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At least 289 records · Page 16

Functional Responses in Otolith Structures from Micro- to Hyper-Gravity

Vertebrates and invertebrates sense gravito-inertial acceleration by mechanoreceptors in the otolith and statolith organs, respectively. These structures consist of ciliated sensory hair cells surmounted by biomineral grains of calcium carbonate (CaCO3) called oto-orstato-conia. The grains provide mechanical loading of hair cell cilia, and their high density increases sensitivity to acceleration. A widely considered mechanism by which the animal responds to a chronic change in amplitude of gravity is a change in weight lending otoconia. In G, it is argued, the organism counters the loss of gravity by increasing CaCO3 production, thereby increasing otolith mass, as a means to increase system gain. In hypergravity (HG), the converse is argued. Here, we present the results obtained in 3 species exposed both to G and HG. Adult toadfish, Opsanus tau, were exposed to G in 2 short-duration shuttle missions and to 1.24 1.73G centrifugation for 1-32 days; re-adaptation was studied following 1-8 days of 1G. Results show a biphasic pattern in response to 1.73G: initial hypersensitivity, similar to that observed after G exposure, followed by transition to a significant decrease at 16-32 days. Recovery from HG exposure is 4-8 days. Next, we examined directly the responses of statocyst receptors in the land snail after exposure to G on two unmanned Russian Orbital missions and at 1.24G. Similar to vertebrate afferents snail receptors increased their sensitivity to tilt after G exposure, and decrease it after 16-32 days of HG. Two major pieces of information are still needed: vertebrate hair cell response to altered gravity and impact of longer duration exposures on sensory plasticity. To address the latter, we applied electron microscopic techniques to image otoconia mass obtained from 1) mice subjected to 91-days of weightlessness in the Mouse Drawer System (MDS) flown on International Space Station, 2) mice subjected to 91-days of 1.24G centrifugation on ground, and 3) mice flown on 2 short-duration orbital missions. Images indicate a clear restructuring of individual otoconia, suggesting deposition to the outer shell. Images from their HG counterparts indicate the converse - an ablation of the otoconia mass. For shorter duration exposures to weightlessness on 13-day shuttle missions, mice otoconia appear normal. Despite the permanence of 1G in evolution, the animal senses exposure to a novel, non-1G, environment and adaptive mechanisms are initiated - in the short term, compensation is likely confined to the peripheral sensory receptors, the brain or both. For longer exposures structural modifications of the endorgan may also result. Support Contributed By: NASA 03-OBPR-04 and 11-11_Omni_2-0002

Vertebrates↗

Oxidative Stress and the Neuroconsequences of Spaceflight Environment - Immune Dysregulation and Antioxidant Dietary Countermeasure Efficacy

In this project, we will test the hypothesis that Ionizing Radiation (IR), microgravity and social isolation combine synergistically to trigger an oxidative stress response that alters immune homeostasis, brain structure and function, and neurobehavioral and cognitive performance. Specific Aims for this project are: (1) Determine dose-response curves for acute ‘Five-Ion GCR Simulation’ exposure for immune, brain and performance responses in crew age-matched adult male and female mice; (2) Determine effects of acute ‘Five-Ion GCR Simulation’ exposure singly and in combination with simulated microgravity and social isolation, on immune, brain and performance responses in crew age-matched male and female mice mimicking deep space missions; and (3) Determine efficacy of the dietary antioxidant, Nicotinamide Mononucleotide (NMN), a key intermediate in nicotinamide adenine dinucleotide (NAD+) biosynthesis. The project relies on established and highly translatable ground-based mouse models and assays with IR exposures to be performed at the NASA Space Radiation Laboratory (NSRL). The experimental approach will provide definitive data on the timing and mechanisms involved in the oxidative stress response, immune and brain changes, and ensuing functional (behavioral/cognitive) impairments expected during human transit to Mars. This project will identify potential biomarkers for, and mechanisms underlying, structural and functional changes in the immune and nervous systems leading to behavioral/cognitive performance deficits, and its potential application to develop effective countermeasures to mitigate negative health effects of long duration space habitation. The project will address NASA’s efforts to rapidly advance the characterization of risks and identify appropriate countermeasures in anticipation of future deep space missions. Ensuring crew health and performance during extended transits necessitates that sensorimotor and cognitive abilities remain strong to avoid potentially catastrophic health and safety outcomes. Further, despite historically low numbers of female astronauts, the two most recent NASA Astronaut Corps class selections, comprised of ~50% women as compared to men, signal the need to understand how sex differences affect physiological adaptation and health in the space environment. Here, we will determine how key features of the deep space environment may interact to increase risk to crewmembers by negatively impacting health and performance, and identify and develop strategies to characterize and mitigate the potential risks via countermeasures. Supported by the NASA Human Research Program (HRP) Human Factors Behavioral Performance Element Grant 18-18FLAG_2-0028.

radiation↗

Mechanical Unloading Effects Hematopoiesis and Subsequent Red Blood Cell Life Cycle Evaluated at Singe Cell Resolution

Red blood cell formation or erythropoiesis in the bone marrow and exit into circulation are known to be affected by mechanical loading. Specifically, space anemia is a condition observed during prolonged microgravity unloading in which the red blood cell (RBC) mass in circulation is reduced. However, the mechanisms causing space anemia are yet to be clearly established, but may include increased hemolysis of RBC in circulation, decreased RBC production or a combination of both factors. The presentation of space anemia is comparable to chronic anemia conditions associated with aging, disuse, and poor health. Molecular dysregulation in the RBC's life cycle is poorly defined and is a significant concern in the context of disuse anemia as mechanotransduction significantly alters of gene expression, protein synthesis and cell signaling pathways. Our study analyzes mouse single cell RNA sequencing libraries from the bone marrow, circulating blood, and spleen and integrates the RBC lineage populations from the tissues into a RBC life cycle atlas. This study also probes how age at time of spaceflight contributes to the molecular signature of space anemia. The overarching objective of the study is to develop a mechanistic understanding of space anemia and translate the findings to a better understanding of aging, disuse, and poor health-related anemia to defining the role of mechanical loading in health and devise potential therapeutic interventions. Important findings of our study are: 1) that mechanical unloading in microgravity alters the proportion of developmental RBC lineage cells, skewing toward progenitor, indicating that fewer RBCs may be present in blood; 2) that late reticulocyte number is elevated in the bone marrow of older animals, suggesting a failure to enter circulation; and 3) that the molecular signature of the circulating RBCs is not significantly altered in microgravity. However, expression markers for eryptosis and erythrophagocytosis are elevated in circulating and spleen RBCs, suggesting spaceflight may shorten the lifetime of RBCs after exit from the marrow. In conclusion our results suggest early stages of erythropoiesis proliferation and differentiation in the marrow are key factors in space anemia and mechanical loading may be a necessary step of RBC entry in circulation.

blood↗

RBE for late somatic effects in mice irradiated with 60 MeV protons relative to X-rays.

Investigation of the relative biological effectiveness of energetic protons for the induction of somatic effects in a mammal (mice) following whole body irradiation. The proton energy used approximates the mean energy for proton spectra accompanying solar events. The effects on longevity and the incidence of major neoplastic diseases are summarized. The results obtained suggest that medium energy proton irradiation is no more effective, and on the whole, probably less effective, than conventional X radiation for the induction of late radiation effects in the mouse.

Darden, E. B., Jr.↗

Biochronometry; Proceedings of the Symposium, Friday Harbor, Wash., September 4-6, 1969.

Topics discussed include circadian activity rhythms in birds and man, variation of circadian rhythms in monkeys, resetting of circadian eclosion rhythm in fruitflies, the effectiveness of mathematical models of circadian rhythms, the influence of ac electric fields on circadian rhythms in man, the relation between changes in the metabolic rate and circadian periodicity of the resistance of pocket mice to ionizing radiation, the relation between circadian organization and the photoperiodic time measurement in moths, the circadian rhythm of optic nerve potentials in the isolated eye of the sea hare, phasing of circadian temperature rhythms in the pocket mouse by specific spectral regions, the phase-shifting effect of light on circadian rhymicity in the fruifly, hormonal control of circadian rhythms in the fruitfly, metabolically controlled temperature compensation in the circadian rhythm of algae, and circadian rhythms in the chloroplasts of algae. Individual items are abstracted in this issue.

Menaker, M.↗

Oxygen consumption measurements during continual centrifugation of mice.

A simple method is described for measurement of metabolism of conscious, unrestrained animals, during chronic centrifugation or other conditions of isolation (23.75 hr/day) from the investigators in an essentially normal atmospheric environment for as long as seven days. This involves telemetry of pressure changes in a metabolic chamber. At 7 G's, increased O2 intake lasting two to seven days and a decreased excursion of the day-night difference were measured for male white mice with less effect or even an opposite effect at lower fields. Base-line measurements of metabolic rate per mouse are less affected by animal size than expected from the surface area law.

Fethke, W.↗

Skylab SO71/SO72 circadian periodicity experiment

The circadian rhythm hardware activities from 1965 through 1973 are considered. A brief history of the programs leading to the development of the combined Skylab SO71/SO72 Circadian Periodicity Experiment (CPE) is given. SO71 is the Skylab experiment number designating the pocket mouse circadian experiment, and SO72 designates the vinegar gnat circadian experiment. Final design modifications and checkout of the CPE, integration testing with the Apollo service module CSM 117 and the launch preparation and support tasks at Kennedy Space Center are reported.

Fairchild, M. K.↗

Biocore experiment

The Apollo 17 biological cosmic ray experiment to determine the effect of heavy cosmic ray particles on the brain and eyes is reported. The pocket mouse was selected as the biological specimen for the experiment. The radiation monitors, animal autopsy and animal processing are described, and the radiation effects on the scalp, retina, and viscera are analyzed.

Bailey, O. T.↗

Effects of mutation and some environmental factors on the physiology and pathogenicity of selected bacteria

Studies with mutants of Staphylococcus aureus lacking some virulence factors suggest that the presence of deoxyribonuclease correlates with mouse pathogenicity of S. aureus, while the ability to ferment mannitol or the possession of coagulases are not required for virulence. Autotrophy investigations on mycobacteria demonstrate a complete correlation between the ability to grow with hydrogen and the species of scotochromogenic mycobacterium tested. All tested strains of M. gordonae, a saprophyte, could grow autotrophically while none of the tested strains of M. scrofulaceum, a clinically important species, possessed this ability. A series of heat tolerant mutants of Pseudomonas fluorescences were obtained which can grow at temperatures up to 54 C, in contrast to a maximum growth temperature of 37 C for the wild type.

Decicco, B. T.↗

The effect of continuous low dose-rate gamma irradiation on cell population kinetics of lymphoid tissue

Cellular response and cell population kinetics were studied during lymphopoiesis in the thymus of the mouse under continuous gamma irradiation using autoradiographic techniques and specific labeling with tritiated thymidine. On the basis of tissue weights, it is concluded that the response of both the thymus and spleen to continuous low dose-rate irradiation is multiphasic. That is, alternating periods of steady state growth, followed by collapse, which in turn is followed by another period of homeostasis. Since there are two populations of lymphocytes - short lived and long-lived, it may be that different phases of steady state growth are mediated by different lymphocytes. The spleen is affected to a greater extent with shorter periods of steady-state growth than exhibited by the thymus.

Foster, B. R.↗

Proceedings of the 1972 Lyndon B. Johnson Space Center Endocrine Program Conference

Subjects covered during the Endocrine Program Conference include the following: (1) endocrine/metabolic studies on the Apollo 16 crewmen; (2) changes in glucose, insulin, and growth hormone levels associated with bed rest; (3) circadian rhythms of heart rate and body temperature during 56 days of bed rest; (4) stress-induced changes in corticosteroid metabolism in man; (5) present status of physiological studies on parathyroid hormone and vitamin D; (6) antagonistic effect of lithium on antidiuretic hormone action; (7) proposed Skylab body-fluid volumes study; (8) daily rhythmic changes in serotonin content in areas of the mouse brain and norepinephrine content in areas of the hamster brain; (9) studies of sodium homeostasis during simulated weightlessness; and (10) application of the water immersion model to man.

Source record↗

Telemetry in animal and human biometeorology

Radio transmitters swallowed, surgically implanted, or carried externally make it possible to study a subject with minimum disturbance to normal patterns of activity. The radio frequency of transmission chosen will depend on the application, and will generally fall in the range from 50 kHz to 300 MHz. A number of specific experiments are reported, including the case of a snake which has swallowed a mouse containing a transmitter of pressure and temperature. Questions of monitoring are explored. Satellite Doppler tracking considerations are discussed together with the attachment of the transmitter package in the case of a study of birds.

Mackay, R. S.↗