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At least 199 records · Page 11

Models to study gravitational biology of Mammalian reproduction

Mammalian reproduction evolved within Earth's 1-g gravitational field. As we move closer to the reality of space habitation, there is growing scientific interest in how different gravitational states influence reproduction in mammals. Habitation of space and extended spaceflight missions require prolonged exposure to decreased gravity (hypogravity, i.e., weightlessness). Lift-off and re-entry of the spacecraft are associated with exposure to increased gravity (hypergravity). Existing data suggest that spaceflight is associated with a constellation of changes in reproductive physiology and function. However, limited spaceflight opportunities and confounding effects of various nongravitational factors associated with spaceflight (i.e., radiation, stress) have led to the development of ground-based models for studying the effects of altered gravity on biological systems. Human bed rest and rodent hindlimb unloading paradigms are used to study exposure to hypogravity. Centrifugation is used to study hypergravity. Here, we review the results of spaceflight and ground-based models of altered gravity on reproductive physiology. Studies utilizing ground-based models that simulate hyper- and hypogravity have produced reproductive results similar to those obtained from spaceflight and are contributing new information on biological responses across the gravity continuum, thereby confirming the appropriateness of these models for studying reproductive responses to altered gravity and the underlying mechanisms of these responses. Together, these unique tools are yielding new insights into the gravitational biology of reproduction in mammals.

Review, Tutorial↗

Next Steps Toward Understanding Human Habitation of Space: Environmental Impacts and Mechanisms

Entry into low earth orbit and beyond causes profound shifts in environmental conditions that have the potential to influence human productivity, long term health, and even survival. We now have evidence that microgravity, radiation and/or confinement in space can lead to demonstrably detrimental changes in the cardiovascular (e.g. vessel function, orthostatic intolerance), musculoskeletal (muscle atrophy, bone loss) and nervous (eye, neurovestibular) systems of astronauts. Because of both the limited number of astronauts who have flown (especially females) and the high degree of individual variability in the human population, important unanswered questions about responses to the space environment remain: What are the sex differences with respect to specific physiological systems? Are the responses age-dependent and/or reversible after return to Earth? Do observed detrimental changes that resemble accelerated aging progress continuously over time or plateau? What are the mechanisms of the biological responses? Answering these important questions certainly demands a multi-pronged approach, and the study of multicellular model organisms (such as rodents and flies) already has provided opportunities for exploring those questions in some detail. Recent long duration spaceflight experiments with rodents show that mice in space provide a mammalian model that uniquely combines the influence of reduced gravitational loading with increased physical activity. In addition, multiple investigators have shown that ground-based models that simulate aspects of spaceflight (including rodent hind limb unloading to mimic weightlessness and exposure to ionizing radiation), cause various transient and persistent detrimental consequences in multiple physiological systems. In general, we have found that adverse skeletal effects of simulated weightlessness and space radiation when combined, can be quantitatively, if not qualitatively, different from the influence of each environmental factor alone implying at least some shared underlying mechanisms. Thus, both ground based and spaceflight research utilizing model organisms provide the opportunity to better understand environmental factors and biological mechanisms that contribute to human health and survival in space.

skeleton↗

BRN 3.1 Knockouts Affect the Vestibular, Autonomic, and Circadian Rhythm Responses to 2G Exposure

Our previous studies have demonstrated that 2G exposure via centrifugation significantly attenuated the daily mean and circadian rhythm amplitude of rat body temperature (Tb), heart rate, and activity (Act). In addition, 2G exposure activates neural responses in several vestibular, autonomic, and circadian nuclei. Although we have characterized the effect of 2G on an animal's physiological, neuronal, and behavioral responses, it will be important to understand the underlying neural and physiological mechanisms that mediate those responses. For example, the vestibular responses, proprioceptive feedback, or fluid shifts may be the critical factors that mediate the responses to 2G. As a first step to understand the relative importance of these different response pathways to altered gravitational fields, this study examined the contribution of the vestibular system by utilizing an animal model from molecular biology. Brain 3.1 (Bm 3.1) is a POU domain homeobox gene involved in the normal development of the vestibular and auditory system. Brn 3.1 deletion results in a loss of hair cells in the otoliths, semicircular canals, and cochlea. As a result mice with a Brn 3.1 deletion do not have a functioning vestibular or auditory system. The BRN 3.1 knockout mouse could be a very useful animal model for isolating the role of the vestibular system in mediating the physiological responses to 2G exposure. Therefore, this study compared the effect of 2G exposure via centrifugation between Brn 3.1 knockout (KO) versus Wildtype (W) mice.

Murakami, D. M.↗

Cardiovascular Adjustments to Gravitational Stress

The effects of gravity on the cardiovascular system must be taken into account whenever a hemodynamic assessment is made. All intravascular pressure have a gravity-dependent hydrostatic component. The interaction between the gravitational field, the position of the body, and the functional characteristics of the blood vessels determines the distribution of intravascular volume. In turn this distribution largely determines cardiac pump function. Multiple control mechanisms are activated to preserve optimal tissue perfusion when the magnitude of the gravitational field or its direction relative to the body changes. Humans are particularly sensitive to such changes because of the combination of their normally erect posture and the large body mass and blood volume below the level of the heart. Current aerospace technology also exposes human subjects to extreme variations in the gravitational forces that range from zero during space travel to as much an nine-times normal during operation of high-performance military aircraft. This chapter therefore emphasizes human physiology.

Blomqvist, C. Gunnar↗

Dependence of normal development of skeletal muscle in neonatal rats on load bearing

Antigravity function plays an important role in determining the morphological and physiological properties of the neuromuscular system. Inhibition of the normal development of the neuromuscular system is induced by hindlimb unloading during the neonatal period in rats. However, the role of gravitational loading on the development of skeletal muscle in rats is not well understood. It could be hypothesized that during the early postnatal period, i.e. when minimal weight-supporting activity occurs, the activity imposed by gravity would be of little consequence in directing the normal development of the skeletal musculature. We have addressed this issue by limiting the amount of postnatal weight-support activity of the hindlimbs of rats during the lactation period. We have focused on the development of three characteristics of the muscle fibers, i.e. size, myonuclear number and myosin heavy chain expression.

Non-NASA Center↗

Reduced receptor aggregation and altered cytoskeleton in cultured myocytes after space-flight

We carried out parallel experiments first on the slow clinostat and then in space-flight to examine the effects of altered gravity on the aggregation of the nicotinic acetylcholine receptors and the structure of the cytoskeleton in cultured Xenopus embryonic muscle cells. By examining the concordance between results from space flight and the clinostat, we tested whether the slow clinostat is a relevant simulation paradigm. Space-flown cells showed marked changes in the distribution and organization of actin filaments and had a reduced incidence of acetylcholine receptor aggregates at the site of contact with polystyrene beads. Similar effects were found after clinostat rotation. The sensitivity of synaptic receptor aggregation and cytoskeletal morphology suggests that in the microgravity of space cell behavior may be importantly altered.

STS-56 Shuttle Project↗

Synthetic Biology and Human Health: Potential Applications for Spaceflight

Human space travelers experience a unique environment that affects homeostasis and physiologic adaptation. Spaceflight-related changes have been reported in the musculo-skeletal, cardiovascular, neurovestibular, endocrine, and immune systems. The spacecraft environment further subjects the traveler to noise and gravitational forces, as well as airborne chemical, microbiological contaminants, and radiation exposure. As humans prepare for longer duration missions effective countermeasures must be developed, verified, and implemented to ensure mission success. Over the past ten years, synthetic biology has opened new avenues for research and development in areas such as biological control, biomaterials, sustainable energy production, bioremediation, and biomedical therapies. The latter in particular is of great interest to the implementation of long-duration human spaceflight capabilities. This article discusses the effects of spaceflight on humans, and reviews current capabilities and potential needs associated with the health of the astronauts where synthetic biology could play an important role in the pursuit of space exploration.

Karouia, Fathi↗

Ceratopteris richardii: a productive model for revealing secrets of signaling and development

Ceratopteris richardii is an aquatic fern grown in tropical and subtropical regions of the world. It is proven to be a productive model system for studies in the genetics, biochemistry, and cell biology of basic biologic processes that occur in early gametophytic development. It provides several advantages to biologists, especially those interested in gravitational biology, polarity development, and in the genetics of sexual development. It is easy to culture, has a relatively short life cycle, and offers an array of attractive features that facilitate genetic studies. The germination and early development of large populations of genetically identical spores are easy to synchronize, and both the direction of polarity development and cell-level gravity responses can be measured and readily manipulated within the first 24 h of spore development. Although there is no reliable transformation system available yet in Ceratopteris, recent studies suggest that the technique of RNA interference can be used to block translation of specific genes in a related fern, Marsilea, and current studies will soon reveal the applicability of this approach, as well as of other transformation approaches, in Ceratopteris. A recently completed expressed sequence tag (EST) sequencing project makes available the partial sequence of more than 2000 cDNAs, representing a significant percentage of the genes being expressed during the first 24 h of spore germination, when many developmentally interesting processes are occurring. A microarray of these ESTs is being constructed, so especially for those scientists interested in basic cellular phenomena that occur early in spore germination, the availability of the ESTs and of the microarray will make Ceratopteris an even more attractive model system.

NASA Discipline Plant Biology↗

NASA space biology accomplishments, 1983-84

Approximately 42 project summaries from NASA's Space Biology Program are presented. Emphasis is placed on gravitational effects on plant and animal life. The identification of gravity perception; the effects of weightlessness on genetic integrity, cellular differentiation, reproduction, development, growth, maturation, and senescence; and how gravity affects and controls physiology, morphology, and behavior of organisms are studied.

Halstead, T. W.↗

Mechanisms of the early phases of plant gravitropism

Gravitropism is directed growth of a plant or plant organ in response to gravity and can be divided into the following temporal sequence: perception, transduction, and response. This article is a review of the research on the early events of gravitropism (i.e., phenomena associated with the perception and transduction phases). The two major hypotheses for graviperception are the protoplast-pressure and starch-statolith models. While most researchers support the concept of statoliths, there are suggestions that plants have multiple mechanisms of perception. Evidence supports the hypothesis that the actin cytoskeleton is involved in graviperception/transduction, but the details of these mechanisms remain elusive. A number of recent developments, such as increased use of the molecular genetic approach, magnetophoresis, and laser ablation, have facilitated research in graviperception and have allowed for refinement of the current models. In addition, the entire continuum of acceleration forces from hypo- to hyper-gravity have been useful in studying perception mechanisms. Future interdisciplinary molecular approaches and the availability of sophisticated laboratories on the International Space Station should help to develop new insights into mechanisms of gravitropism in plants.

NASA Discipline Plant Biology↗

Vivid Motor Imagery as an Adaptation Method for Head Turns on a Short-Arm Centrifuge

Artificial gravity (AG) has been proposed as a potential countermeasure to the debilitating physiological effects of long duration space flight. The most economical means of implementing AG may be through the use of a short-radius (2m or less) centrifuge. For such a device to produce gravitational forces comparable to those on earth requires rotation rates in excess of 20 revolutions per minute (rpm). Head turns made out of the plane of rotation at these rates, as may be necessary if exercise is combined with AG, result in cross-coupled stimuli (CCS) that cause adverse side effects including motion sickness, illusory sensations of motion, and inappropriate eye movements. Recent studies indicate that people can adapt to CCS and reduce these side effects by making multiple head turns during centrifuge sessions conducted over consecutive days. However, about 25% of the volunteers for these studies have difficulty tolerating the CCS adaptation paradigm and often drop out due to motion sickness symptoms. The goal of this investigation was to determine whether vivid motor imagery could be used as a pseudostimulus for adapting subjects to this unique environment. Twenty four healthy human subjects (14 males, 10 females), ranging in age from 21 to 48 years (mean 33, sd 7 years) took part in this study. The experimental stimuli were produced using the NASA JSC short-arm centrifuge (SAC). Subjects were oriented supinely on this device with the nose pointed toward the ceiling and head centered on the axis of rotation. Thus, centrifuge rotation was in the body roll plane. After ramp-up the SAC rotated clockwise at a constant rate of 23 rpm, producing a centrifugal force of approximately 1 g at the feet. Semicircular canal CCS were produced by having subjects make yaw head turns from the nose up (NU) position to the right ear down (RED) position and from RED to NU. Each head turn was completed in about one second, and a 30 second recovery period separated consecutive head movements. Participants were randomly assigned to one of three groups (n=8 per group): physical adapters (PA), mental adapters (MA), or a control group (CG). Each subject participated in a one hour test session on each of three consecutive days. Each test session consisted of an initial (preadaptation) period during which the subject performed six CCS maneuvers in the dark, followed by an adaptation period with internal lighting on the centrifuge, and a final (postadaptation) period during which six more CCS maneuvers were performed in the dark. For the PA group, the adaptation period consisted of performing 30 additional CCS maneuvers in the light. For the MA and CG group the centrifuge was ramped down to 0 rpm after the pre-adaptation period and ramped back up to 23 rpm before the post-adaptation period. For the both of these groups, the adaptation period consisted of making 30 CCS maneuvers in the light with the centrifuge stationary (so no cross-coupling occurred). MA group subjects were instructed to vividly imagine the provocative sensations produced by the preadaptation CCS maneuvers in terms of magnitude, duration, and direction of illusory body tilt, as well as any accompanying levels of motion sickness. CG group subjects were asked to answer low imagery content questions (trivial pursuit) during each adaptation period head turn. During the 30 second recovery following each head turn, psychophysical data were collected including self reports of motion sickness, magnitude and direction estimates of illusory body tilt, and the overall duration of these sensations. A multilevel mixed effects linear regression analysis performed on all response variables indicated that all three groups experienced some psychophysical adaptation across the three test sessions. For illusory tilt magnitude, the PA group exhibited the most overall adaptation, followed by the MA group, and the CG group. The slopes of these adaptation trajectories by group over day were significantly diffent from one another. For the perceived duration of sensations, the CG group again exhibited the least amount of adaptation. However, the rates of adaptation of the PA and the MA groups were indistinguishable, suggesting that the imagined pseudostimulus appeared to be just as effective a means of adaptation as the actual stimulus. The MA group's rate of adaptation to motion sickness symptoms was also comparable to the PA group. The use of vivid motor imagery may be an effective method for adapting to the illusory sensations and motion sickness symptoms produced by cross-coupled stimuli. For space-based AG applications, this technique may prove quite useful in retaining astronauts considered highly susceptible to motion sickness as it reduces the number of actual CCS required to attain adaptation.

Newby, N. J.↗

Cardiopulmonary discipline science plan

Life sciences research in the cardiopulmonary discipline must identify possible consequences of space flight on the cardiopulmonary system, understand the mechanisms of these effects, and develop effective and operationally practical countermeasures to protect crewmembers inflight and upon return to a gravitational environment. The long-range goal of the NASA Cardiopulmonary Discipline Research Program is to foster research to better understand the acute and long-term cardiovascular and pulmonary adaptation to space and to develop physiological countermeasures to ensure crew health in space and on return to Earth. The purpose of this Discipline Plan is to provide a conceptual strategy for NASA's Life Sciences Division research and development activities in the comprehensive area of cardiopulmonary sciences. It covers the significant research areas critical to NASA's programmatic requirements for the Extended-Duration Orbiter, Space Station Freedom, and exploration mission science activities. These science activities include ground-based and flight; basic, applied, and operational; and animal and human research and development. This document summarizes the current status of the program, outlines available knowledge, establishes goals and objectives, identifies science priorities, and defines critical questions in the subdiscipline areas of both cardiovascular and pulmonary function. It contains a general plan that will be used by both NASA Headquarters Program Offices and the field centers to review and plan basic, applied, and operational (intramural and extramural) research and development activities in this area.

Source record↗

Effect of gravitational sedimentation on simulated aerosol dispersion in the human acinus

We studied the effect of gravitational sedimentation on the dispersion of 0.5 and 1 micrometer-diameter particle boluses within a two-dimensional symmetric six-generation model of the human acinus. Boluses were introduced at the beginning of a 2-s inspiration immediately followed by a 4-s expiration, in normal gravity (1 G) and in the absence of gravity (0 G). The flow corresponded to a flow rate at the mouth of 500 ml/s. In 0 G, simulated dispersion (Hsim) was 16 ml for both particle sizes. In 1 G, Hsim was 71 and 242 ml for 0.5 and 1 micrometer-diameter particles, respectively, showing the effect of gravitational sedimentation. The difference between experimental data (J. Appl. Physiol. 86 (1999) 1402) and simulations was independent of particle size. This suggests that the residual dispersion was independent of the intrinsic properties of the particles and was more likely due to other mechanisms such as ventilation inhomogeneities, cardiogenic oscillations and alveolar wall motion. c2003 Elsevier Science Ltd. All rights reserved.

short duration↗

Effects of inversion on plastid position and gravitropism in Ceratodon protonemata

When dark-grown tip cells of protonemata of the moss Ceratodon purpureus are turned to the horizontal, plastids first sediment towards gravity in a specific zone and then the tip curves upward. To determine whether gravitropism and plastid sedimentation occur in other orientations, protonemata were reoriented to angles other than 90 degrees. Qualitative and quantitative light microscopic observations show that plastid sedimentation along the cell axis occurs in both upright and inverted cells. However, only some plastids fall and sedimentation is incomplete; plastids remain distributed throughout the length of the cell, and those plastids that sediment do not fall all the way to the bottom of the cell. Tip cells are gravitropic regardless of stimulation angle, and as in higher plants, the maximal rate of initial curvature is in response to a 120 degrees reorientation. Infrared videomicroscopy, time-lapse studies of living, inverted protonemata indicate that amyloplast sedimentation precedes upward curvature. Together, these data further support (i) the hypothesis that amyloplast sedimentation functions in gravitropic sensing in these cells, and (ii) the idea that gravity affected the evolution of cell organization.

NASA Program Space Biology↗

Life Sciences Division Spaceflight Hardware

The Ames Research Center (ARC) is responsible for the development, integration, and operation of non-human life sciences payloads in support of NASA's Gravitational Biology and Ecology (GB&E) program. To help stimulate discussion and interest in the development and application of novel technologies for incorporation within non-human life sciences experiment systems, three hardware system models will be displayed with associated graphics/text explanations. First, an Animal Enclosure Model (AEM) will be shown to communicate the nature and types of constraints physiological researchers must deal with during manned space flight experiments using rodent specimens. Second, a model of the Modular Cultivation System (MCS) under development by ESA will be presented to highlight technologies that may benefit cell-based research, including advanced imaging technologies. Finally, subsystems of the Cell Culture Unit (CCU) in development by ARC will also be shown. A discussion will be provided on candidate technology requirements in the areas of specimen environmental control, biotelemetry, telescience and telerobotics, and in situ analytical techniques and imaging. In addition, an overview of the Center for Gravitational Biology Research facilities will be provided.

Yost, B.↗

Effects of Space Flight-Associated Stimuli on Development of Murine and Medaka Sensory-Motor Systems

The major goal of these studies was to continue investigations into the influence of altered gravitational fields on the development and function of the vertebrate brain and nervous system. Of major focus during the 18-month finding period of this award was the maintenance of the animals used in the experimental mouse and medaka model paradigms. The experiments focused on characterization of stress-sensitive periods in neural development and immediate or delayed effects on gene expression, physiology and behavior. The hypothesis under investigation was that the environment of space will have biologically significant effects on the development and function of the vertebrate nervous system. We have postulated that these effects will be more significant on certain neural compartments, such as the vestibular-motor system, and that these effects will have greater impact at particular stages of embryonic and post-natal development of the animal. Development of the central nervous system is well known for its vulnerability and sensitivity to environmental stimuli, although the effects of gravitational influences are poorly understood. The long-term goals of this research effort, initiated previously and continued in limited capacity during this interim period, were to provide important new information on the effects of altered environments during these critical periods.

Wolgemuth, Debra J.↗