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NASA NTRS2016

Risk of Adverse Cognitive or Behavioral Conditions and Psychiatric Disorders: Evidence Report

In April 2010, President Obama declared a space pioneering goal for the United States in general and NASA in particular. "Fifty years after the creation of NASA, our goal is no longer just a destination to reach. Our goal is the capacity for people to work and learn and operate and live safely beyond the Earth for extended periods of time, ultimately in ways that are more sustainable and even indefinite." Thus NASA's Strategic Objective 1.1 emerged as "expand human presence into the solar system and to the surface of Mars to advance exploration, science, innovation, benefits to humanity, and international collaboration" (NASA 2015b). Any space flight, be it of long or short duration, occurs in an extreme environment that has unique stressors. Even with excellent selection methods, the potential for behavioral problems among space flight crews remain a threat to mission success. Assessment of factors that are related to behavioral health can help minimize the chances of distress and, thus, reduce the likelihood of adverse cognitive or behavioral conditions and psychiatric disorders arising within a crew. Similarly, countermeasures that focus on prevention and treatment can mitigate the cognitive or behavioral conditions that, should they arise, would impact mission success. Given the general consensus that longer duration, isolation, and confined missions have a greater risk for behavioral health ensuring crew behavioral health over the long term is essential. Risk, which within the context of this report is assessed with respect to behavioral health and performance, is addressed to deter development of cognitive and behavioral degradations or psychiatric conditions in space flight and analog populations, and to monitor, detect, and treat early risk factors, predictors and other contributing factors. Based on space flight and analog evidence, the average incidence rate of an adverse behavioral health event occurring during a space mission is relatively low for the current conditions. While mood and anxiety disturbances have occurred, no behavioral emergencies have been reported to date in space flight. Anecdotal and empirical evidence indicate that the likelihood of an adverse cognitive or behavioral condition or psychiatric disorder occurring greatly increases with the length of a mission. Further, while cognitive, behavioral, or psychiatric conditions might not immediately and directly threaten mission success, such conditions can, and do, adversely impact individual and crew health, welfare, and performance.

Slack, Kelley J.↗

NASA NTRS2015

Individualized Behavioral Health Monitoring Tool

Behavioral health risks during long-duration space exploration missions are among the most difficult to predict, detect, and mitigate. Given the anticipated extended duration of future missions and their isolated, extreme, and confined environments, there is the possibility that behavior conditions and mental disorders will develop among astronaut crew. Pulsar Informatics, Inc., has developed a health monitoring tool that provides a means to detect and address behavioral disorders and mental conditions at an early stage. The tool integrates all available behavioral measures collected during a mission to identify possible health indicator warning signs within the context of quantitatively tracked mission stressors. It is unobtrusive and requires minimal crew time and effort to train and utilize. The monitoring tool can be deployed in space analog environments for validation testing and ultimate deployment in long-duration space exploration missions.

Mollicone, Daniel↗

NASA NTRS2016

A Year in Space: Early Results and Lessons Learned from the First Year-Long Expedition Aboard the International Space Station

Two ISS crewmembers recently completed the first year-long orbital stay in two decades. International cooperation was central to the success of Mikhail Kornienko from Russia and Scott Kelly from the United States. Their expedition leveraged current mission experience and capitalized on recent advances in health monitoring technology. This unique effort began in 2012 when the program managers of the ISS partner nations adopted two separate goals: greater multilateral cooperation to increase efficiency of inflight research and a year-long expedition to gain familiarity with in-flight durations approaching that required for a Mars mission. These goals were unified when a set of bilateral Russian and American human research investigations was assigned to the year-long mission, augmented by additional investigations from Europe and Japan. For example, Kelly was assigned 18 investigations (twice the complement on standard six-month missions) including two joint U.S.-Russian studies, and two Russian and two Japanese studies. The core set of American investigations was a repetition of six studies Kelly had done on his previous six-month ISS mission, to allow a direct comparison of physiological and behavioral responses of the longer and shorter durations in this single individual. The remainder of his assignments plus those of Kornienko were drawn from currently active national investigations documenting human adaptation to long-duration spaceflight factors or effectiveness of countermeasures against known deleterious adaptations. The two joint U.S.-Russian investigations were the flagship biomedical studies of the year-long expedition. The "Fluid Shifts" study collocated American research equipment alongside a Russian operational stressor device to document the pattern and impacts of the headward fluid shift long known to occur in weightlessness, including its role in ocular changes recently observed in some astronauts. The "Field Test" study investigated the ability of the astronaut and cosmonaut to perform rudimentary tasks requiring sensorimotor coordination immediately after landing to define human capabilities soon after landing on Mars after an extended transit. Both investigations were highly successful in large part to the thorough integration of the implementation processes of the two partners. Kelly's assignment as the one-year crewmember also provided a serendipitous opportunity for the "Twins Study" comparing changes in his body at the genetic level with those occurring on Earth in his identical twin brother Mark Kelly. Data analysis from this expedition will commence in earnest after frozen in-flight samples are delivered to Earth in May aboard a commercial cargo spacecraft. Detailed results are expected in early 2017. Preliminary results and implementation improvements will be reviewed in this presentation.

Charles, J. B.↗

NASA NTRS2016

NASA HRP Plans for Collaboration at the IBMP Ground-Based Experimental Facility (NEK)

NASA and IBMP are planning research collaborations using the IBMP Ground-based Experimental Facility (NEK). The NEK offers unique capabilities to study the effects of isolation on behavioral health and performance as it relates to spaceflight. The NEK is comprised of multiple interconnected modules that range in size from 50-250m(sup3). Modules can be included or excluded in a given mission allowing for flexibility of platform design. The NEK complex includes a Mission Control Center for communications and monitoring of crew members. In an effort to begin these collaborations, a 2-week mission is planned for 2017. In this mission, scientific studies will be conducted to assess facility capabilities in preparation for longer duration missions. A second follow-on 2-week mission may be planned for early in 2018. In future years, long duration missions of 4, 8 and 12 months are being considered. Missions will include scenarios that simulate for example, transit to and from asteroids, the moon, or other interplanetary travel. Mission operations will be structured to include stressors such as, high workloads, communication delays, and sleep deprivation. Studies completed at the NEK will support International Space Station expeditions, and future exploration missions. Topics studied will include communication, crew autonomy, cultural diversity, human factors, and medical capabilities.

Cromwell, Ronita L.↗

NASA NTRS2016

Architectural and Behavioral Systems Design Methodology and Analysis for Optimal Habitation in a Volume-Limited Spacecraft for Long Duration Flights

As our human spaceflight missions change as we reach towards Mars, the risk of an adverse behavioral outcome increases, and requirements for crew health, safety, and performance, and the internal architecture, will need to change to accommodate unprecedented mission demands. Evidence shows that architectural arrangement and habitability elements impact behavior. Net habitable volume is the volume available to the crew after accounting for elements that decrease the functional volume of the spacecraft. Determination of minimum acceptable net habitable volume and associated architectural design elements, as mission duration and environment varies, is key to enabling, maintaining, andor enhancing human performance and psychological and behavioral health. Current NASA efforts to derive minimum acceptable net habitable volumes and study the interaction of covariates and stressors, such as sensory stimulation, communication, autonomy, and privacy, and application to internal architecture design layouts, attributes, and use of advanced accommodations will be presented. Furthermore, implications of crew adaptation to available volume as they transfer from Earth accommodations, to deep space travel, to planetary surface habitats, and return, will be discussed.

Human Space Flight↗

NASA NTRS2017

Cancer Risk in Astronauts: A Constellation of Uncommon Consequences

Excess cancers resulting from external radiation exposures have been noted since the early 1950s, when a rise in leukemia rates was first reported in young atomic bomb survivors [1]. Further studies in atomic bomb survivors, cancer patients treated with radiotherapy, and nuclear power plant workers have confirmed that radiation exposure increases the risk of not only leukemia, but also a wide array of solid cancers [2,3]. NASA has long been aware of this risk and limits astronauts' risk of exposure-induced death (REID) from cancer by specifying permissible mission durations (PMD) for astronauts on an individual basis. While cancer is present among astronauts, current data does not suggest any excess of known radiation-induced cancers relative to a comparable population of U.S. adults; however, very uncommon cancers have been diagnosed in astronauts including nasopharyngeal cancer, lymphoma of the brain, and acral myxoinflammatory fibroblastic sarcoma. In order to study cancer risk in astronauts, a number of obstacles must be overcome. Firstly, several factors make the astronaut cohort considerably different from the cohorts that have previously been studied for effects resulting from radiation exposure. The high rate of accidents and the much healthier lifestyle of astronauts compared to the U.S. population make finding a suitable comparison population a problematic task. Space radiation differs substantially from terrestrial radiation exposures studied in the past; therefore, analyses of galactic cosmic radiation (GCR) in animal models must be conducted and correctly applied to the human experience. Secondly, a large enough population of exposed astronauts must exist in order to obtain the data necessary to see any potential statistically significant differences between the astronauts and the control population. Thirdly, confounders and effect modifiers, such as smoking, diet, and other space stressors, must be correctly identified and controlled for in those analyses. In order to begin work assessing the astronaut population, the earliest groups of astronauts (selection groups 1-7) provide a unique model. These astronauts were relatively homogenous, white males whose lifestyle characteristics were similar to an average U.S. citizen of the same birth cohort. This work reviews radiation exposure levels, age, and causes of mortality among these early NASA astronauts and discusses the benefits and limitations of assessing such a cohort for radiation-induced cancer risk.

Milder, Caitlin M.↗

NASA NTRS2017

Mind the Gap: Exploring the Underground of the NASA Space Cancer Risk Model

The REID quantifies the lifetime risk of death from radiation-induced cancer in an exposed astronaut. The NASA Space Cancer Risk (NSCR) 2012 mode incorporates elements from physics, biology, epidemiology, and statistics to generate the REID distribution. The current model quantifies the space radiation environment, radiation quality, and dose-rate effects to estimate a NASA-weighted dose. This weighted dose is mapped to the excess risk of radiation-induced cancer mortality from acute exposures to gamma rays and then transferred to an astronaut population. Finally, the REID is determined by integrating this risk over the individual's lifetime. The calculated upper 95% confidence limit of the REID is used to restrict an astronaut's permissible mission duration (PMD) for a proposed mission. As a statistical quantity characterized by broad, subjective uncertainties, REID estimates for space missions result in wide distributions. Currently, the upper 95% confidence level is over 350% larger than the mean REID value, which can severely limit an astronaut's PMD. The model incorporates inputs from multiple scientific disciplines in the risk estimation process. Physics and particle transport models calculate how radiation moves through space, penetrates spacecraft, and makes its way to the human beings onboard. Epidemiological studies of exposures from atomic bombings, medical treatments, and power plants are used to quantify health risks from acute and chronic low linear energy transfer (LET) ionizing radiation. Biological studies in cellular and animal models using radiation at various LETs and energies inform quality metrics for ions present in space radiation. Statistical methodologies unite these elements, controlling for mathematical and scientific uncertainty and variability. Despite current progress, these research platforms contain knowledge gaps contributing to the large uncertainties still present in the model. The NASA Space Radiation Program Element (SRPE) defines the knowledge gaps that impact our understanding of the cancer risks. These gaps are outlined in NASA's Human Research Roadmap [4], which identifies the research questions and actions recommended for reducing the uncertainty in the current NSCR model and for formulation of future models. The greatest contributors to uncertainty in the current model include radiation quality, dose rate effects, and the transfer of exposure-based risk from other populations to an astronaut population. Future formulations of the risk model may benefit from including other potential sources of uncertainty such as space dosimetry, errors in human epidemiology data, and the impact of microgravity and other spaceflight stressors. Here, we discuss the current capabilities of the NSCR-2012 model and several immediate research needs, highlighting areas expected to have an operational impact on the current model schema. The following subway-style route map outlines the NSCR-2012 model (Green Line), emphasizing the research gaps in the Human Research Roadmap for risk of radiation-induced carcinogenesis (Stops on Dashed Lines). The map diagrams how these research gaps feed specific portions of the model.

Chappell, L. J.↗

NASA NTRS2017

The Integrated Impact of Diet On Human Immune Response, the Gut Microbiota, and Nutritional Status During Adaptation to a Spaceflight Analog

Spaceflight impacts human physiology, including well documented immune system dysregulation. Diet, immune function, and the microbiome are interlinked, but diet is the only one of these factors that we have the ability to easily, and significantly, alter on Earth or during flight. As we understand dietary impacts on physiology more thoroughly, we may then improve the spaceflight diet to improve crew health and potentially reduce flight-associated physiological alterations. It is expected that increasing the consumption of fruits and vegetables and bioactive compounds (e.g.,omega-3 fatty acids, lycopene, flavonoids) and therefore enhancing overall nutritional intake from the nominal shelf-stable, fully-processed space food system could serve as a countermeasure to improve human immunological profiles, the taxonomic profile of the gut microbiota, and nutritional status, especially where currently dysregulated during spaceflight. This interdisciplinary study will determine the effect of the current shelf-stable spaceflight diet compared to an "enhanced" shelf-stable spaceflight diet (25% more foods rich in omega-3 fatty acids, lycopene, flavonoids, fruits, and vegetables). The NASA Human Exploration Research Analog (HERA) 2017 missions, consisting of closed chamber confinement, realistic mission simulation, in a high-fidelity mock space vehicle, will serve as a platform to replicate mission stressors and the dysregulated physiology observed in astronauts. Biosampling of crew members will occur at selected intervals, with complete dietary tracking. Outcome measures will include immune markers (e.g., peripheral leukocyte distribution, inflammatory cytokine profiles, T cell function), the taxonomic and metatranscriptomic profile of the gut microbiome, and nutritional status biomarkers and metabolites. Data collection will also include complete dietary tracking. Statistical evaluations will determine physiological and biochemical shifts in relation to nutrient in take and study phase. Beneficial improvements will provide evidence of the impact of diet on crew health and adaptation to this spaceflight analog, and will aid in the design and development of more-efficient targeted dietary interventions.

Douglas, G. L.↗

NASA NTRS2017

The Nitty Gritty: How We Make Analogs Work

NASA's Human Research Program (HRP) is becoming increasingly reliant on Isolated, Confined and Controlled (ICC) analogs to accomplish many of its research objectives. Compared to other research platforms, ICC analogs present a unique set of operational challenges that must be addressed in order to ensure a high fidelity research environment. In particular, the Human Exploration Research Analog (HERA) habitat, which is classified as an ICC environment, has been developed over the past three years to accommodate the operational needs of research investigations from each of the HRP Elements. During the development period, various types of requirements have contributed to the current operational model, which strives to achieve the highest possible level of mission fidelity with limited resources. This presentation will focus on the operational aspects of the HERA habitat, with emphasis on how we develop the analog research environment to meet researchers' needs. Specific discussion topics include mission scenario development, operational tasks, mission timeline integration, stressor implementation, console support, and improvements based on lessons learned. The information is intended to help investigators better understand the details behind HERA operations and the benefits to their research goals.

Self, A. L.↗

NASA NTRS2015

Forest Disturbance Across the Conterminous United States from 1985-2012: The Emerging Dominance of Forest Decline

Evidence of shifting dominance among major forest disturbance agent classes regionally to globally has been emerging in the literature. For example, climate-related stress and secondary stressors on forests (e.g., insect and disease, fire) have dramatically increased since the turn of the century globally, while harvest rates in the western US and elsewhere have declined. For shifts to be quantified, accurate historical forest disturbance estimates are required as a baseline for examining current trends. We report annual disturbance rates (with uncertainties) in the aggregate and by major change causal agent class for the conterminous US and five geographic subregions between 1985 and 2012. Results are based on human interpretations of Landsat time series from a probability sample of 7200 plots (30 m) distributed throughout the study area. Forest disturbance information was recorded with a Landsat time series visualization and data collection tool that incorporates ancillary high-resolution data. National rates of disturbance varied between 1.5% and 4.5% of forest area per year, with trends being strongly affected by shifting dominance among specific disturbance agent influences at the regional scale. Throughout the time series, national harvest disturbance rates varied between one and two percent, and were largely a function of harvest in the more heavily forested regions of the US (Mountain West, Northeast, and Southeast). During the first part of the time series, national disturbance rates largely reflected trends in harvest disturbance. Beginning in the mid-90s, forest decline-related disturbances associated with diminishing forest health (e.g., physiological stress leading to tree canopy cover loss, increases in tree mortality above background levels), especially in the Mountain West and Lowland West regions of the US, increased dramatically. Consequently, national disturbance rates greatly increased by 2000, and remained high for much of the decade. Decline-related disturbance rates reached as high as 8% per year in the western regions during the early-2000s. Although low compared to harvest and decline, fire disturbance rates also increased in the early- to mid-2000s. We segmented annual decline-related disturbance rates to distinguish between newly impacted areas and areas undergoing gradual but consistent decline over multiple years. We also translated Landsat reflectance change into tree canopy cover change information for greater relevance to ecosystem modelers and forest managers, who can derive better understanding of forest-climate interactions and better adapt management strategies to changing climate regimes. Similar studies could be carried out for other countries where there are sufficient Landsat data and historic temporal snapshots of high-resolution imagery.

Cohen, Warren B.↗

NASA NTRS2017

Development OF A Multi-Scale Framework for Mapping Global Evapotranspiration

As the worlds water resources come under increasing tension due to dual stressors of climate change and population growth, accurate knowledge of water consumption through evapotranspiration (ET) over a range in spatial scales will be critical in developing adaptation strategies. Remote sensing methods for monitoring consumptive water use (e.g, ET) are becoming increasingly important, especially in areas of significant water and food insecurity. One method to estimate ET from satellite-based methods, the Atmosphere Land Exchange Inverse (ALEXI) model uses the change in mid-morning land surface temperature to estimate the partitioning of sensible and latent heat fluxes which are then used to estimate daily ET. This presentation will outline several recent enhancements to the ALEXI modeling system, with a focus on global ET and drought monitoring.

Drought↗

NASA NTRS2018

The Integrated Impact of Diet on Human Immune Response, the Gut Microbiota, and Nutritional Status During Adaptation to a Spaceflight Analog

Spaceflight impacts human physiology, including well documented immune system dysregulation. Diet, immune function, and the microbiome are interlinked, but diet is the only one of these factors that we have the ability to easily, and significantly, alter on Earth or during flight. As we understand dietary impacts on physiology more thoroughly, we may then improve the spaceflight diet to improve crew health and potentially reduce spaceflight-associated physiological alterations. It is expected that increasing the consumption of fruits and vegetables and bioactive compounds (e.g., omega-3 fatty acids, lycopene, flavonoids) and therefore enhancing overall nutritional intake from the nominal shelf-stable, fully-processed space food system could serve as a countermeasure to improve human immunological profiles, the taxonomic profile of the gut microbiota, and nutritional status, especially where currently dysregulated during spaceflight. This interdisciplinary study will determine the effect of the current shelf-stable spaceflight diet compared to an "enhanced" shelf-stable spaceflight diet (25% more foods rich in omega-3 fatty acids, lycopene, flavonoids, and more fruits, and vegetables in general). The NASA Human Exploration Research Analog (HERA) 2017 missions, consisting of four 45-day missions with closed chamber confinement and realistic mission simulation in a high-fidelity mock space vehicle, will serve as a platform to replicate mission stressors and the effects on crew biochemistry, immunology, and the gut microbiome. Bio sampling of crewmembers is scheduled for selected intervals pre- and in-mission. Data collection also includes dietary intake recording. Outcome measures will include immune markers (e.g., peripheral leukocyte distribution, inflammatory cytokine profiles, T cell function), the taxonomic and metatranscriptomic profile of the gut microbiome, and nutritional status biomarkers and metabolites. Statistical evaluations will determine physiological and biochemical shifts in relation to nutrient intake and study phase. To date, sample collection has been completed for 2 crewmembers from the first mission, aka Campaign 4 Mission 1. Mission 2 was terminated after 22 days due to effects of Hurricane Harvey, and sample collection was not completed. Sample collection will continue for Campaign 4 Mission 3 and 4 prior to comprehensive sample analysis. Beneficial improvements will provide evidence of the impact of diet on crew health and adaptation to this spaceflight analog, and will aid in the design and development of more-efficient targeted dietary interventions for exploration missions.

Douglas, G. L.↗

NASA NTRS2017

Intrauterine Exposure to Maternal Stress Alters Bdnf IV DNA Methylation and Telomere Length in the Brain of Adult Rat Offspring

DNA methylation (addition of methyl groups to cytosines which normally represses gene transcription) and changes in telomere length (TTAGGG repeats on the ends of chromosomes) are two molecular modifications that result from stress and could contribute to the long-term effects of intrauterine exposure to maternal stress on offspring behavioral outcomes. Here, we measured methylation of Brain-derived neurotrophic factor (Bdnf), a gene important in development and plasticity, and telomere length in the brains of adult rat male and female offspring whose mothers were exposed to unpredictable and variable stressors throughout gestation. Males exposed to prenatal stress had greater methylation (Bdnf IV) in the medial prefrontal cortex (mPFC) compared to non-stressed controls. Further, prenatally-stressed males had shorter telomeres than controls in the mPFC. This study provides the first evidence in a rodent model of an association between prenatal stress exposure and subsequent shorter brain telomere length. Together findings indicate a long-term impact of prenatal stress on DNA methylation and telomere biology with relevance for behavioral and health outcomes, and contribute to a growing literature linking stress to intergenerational epigenetic alterations and changes in telomere length.

prenatal stress↗

NASA NTRS2016

Instrumentation for Examining Microbial Response to Changes In Environmental Pressures

The Automated Adaptive Directed Evolution Chamber (AADEC) is a device that allows operators to generate a micro-scale analog of real world systems that can be used to model the local-scale effects of climate change on microbial ecosystems. The AADEC uses an artificial environment to expose cultures of micro-organisms to environmental pressures, such as UV-C radiation, chemical toxins, and temperature. The AADEC autonomously exposes micro-organisms to selection pressures. This improves upon standard manual laboratory techniques: the process can take place over a longer period of time, involve more stressors, implement real-time adjustments based on the state of the population, and minimize the risk of contamination. We currently use UV-C radiation as the main selection pressure, UV-C is well studied both for its cell and DNA damaging effects as a type of selection pressure and for its related effectiveness as a mutagen; having these functions united makes it a good choice for a proof of concept. The AADEC roadmap includes expansion to different selection pressures, including heavy metal toxicity, temperature, and other forms of radiation.The AADEC uses closed-loop control to feedback the current state of the culture to the AADEC controller that modifies selection pressure intensity during experimentation, in this case culture density and growth rate. Culture density and growth rate are determined by measuring the optical density of the culture using 600 nm light. An array of 600 nm LEDs illuminate the culture and photodiodes are used to measure the shadow on the opposite side of the chamber.Previous experiments showed that we can produce a million fold increase to UV-C radiation over seven iterations. The most recent implements a microfluidic system that can expose cultures to multiple different selection pressures, perform non-survival based selection, and autonomously perform hundreds of exposure cycles. A scalable pump system gives the ability to pump in various different growth media to individual cultures and introduce chemical toxins during experimentation; AADEC can perform freeze and thaw cycles. We improved our baseline characterization by building a custom UV-C exposure hood, a shutter operates on a preset timer allowing the user to set exposure intensity consistently for multiple iterations.

Environment↗

NASA NTRS2017

Informing Rodent Behavior in Space: Gene Expression and Hyper-Emotionality Following Prenatal Stress

As space exploration pushes our boundaries further away from Earth and for longer durations, we will inevitably require the use of multi-generational studies to continue our expansion. Space is a stressful environment not only due to the deleterious effect of spaceflight on physiology, but also due to confinement, limited social interactions, inherently dangerous circumstances, and many other stresses of an unknown environment. Stress can alter the brain chemistry, and these alterations can affect behavior at all stages of development, but it is especially pronounced during the perinatal period and can have longstanding effects, even into adulthood, which manifest through augmented brain function and psychopathology. This study investigated the nexus of brain chemistry and brain function by observing behavior of adult rats whose mothers were exposed to unpredictable variable prenatal stress (UVPS) while they were in the womb. The UVPS consisted of strobe light, tube restraint, and white noise, and was administered at unpredictable times of the day and also varied in length, both of which were measures taken to prevent habituation to the stressor. The offspring rats were then allowed to reach adulthood and at 90 days were subjected to a series of behavioral tests including novel object, startle response, and an unknown intruder to quantify the adult rats stress response and anxiety. Here we report these results of the behavioral analysis and correlate adult behavioral measures with the expression of genes involved in the hypothalamic-pituitary-adrenal axis, which modulates the animals stress response. We hypothesized that hyper-expression of genes involved in the HPA axis would correlate with the observed anxiety-like behaviors associated with early stress.

Moyer, E. L.↗

NASA NTRS2017

Systemic Response to Microgravity: Utilizing GeneLab Datasets to Identify Molecular Targets for Future Hypotheses-Driven Spaceflight Studies

Biological risks associated with microgravity are a major concern for long-term space travel. Although determination of risk has been a focus for NASA research, data examining systemic (i.e., multi- or pan-tissue) responses to space flight are sparse. To perform our analysis, we utilized the NASA GeneLab database which is a publicly available repository containing a wide array of omics results from experiments conducted with: i) with different flight conditions (space shuttle (STS) missions vs. International Space Station (ISS); ii) a variety of tissues; and 3) assays that measure epigenetic, transcriptional, and protein expression changes. Meta-analysis of the transcriptomic data from 7 different murine and rat data sets, examining tissues such as liver, kidney, adrenal gland, thymus, mammary gland, skin, and skeletal muscle (soleus, extensor digitorum longus, tibialis anterior, quadriceps, and gastrocnemius) revealed for the first time, the existence of potential master regulators coordinating systemic responses to microgravity in rodents. We identified p53, TGF(beta)1 and immune related pathways as the highly prevalent pan-tissue signaling pathways that are affected by microgravity. Some variability in the degree of change in their expression across species, strain and time of flight was also observed. Interestingly, while certain skeletal muscle (gastrocnemius and soleus) exhibited an overall down-regulation of these genes, some other muscle types such as the extensor digitorum longus, tibialis anterior and quadriceps, showed an up-regulated expression, indicative of potential compensatory mechanisms to prevent microgravity-induced atrophy. Key genes isolated by unbiased systems analyses displayed a major overlap between tissue types and flight conditions and established TGF(beta)1 to be the most connected gene across all data sets. Finally, a set of microgravity responsive miRNA signature was identified and based on their predicted functional state and subsequent impact on health, a theoretical health risk score was calculated. The genes and miRNAs identified from our analyses can be targeted for future research involving efficient countermeasure design. Our study thus exemplifies the utility of GeneLab data repository to aid in the process of performing novel hypothesis based spaceflight research aimed at elucidating the global impact of environmental stressors at multiple biological scales.

GeneLab↗

NASA NTRS2017

Systemic Microgravity Response: Utilizing GeneLab to Develop Hypotheses for Spaceflight Risks

Biological risks associated with microgravity are a major concern for long-term space travel. Although determination of risk has been a focus for NASA research, data examining systemic (i.e., multi- or pan-tissue) responses to space flight are sparse. To perform our analysis, we utilized the NASA GeneLab database which is a publicly available repository containing a wide array of omics results from experiments conducted with: i) with different flight conditions (space shuttle (STS) missions vs. International Space Station (ISS); ii) a variety of tissues; and 3) assays that measure epigenetic, transcriptional, and protein expression changes. Meta-analysis of the transcriptomic data from 7 different murine and rat data sets, examining tissues such as liver, kidney, adrenal gland, thymus, mammary gland, skin, and skeletal muscle (soleus, extensor digitorum longus, tibialis anterior, quadriceps, and gastrocnemius) revealed for the first time, the existence of potential master regulators coordinating systemic responses to microgravity in rodents. We identified p53, TGF1 and immune related pathways as the highly prevalent pan-tissue signaling pathways that are affected by microgravity. Some variability in the degree of change in their expression across species, strain and time of flight was also observed. Interestingly, while certain skeletal muscle (gastrocnemius and soleus) exhibited an overall down-regulation of these genes, some other muscle types such as the extensor digitorum longus, tibialis anterior and quadriceps, showed an up-regulated expression, indicative of potential compensatory mechanisms to prevent microgravity-induced atrophy. Key genes isolated by unbiased systems analyses displayed a major overlap between tissue types and flight conditions and established TGF1 to be the most connected gene across all data sets. Finally, a set of microgravity responsive miRNA signature was identified and based on their predicted functional state and subsequent impact on health, a theoretical health risk score was calculated. The genes and miRNAs identified from our analyses can be targeted for future research involving efficient countermeasure design. Our study thus exemplifies the utility of GeneLab data repository to aid in the process of performing novel hypothesis based spaceflight research aimed at elucidating the global impact of environmental stressors at multiple biological scales.

GeneLab↗

NASA NTRS2017

Development of Storage Methods for Saccharomyces Strains to be Utilized for In situ Nutrient Production in Long-Duration Space Missions

Long-duration space missions will benefit from closed-loop life support technologies that minimize mass, volume, and power as well as decrease reliance on Earth-based resupply. A system for In situ production of essential vitamins and nutrients can address the documented problem of degradation of stored food and supplements. Research has shown that the edible yeast Saccharomyces cerevisiae can be used as an on-demand system for the production of various compounds that are beneficial to human health. A critical objective in the development of this approach for long-duration space missions is the effective storage of the selected microorganisms. This research investigates the effects of different storage methods on survival rates of the non-sporulating probiotic S. boulardii, and S. cerevisiae spores and vegetative cells. Dehydration has been shown to increase long-term yeast viability, which also allows increased shelf-life and reduction in mass and volume. The process of dehydration causes detrimental effects on vegetative cells, including oxidative damage and membrane disruption. To maximize cell viability, various dehydration methods are tested here, including lyophilization (freeze-drying), air drying, and dehydration by vacuum. As a potential solution to damage caused by lyophilization, the efficacy of various cryoprotectants was tested. Furthermore, in an attempt to maintain higher survival rates, the effect of temperature during long-term storage was investigated. Data show spores of the wild-type strain to be more resilient to dehydration-related stressors than vegetative cells of either strain, and maintain high viability rates even after one year at room temperature. In the event that engineering the organism to produce targeted nutrient compounds interferes with effective sporulation of S. cerevisiae, a more robust method for improving vegetative cell storage is being sought. Therefore, anhydrobiotic engineering of S. cerevisiae and S. boulardii is being conducted

nutrient↗