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NASA NTRS2019

Synthesis of Meteoritic Reaction Intermediates

The organic compounds of carbo- naceous chondrites are structurally diverse products of the prolonged abiotic chemistry that occurred before and during the early stages of the solar system [1]. They also represent the types of prebiotic compounds that may have participated in chemical evolutionary processes that gave rise to life [2]. Pyruvic acid is a key component of primary metabolism that has recently been found in carbonaceous chondrites [3]. Its prominence in biology has inspired us to explore its chemistry and possible role in the origin of metabolism. Our laboratory investigations have found that pyruvate (the ionized form of pyruvic acid) can serve as a single-source reactant to generate what we term a pyruvate reaction network (PRN). The core of the PRN is driven by pyruvate aldol polymerization and decay reactions. These decay reactions lead to the production of stable and unstable compounds which include mono, di, and tricarboxylic acids and a variety of keto acids. Finding evidence of this reaction network in meteorites would establish that the chemistry of pyruvate did occur in a prebiotic environment. Many of the known compounds found in pyruvate reaction mixtures were originally detected in meteorite samples by Cooper et al in 2011. However, multiple synthetic origins not tied to pyruvate chemistry might also explain their meteoritic presence. Thus, a search to find compounds unique to the PRN, such as reaction intermediates, would provide stronger evidence to demonstrate its prebiotic relevance. The identity of these intermediates can only be confirmed by acquiring chemical standards, however, as most are not available commercially, they need to be accessed through chemical synthesis.

Rios, Andro C.↗

NASA NTRS2019

Estuarine Dissolved Organic Carbon Flux From Space: With Application to Chesapeake and Delaware Bays

This study uses a neural network model trained with in situ data, combined with satellite data and hydrodynamic model products, to compute the daily estuarine export of dissolved organic carbon (DOC) at the mouths of Chesapeake Bay (CB) and Delaware Bay (DB) from 2007 to 2011. Both bays show large flux variability with highest fluxes in spring and lowest in fall as well as interannual flux variability (0.18 and 0.27 Tg C/year in 2008 and 2010 for CB; 0.04 and 0.09 Tg C/year in 2008 and 2011 for DB). Based on previous estimates of total organic carbon (TOCexp) exported by all Mid-Atlantic Bight estuaries (1.2 Tg C/year), the DOC export (CB + DB) of 0.3 Tg C/year estimated here corresponds to 25% of the TOCexp. Spatial and temporal covariations of velocity and DOC concentration provide contributions to the flux, with larger spatial influence. Differences in the discharge of fresh water into the bays (74 billion cu. m/year for CB and 21 billion cu. m/year for DB) and their geomorphologies are major drivers of the differences in DOC fluxes for these two systems. Terrestrial DOC inputs are similar to the export of DOC at the bay mouths at annual and longer time scales but diverge significantly at shorter time scales (days to months). Future efforts will expand to the Mid-Atlantic Bight and Gulf of Maine, and its major rivers and estuaries, in combination with coupled terrestrial-estuarine-ocean biogeochemical models that include effects of climate change, such as warming and CO2 increase.

Estuarine DOC export↗

NASA NTRS2003

Tensegrity II. How structural networks influence cellular information processing networks

The major challenge in biology today is biocomplexity: the need to explain how cell and tissue behaviors emerge from collective interactions within complex molecular networks. Part I of this two-part article, described a mechanical model of cell structure based on tensegrity architecture that explains how the mechanical behavior of the cell emerges from physical interactions among the different molecular filament systems that form the cytoskeleton. Recent work shows that the cytoskeleton also orients much of the cell's metabolic and signal transduction machinery and that mechanical distortion of cells and the cytoskeleton through cell surface integrin receptors can profoundly affect cell behavior. In particular, gradual variations in this single physical control parameter (cell shape distortion) can switch cells between distinct gene programs (e.g. growth, differentiation and apoptosis), and this process can be viewed as a biological phase transition. Part II of this article covers how combined use of tensegrity and solid-state mechanochemistry by cells may mediate mechanotransduction and facilitate integration of chemical and physical signals that are responsible for control of cell behavior. In addition, it examines how cell structural networks affect gene and protein signaling networks to produce characteristic phenotypes and cell fate transitions during tissue development.

Review↗

NASA NTRS2000

The origin of intermediary metabolism

The core of intermediary metabolism in autotrophs is the citric acid cycle. In a certain group of chemoautotrophs, the reductive citric acid cycle is an engine of synthesis, taking in CO(2) and synthesizing the molecules of the cycle. We have examined the chemistry of a model system of C, H, and O that starts with carbon dioxide and reductants and uses redox couples as the energy source. To inquire into the reaction networks that might emerge, we start with the largest available database of organic molecules, Beilstein on-line, and prune by a set of physical and chemical constraints applicable to the model system. From the 3.5 million entries in Beilstein we emerge with 153 molecules that contain all 11 members of the reductive citric acid cycle. A small number of selection rules generates a very constrained subset, suggesting that this is the type of reaction model that will prove useful in the study of biogenesis. The model indicates that the metabolism shown in the universal chart of pathways may be central to the origin of life, is emergent from organic chemistry, and may be unique.

Non-NASA Center↗

NASA NTRS2010

Mapping and Quantification of Vascular Branching in Plants, Animals and Humans by VESGEN Software

Humans face daunting challenges in the successful exploration and colonization of space, including adverse alterations in gravity and radiation. The Earth-determined biology of plants, animals and humans is significantly modified in such extraterrestrial environments. One physiological requirement shared by larger plants and animals with humans is a complex, highly branching vascular system that is dynamically responsive to cellular metabolism, immunological protection and specialized cellular/tissue function. VESsel GENeration (VESGEN) Analysis has been developed as a mature beta version, pre-release research software for mapping and quantification of the fractal-based complexity of vascular branching. Alterations in vascular branching pattern can provide informative read-outs of altered vascular regulation. Originally developed for biomedical applications in angiogenesis, VESGEN 2D has provided novel insights into the cytokine, transgenic and therapeutic regulation of angiogenesis, lymphangiogenesis and other microvascular remodeling phenomena. Vascular trees, networks and tree-network composites are mapped and quantified. Applications include disease progression from clinical ophthalmic images of the human retina; experimental regulation of vascular remodeling in the mouse retina; avian and mouse coronary vasculature, and other experimental models in vivo. We envision that altered branching in the leaves of plants studied on ISS such as Arabidopsis thaliana cans also be analyzed.

Parsons-Wingerter, P. A.↗

NASA NTRS2010

Mapping and Quantification of Vascular Branching in Plants, Animals and Humans by VESGEN Software

Humans face daunting challenges in the successful exploration and colonization of space, including adverse alterations in gravity and radiation. The Earth-determined biology of humans, animals and plants is significantly modified in such extraterrestrial environments. One physiological requirement shared by humans with larger plants and animals is a complex, highly branching vascular system that is dynamically responsive to cellular metabolism, immunological protection and specialized cellular/tissue function. The VESsel GENeration (VESGEN) Analysis has been developed as a mature beta version, pre-release research software for mapping and quantification of the fractal-based complexity of vascular branching. Alterations in vascular branching pattern can provide informative read-outs of altered vascular regulation. Originally developed for biomedical applications in angiogenesis, VESGEN 2D has provided novel insights into the cytokine, transgenic and therapeutic regulation of angiogenesis, lymphangiogenesis and other microvascular remodeling phenomena. Vascular trees, networks and tree-network composites are mapped and quantified. Applications include disease progression from clinical ophthalmic images of the human retina; experimental regulation of vascular remodeling in the mouse retina; avian and mouse coronary vasculature, and other experimental models in vivo. We envision that altered branching in the leaves of plants studied on ISS such as Arabidopsis thaliana cans also be analyzed.

Parsons-Wingerter, Patricia A.↗

NASA NTRS1972

Simulation of a steady-state integrated human thermal system.

The mathematical model of an integrated human thermal system is formulated. The system consists of an external thermal regulation device on the human body. The purpose of the device (a network of cooling tubes held in contact with the surface of the skin) is to maintain the human body in a state of thermoneutrality. The device is controlled by varying the inlet coolant temperature and coolant mass flow rate. The differential equations of the model are approximated by a set of algebraic equations which result from the application of the explicit forward finite difference method to the differential equations. The integrated human thermal system is simulated for a variety of combinations of the inlet coolant temperature, coolant mass flow rate, and metabolic rates. Two specific cases are considered: (1) the external thermal regulation device is placed only on the head and (2) the devices are placed on the head and the torso. The results of the simulation indicate that when the human body is exposed to hot environment, thermoneutrality can be attained by localized cooling if the operating variables of the external regulation device(s) are properly controlled.

Hsu, F. T.↗

NASA NTRS1972

Simulation of a steady-state integrated human thermal system.

Hsu, F. T.↗

NASA NTRS2011

Deployment of an Advanced Electrocardiographic Analysis (A-ECG) to Detect Cardiovascular Risk in Career Firefighters

INTRODUCTION Sudden cardiac death is the leading cause of line of duty death among firefighters, accounting for approximately 45% of fatalities annually. Firefighters perform strenuous muscular work while wearing heavy, encapsulating personal protective equipment in high ambient temperatures, under chaotic and emotionally stressful conditions. These factors can precipitate sudden cardiac events like myocardial infarction, serious dysrhythmias, or cerebrovascular accidents in firefighters with underlying cardiovascular disease. Screening for cardiovascular risk factors is recommended but not always followed in this population. PHASER is a project charged with identifying and prioritizing risk factors in emergency responders. We have deployed an advanced ECG (A-ECG) system developed at NASA for improved sensitivity and specificity in the detection of cardiac risk. METHODS Forty-four professional firefighters were recruited to perform comprehensive baseline assessments including tests of aerobic performance and laboratory tests for fasting lipid profiles and glucose. Heart rate and conventional 12-lead ECG were obtained at rest and during incremental treadmill exercise testing (XT). In addition, a 5-min resting 12-lead A-ECG was obtained in a subset of firefighters (n=18) and transmitted over a secure networked system to a physician collaborator at NASA for advanced-ECG analysis. This A-ECG system has been proven, using myocardial perfusion and other imaging, to accurately identify a number of cardiac pathologies including coronary artery disease (CAD), left ventricular hypertrophy, hypertrophic cardiomyopathy, non-ischemic cardiomyopathy, and ischemic cardiomyopathy. RESULTS Subjects mean (SD) age was 43 (8) years, weight 91 (13) kg, and BMI of 28 (3) kg/square meter. Maximum oxygen uptake (VO2max) was 39 (9) ml/kg/min. This compares with the 45th %ile in healthy reference values and a recommended standard of 42 ml/kg/min for firefighters. The metabolic threshold (VO2Theta) above which lactate accumulates was 23 (8) ml/kg/min. The chronotropic index, a measure of cardiovascular strain during XT was 35 (8) /L compared with reference values for men of 40 /L. Total cholesterol, LDL-C and HDL-C were 202 (34),126 (29), and 55 (15) mg/dl, respectively. Fifty-one percent of subjects had .3 cardiovascular risk factors, 2 subjects had resting hypertension (BP.140/90), and 23 had pre-hypertension (.120/80 but <140/90). Seven had exaggerated exercise induced hypertension but only one had ST depression on XT ECG, at least one positive A-ECG score for CAD, and documented CAD based on cardiology referral. While all other subjects, including those with fewer risk factors, higher aerobic fitness, and normal exercise ECGs, were classified as healthy by A-ECG, there was no trend for association between risk factors and any of 20 A-ECG parameters in the grouped data. CONCLUSIONS A-ECG screening correctly identified the individual with CAD although there was no trend for A-ECG parameters to distinguish those with elevated BP or multiple risk factors but normal XT ECG. We have demonstrated that a new technology, advanced-ECG, can be introduced for remote firefighter risk assessment. This simple, time and cost-effective approach to risk identification that can be acquired remotely and transmitted securely can detect individuals potentially at risk for line-of-duty death. Additional research is needed to further document its value.

Dolezal, B. A.↗

NASA NTRSDate not supplied

An Optimization Approach to Support Science Decision Making for Lunar Surface Exploration

Introduction: Scientific exploration is one of the three pillars of NASA’s Moon2Mars architecture, with crew surface extra vehicular activities (EVA) serving a critical enabling function. Development of surface EVA operational planning and execution, specifically integrating science and flight control teams (FCT), is currently being explored through analog scenarios. This integration, exercised, for example, through the Joint EVA and Hu-man Surface Mobility Test Team (JETT), allows for science input on EVA activities in near real-time through a Science Evaluation Room (SER), or Arte-mis science backroom, which integrates with the broader FCT through the Science Officer. The SER works within the FCT to support dynamic EVA planning in response to changes in operational constraints as well as science opportunities and re-prioritization, increasing the mission science return and accelerating the accomplishment of the Moon2Mars science objectives. The SER works within the FCT to provide recommendations to traverse execution in near real-time. One challenge is the requirement to deliver SER inputs to the FCT on operationally relevant timelines. Failure to do so may result in suboptimal execution of science exploration EVAs or even loss of key science objectives. To close this gap, we present a network optimization tool to allow the SER to provide rapid input to the FCT in response to changes in operational constraints or science opportunities. Inputs are predicated on approved science objectives, and clear rationale must be provided to the FCT for any requested change. Accordingly, this tool incorporates the Science Traceability Matrix (STM), SER prioritization scheme, and station characterization and action planning with operational constraints such as duration, traverse speed, and distance to maximize science objectives based on SER priorities, consistent with FCT operational requirements. Method: As a proof of concept, we used an existing linear programing software package used to simulate optimal routes through cellular metabolism. We built a Demonstrative Model with three STM objectives and four stations on a region of the Moon. The objectives were given an arbitrary prioritization and mapped to the stations through four possible crew actions. (Figs. 1 and 2). This station to STM mapping is consistent with the method used by the JETT5 Science Team to develop analog surface EVA science planning. We used a grid system with the landing site at the origin and the four stations placed across the positive x,y quadrant. Actions were assigned to each station and the accomplishment of those actions resulted in a numerical “reward” based on the ability of that action to achieve science objectives. The aggregate reward from each individual STM objective contributes to a global score (Science Yield), weighted by its priority. Operational constraints included a requirement to start and end at the landing site, 5 minutes each for initial station characterization and “clean up,” and variable total EVA time, traverse rate (fixed to 0.5 meters per second in our example), and time to perform each action (10, 5, 7, and 15 min for actions 1, 2, 3, and 4, respectively). Additional constraints and variables will be added in the future (e.g., sample mass, number of stations, traverse route constraints, illumination). Optimization. We converted the connections (arcs) between these stations (nodes) into a mixed integer linear programming optimization problem (arcs = constraints, nodes = variables) with the objective to maximize Science Yield. For any action, the Science Yield is equal to the relevance of that action to an STM objective [3, 2, and 1 point(s) for High, Med., and Low relevance, respectively], multiplied by the STM Objective Priority [3, 2, and 1 point(s) for High, Med., and Low priority, respectively]. This resulted in a model that computes the optimal station and action combination to maximize the Science Yield. These weightings can be adjusted by the SER as desired. Results: We explored three test cases for the Demonstrative Model. First, we set the maximum EVA duration to 120 minutes and computed the optimal route (Fig. 3A). The model suggested per-forming Actions 1 and 2 at Station P01, followed by Actions 1 and 2 at Station P02, and finally Actions 1 and 3 at Station P04 before returning to the Landing Site. Second, we adjusted the STM Objective Priori-ty order and computed the new optimal route (Fig. 3B). Under this situation, the model suggested per-forming all Actions at Station P02 followed by all Actions at Station P03. The previous test cases were relevant to SER planning activities. Next, we explored providing mid-EVA replanning input to the FCT. Scenario: While executing the Route in Fig. 3A the crew finishes at Station P01 and FCT decides that the EVA needs to finish in 45 minutes back at the Landing Site. FCT asks SER to recommend changes to the plan to accommodate this operation-al change. Using the model and incorporating these new constraints (start at Station P01, max. time of 45 min), the model suggested performing Actions 2 and 4 at Station P03 (Fig. 4), requiring 41 minutes to complete and return to the Landing Site. Interestingly, Station 3 was not part of the original route. Using the model, we determined the EVA would need 66 minutes, instead of 45, in order for the original Station P04 to yield a larger Science Yield than Station P03. The parametrization and simulation was per-formed in less than a minute, demonstrating the operational relevance of the approach. Future Efforts: The results from the Demonstrative Model suggest this tool can accelerate SER decision making on operationally relevant timelines. Use in analog activities, such as JETT5 or follow-ons, which have over a dozen stations for a crew to explore and over a dozen actions per station, will provide needed validation of the utility of this tool for planning EVAs, replanning mid-EVA, or planning follow-on EVAs based on previous results. Further integration with FCT execution monitoring tools may provide additional efficiency gains, al-lowing rapid and iterative exploration of operation-al and science decision space by the FCT and SER.

Science Operations↗

NASA NTRS2016

Mechanotransductive Regulation of Gap-Junction Activity Between MLO-Y4 Osteocyte-Like and MC3T3-E1 Osteoblast-Like Cells in Three-Dimensional Co-Culture.

Cell and animal studies conducted onboard the International Space Station and formerly on Shuttle flights have provided groundbreaking data illuminating the deleterious biological response of bone to mechanical unloading. However the intercellular communicative mechanisms associated with the regulation of bone synthesis and bone resorption cells are still largely unknown. Connexin-43 (CX43), a gap junction protein, is hypothesized to play a significant role in osteoblast and osteocyte signaling. The purpose of this investigation was to evaluate within a novel three-dimensional microenvironment how the osteocyte-osteoblast gap-junction expression changes when cultures are exposed to exaggerated mechanical load. MLO-Y4 osteocyte-like cells were cultured on a 3D-Biotek polystyrene insert and placed in direct contact with an MC3T3-E1 pre-osteoblast co-cultured monolayer and exposed to 48 h of mechanical stimulation (pulsatile fluid flow (PFF) or monolayer cyclic stretch (MCS)) then evaluated for viability, proliferation, metabolism, and CX43 expression. Mono-cultured MLO-Y4 and MC3T3-E1 control experiments were conducted under PFF and MCS stimulation to observe how strain application stimuli (PFF cell membrane shear or MCS cell focal adhesion/attachment loading) initiates different signaling pathways or downstream regulatory controls. TotalLive cell count, viability and metabolic reduction (Trypan Blue, LIVEDead and Alamar Blue analysis respectively) indicate that mechanical activation of MC3T3-E1 cells inhibits proliferation while maintaining an average 1.04E4 reductioncell metabolic rate, *p0.05 n4. MLO-Y4s in monolayer culture increase in number when exposed to MCS loading but the percent of live cells within the population is low (46.3 total count, *p0.05 n4), these results may indicate an apoptotic signaling cascade. PFF stimulation of the three-dimensional co-cultures elicits a universal increase in CX43 in MLO-Y4 and MC3T3-E1 cells, illustrated by immunohistological observation. Increased CX43 expression is also observed with the three-dimensional co-cultures with MC3T3-E1 MCS stimulation but the increased gap-junction protein presence was limited to the osteoblast-osteocyte interface region. Previously reported PCR evaluation of osteogenic markers further corroborate that the co-cultured populations communicative networks play a role in translating mechanical signals to molecular messaging. These findings suggests an osteocyte-osteoblast gap-junction signaling feedback mechanism may regulate mechanotransduction of apoptosis initiation and transcription of cytokine signaling proteins responsible for stem cell niche recruitment much more directly than previously believed.

mechanical loading↗

NASA NTRS2016

Mechanotransductive Regulation of Gap-Junction Activity Between MLO-Y4 Osteocyte-Like and MC3T3-E1 Osteoblast-Like Cells in Three-Dimensional Co-Culture

Cell and animal studies conducted onboard the International Space Station and formerly on Shuttle flights have provided groundbreaking data illuminating the deleterious biological response of bone to mechanical unloading. However the intercellular communicative mechanisms associated with the regulation of bone synthesis and bone resorption cells are still largely unknown. Connexin-43 (CX43), a gap junction protein, is hypothesized to play a significant role in osteoblast and osteocyte signaling. The purpose of this investigation was to evaluate within a novel three-dimensional microenvironment how the osteocyte-osteoblast gap-junction expression changes when cultures are exposed to exaggerated mechanical load. MLO-Y4 osteocyte-like cells were cultured on a 3D-Biotek polystyrene insert and placed in direct contact with an MC3T3-E1 pre-osteoblast co-cultured monolayer and exposed to 48 h of mechanical stimulation (pulsatile fluid flow (PFF) or monolayer cyclic stretch (MCS)) then evaluated for viability, proliferation, metabolism, and CX43 expression. Mono-cultured MLO-Y4 and MC3T3-E1 control experiments were conducted under PFF and MCS stimulation to observe how strain application stimuli (PFF cell membrane shear or MCS cell focal adhesionattachment loading) initiates different signaling pathways or downstream regulatory controls. TotalLive cell count, viability and metabolic reduction (Trypan Blue, LIVEDead and Alamar Blue analysis respectively) indicate that mechanical activation of MC3T3-E1 cells inhibits proliferation while maintaining an average 1.04E4 reductioncell metabolic rate, *p0.05 n4. MLO-Y4s in monolayer culture increase in number when exposed to MCS loading but the percent of live cells within the population is low (46.3 total count, *p0.05 n4), these results may indicate an apoptotic signaling cascade. PFF stimulation of the three-dimensional co-cultures elicits a universal increase in CX43 in MLO-Y4 and MC3T3-E1 cells, illustrated by immunohistological observation. Increased CX43 expression is also observed with the three-dimensional co-cultures with MC3T3-E1 MCS stimulation but the increased gap-junction protein presence was limited to the osteoblast-osteocyte interface region. Previously reported PCR evaluation of osteogenic markers further corroborate that the co-cultured populations communicative networks play a role in translating mechanical signals to molecular messaging. These findings suggests an osteocyte-osteoblast gap-junction signaling feedback mechanism may regulate mechanotransduction of apoptosis initiation and transcription of cytokine signaling proteins responsible for stem cell niche recruitment much more directly than previously believed.

Juran, C. M.↗

NASA NTRSDate not supplied

Enabling Model Organism and Commercial Astronaut Data Access Through the NASA Open Science Data Repository

NASA’s Open Science Data Repository (OSDR) brings together omics data from NASA’s GeneLab project and non-omics data, including physiological, phenotypic, imaging, and behavioral data from NASA’s Ames Life Sciences Data Archive (ALSDA) collected from decades of space biology research, providing open and FAIR (findable, accessible, interoperable, and reusable) access of these precious data to scientists world-wide. This rich source of meticulously curated metadata and data from spaceflight and analog studies has been mined by the scientific community resulting in dozens of high impact scientific publications that reveals a complex network of molecular and physiological effects of spaceflight across living systems, from microbes to plants, to mammals. Understanding how these effects translate to the human condition is critical as we move deeper into the era of commercial space travel. However, the integration of data, specifically omics data, from astronauts is particularly challenging due to their sensitive nature. OSDR has risen to this challenge by developing a mechanism to control access to identifiable levels of omics data, such as raw sequence data, while enabling public access to processed, unidentifiable, data and associated metadata that will allow the scientific community to interrogate human astronaut data alongside data from model organisms to begin answering these critical questions. The 2021 SpaceX Inspiration4 (I4) mission collected a comprehensive atlas of biological measurements from four civilian astronauts, providing a wealth of data to characterize the effects of spaceflight on the human body. These data include both non-omics and omics assays such as direct RNA sequencing (RNA-seq), single nuclei ATAC-seq and RNA-seq, metagenomics, proteomics, and comprehensive metabolic and cytokine panels, all of which have been integrated into the OSDR system across no less than 9 studies. Each study has been carefully curated using community-backed OSDR standards for sample and assay level metadata ensuring these data are findable and accessible. In addition to hosting both raw and processed data from the principal investigator team for each assay type, the GeneLab team plans to re-process the I4 omics data using GeneLab’s standard processing pipelines. The GeneLab processed data outputs will allow for comparisons across studies on OSDR and enable visualization of these data through the OSDR data visualization platform thereby enabling data reusability and interoperability. Here we describe the robust privacy and security protocols implemented by OSDR to safeguard sensitive health data from astronauts while facilitating metadata and processed data sharing for research purposes. We further provide a road map for navigating the vast amount of data provided for each I4 study on the OSDR, including experimental design, associated experiments, payloads, and missions, data generation and analysis protocols, and associated scientific articles. Additionally, we illustrate how to interrogate the standardized metadata provided in the sample and assay tables as well as various means to download and access the data including programmatically through the GeneLab Open API (GLOpenAPI). The open access of datasets in NASA’s OSDR provides a unique opportunity for the scientific community, as well as citizen scientists and students, to continue using OSDR resources to further unlock profound insights into the consequences of space travel on the human body. Through implementation of security measures to protect sensitive human data, the OSDR seeks to strengthen the science exchange between the Biological and Physical Sciences Program and the Human Research Program, per recommendation 4-1 of the 2023-2032 Decadal Survey, and encourage further sharing and dissemination of astronaut data to provide the scientific community with the resources needed to lay the groundwork for developing targeted mitigation strategies to help withstand the rigors of long-duration spaceflight.

Amanda Marie Saravia-butler↗

NASA NTRSDate not supplied

Enabling Model Organism and Commercial Astronaut Data Access Through the NASA Open Science Data Repository

NASA’s Open Science Data Repository (OSDR) brings together omics data from NASA’s GeneLab project and non-omics data, including physiological, phenotypic, imaging, and behavioral data from NASA’s Ames Life Sciences Data Archive (ALSDA) collected from decades of space biology research, providing open and FAIR (findable, accessible, interoperable, and reusable) access of these precious data to scientists world-wide. This rich source of meticulously curated metadata and data from spaceflight and analog studies has been mined by the scientific community resulting in dozens of high impact scientific publications that reveals a complex network of molecular and physiological effects of spaceflight across living systems, from microbes to plants, to mammals. Understanding how these effects translate to the human condition is critical as we move deeper into the era of commercial space travel. However, the integration of data, specifically omics data, from astronauts is particularly challenging due to their sensitive nature. OSDR has risen to this challenge by developing a mechanism to control access to identifiable levels of omics data, such as raw sequence data, while enabling public access to processed, unidentifiable, data and associated metadata that will allow the scientific community to interrogate human astronaut data alongside data from model organisms to begin answering these critical questions. The 2021 SpaceX Inspiration4 (I4) mission collected a comprehensive atlas of biological measurements from four civilian astronauts, providing a wealth of data to characterize the effects of spaceflight on the human body. These data include both non-omics and omics assays such as direct RNA sequencing (RNA-seq), single nuclei ATAC-seq and RNA-seq, metagenomics, proteomics, and comprehensive metabolic and cytokine panels, all of which have been integrated into the OSDR system across no less than 9 studies. Each study has been carefully curated using community-backed OSDR standards for sample and assay level metadata ensuring these data are findable and accessible. In addition to hosting both raw and processed data from the principal investigator team for each assay type, the GeneLab team plans to re-process the I4 omics data using GeneLab’s standard processing pipelines. The GeneLab processed data outputs will allow for comparisons across studies on OSDR and enable visualization of these data through the OSDR data visualization platform thereby enabling data reusability and interoperability. Here we describe the robust privacy and security protocols implemented by OSDR to safeguard sensitive health data from astronauts while facilitating metadata and processed data sharing for research purposes. We further provide a road map for navigating the vast amount of data provided for each I4 study on the OSDR, including experimental design, associated experiments, payloads, and missions, data generation and analysis protocols, and associated scientific articles. Additionally, we illustrate how to interrogate the standardized metadata provided in the sample and assay tables as well as instructions for how to download and access the data. The I4 datasets described here re present the first ever comprehensive collection of commercial astronaut data.

Amanda M Saravia-Butler↗

NASA NTRS2020

GeneLab

GeneLab collects and enables analysis of spaceflight and ground-based spaceflight simulation genomic data, RNA and protein expression, and metabolic profiles. It interfaces with other existing databases containing spaceflight omic data. The 2011 National Research Council (NRC) Decadal Survey on NASA Life and Physical Sciences called for increased opportunities for multi-investigator spaceflight opportunities and greater use of genomic approaches to meet the needs of NASA researchers. To address these recommendations of the NRC Decadal Survey, the Space Life and Physical Sciences Research and Applications Division of NASA's Human Exploration and Operations Mission Directorate has initiated a transition to an Open Science architecture to increase research opportunities, and has developed the GeneLab Platform based on highly leveraged and integrated bioinformatics analytics. GeneLab is an interactive, open-access resource where scientists can upload, download, store, search, share, transfer, and analyze omics data from spaceflight and corresponding analogue experiments. Users can explore GeneLab datasets in the Data Repository, analyze data using the Analysis Platform, visualize high-order data and create collaborative projects using the Collaborative Workspace. Our primary goal is to maximize the utilization of the valuable biological research conducted aboard the International Space Station (ISS) by collecting genomic, transcriptomic, proteomic, and metabolomics data known as “omics”. By providing a portal linking processed data to flight parameters, GeneLab enables exploration of the molecular network responses of terrestrial biology to the space environment. This allows researchers to understand the complex responses of biological systems to the space environment. This technology development activity was transferred from the Human Exploration and Operations Mission Directorate to the Science Mission Directorate Division of Biological and Physical Sciences (BPS) in October 2020.

GeneLab↗

NASA NTRS2000

Deconditioning and Reconditioning: Humans in Stressful Environments

Deconditioning is an integrated physiological response of the body to a reduction in metabolic rate; that is, to a reduction in energy use or in exercise level. While it may involve assumption of a horizontal body position, it certainly perturbs bodily homeostasis - at least temporarily. The reduction in physical activity that causes deconditioning is often associated with an increase in the time spent, for whatever reason, in a sitting or horizontal position. As a result, orthostatic factors may also contribute to the deconditioning mechanism. The word decondition may be defined as "1: to cause extinction of (a conditioned response) 2: to cause to lose physical fitness". This definition implies that psychological/emotional factors may accompany physical deconditioning, and it is this interpretation of the word that is used throughout this volume. It is apparent that deconditioning plays a major role in the mechanism of the general adaptive (homeostatic) response that is initiated by exposure to prolonged bed rest (BR). And the total homeostatic response to BR involves more than deconditioning per se. For example, it has been shown that the restoration of plasma volume and maximal work capacity after 4 weeks of BR deconditioning left other bodily functions (submaximal exercise oxygen uptake and cardiac output, leg proprioception and posterior leg muscle thickness and volume, head-up tilt tolerance, and sleep quality) functioning at decreased levels. The precise effect of deconditioning on BR homeostasis is difficult to determine, because the fundamental interactive neuro-endocrine-immune control networks that facilitate conditioning and deconditioning also act to maintain basic wholebody homeostasis. For example, is the mechanism of BR-induced deconditioning independent of the mechanism that provokes concomitant orthostatic intolerance; that is, fainting? Assumption of the recumbent body position for prolonged periods of time, results in a new adaptive-homeostatic state. This state occurs in response to the mutually interactive effects of the change in bodily position (hydrostatic pressure), to the virtual elimination of longitudinal pressure on the bones, to the increased confinement with possible reduction in total daily energy (exercise) expenditure, to the reorientation of stimuli within the vestibular organs, and (often) to altered socio-psychological conditions. The exercise-training (reconditioning) syndrome affects total body homeostasis by facilitating increases in work capacity and endurance, whereas deconditioning decreases physical performance. There are many interrelated factors that influence the control parameters that seek to maintain the adaptive conditioning-deconditioning syndrome. These control parameters can be better elucidated by subjecting otherwise healthy ambulatory people to various stresses, such as exercise training and prolonged spaceflight, bed rest, water immersion, hyperbaria, and isolation and confinement. Changes in control parameters will be manifested in muscle function, orthostatic tolerance, cardiorespiratory responses, musculo-skeletal systems, free-radical processes, and body thermoregulation with overarching effects on the subjects' psycho-sociological states. A discussion of these factors and the control parameters constitutes the substance of this volume. Special emphasis is placed on delineating practical applications of the findings that will be of special interest to physicians, nurses, and other health-care workers.

Greenleaf, John E.↗

NASA NTRS2000

Depositional facies and aqueous-solid geochemistry of travertine-depositing hot springs (Angel Terrace, Mammoth Hot Springs, Yellowstone National Park, U.S.A.)

Petrographic and geochemical analyses of travertine-depositing hot springs at Angel Terrace, Mammoth Hot Springs, Yellowstone National Park, have been used to define five depositional facies along the spring drainage system. Spring waters are expelled in the vent facies at 71 to 73 degrees C and precipitate mounded travertine composed of aragonite needle botryoids. The apron and channel facies (43-72 degrees C) is floored by hollow tubes composed of aragonite needle botryoids that encrust sulfide-oxidizing Aquificales bacteria. The travertine of the pond facies (30-62 degrees C) varies in composition from aragonite needle shrubs formed at higher temperatures to ridged networks of calcite and aragonite at lower temperatures. Calcite "ice sheets", calcified bubbles, and aggregates of aragonite needles ("fuzzy dumbbells") precipitate at the air-water interface and settle to pond floors. The proximal-slope facies (28-54 degrees C), which forms the margins of terracette pools, is composed of arcuate aragonite needle shrubs that create small microterracettes on the steep slope face. Finally, the distal-slope facies (28-30 degrees C) is composed of calcite spherules and calcite "feather" crystals. Despite the presence of abundant microbial mat communities and their observed role in providing substrates for mineralization, the compositions of spring-water and travertine predominantly reflect abiotic physical and chemical processes. Vigorous CO2 degassing causes a +2 unit increase in spring water pH, as well as Rayleigh-type covariations between the concentration of dissolved inorganic carbon and corresponding delta 13C. Travertine delta 13C and delta 18O are nearly equivalent to aragonite and calcite equilibrium values calculated from spring water in the higher-temperature (approximately 50-73 degrees C) depositional facies. Conversely, travertine precipitating in the lower-temperature (< approximately 50 degrees C) depositional facies exhibits delta 13C and delta 18O values that are as much as 4% less than predicted equilibrium values. This isotopic shift may record microbial respiration as well as downstream transport of travertine crystals. Despite the production of H2S and the abundance of sulfide oxidizing microbes, preliminary delta 34S data do not uniquely define the microbial metabolic pathways present in the spring system. This suggests that the high extent of CO2 degassing and large open-system solute reservoir in these thermal systems overwhelm biological controls on travertine crystal chemistry.

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