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At least 19 records

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.↗

Characterizing the Effects of Chronic 2G Centrifugation on the Rat Skeletal System

During weightlessness, the skeletal system of astronauts is negatively affected by decreased calcium absorption and bone mass loss. Therefore, it is necessary to counteract these changes for long-term skeletal health during space flights. Our long-term plan is to assess artificial gravity (AG) as a possible solution to mitigate these changes. In this study, we aim to determine the skeletal acclimation to chronic centrifugation. We hypothesize that a 2G hypergravity environment causes an anabolic response in growing male rats. Specifically, we predict chronic 2G to increase tissue mineral density, bone volume fraction of the cancellous tissue and to increase overall bone strength. Systemically, we predict that bone formation markers (i.e., osteocalcin) are elevated and resorption markers (i.e., tartrate resistant acid phosphatase) are decreased or unchanged from controls. The experiment has three groups, each with an n8: chronic 2g, cage control (housed on the centrifuge, but not spun), and a vivarium control (normal rat caging). Pre-pubescent, male Long-Evans rats were used to assess our hypothesis. This group was subject to 90 days of 2G via centrifugation performed at the Chronic Acceleration Research Unit (CARU) at University of California Davis. After 90 days, animals were euthanized and tissues collected. Blood was drawn via cardiac puncture and the right leg collected for structural (via microcomputed tomography) and strength quantification. Understanding how counteract these skeletal changes will have major impacts for both the space-faring astronauts and the people living on Earth.

rat↗

Effects of 2G on Gene Expression of Stress-Related Hormones in Rat Placenta

Understanding the effects of spaceflight on mammalian reproductive and developmental physiology is important to future human space exploration and permanent settlement beyond Earth orbit. Fetal developmental programming, including modulation of the HPA axis, is thought to originate at the placental-uterine interface, where both transfer of maternal hormones to the fetus and synthesis of endogenous hormones occurs. In healthy rats, fetal corticosterone levels are kept significantly lower by 11BetaHSD-2, which inactivates corticosterone by conversion into cortisone. Placental tissues express endogenous HPA axis-associated hormones including corticotropin-releasing hormone (CRH), pre-opiomelanocortin (POMC), and vasopressin, which may contribute to fetal programming alongside maternal hormones. DNA methylase 3A, 11BetaHSD-2, and 11BetaHSD-1, which are involved in the regulation of maternal cortisol transfer and modulation of the HPA axis, are also expressed in placental tissues along with glucocorticoid receptor and may be affected by differential gravity exposure during pregnancy. Fetuses may respond differently to maternal glucocorticoid exposure during gestation through sexually dimorphic expression of corticosterone-modulating hormones. To elucidate effects of altered gravity on placental gene expression, here we present a ground-based analogue study involving continuous centrifugation to produce 2g hypergravity. We hypothesized that exposure to 2g would induce a decrease in 11BetaHSD-2 expression through the downregulation of DNA methylase 3a and GC receptor, along with concurrent upregulation in endogenous CRH, POMC, and vasopressin expression. Timed pregnant female rats were exposed to 2G from Gestational day 6 to Gestational day 20, and comparisons made with Stationary Control (SC) and Vivarium Control (VC) dams at 1G. Dams were euthanized and placentas harvested on G20. We homogenized placental tissues, extracted and purified RNA, synthesized cDNA, and quantified the expression levels of the genes of interest relative to the GAPDH housekeeping gene, using RT-qPCR and gene-specific cDNA probes. Elucidation of glucocorticoid transfer and synthesis in the placenta can provide new insights into the unique dynamics of mammalian development in microgravity and guide future multi-generational studies in space.

Benson, S.↗

Benchmarking GOCART-2G in the Goddard Earth Observing System (GEOS)

The Goddard Chemistry Aerosol Radiation and Transport (GOCART) model, which controls the sources sinks and chemistry within the Goddard Earth Observing System, recently underwent a major refactoring and update to the representation of physical processes. This paper serves to document code changes that were included in GOCART 2nd Generation (GOCART-2G) and establishes a benchmark simulation that is to be used for future development of the system. The code refactoring increases flexibility such multiple instances of an aerosol species can be run and interact with radiation and cloud microphysics, in addition to the output of multiple wavelength aerosol optical properties in support of data assimilation. From a science perspective, a new radiatively active tracer, brown carbon, was added to distinguish smoke from other sources of organic aerosol thereby improving optical properties entering the radiative calculations. A four-year benchmark simulation was evaluated using in situ and space borne measurements to develop a baseline and prioritize future development. A comparison of simulated aerosol optical depth between GOCART-2G and MODIS retrievals indicates the model captures the overall spatial pattern and seasonal cycle of aerosol optical depth but overestimates aerosol extinction over dusty regions and underestimates aerosol extinction over northern hemisphere boreal forests, requiring further tuning of emissions. This MODIS-based analysis is corroborated by comparisons to MISR and selected AERONET stations. Despite the underestimate of aerosol optical depth in biomass burning regions in GEOS, there is an overestimate in the surface mass of organic carbon in the United States, especially during the summer months.

Allison B Collow↗

Quantification of Bone Growth Rate Variability in Rats Exposed to Micro- (near zero G) and Macrogravity (2G)

Our stated primary objective is to quantify the growth rate variability of rat lamellar bone exposed to micro and macrogravity (2G). The primary significance of the proposed work is that an elegant method will be established that unequivocally characterizes the morphological consequences of gravitational factors on developing bone. The integrity of this objective depends upon our successful preparation of thin sections suitable for imaging individual bone lamellae, and our imaging and quantitation of growth rate variability in populations of lamellae from individual bone samples.

Bromage, Timothy G.↗

Quantitation of Bone Growth Rate Variability in Rats Exposed to Micro-(near zero G) and Macrogravity (2G)

Our stated primary objective is to quantify the growth rate variability of rat lamellar bone exposed to micro- (near zero G: e.g., Cosmos 1887 & 2044; SLS-1 & SLS-2) and macrogravity (2G). The primary significance of the proposed work is that an elegant method will be established that unequivocally characterizes the morphological consequences of gravitational factors on developing bone. The integrity of this objective depends upon our successful preparation of thin sections suitable for imaging individual bone lamellae, and our imaging and quantitation of growth rate variability in populations of lamellae from individual bone samples.

Bromage, Timothy G.↗

The effect of a BRN 3.1 deletion on the temperature response to 2G

Researchers studied the effect of 2G exposure on body temperature in Wild type and BRN 3.1 Knockout mice to determine the feasibility to using BRN 3.1 Knockout mice as an animal model of the effects of altered gravitational fields on vestibular system physiology.

NASA Discipline Neuroscience↗

Prenatal 2g Exposure Alters Placental Expression of Stress-Related Genes

Extra-terrestrial colonization is of growing interest to space agencies and private entities, emphasizing the importance of research on reproduction and development in the absence of Earth's 1G. Maternal stressors can modify offspring development, exerting significant lifespan and crossgenerational changes through prenatal programming. The space environment is stressful, therefore exposure to altered gravity during pregnancy may impact later life outcomes in offspring. In ground-based studies, we exposed pregnant rats to continuous +G (above Earth gravity), and observed overweight and elevated anxiety in adult male (but not female) offspring, common phenotypes associated with prenatal maternal stress. Here we hypothesize that exposure to increased gravity during pregnancy elicits changes in the expression of stress-related genes in placenta that may mediate emergence of later life outcomes. While the placenta transports maternal factors to the fetus and produces endogenous fetal hormones, stress-induced changes at the placental-uterine interface may also alter communication between mother and fetus, facilitating prenatal transmission of unfavorable later life outcomes and cross-generational epigenetic alterations. Maternal stress elevates maternal glucocorticoids however placental 11b-hydroxysteroid dehydrogenase type 2 (HSD11B2) buffers fetal exposure by converting cortisol/corticosterone into inactive metabolites. Maternal stress during pregnancy down-regulates this enzyme and can induce epigenetic changes in placental and fetal tissues accounting for heightened adult HPA reactivity. Past studies have shown a placenta-specific increase in DNA methyltransferase (DNMT3a) mRNA in stressed mothers, an effect with implications for genome-wide epigenetic changes that may account for diverse phenotypic outcomes following maternal stress. Here we exposed groups of pregnant rats to one of five gravity loads (1, 1.5, 1.75 and 2G) and analyzed placental samples during late gestation. We predicted a systematic dose-response relationship between gravity load and the expression of the HSD11B2 and DNMT3 genes, thereby linking maternal exposure to altered gravity during pregancy with maternal stress.

Kalotia, Simranjit K.↗

Development of the GeoNEX Level 2G Products: Exploiting the Diurnal Variability of TOA Reflectance in Atmospheric Correction

This study develops a new atmospheric correction algorithm to generate the Level 2G products, in particular the gap-filled Surface Reflectance at 10-minute time steps, for the Geostationary-NASA Earth Exchange (GeoNEX) project. The algorithm is based on the MODIS MAIAC (Multi-Angle Implementation of Atmospheric Correction) framework but with significant modifications to exploit angular/temporal information from the diurnal variability of the GeoNEX L1G TOA (Top-of-Atmosphere) reflectance. The algorithm starts by evaluating the roughness/smoothness of the diurnal time series of the TOA reflectance. Because rapid changes in TOA reflectance are generally caused by passing clouds or shadows, rough segments of the time series are automatically filtered out while the smooth segments are further tested for brightness and temperature to identify clear-sky and snow-free observations. Next the algorithm runs the MAIAC RTM (Radiative Transfer Model) to retrieve the Ross-Thick-Li-Sparse (RTLS) BRDF model parameters and the daily-mean atmospheric optical depth (AOD) that allow the RTM to optimally simulate the observed diurnal variability of clear-sky TOA reflectance. Once the initial RTLS parameters are retrieved after the algorithm’s burn-in period, they are used as the prior information to predict the AOD level for the next days, while the subsequent clear-sky observations are used to make necessary adjustments to the RTLS parameters in an continuous fashion. This “prediction-analysis” cycle is then iterated to process the full time series of the L1G data, skipping only total-cloudy days or when surface snow is detected. We tested the algorithm over a list of selected AERONET sites. The retrieved results (the daily mean AOD and the RTLS parameters) reasonably agree with the ground-based measurements. Importantly, the results indicate that the diurnal cycles of surface reflectance are continuous functions of the illumination-view geometry. Thus we can use the retrieved RTLS model to accurately fill in data gaps on partial cloudy days. Also, our algorithm is totally independent from the traditional approaches based on the use of spectral band ratios between the shortwave infrared (e.g., 2.2µm) and the visible (e.g., 0.47µm and 0.64µm) bands. Our results thus demonstrate that the high-frequent diurnal geostationary observations contain unique information that helps us improve atmospheric correction of remote sensing data.

GeoNEX↗

Benchmarking GOCART-2G in the Goddard Earth Observing System (GEOS)

The Goddard Chemistry Aerosol Radiation and Transport (GOCART) model, which controls the sources sinks and chemistry within the Goddard Earth Observing System, recently underwent a major refactoring and update to the representation of physical processes. The code refactoring increases flexibility such multiple instances of an aerosol species can be run and interact with radiation and cloud microphysics, in addition to the output of multiple wavelength aerosol optical properties in support of data assimilation. From a science perspective, a new radiatively active tracer, brown carbon, was added to distinguish smoke from other sources of organic aerosol thereby improving optical properties entering the radiative calculations. A four-year benchmark simulation was evaluated using in situ and space borne measurements to develop a baseline and prioritize future development. A comparison of simulated aerosol optical depth between GOCART-2G and MODIS retrievals indicates the model captures the overall spatial pattern and seasonal cycle of aerosol optical depth but overestimates aerosol extinction over dusty regions and underestimates aerosol extinction over northern hemisphere boreal forests, requiring further tuning of emissions. This MODIS-based analysis is corroborated by comparisons to MISR and selected AERONET stations. Despite the underestimate of aerosol optical depth in biomass burning regions in GEOS, there is an overestimate in the surface mass of organic carbon in the United States, especially during the summer months.

Allison Collow↗

Critical Current Stability of 2G REBCO Tape for Space-Flight HTS Leads

High reliability is an essential requirement for all spaceflight hardware. XRISM, a follow-on mission to the Hitomi x-ray observatory, also uses 2G REBCO tapes as current leads for the superconducting magnets that are a key component of the Adiabatic Demagnetization Refrigerator (ADR) that cools the detector array. While the Hitomi Soft X-ray Spectrometer (SXS) worked flawlessly in orbit, during its development there were indications that the critical current of its specialized REBCO tapes could degrade over time when exposed to normal-humidity air. To demonstrate that the updates to the XRISM HTS lead assemblies had mitigated this risk, a series of tests were carried out to measure the stability of Ic of dozens of samples over a period greater than the flight assemblies were exposed to air during integration and test. The test rig allowed not only the measurement of the sample Ic, but also the localization of the voltage rise as the current approached Ic. We will discuss the trends in the critical current of the samples, as well as localization of lower Ic regions.

Edgar R. Canavan↗

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.↗

2nd Generation Reusable Launch Vehicle (2G RLV)

This is a revised final report and addresses all of the work performed on this program. Specifically, it covers vehicle architecture background, definition of six baseline engine cycles, reliability baseline (space shuttle main engine QRAS), and component level reliability/performance/cost for the six baseline cycles, and selection of 3 cycles for further study. This report further addresses technology improvement selection and component level reliability/performance/cost for the three cycles selected for further study, as well as risk reduction plans, and recommendation for future studies.

Matlock, Steve↗

Alterations of Body Mass Gain of Neonates (P7&P14) During Certrifugation AT 2G

Previous research has shown animal body mass to be significantly affected by centrifugation. At the onset of centrifugation, animals have a selective loss of fat, causing an initial body mass loss. Body mass gain will resume at the same rate as uncentrifuged animals, but this subsequent gain will be lower. For this study, two different ages of Sprague Hawley neonate families were observed during centrifugation. Eight litters (dam with eight neonates) of postnatal day (PN) seven and four litters (dam with ten neonates) of PN 14 were separated into two separate groups each, centrifuge (+2G(sub z)) and environmental controls (EC) and placed into either the centrifuge or an animal holding unit in the centrifuge rotunda for a total of 16 days. P7: Total litter start mass of +2G(sub z) litter = 138.90 g/end = 311.0 g EC litter = 150.85 g/end = 516.9 g. P14: Total litter start mass of +2G(sub z) litter = 287.70 g/end = 762.5g; EC litter = 245 g/end = 942.9 g. An initial body mass loss was observed in both groups of +2G(sub z) animals for two days after the onset of centrifugation, but then an increase began to occur. Literature suggests adult animals at +2G(sub z), will have an initial loss, but will resume similar growth rates over time as compared to control animals. The P7 +2G(sub z) animals began to gain body mass, but showed a significantly slower growth rate than their EC animals for the duration of the test (pace). The P14 +2G(sub z) animals began to show similar growth rates to their EC after day nine. At day 16, both groups of +2Gz animals were significantly smaller than the EC animals (pace). At +2Gz, animals experience an initial body mass loss. Older animals are able to resume similar growth rates as their controls, but younger animals showed growth rates to be significantly reduced.

Baer, L. A.↗

Changes in hypothalamic staining for c-Fos following 2G exposure in rats

The static gravitational field of the earth has been an important selective pressure that has shaped the evolution of biological organisms. This is illustrated by the evolution of tetrapods from a water environment where gravitational force was partially negated to a terrestrial environment where gravity is of greater consequence. Terrestrial invasion resulted in a series of new structural, physiological, and behavioral features. Therefore, it is not surprising that alterations in the gravitational field can cause widespread effects in many physiological systems and behaviors. Our previous studies have demonstrated that both exposure to hyperdynamic fields and the microgravity condition of space flight have significant effects on body temperature, heartrate, activity, feeding, drinking, and circadian rhythms. However, it has not been determined whether these physiological adaptations are associated with changes in neural activity within the hypothalamic nuclei that regulate these functions. This study examined the changes in body temperature, activity, body weight and food and water intake in rats caused by exposure to a hyperdynamic field. In addition, the immediate early gene activation marker, c-Fos, was used to examine potential protein synthesis changes in the hypothalamic nuclei that regulate these functions.

NASA Discipline Regulatory Physiology↗