and habitats

The results are presented for a NASA Phase 1 study conducted from mid 1987 through mid 1989 at Ames Research Center. The Centrifuge Facility is the major element of the biological research facility for the implementation of NASA's Life Science Research Program on Space Station Freedom using non-human specimens (such as small primates, rodents, plants, insects, cell tissues). Five systems are described which comprise the Facility: habitats, holding units, centrifuge, glovebox, and service unit. Volume 1 presents a facility overview and describes the habitats - modular units which house living specimens.

Synnestvedt, Robert↗