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NASA NTRSDate not supplied

Working at NASA as a (Molecular) Biologist...

Trained as a biologist, I landed my first job at NASA as a mission scientist on the Rodent Research project. As a mission scientist, I led science activities associated with development, flight, and post-flight analysis of rodent research missions on the ISS in consultation with project engineers, operational specialists, mission PI(s), and mission Implementation Partner(s). I also assessed the feasibility of scientific experiments as a technical and scientific expert in rodent research on the ISS. Eager to learn more about the molecular changes that occur as a result of spaceflight exposure, I transitioned to the NASA GeneLab project where I eventually became the data processing lead. NASA’s GeneLab helps scientists understand how the fundamental building blocks of life – DNA, RNA, proteins, and metabolites – change from exposure to the space environment including microgravity and cosmic radiation exposure. GeneLab does so by providing fully coordinated epigenomics, genomics, transcriptomics, proteomics, and metabolomics data (collectively known as omics data) alongside essential metadata describing each spaceflight and space-relevant experiment. In order to maximize the intelligibility of these data, particularly for users with limited bioinformatics knowledge, GeneLab has started processing and analyzing these datasets to generate differential gene expression data and identify biological and physiological pathways that are dysregulated as a result of spaceflight. The user interface was designed to be accessible to a broad variety of users, including high school and college students who can use it to learn about omics data analysis and space biology. During the CA Space Grant NASA Panel event, I will provide an overview of my work at NASA on both the Rodent Research and GeneLab projects and will conclude by providing resources for opportunities to work with GeneLab and NASA at large.

Amanda M Saravia-Butler↗
NASA NTRS2025

Astronaut Physiological Deconditioning and Exercise Prescription Countermeasures in Spaceflight

The human skeletal muscular and cardiovascular systems are adapted to the upright posture of Earth’s gravitational environment. Astronauts experience an altered gravity environment in spaceflight that leads to a number of physiological changes and decrements to these systems that can decrease overall crew performance. Countermeasures, including prescribed exercise during spaceflight, is vital for astronauts to maintain optimal health and performance. The degree of physiological deconditioning is dependent on a multitude of factors such as sex, age, mission duration, fitness level, and gravity environments experienced. Deconditioning begins immediately upon entering an altered gravity environment and physiological decrements of the skeletal muscular and cardiovascular systems are measurable among astronauts within a few days. Thus, to maintain their physical fitness, ability to perform mission duties, and be able to egress vehicles when needed, it is imperative that astronauts participate in exercise during all phases of flight. This is especially important for long duration flights where deconditioning effects can be more deleterious. The NASA Office of the Chief Health and Medical Officer 3001 Standards Team develops requirements utilized by commercial and international partners to better understand spaceflight-induced physiological changes and countermeasures and expected outcomes with or without exercise.

exercise physiology↗
NASA NTRS2012

NASA's Current Evidence and Hypothesis for the Visual Impairment and Intracranial Pressure Risk

While 40 years of human spaceflight exploration has reported visual decrement to a certain extent in a subgroup of astronauts, recent data suggests that there is indeed a subset of crewmembers that experience refraction changes (hyperoptic shift), cotton wool spot formation, choroidal fold development, papilledema, optic nerve sheath distention and/or posterior globe flattening with varying degrees of severity and permanence. Pre and postflight ocular measures have identified a potential risk of permanent visual changes as a result of microgravity exposure, which has been defined as the Visual Impairment and Intracranial Pressure risk (VIIP). The combination of symptoms are referred to as the VIIP syndrome. It is thought that the ocular structural and optic nerve changes are caused by events precipitated by the cephalad fluid shift crewmembers experience during long-duration spaceflight. Three important systems, ocular, cardiovascular, and central nervous, seem to be involved in the development of symptoms, but the etiology is still under speculation. It is believed that some crewmembers are more susceptible to these changes due to genetic/anatomical predisposition or lifestyle (fitness) related factors. Future research will focus on determining the etiology of the VIIP syndrome and development of mechanisms to mitigate the spaceflight risk.

Otto, Christian A.↗
NASA NTRS1987

Cardiovascular results from a rhesus monkey flown aboard the Cosmos 1514 spaceflight

The results of the Cosmos 1514 cardiovascular experiment, in which the blood flow to the head and the carotid pressure of a rhesus monkey were measured during the 5-d spaceflight, are reported. A single cylindrical probe containing both pressure and flow transducers was chronically implanted as a cuff around the left common carotid artery; measurements were obtained for 4 min every 2 h and compared to identical recordings obtained during a preflight control period and during 12 h on a launch pad. Immediately on its insertion into orbit, mean arterial pressure increased by 10 percent and has maintained a 16-27 percent increase over the first few hours of flight before returning to baseline level. Blood flow showed reciprocal changes to pressure on orbital insertion. Cardiovascular system changes persisted into the second day of flight, with the signs of adaptation appearing on days 3-5.

Sandler, H.↗
NASA NTRSDate not supplied

Spaceflight-Induced Changes in Microbial Virulence and the Impact to the Host Immune Response

Over the past 50 years, microorganisms have displayed unexpected responses relevant to infectious disease when grown in spaceflight and spaceflight analogues, including changes in final cell concentration, biofilm production, stress resistance, antibiotic sensitivity, gene expression, and virulence. •Seminal studies demonstrated that the foodborne pathogen, Salmonella enterica serovar Typhimurium, increased its virulence and pathogenesis-related characteristics in response to both spaceflight and spaceflight analogue culture. Since those experiments, alterations in the pathogenesis-related characteristics of other pathogens have been documented in response to growth in these environments4,5,6, and a recent study has demonstrated an increase in virulence of Serratia marcescens cultured during spaceflight7. However, our overall knowledge of which microorganisms will alter their virulence in response to spaceflight and spaceflight analogue culture remains very limited

C. M. Ott↗
NASA NTRS2013

Career Exploration Program Exit Presentation

Mouse liver cells on short-term shuttle flights (STS- 135) have been shown to exhibit changes. By replicating aspects of spaceflight in the laboratory, we can conduct experiments without impacting mission resources. Astronauts are on a high-iron diet during spaceflight. Galactic Cosmic Rays (GCRs) and Solar Particle Events (SPEs) are ionizing radiation sources that can alter physiological functions. Preliminary medication usage data from the International Space Station (ISS) crew shows that the most common reasons for using medications in space are the same for healthy people on earth.

Wotring, Virginia↗
NASA NTRS1981

Experiment K-308: Automatic analysis of muscle fibers from rats subjected to spaceflight

The morphology of histochemically prepared muscle sections from the gastrocnemius and plantaris muscles of flight and vivarium control rats was studied quantitatively. Both fast-twitch and slow-twitch fibers were significantly smaller in flight groups than in control groups. Fibers in group 4F were somewhat larger than in 1F, presumably due to growth after recovery. Fibers in 4V were slightly larger than in 1V, presumably due to age. The slow fibers showed more spaceflight induced size loss than fast fibers, suggesting they suffered more from hypogravity. The proportion of slow fibers was also lower in the flight groups, suggesting spaceflight induced fiber type conversion from slow to fast.

Castleman, K. R.↗
NASA NTRS1990

Experiment K-6-07. Metabolic and morphologic properties of muscle fibers after spaceflight

The present study demonstrates that the general capability of skeletal muscle to maintain its proteins decreases rapidly in response to space flight. The present findings suggest further that the magnitude of enzymatic and cell volumes changes in response to space flight depend on several factors including the muscle and its fiber type composition. It appears that in order to associate physiological relevance to the observed enzymatic changes, cell volume should be considered also. Although it remains unclear as to the stimulus, or lack of stimulus, that triggers the rapid changes in muscle proteins in response to space flight, ground-based models of muscle atrophy suggest that the reduction in mechanical loading of muscle may be more important than the total amount of activation over a 24-hr period.

Edgerton, R.↗
NASA NTRS1977

Survey of cell biology experiments in reduced gravity

The effects of spaceflight on terrestrial cell systems are discussed. With some important exceptions, static cell systems carried aboard U.S.A. and U.S.S.R. space flights have failed to reveal space related anomalies. Some sophisticated devices which were developed for viewing directly, or continuously recording, the growth of cells, tissue cultures and eggs in flight, are described and the results summarized. The unique presence of high energy, multicharged (HZE) particles and full-range ultraviolet irradiation in space prompted evaluation of the response of single cells to these factors. Summary results and general conclusions are presented. Potential areas of research in future space flights are identified.

Taylor, G. R.↗
NASA NTRSDate not supplied

Multi-Omics Analysis of Mouse Retina Following Low Dose Radiation and/or Hindlimb Unloading

Rodent models have been used as analogs for studying the effects of spaceflight. NASA’s GeneLab provides access to omics datasets generated from spaceflight and ground-based experiments allowing for additional retrospective analysis. We used GeneLab’s GLDS-203, a dataset generated by researchers at Loma Linda University to study the impact of prolonged unloading and/or low-dose radiation on mouse retina. The purpose of this study was to understand the effect of gamma radiation and/or hindlimb unloading on mice retinas through a multi-omics analysis. In the experiment that generated the omics data, mice were irradiated with gamma-ray and/or subjected to hindlimb unloading for 21 days and multi-omics analysis was performed at 7 days, 1 month, or 4 months post exposure. In the current study, for each of the three timepoints, we compared epigenomic profiles for retinas from exposed mice against timepoint-matched controls. We identified a total of 5,271 differentially methylated loci (DML) and 321 differentially methylated regions (DMR; using a sliding window and step size of 500 bp) with methylation difference > 10% and q-value < 0.05 (sliding linear model corrected p-value) across the nine exposure groups. Highest correlation in methylation difference was seen for significant DMLs (q-value < 0.05) across different conditions at same post exposure timepoint (Figure 1).The location of DMLs and DMRs were characterized with respect to CpG islands and shores, putative promoters, gene body, and intergenic regions (Table 1). We analyzed RNA-seq counts and performed gene set enrichment analysis using differential expression results from comparing each exposure group to its timepoint-matched control group. Significant pathways (adjusted p-value <0.05) enriched in all three microgravity-only groups were related to morphogenesis of a branching epithelium, skeletal muscle cell differentiation, and response to fibroblast growth factor. Common processes across all timepoints in the radiation-only groups were retina homeostasis, synaptic vesicle exocytosis-endocytosis, and chemotaxis. In the combination groups, regulation of trans-synaptic signaling, and Rho protein signal transduction were enriched at all three timepoints. Processes related to purine nucleotide metabolism were enriched in all nine exposure groups, with activation at 1 month, and suppression at 7 days and 4 months. A total of 14 genes contained at least one DML and were differentially expressed at adjusted p-value < 0.05, including genes implicated in cataract development (Sipa1l3, Crybb3) and those involved in cytoskeletal organization (Plec, Flnb, Eef1a1). This analysis is part of a larger effort to understand the molecular mechanisms following spaceflight exposures that can help translate effects observed in animal models to human impacts.

Prachi Kothiyal↗
NASA NTRS2017

MS Non-Pharmacological Countermeasure to Decrease Landing Sickness and Improve Functional Performance While Disorientad

Upon return from spaceflight, a majority of crewmembers experience motion sickness (MS) symptoms. The interactions between crewmembers' adaptation to a gravitational transition, the performance decrements resulting from MS and/or use of promethazine (PMZ), and the constraints imposed by mission task demands could significantly challenge and limit an astronaut's ability to perform functional tasks during gravitational transitions. No operational countermeasure currently exists to mitigate the risks associated with these sensorimotor disturbances. Stochastic resonance (SR) can be thought of simply as "noise benefit" or an increase in information transfer by a system when in the presence of a non-zero level of noise. We have shown that low levels of stochastic vestibular stimulation (SVS) improve balance and locomotor performance due to SR (Goel et al. 2015, Mulavara et al. 2011, 2015). Additionally, a study in a 6-hydroxydopamine (6-OHDA) hemi-lesioned rat model of Parkinson's disease demonstrated improvements in locomotor activity after low-level SVS delivery possibly due to an increase in nigral gamma-aminobutyric acid (GABA) release in a dopamine independent way (Samoudi et al. 2012). SVS specifically increased GABA release on the lesioned, but not the intact side. These results suggest that SVS can cause targeted alterations of GABA release to affect performance of functional tasks. Activation of the GABA pathway is important in modulating MS and promoting adaptability (Cohen 2008). Magnusson et al. (2000) supported this finding by showing that the administration of a GABAB agonist caused a reversal of the symptoms that is normally seen after unilateral labyrinthectomy. Thus, GABA could play a significant role in reducing MS and promoting adaptability. We have taken advantage of the SR mechanism as a modulator of neurotransmitters to develop a unique SVS countermeasure system to mitigate MS symptoms and improve functional performance after landing. Healthy subjects (n=20) participated in two test sessions, one in which they received +/-400 microA of SVS and one where they received no stimulation (0 microA); the study design was counterbalanced. Subjects began by performing a series of four functional tasks 3-5 times as baseline measurements of task performance. Then, to induce MS, subjects walked an obstacle course with up-down reversing prisms. If they completed the course before achieving our pre-determined level of MS, they were asked to read a poster while making large up-down head movements to a metronome while still wearing the reversing prism goggles. Subjects were stopped every two minutes and asked to report their MS symptoms. Using the Pensacola Scale for motion sickness, test operators evaluated the level of MS of each subject. Once a subject reached an 8 on this scale, which is equivalent to mild malaise, or 30 minutes had passed since the start of the MS induction, this protocol was stopped. Finally, immediately after MS induction, subjects were asked to complete the four functional tasks again. Although, 100% of our subjects experienced at least one MS symptom, only 55% of our subjects experienced stomach awareness to any degree. Without SVS, only 40% of subjects lasted the full 30-minute MS induction protocol, while 65% of subjects lasted the full 30 minutes with SVS, which is nearly a significant increase (p=0.056). In addition, subjects showed significant improvement from baseline when performing a tandem walk and a prone-to-stand test immediately after the MS induction protocol was stopped but the stimulation level was continued. The results are promising and future work includes comparing MS progression between PMZ and SVS directly in subjects that are provoked to a minimum of nausea. Low levels of SVS stimulation may serve as a non-pharmacological countermeasure to replace or reduce the PMZ dosage requirements and concurrently improve functional performance during transitions to new gravitational environments after spaceflight.

Rosenberg, M. J. F.↗
NASA NTRS2017

Integrating Bioregenerative Foods into the Exploration Spaceflight Food System

Food, the nutrition it provides, and the eating experiences surrounding it, are central to performance, health, and psychosocial wellbeing on long duration spaceflight missions. Exploration missions will require a spaceflight food system that is safe, nutritious, and acceptable for up to five years, possibly without cold storage. Many of the processed and packaged spaceflight foods currently used on the International Space Station will not retain acceptable quality or required levels of key nutrients under these conditions. The addition of bioregenerative produce to exploration missions may become an important countermeasure to the nutritional gaps and a resource to support psychosocial health. Bioregenerative produce will be central to establishment of Earth-independence as exploration extends deeper into space. However, bioregenerative foods introduce food safety and scarcity risks that must be eliminated prior to crew reliance on these systems. The pathway to Earth independence will require small-scale integration and validation prior to large scale bioregenerative dependence. Near term exploration missions offer the opportunity to establish small scale supplemental salad crop and fruit systems and validate infrastructure reliability, nutritional potential, and the psychosocial benefits necessary to promote further bioregenerative integration.

Douglas, Grace L.↗
NASA NTRS1998

Changes in Arabidopsis leaf ultrastructure, chlorophyll and carbohydrate content during spaceflight depend on ventilation

Leaf structure and function under spaceflight conditions have received little study despite their important implications for biological life support systems using plants. Previous reports described disruption of the membrane apparatus for photosynthesis and a general decrease in carbohydrate content in foliage. During a series of three short-duration experiments (Chromex-03, -04, -05) on the US space shuttle (STS-54, STS-51, STS-68), we examined Arabidopsis thaliana leaves. The plants were at the rosette stage at the time of loading onto the space shuttle, and received the same light, temperature, carbon dioxide and humidity regimes in the orbiter as in ground controls. The experiments differed according to the regime provided in the headspace around the plants: this was either sealed (on mission STS-54); sealed with high levels of carbon dioxide (on mission STS-51) or vented to the cabin air through a filtration system (on mission STS-68). Immediately post-flight, leaf materials were fixed for microscopy or frozen in liquid nitrogen for subsequent analyses of chlorophyll and foliar carbohydrates. At the ultrastructural level, no aberrations in membrane structure were observed in any of the experiments. When air-flow was provided, plastids developed large starch grains in both spaceflight and ground controls. In the experiments with sealed chambers, spaceflight plants differed from ground controls with regard to measured concentrations of carbohydrate and chlorophyll, but the addition of airflow eliminated these differences. The results point to the crucial importance of consideration of the foliage microenvironment when spaceflight effects on leaf structure and metabolism are studied.

STS-51 Shuttle Project↗
NASA NTRS1981

Biomedical research

Biomedical problems encountered by man in space which have been identified as a result of previous experience in simulated or actual spaceflight include cardiovascular deconditioning, motion sickness, bone loss, muscle atrophy, red cell alterations, fluid and electrolyte loss, radiation effects, radiation protection, behavior, and performance. The investigations and the findings in each of these areas were reviewed. A description of how biomedical research is organized within NASA, how it is funded, and how it is being reoriented to meet the needs of future manned space missions is also provided.

Source record↗
NASA NTRS1994

Development of a Metabolic Cage for Simulation of Weightlessness in a Laboratory Environment

Astronauts experience many physiological changes during spaceflight and exposure to microgravity. There is a headwardshift of fluids, muscles atrophy, and changes occur in the body's bone structure and hormone levels. This paper describes a unique metabolic cage that was developed to evaluate ground simulation of these effects. Hindlimb or tail suspension in rats has been studied as a model to create the effects of microgravity in order to study how to counteract them. This suspension model, developed by Holton, accurately simulates the effects of weightlessness during spaceflight by unloading the hindlimbs and producing a head-ward shift of fluids. However, obtaining quantitative data on the nutritional state, the gastrointestinal and renal function of these animals has not been possible, until now. Using Holton's tail suspension model, the new metabolic suspension cage effectively separates urine and feces samples for analysis allowing investigators to examine the effects of microgravity in many complex body systems. A description of the cage system, its design, and results of its use is provided along with pictures and details for replication of the cages.

Mulenburg, Gerald M.↗
NASA NTRS2001

Effects of 17 days of head-down bed rest on hydro-electrolytic regulation in men

Prolonged periods of head-down bed rest (HDBR) are commonly used to mimic the effects of microgravity. HDBR has been shown to produce, as in space, a cephalad redistribution of circulating blood volume with an increase in central blood volume which induces the early adaptations in blood volume regulating hormones. Changes in atrial natriuretic peptide (ANP), arginine vasopressin (AVP), renin activity and aldosterone have been observed. Many reports describe these endocrine adaptations but few investigations of rhythms are in the literature. We proposed to evaluate the circadian rhythms of the hormones and electrolytes involved in the hydro-electrolytic regulation during a HDBR study which was designed to simulate a 17-day spaceflight (Life and Microgravity Spacelab experiment, LMS, NASA).

NASA Center ARC↗
NASA NTRS2007

Space Environment (Natural and Induced)

Considerable effort and improvement have been made in the study of ionizing radiation exposure occurring in various regions of space. Satellites and spacecrafts equipped with innovative instruments are continually refining particle data and providing more accurate information on the ionizing radiation environment. The major problem in accurate spectral definition of ionizing radiation appears to be the detailed energy spectra, especially at high energies, which is important parameter for accurate radiation risk assessment. Magnitude of risks posed by exposure to radiation in future space missions is subject to the accuracies of predictive forecast of event size of SPE, GCR environment, geomagnetic fields, and atmospheric radiation environment. Although heavy ion fragmentations and interactions are adequately resolved through laboratory study and model development, improvements in fragmentation cross sections for the light nuclei produced from HZE nuclei and their laboratory validation are still required to achieve the principal goal of planetary GCR simulation at a critical exposure site. More accurate prediction procedure for ionizing radiation environment can be made with a better understanding of the solar and space physics, fulfillment of required measurements for nuclear/atomic processes, and their validation and verification with spaceflights and heavy ion accelerators experiments. It is certainly true that the continued advancements in solar and space physics combining with physical measurements will strengthen the confidence of future manned exploration of solar system. Advancements in radiobiology will surely give the meaningful radiation hazard assessments for short and long term effects, by which appropriate and effective mitigation measures can be placed to ensure that humans safely live and work in the space, anywhere, anytime.

Kim, Myung-Hee Y.↗
NASA NTRS2009

Antarctica Meta-Analysis: Psychosocial Factors Related to Long Duration Isolation and Confinement

This meta-analysis is examining the psychological effects of wintering-over in Antarctica. As an isolated, confined, and extreme (ICE) environment, Antarctica provides invaluable opportunities to experience stressors more common to spaceflight than to the average person s everyday life. Increased prevalence of psychological symptoms, syndromes, and psychiatric disorders, as well as positive effects, are expected to be associated with various demographic and environmental factors. Implications for spaceflight are discussed. Findings from statistical review of the Antarctic articles will be shared.

Leveton, Lauren↗