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All sourcesNASA NTRSDOE OSTI
NASA NTRS2003

WVD2 and WDL1 modulate helical organ growth and anisotropic cell expansion in Arabidopsis

Wild-type Arabidopsis roots develop a wavy pattern of growth on tilted agar surfaces. For many Arabidopsis ecotypes, roots also grow askew on such surfaces, typically slanting to the right of the gravity vector. We identified a mutant, wvd2-1, that displays suppressed root waving and leftward root slanting under these conditions. These phenotypes arise from transcriptional activation of the novel WAVE-DAMPENED2 (WVD2) gene by the cauliflower mosaic virus 35S promoter in mutant plants. Seedlings overexpressing WVD2 exhibit constitutive right-handed helical growth in both roots and etiolated hypocotyls, whereas the petioles of WVD2-overexpressing rosette leaves exhibit left-handed twisting. Moreover, the anisotropic expansion of cells is impaired, resulting in the formation of shorter and stockier organs. In roots, the phenotype is accompanied by a change in the arrangement of cortical microtubules within peripheral cap cells and cells at the basal end of the elongation zone. WVD2 transcripts are detectable by reverse transcriptase-polymerase chain reaction in multiple organs of wild-type plants. Its predicted gene product contains a conserved region named "KLEEK," which is found only in plant proteins. The Arabidopsis genome possesses seven other genes predicted to encode KLEEK-containing products. Overexpression of one of these genes, WVD2-LIKE 1, which encodes a protein with regions of similarity to WVD2 extending beyond the KLEEK domain, results in phenotypes that are highly similar to wvd2-1. Silencing of WVD2 and its paralogs results in enhanced root skewing in the wild-type direction. Our observations suggest that at least two members of this gene family may modulate both rotational polarity and anisotropic cell expansion during organ growth.

NASA Discipline Plant Biology↗
NASA NTRSDate not supplied

BLOOD-BASED MULTI-SCALE MODEL FOR CANCER RISK FROM GCR IN GENETICALLY DIVERSE POPULATIONS

OBJECTIVES AND METHODS This project addresses the challenge of understanding and predicting individual radiation sensitivity by integrating genetics, demographics and biomarker characteristics across species (mice and humans). We hypothesize that ex vivo DNA repair response to GCR components is a central determinant of cancer risk from space radiation and can serve as a biomarker of radiation risk in combination with genetics. Automated image quantification of 53BP1+ radiation-induced foci (RIF) during the first 4-48 h post-irradiation was performed as a function of dose and LET in non-immortalized primary skin fibroblasts derived from 76 mice across 15 strains (5 inbred reference strains and 10 collaborative-cross strains) exposed to X rays (0.1, 1 and 4 Gy), 350 MeV/n 40Ar and 600 MeV/n 56Fe (1.1 and 3 particles/100μm2), as well as in peripheral blood mononuclear cells (PBMCs) from 768 healthy donors (matched ethnicity, 50/50 male/female, 18-70 years old) exposed to gamma rays (0.1 and 1 Gy), 350 MeV/n 28Si, 350 MeV/n 40Ar and 600 MeV/n 56Fe (1.1 and 3 particles/100μm2). QUANTIFICATION OF 53BP1+ FOCI IN VITRO AND ASSOCIATIONS TO IN VIVO RADIATION SUSCEPTIBILITY IN 15 MOUSE STRAINS We reported in vitro repair kinetic and repairable fractions of RIF for the 15 mouse strains and introduced a mathematical model for RIF as a function of time, dose and LET. We noted that the metabolic activity of cells modulates the RIF response, and we introduced the open access tool terRIFic (Tool for Enhanced Results of RIF In Cells, https://radbiolab.shinyapps.io/terrific/) to correct for such bias using confluence level. Notably, at 4h post-irradiation, RIF/Gy decreased with dose or LET: as the dose or LET increases, so does the proximity of DNA double-strand-breaks (DSB) and our data suggest that proximal DSBs are brought together inside isolated RIF for repair. The RIF/Gy trend was inverted at 24h, suggesting RIF with high DSB content are more difficult to repair. We showed that in vitro metrics correlate with in vivo measurements in the same 15 mouse strains, such as survival levels of immune cells or spontaneous cancer incidence, suggesting a relationship between the efficiency of DSB repair and cancer risk or radiation toxicity. In addition to the efficiency of repair and persistent RIF, the amount of spontaneous foci before irradiation was also found to be strain dependent. Finally, we performed genome-wide association study in the same 15 mouse strains using all RIF phenotypes measured in vitro, identifying genes of interest and validating RIF as an ideal biomarker for individual radiation sensitivity. BASELINE 53BP1+ FOCI PREDICTS INDIVIDUAL HUMAN RESPONSE TO GCR COMPONENTS Based on the analysis of radiation responses of 576 donor PBMCs (using quantification of 53BP1+ foci, oxidative stress and cell death), we observed a wide variability of subject- and LET-dependent radiation responses, with radiation-induced DNA repair foci increasing with LET, though oxidative stress being notably reduced by high-LET irradiation, potentially due to a switch between hydrogen peroxide and oxygen radical-based mechanisms. We identified a relationship between few spontaneous DNA foci at baseline and increased DNA repair after irradiation, accompanied by an alteration in immunoregulatory cytokine secretion, which might be adapted as biomarkers to predict ionizing radiation sensitivity. Among demographic variables, only latent cytomegalovirus infection and age were predictive of high baseline foci formation. Finally, we have performed low-throughput whole genome sequencing of all samples and are currently in the process of identifying the genes and pathways associated with low and high-LET ionizing radiation sensitivity in humans.

53BP1↗
NASA NTRS2019

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.↗
NASA NTRSDate not supplied

High School Citizen Scientists Use AI/ML to Predict Intra-Ocular Pressure From Gene Expression Data for Spaceflown Mice

Artificial Intelligence (AI) and Machine Learning (ML) have increasingly become pivotal in biological and biomedical research, largely due to the culture of open data sharing and its associated benefits. The methodologies inherent in AI/ML are particularly adept at identifying and forecasting biological phenotypes from the vast amounts of data generated by next-generation sequencing technologies. These techniques offer substantial promise for advancing research in space biosciences and for the development of automated systems for monitoring space health. Nevertheless, there are crucial aspects to consider when training, validating, and testing machine learning models in both biological research and clinical contexts. It is essential that Open Science principles, including data sharing and the availability of open-source code, are complemented by high-quality, publicly accessible training resources. These resources should focus on best practices and include modules based on real-world scientific cases and data to ensure that future AI/ML practitioners gain practical experience with genuine problems. Addressing this knowledge gap, we have designed, developed, and delivered both interactive and self-paced training programs for citizen scientists worldwide, enabling them to utilize AI/ML for space biology research. This initiative was made possible through generous funding from a Transformation to Open Science Training grant. The interactive training sessions, conducted this summer, utilized AI/ML techniques to analyze data from the Open Science Data Repository, specifically targeting the effects of spaceflight on ocular structure and function. The dataset OSD-583, from the Rodent Research 9 mission, provides experimental data detailing the ocular responses of mice subjected to a 35-day spaceflight, compared with ground control counterparts. Using OSD-583 as observational data, our summer training participants applied AI/ML methods to predict intraocular pressure from RNA-seq data and identify the genes most predictive of the observed responses. Further analysis through pathway enrichment and gene set enrichment revealed that these genes are involved in molecular and cellular processes contributing to retinal degeneration.

James Casaletto↗
NASA NTRS2010

Agricultural Productivity Forecasts for Improved Drought Monitoring

Water stresses on agricultural crops during critical phases of crop phenology (such as grain filling) has higher impact on the eventual yield than at other times of crop growth. Therefore farmers are more concerned about water stresses in the context of crop phenology than the meteorological droughts. However the drought estimates currently produced do not account for the crop phenology. US Department of Agriculture (USDA) and National Oceanic and Atmospheric Administration (NOAA) have developed a drought monitoring decision support tool: The U.S. Drought Monitor, which currently uses meteorological droughts to delineate and categorize drought severity. Output from the Drought Monitor is used by the States to make disaster declarations. More importantly, USDA uses the Drought Monitor to make estimates of crop yield to help the commodities market. Accurate estimation of corn yield is especially critical given the recent trend towards diversion of corn to produce ethanol. Ethanol is fast becoming a standard 10% ethanol additive to petroleum products, the largest traded commodity. Thus the impact of large-scale drought will have dramatic impact on the petroleum prices as well as on food prices. USDA's World Agricultural Outlook Board (WAOB) serves as a focal point for economic intelligence and the commodity outlook for U.S. WAOB depends on Drought Monitor and has emphatically stated that accurate and timely data are needed in operational agrometeorological services to generate reliable projections for agricultural decision makers. Thus, improvements in the prediction of drought will reflect in early and accurate assessment of crop yields, which in turn will improve commodity projections. We have developed a drought assessment tool, which accounts for the water stress in the context of crop phenology. The crop modeling component is done using various crop modules within Decision Support System for Agrotechnology Transfer (DSSAT). DSSAT is an agricultural crop simulation system, which integrates the effects of soil, crop phenotype, weather, and management options. It has been in use for more than 15 years by researchers, growers and has become a de-facto standard in crop modeling communities spanning over 100 countries. The meteorological forcings to DSSAT are provided by NASA s National Land Data Assimilation System (NLDAS) datasets. NLDAS is a framework that incorporates atmospheric forcing and land parameter values along with land surface models to diagnose and predict the state of the land surface.

Limaye, Ashutosh↗
NASA NTRS2017

Metabolomic and Genomic Markers of Atherosclerosis as Related to Oxidative Stress, Inflammation, and Vascular Function in Twin Astronauts

BACKGROUND: Future human space travel will consist primarily of long-duration missions onboard the International Space Station (ISS) or exploration-class missions to Mars, its moons, or nearby asteroids. Astronauts participating in long-duration missions may be at an increased risk of oxidative stress and inflammatory damage due to radiation, psychological stress, altered physical activity, nutritional insufficiency, and hyperoxia during extravehicular activity. By studying one identical twin during his 1-year ISS mission and his ground-based twin, this work extends a current NASA-funded investigation to determine whether these spaceflight factors contribute to an accelerated progression of atherosclerosis. This study of twins affords a unique opportunity to examine spaceflight-related atherosclerosis risk that is independent of the confounding factors associated with different genotypes. PURPOSE: The purpose of this investigation was to determine whether biomarkers of oxidative and inflammatory stress are elevated during and after long-duration spaceflight and determine if a relation exists between levels of these biomarkers and structural and functional indices of atherosclerotic risk measured in the carotid and brachial arteries. These physiological and biochemical data will be extended by using an exploratory approach to investigate the relationship between intermediate phenotypes and risk factors for atherosclerosis and the metabolomic signature from plasma and urine samples. Since metabolites are often the indirect products of gene expression, we simultaneously assessed gene expression and DNA methylation in leukocytes. HYPOTHESIS: We predict that, compared to the ground-based twin, the space-flown twin will experience elevated biomarkers of oxidative stress and inflammatory damage, altered arterial structure and function, accelerated telomere shortening, dysregulation of genes associated with oxidative stress and inflammation, and a metabolic profile shift that is associated with elevated atherosclerosis risk factors. METHODS: In the space-flown twin, a panel of biomarkers of oxidative and inflammatory stress were measured in venous blood samples and in 24-h (in-flight) and 48-h (pre- and post-flight) urine pools collected twice before flight, six times during the mission (~FD15, 75, 180, 240, 300, 335), and early in the post-flight recovery phase (3-5 days after landing). We also measured metabolomic (targeted and untargeted approaches) and genomic markers (DNA methylation, mRNA gene expression, telomere length) in these samples. Arterial structure, assessed from measures of intima-media thickness, also were measured using standard clinical ultrasound at the same time points. Arterial function was assessed using brachial flow-mediated dilation, a well-validated measure used to assess endothelium-dependent vasodilation and a sensitive predictor of atherosclerotic risk, only before and after spaceflight. All of the same measures were obtained in the ground-based twin, but less frequently. DISCUSSION: All data collection has been completed for both the space-flown twin and the ground-based twin. Vascular structure and function measures have been analyzed, blood and urine samples have been batch-processed. Results from these individuals will be compared to each other, to data from other Twin Study investigations, and to the larger complement of subjects participating in the companion study currently ongoing in ISS astronauts.

Lee, Stuart M. C.↗
NASA NTRS2016

Metabolomic and Genomic Markers of Atherosclerosis as Related to Oxidative Stress, Inflammation, and Vascular Function in Twin Astronauts

Background: Future human space travel will consist primarily of long-duration missions onboard the International Space Station (ISS) or exploration-class missions to Mars, its moons, or nearby asteroids. Astronauts participating in long-duration missions may be at an increased risk of oxidative stress and inflammatory damage due to radiation, psychological stress, altered physical activity, nutritional insufficiency, and hyperoxia during extravehicular activity. By studying one identical twin during his 1-year ISS mission and one ground-based twin, this work extends a current NASA-funded investigation to determine whether these spaceflight factors contribute to an accelerated progression of atherosclerosis. This study of twins affords a unique opportunity to examine the spaceflight-related atherosclerosis risk independent of the confounding factors associated with different genotypes. Purpose: The purpose of this investigation is to determine whether biomarkers of oxidative and inflammatory stress are elevated during and after long-duration spaceflight and determine if a relation exists between levels of these biomarkers and structural and functional indices of atherosclerotic risk measured in the carotid and brachial arteries. These physiological and biochemical data will be extended by using an exploratory approach to investigate the relationship between intermediate phenotypes and risk factors for atherosclerosis and the metabolomic signature from plasma and urine samples. Since metabolites are often the indirect products of gene expression, we will simultaneously assess gene expression and DNA methylation in leukocytes. Hypothesis: We predict that the space-flown twin will experience elevated biomarkers of oxidative stress and inflammatory damage, altered arterial structure and function, accelerated telomere shortening, dysregulation of genes associated with oxidative stress and inflammation, and a metabolic profile shift that is associated with elevated atherosclerosis risk factors. Conversely, these will not be observed in the ground-based twin. Methods: We will measure blood and urine biomarkers of oxidative stress and inflammation as well as arterial structure and function (carotid intima-medial thickness and brachial artery flow-mediated dilation) in one twin astronaut before, during, and after long-duration spaceflight and in his twin serving as a ground-based control. Furthermore, we will measure metabolomics (targeted and untargeted approaches) and genomic markers (DNA methylation, mRNA gene expression, telomere length) to elucidate the molecular mechanisms involved. A panel of biomarkers of oxidative and inflammatory stress will be measured in venous blood samples and 24-hour (in-flight) and 48-hour (pre- and post-flight) urine pools twice before flight, early (flight days 15 and 60) and late (2 weeks before landing) during the mission, and early in the post-flight recovery phase (approximately 3-5 days after landing). Arterial structure, assessed from measures of intima-media thickness, will be measured at the same times. Arterial function will be assessed using brachial flow-mediated dilation, a well-validated measure used to assess endothelium-dependent vasodilation and a sensitive predictor of atherosclerotic risk, only before and after spaceflight. Discussion: Pre- and in-flight data collection is in progress for the space-flown twin, and similar data have been obtained from the ground-based twin. Blood and urine samples will be batch processed when received from ISS after the conclusion of the 1-year mission. Results from these individual subjects will be compared to the larger complement of subjects participating in the companion study currently ongoing in ISS astronauts.

Lee, Stuart M. C.↗
NASA NTRS2010

Bird Migration Under Climate Change - A Mechanistic Approach Using Remote Sensing

The broad-scale reductions and shifts that may be expected under climate change in the availability and quality of stopover habitat for long-distance migrants is an area of increasing concern for conservation biologists. Researchers generally have taken two broad approaches to the modeling of migration behaviour to understand the impact of these changes on migratory bird populations. These include models based on causal processes and their response to environmental stimulation, "mechanistic models", or models that primarily are based on observed animal distribution patterns and the correlation of these patterns with environmental variables, i.e. "data driven" models. Investigators have applied the latter technique to forecast changes in migration patterns with changes in the environment, for example, as might be expected under climate change, by forecasting how the underlying environmental data layers upon which the relationships are built will change over time. The learned geostatstical correlations are then applied to the modified data layers.. However, this is problematic. Even if the projections of how the underlying data layers will change are correct, it is not evident that the statistical relationships will remain the same, i.e. that the animal organism may not adapt its' behaviour to the changing conditions. Mechanistic models that explicitly take into account the physical, biological, and behaviour responses of an organism as well as the underlying changes in the landscape offer an alternative to address these shortcomings. The availability of satellite remote sensing observations at multiple spatial and temporal scales, coupled with advances in climate modeling and information technologies enable the application of the mechanistic models to predict how continental bird migration patterns may change in response to environmental change. In earlier work, we simulated the impact of effects of wetland loss and inter-annual variability on the fitness of migratory shorebirds in the central fly ways of North America. We demonstrated the phenotypic plasticity of a migratory population of Pectoral sandpipers consisting of an ensemble of 10,000 individual birds in response to changes in stopover locations using an individual based migration model driven by remotely sensed land surface data, climate data and biological field data. With the advent of new computing capabilities enabled hy recent GPU-GP computing paradigms and commodity hardware, it now is possible to simulate both larger ensemble populations and to incorporate more realistic mechanistic factors into migration models. Here, we take our first steps use these tools to study the impact of long-term drought variability on shorebird survival.

Smith, James A.↗
NASA NTRS2001

Rapid evolution of cis-regulatory sequences via local point mutations

Although the evolution of protein-coding sequences within genomes is well understood, the same cannot be said of the cis-regulatory regions that control transcription. Yet, changes in gene expression are likely to constitute an important component of phenotypic evolution. We simulated the evolution of new transcription factor binding sites via local point mutations. The results indicate that new binding sites appear and become fixed within populations on microevolutionary timescales under an assumption of neutral evolution. Even combinations of two new binding sites evolve very quickly. We predict that local point mutations continually generate considerable genetic variation that is capable of altering gene expression.

Non-NASA Center↗
NASA NTRS1989

The effects of simulated hypogravity on murine bone marrow cells

Mouse bone marrow cells grown in complete medium at unit gravity were compared with a similar population cultured in conditions that mimic some aspects of microgravity. After the cells adjusted to the conditions that simulated microgravity, they proliferated as fetal or oncogenic populations; their numbers doubled in twelve hour periods. Differentiated subpopulations were depleted from the heterogeneous mixture with time and the undifferentiated hematopoietic stem cells increased in numbers. The cells in the control groups in unit gravity and those in the bioreactors in conditions of microgravity were monitored under a number of parameters. Each were phenotyped as to cell surface antigens using a panel of monoclonal antibodies and flow cytometry. Other parameters compared included: pH, glucose uptake, oxygen consumption and carbon-dioxide production. Nuclear DNA was monitored by flow cytometry. Functional responses were studied by mitogenic stimulation by various lectins. The importance of these findings should have relevance to the space program. Cells should behave predictably in zero gravity; specific populations can be eliminated from diverse populations and other populations isolated. The availability of stem cell populations will enhance both bone marrow and gene transplant programs. Stem cells will permit developmental biologists study the paths of hematopoiesis.

Lawless, Desales↗
NASA NTRS2002

Bystander effects in radiation-induced genomic instability

Exposure of GM10115 hamster-human hybrid cells to X-rays can result in the induction of chromosomal instability in the progeny of surviving cells. This instability manifests as the dynamic production of novel sub-populations of cells with unique cytogenetic rearrangements involving the "marker" human chromosome. We have used the comet assay to investigate whether there was an elevated level of endogenous DNA breaks in chromosomally unstable clones that could provide a source for the chromosomal rearrangements and thus account for the persistent instability observed. Our results indicate no significant difference in comet tail measurement between non-irradiated and radiation-induced chromosomally unstable clones. Using two-color fluorescence in situ hybridization we also investigated whether recombinational events involving the interstitial telomere repeat-like sequences in GM10115 cells were involved at frequencies higher than random processes would otherwise predict. Nine of 11 clones demonstrated a significantly higher than expected involvement of these interstitial telomere repeat-like sequences at the recombination junction between the human and hamster chromosomes. Since elevated levels of endogenous breaks were not detected in unstable clones we propose that epigenetic or bystander effects (BSEs) lead to the activation of recombinational pathways that perpetuate the unstable phenotype. Specifically, we expand upon the hypothesis that radiation induces conditions and/or factors that stimulate the production of reactive oxygen species (ROS). These reactive intermediates then contribute to a chronic pro-oxidant environment that cycles over multiple generations, promoting chromosomal recombination and other phenotypes associated with genomic instability.

NASA Discipline Radiation Health↗
NASA NTRS1997

Theories of Simplification and Scaling of Spatially Distributed Processes

The problem of scaling is at the heart of ecological theory, the essence of understanding and of the development of a predictive capability. The description of any system depends on the spatial, temporal, and organizational perspective chosen; hence it is essential to understand not only how patterns and dynamics vary with scale, but also how patterns at one scale are manifestations of processes operating at other scales. Evolution has shaped the characteristics of species in ways that result in scale displacement: Each species experiences the environment at its own unique set of spatial and temporal scales and interfaces the biota through unique assemblages of phenotypes. In this way, coexistence becomes possible, and biodiversity is enhanced. By averaging over space, time, and biological interactions, a genotype filters variation at fine scales and selects the arena in which it will face the vicissitudes of nature. Variation at finer scales is then noise, of minor importance to the survival and dynamics of the species, and consequently of minor importance in any attempt at description. In attempting to model ecological interactions in space, contributors throughout this book have struggled with a trade-off between simplification and "realistic" complexity and detail. Although the challenge of simplification is widely recognized in ecology, less appreciated is the intertwining of scaling questions and scaling laws with the process of simplification. In the context of this chapter simplification will in general mean the use of spatial or ensemble means and low-order moments to capture more detailed interactions by integrating over given areas. In this way, one can derive descriptions of the system at different spatial scales, which provides the essentials for the extraction of scaling laws by examination of how system properties vary with scale.

Levin, Simon A.↗
NASA NTRSDate not supplied

The maize rough endosperm6 (rgh6) mutant encodes a predicted DEAD-box RNA helicase

Maize rough endosperm (rgh) mutants have defective seeds with a rough, etched, or pitted endosperm surface. Molecular genetic analysis of this mutant class has identified multiple RNA processing proteins critical to endosperm development. We isolated the rgh6 locus from the UniformMu transposon tagging population. Mutant kernels have reduced grain-fill with defective embryos that fail to germinate. Self-pollination of rgh6 heterozygotes produces mutant seeds at frequency consistent with a single recessive mutation. Molecular mapping localized rgh6 to a 60 kbp interval on chromosome 5. PCR analysis of gene models within the fine-map interval identified a Mutator (Mu) transposon insertion within a predicted DEAD-box RNA helicase gene. A second allele of rgh6 was identified from UniformMu population. Reciprocal crosses between rgh6-umu1 and rgh6-umu2 heterozygotes produces mutant seeds at a frequency consistent with a 3:1 ratio indicating these mutants are allelic. Both rgh6-umu1 and rgh6-umu2 have Mu element insertions at the same insertion site within the DEAD-box RNA helicase gene. However, the terminal inverted repeat sequences are polymorphic between the alleles showing the alleles are independent mutations. We conclude that mutation of the DEAD-box RNA helicase causes the rgh6 phenotype. Further characterization of the rgh6 mutant phenotype and biochemical investigation of the RGH6 protein is expected to give further insights on the roles of RNA processing in endosperm development.

maize↗
NASA NTRS2012

Extreme Ionizing-Radiation-Resistant Bacterium

There is a growing concern that desiccation and extreme radiation-resistant, non-spore-forming microorganisms associated with spacecraft surfaces can withstand space environmental conditions and subsequent proliferation on another solar body. Such forward contamination would jeopardize future life detection or sample return technologies. The prime focus of NASA s planetary protection efforts is the development of strategies for inactivating resistance-bearing microorganisms. Eradification techniques can be designed to target resistance-conferring microbial populations by first identifying and understanding their physiologic and biochemical capabilities that confers its elevated tolerance (as is being studied in Deinococcus phoenicis, as a result of this description). Furthermore, hospitals, food, and government agencies frequently use biological indicators to ensure the efficacy of a wide range of radiation- based sterilization processes. Due to their resistance to a variety of perturbations, the non-spore forming D. phoenicis may be a more appropriate biological indicator than those currently in use. The high flux of cosmic rays during space travel and onto the unshielded surface of Mars poses a significant hazard to the survival of microbial life. Thus, radiation-resistant microorganisms are of particular concern that can survive extreme radiation, desiccation, and low temperatures experienced during space travel. Spore-forming bacteria, a common inhabitant of spacecraft assembly facilities, are known to tolerate these extreme conditions. Since the Viking era, spores have been utilized to assess the degree and level of microbiological contamination on spacecraft and their associated spacecraft assembly facilities. Members of the non-spore-forming bacterial community such as Deinococcus radiodurans can survive acute exposures to ionizing radiation (5 kGy), ultraviolet light (1 kJ/sq m), and desiccation (years). These resistive phenotypes of Deinococcus enhance the potential for transfer, and subsequent proliferation, on another solar body such as Mars and Europa. These organisms are more likely to escape planetary protection assays, which only take into account presence of spores. Hence, presences of extreme radiation-resistant Deinococcus in the cleanroom facility where spacecraft are assembled pose a serious risk for integrity of life-detection missions. The microorganism described herein was isolated from the surfaces of the cleanroom facility in which the Phoenix Lander was assembled. The isolated bacterial strain was subjected to a comprehensive polyphasic analysis to characterize its taxonomic position. This bacterium exhibits very low 16SrRNA similarity with any other environmental isolate reported to date. Both phenotypic and phylogenetic analyses clearly indicate that this isolate belongs to the genus Deinococcus and represents a novel species. The name Deinococcus phoenicis was proposed after the Phoenix spacecraft, which was undergoing assembly, testing, and launch operations in the spacecraft assembly facility at the time of isolation. D. phoenicis cells exhibited higher resistance to ionizing radiation (cobalt-60; 14 kGy) than the cells of the D. radiodurans (5 kGy). Thus, it is in the best interest of NASA to thoroughly characterize this organism, which will further assess in determining the potential for forward contamination. Upon the completion of genetic and physiological characteristics of D. phoenicis, it will be added to a planetary protection database to be able to further model and predict the probability of forward contamination.

Vaishampayan, Parag A.↗
NASA NTRS2013

Extreme Ionizing-Radiation-Resistant Bacterium

There is a growing concern that desiccation and extreme radiation-resistant, non-spore-forming microorganisms associated with spacecraft surfaces can withstand space environmental conditions and subsequent proliferation on another solar body. Such forward contamination would jeopardize future life detection or sample return technologies. The prime focus of NASA s planetary protection efforts is the development of strategies for inactivating resistance-bearing micro-organisms. Eradi cation techniques can be designed to target resistance-conferring microbial populations by first identifying and understanding their physiologic and biochemical capabilities that confers its elevated tolerance (as is being studied in Deinococcus phoenicis, as a result of this description). Furthermore, hospitals, food, and government agencies frequently use biological indicators to ensure the efficacy of a wide range of radiation-based sterilization processes. Due to their resistance to a variety of perturbations, the nonspore forming D. phoenicis may be a more appropriate biological indicator than those currently in use. The high flux of cosmic rays during space travel and onto the unshielded surface of Mars poses a significant hazard to the survival of microbial life. Thus, radiation-resistant microorganisms are of particular concern that can survive extreme radiation, desiccation, and low temperatures experienced during space travel. Spore-forming bacteria, a common inhabitant of spacecraft assembly facilities, are known to tolerate these extreme conditions. Since the Viking era, spores have been utilized to assess the degree and level of microbiological contamination on spacecraft and their associated spacecraft assembly facilities. Members of the non-sporeforming bacterial community such as Deinococcus radiodurans can survive acute exposures to ionizing radiation (5 kGy), ultraviolet light (1 kJ/m2), and desiccation (years). These resistive phenotypes of Deinococcus enhance the potential for transfer, and subsequent proliferation, on another solar body such as Mars and Europa. These organisms are more likely to escape planetary protection assays, which only take into account presence of spores. Hence, presences of extreme radiation-resistant Deinococcus in the cleanroom facility where spacecraft are assembled pose a serious risk for integrity of life-detection missions. The microorganism described herein was isolated from the surfaces of the cleanroom facility in which the Phoenix Lander was assembled. The isolated bacterial strain was subjected to a comprehensive polyphasic analysis to characterize its taxonomic position. This bacterium exhibits very low 16SrRNA similarity with any other environmental isolate reported to date. Both phenotypic and phylogenetic analyses clearly indicate that this isolate belongs to the genus Deinococcus and represents a novel species. The name Deinococcus phoenicis was proposed after the Phoenix spacecraft, which was undergoing assembly, testing, and launch operations in the spacecraft assembly facility at the time of isolation. D. phoenicis cells exhibited higher resistance to ionizing radiation (cobalt-60; 14 kGy) than the cells of the D. radiodurans (5 kGy). Thus, it is in the best interest of NASA to thoroughly characterize this organism, which will further assess in determining the potential for forward contamination. Upon the completion of genetic and physiological characteristics of D. phoenicis, it will be added to a planetary protection database to be able to further model and predict the probability of forward contamination.

Vaishampayan, Parag A.↗
NASA NTRS2016

Microgravity-Driven Optic Nerve/Sheath Biomechanics Simulations

Visual Impairment and Intracranial Pressure (VIIP) syndrome is a concern for long-duration space flight. Current thinking suggests that the ocular changes observed in VIIP syndrome are related to cephalad fluid shifts resulting in altered fluid pressures [1]. In particular, we hypothesize that increased intracranial pressure (ICP) drives connective tissue remodeling of the posterior eye and optic nerve sheath (ONS). We describe here finite element (FE) modeling designed to understand how altered pressures, particularly altered ICP, affect the tissues of the posterior eye and optic nerve sheath (ONS) in VIIP. METHODS: Additional description of the modeling methodology is provided in the companion IWS abstract by Feola et al. In brief, a geometric model of the posterior eye and optic nerve, including the ONS, was created and the effects of fluid pressures on tissue deformations were simulated. We considered three ICP scenarios: an elevated ICP assumed to occur in chronic microgravity, and ICP in the upright and supine positions on earth. Within each scenario we used Latin hypercube sampling (LHS) to consider a range of ICPs, ONH tissue mechanical properties, intraocular pressures (IOPs) and mean arterial pressures (MAPs). The outcome measures were biomechanical strains in the lamina cribrosa, optic nerve and retina; here we focus on peak values of these strains, since elevated strain alters cell phenotype and induce tissue remodeling. In 3D, the strain field can be decomposed into three orthogonal components, denoted as first, second and third principal strains. RESULTS AND CONCLUSIONS: For baseline material properties, increasing ICP from 0 to 20 mmHg significantly changed strains within the posterior eye and ONS (Fig. 1), indicating that elevated ICP affects ocular tissue biomechanics. Notably, strains in the lamina cribrosa and retina became less extreme as ICP increased; however, within the optic nerve, the occurrence of such extreme strains greatly increased as ICP was elevated (Fig. 2). In particular, c. 48 of simulations in the elevated ICP condition showed peak strains in the optic nerve that exceeded the strains expected on earth. Such extreme strains are likely important, since they represent a larger signal for mechano-responsive resident cells [2]. The models predicted little to no anterior motion of the prelaminar neural tissue (optic nerve swelling, or papilledema, secondary to axoplasmic stasis), typically seen with elevated ICP. Specialized FE models to capture axoplasmic stasis would be required to study papilledema. These results suggest that the most notable effect of elevated ICP may occur via direct optic nerve loading, rather than through connective tissue deformation. These FE models can inform the design of future studies designed to bridge the gap between biomechanics and pathophysiological function in VIIP.

biomechanics↗
NASA NTRSDate not supplied

An Open-Science Approach to Address Individual Response to Simulated GCR In Genetically Diverse Populations of Mice and Humans

This project addresses the challenge of understanding and predicting individual radiation sensitivity by integrating genetics, demographics and biomarker characteristics across species (mice and humans). We hypothesize that ex vivo DNA repair response to GCR components is a central determinant of cancer risk from space radiation and can serve as a biomarker of radiation risk in combination with genetics. Automated image quantification of 53BP1+ radiation-induced foci (RIF) during the first 4-48 h post-irradiation was performed as a function of dose and LET in non-immortalized primary skin fibroblasts derived from 76 mice across 15 strains (5 inbred reference strains and 10 collaborative-cross strains) exposed to X rays (0.1, 1 and 4 Gy), 350 MeV/n 40Ar and 600 MeV/n 56Fe (1.1 and 3 particles/100sq. μm), as well as in peripheral blood mononuclear cells (PBMCs) from 768 healthy donors (matched ethnicity, 50/50 male/female, 18-70 years old) exposed to gamma rays (0.1 and 1 Gy), 350 MeV/n 28Si, 350 MeV/n 40Ar and 600 MeV/n 56Fe (1.1 and 3 particles/100sq. μm). A genome-wide association study (GWAS) was performed on the mouse strains between DNA damage responses to space radiation and single nucleotide polymorphisms (SNPs). We found SNPs, which were significantly associated to the RIF phenotype, mapped to genes and pathways that are functionally linked to health hazards for deep space exploration (e.g. carcinogenesis, nervous system damage and immune dysfunction). Some of these SNPs were located within protein coding regions, potentially interfering with protein functions and providing promising genetic targets for countermeasures. We also found correlations between both spontaneous and radiation-induced DNA damage and SNPs mapped to pathways associated with cellular metabolism. GWAS is undergoing for the human data. All data have been made available via the NASA Space Biology Open-Science database (genelab.nasa.gov) and we will discuss how various genomic and transcriptomic datasets can be accessed for modeling and integrated using machine learning methods for discovering new radiation biology.

Sylvain V Costes↗
NASA NTRSDate not supplied

Retrospectives: Intersection of Spaceflight Stressors and Microbial Risk to Crew and Craft

OVERVIEW The spaceflight environment has several unique stressors that affect the health of both the crew and the spacecraft. An area of continued, albeit incomplete, study is the interaction of these stressors on microbial populations inherent to both astronauts and spacecraft surfaces and systems. A primary concern is the potential for the spaceflight environment to perturb the phenotype of these populations towards negative outcomes for crew and craft. In order to effectively mitigate these potential risks, they must first be characterized. We performed a retrospective literature analysis to assess the current state of knowledge regarding the affects of ionizing radiation and elevated CO2 on relevant microbial populations. The results of these retrospectives will guide next steps in the decisions of what (if any) further studies should be pursued and to guide decisions of the need for countermeasures. STRESSORS Ionizing radiation. The health risk involved with increased exposure to cosmic radiation has been studied in crew for 35+ years, with human health and cancer risk being the main focus. However, space radiation could also affect both the resident microorganisms aboard the ISS and the normal, healthy astronaut microbiomes that are of direct concern for crew health. A retrospective review of over 250 publications was accomplished looking at the impact of cumulative ionizing radiation doses lower than 3 Gy (chronic or acute) on microbial populations. Elevated CO2. The health risk involved with elevated atmospheric CO2 in spacecraft, primarily focusing on human toxicological risks, is understudied. The current Spaceflight Maximum Allowance Concentration for 24-hour average CO2 is 0.4% (3 mm Hg), which is significantly higher than terrestrial levels (0.04%). Whether these elevated ambient CO2 levels aboard spacecraft influence the diversity and phenotypic responses of the resident microbial communities from both the spacecraft environment (air, surface, water) and crew members (gut, nasal,skin microbiomes) is not known. A retrospective review was accomplished looking at the impact of chronic CO2 exposure up to 0.7% (5 mm Hg) for up to 6 months and acute exposure up to 2.6% (20 mm Hg) for up to 24 hours. CONCLUSIONS: MICROBIOME OF THE BUILT ENVIRONMENT The microbiome of the built spacecraft environment has been sampled consistently over the course of human spaceflight and significant advancements have been made in identifying microbial populations on the ISS. The dominant source of microbes on spacecraft surfaces are human-derived. Once in the spacecraft built environment,the extreme environment selects for features that enhance survival. While efforts to understand potential antibiotic resistance and pathogenicity of ISS isolates is robust, there is little to no understanding of which spaceflight environmental stressors, to include ionizing radiation or elevated CO2, drive the evolutionary trajectory of spacecraft-associated microbial populations. CONCLUSIONS: MICROBE-HOST INTERACTIONS The host-microbiome field has emerged as an important factor in human health on Earth as well in spaceflight. The field is struggling with the complexity of the system under investigation as there is substantial taxonomic and functional heterogeneity in these communities, making it difficult to establish clear stimulus-response dynamics.Taxonomic characterization is the norm; however, the functional role of each community member is key to linking environmental perturbations to potential dysbiosis. For both ionizing radiation and elevated CO2, the likely target of the perturbation is the host tissue, not the microbes themselves.. Any resulting changes to the microbial community composition and/or function is likely a result of adapting to those changes in the host physiology. RECOMMENDATIONS Emphasize functional characterization as opposed to taxonomic characterization of microbial communities.Increase the number of investigations using chronic, spaceflight-relevant doses of ionizing radiation. MoBE studies should move away from observational studies towards predictive modeling of community dynamics. Continue to develop scale-down models, such as tissues-on-a-chip & defined microbial communities. Focus on the crew response to elevated CO2 over MoBE considerations. Assess how direct contact with the hypercapnic environment affects skin microbiome dynamics.

Countermeasures↗