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NASA NTRSDate not supplied

Efficient Oculometric Assessment of Altered Neural Function

Eye movements have long been known to shed light on the locus and nature of serious brain injuries and pathologies. Recent scientific findings linking eye movements and higher-order psychometric performance and recent technical advances in eye-tracking precision have enabled the harnessing of an assortment of oculometrics as sensitive and reliable biomarkers of mild neural impairment across a wide range of stressors and brain regions. Oculometrics is, therefore, a promising new tool for the assessment of spaceflight effects on sensorimotor performance and on the effectiveness of candidate countermeasures, even with small sample populations

eye movements↗

NASA NTRS2024

Cognitive Performance in ISS Astronauts on 6-Month Low Earth Orbit Missions

Introduction: Current and future astronauts will endure prolonged exposure to spaceflight hazards and environmental stressors that could compromise cognitive functioning, yet cognitive performance in current missions to the International Space Station remains critically under-characterized. We systematically assessed cognitive performance across 10 cognitive domains in astronauts on 6-month missions to the ISS. Methods: Twenty-five professional astronauts were administered the Cognition Battery as part of National Aeronautics and Space Administration (NASA) Human Research Program Standard Measures Cross-Cutting Project. Cognitive performance data were collected at five mission phases: pre-flight, early flight, late flight, early post-flight, and late post-flight. We calculated speed and accuracy scores, corrected for practice effects, and derived z-scores to represent deviations in cognitive performance across mission phases from the sample’s mean baseline (i.e., pre-flight) performance. Linear mixed models with random subject intercepts and pairwise comparisons examined the relationships between mission phase and cognitive performance. Results: Cognitive performance was generally stable over time with some differences observed across mission phases for specific subtests. There was slowed performance observed in early flight on tasks of processing speed, visual working memory, and sustained attention. We observed a decrease in risk-taking propensity during late flight and post-flight mission phases. Beyond examining group differences, we inspected scores that represented a significant shift from the sample’s mean baseline score, revealing that 11.8% of all flight and post-flight scores were at or below 1.5 standard deviations below the sample’s baseline mean. Finally, exploratory analyses yielded no clear pattern of associations between cognitive performance and either sleep or ratings of alertness. Conclusions: There was no evidence for a systematic decline in cognitive performance for astronauts on a 6-month missions to the ISS. Some differences were observed for specific subtests at specific mission phases, suggesting that processing speed, visual working memory, sustained attention, and risk-taking propensity may be the cognitive domains most susceptible to change in Low Earth Orbit for high performing, professional astronauts. We provide descriptive statistics of pre-flight cognitive performance from 25 astronauts, the largest published preliminary normative database of its kind to date, to help identify significant performance decrements in future samples.

Data curation↗

NASA NTRS2024

Expanding Ketamine Application for Treatment of Acute Suicidality in Long-Duration Spaceflight

Introduction. The transition to exploration missions places a heightened risk on behavioral health in spaceflight. Although serious psychiatric emergencies during spaceflight have been rare, longer duration missions increase the possibility of emergence in latent mental health disorders due to genetic predisposition, increased autonomy, isolation, helplessness, loss of family member, or catastrophic events. Complicated grief and bereavement have the highest rate of suicidal ideation. Recently, ketamine has been used as an emergent intervention for acute suicidality, promoting its stability, ease of administration, favorable safety profile, and outcomes for reduction of suicidal intent. The goal of this study was to review current literature and collate the understanding of ketamine as a safe, effective pharmacological adjunct for acute suicidality in spaceflight. Methods. This literature review was conducted to collate data on ketamine use for acute suicidality and inform on stability, limitations and utilization of ketamine within extreme environments. Results. 122 publications were reviewed for relevance including 23 randomized-control trials for ketamine use in behavioral emergencies. Discussion. Ketamine is a diverse pharmaceutical with multiple advantageous indications, including acute suicidality, pain, and sedation. Terrestrial use of ketamine suggests a rapidly efficacious medication for reduction in acute suicidality. As behavioral stressors expand related to extended missions, contingencies for behavioral emergencies become increasingly important. Although this review is not intended to re-develop current International Space Station (ISS) protocols, it is the first to discuss the benefits of ketamine in spaceflight as a potential safe, effective multifaceted tool for future exploration missions and treatment for acute suicidal ideation.

Ketamine, Suicidality, Spaceflight↗

NASA NTRS2024

Enhancing the Payload Development Process for Lunar Gateway and Lunar Surface Science & Exploration: Space Biology Beyond Low-Earth-Orbit Instrumentation and Science Series (BLISS) Science Working Group 2023-2024 Annual Report

Space biology BLEO research is inherently driven by the differences between the LEO and BLEO environments, which can be broadly characterized by the five-hazard “RIDGE” paradigm (Radiation, Isolation, Distance, Gravity, Environment, e.g., similar to Figure 2 in (1)). Thus, the envisioned goals over the next decade will include using the cislunar and lunar surface environments to (A) characterize deep-space environments including biological effects of radiation and other stressors, (B) gain experience from isolation of very small groups in very small enclosures, (C) learn to compensate for distance from Earth via in situ resource utilization (ISRU) and bioregenerative life support, (D) gain assurance that all aspects of deep-space exploration can proceed in altered or artificial gravity environments, (E) develop essential adaptation scenarios for the built (e.g., low pressure) and external (e.g., temperature extremes, dust) environments.

Biology↗

NASA NTRSDate not supplied

A Heritage BioSensor for Lunar Biology Experiments

Introduction: Automated biological experiments on small spacecraft missions have gained prominence over the past decade due to their simplicity, accessibility, and small mass, volume, and power needs. Most recently, the BioSensor microfluidic CubeSat payload aboard BioSentinel used an automated microfluidic cell culture system to study the effects of environmental stressors like deep space radiation and microgravity on yeast growth and metabolism. BioSentinel’s successor, the Lunar Explorer Instrument for space biology Applications (LEIA), will study the effects of lunar gravity and radiation using an improved version of the BioSensor microfluidic platform. The BioSensor payload has great adaptability to host a diverse range of biological experiments with single- and multi-celled organisms in both crewed and uncrewed missions, making it a compelling candidate for future space biology studies in a lunar surface environment. BioSensor Instrumentation on BioSentinel: The first spaceflight mission with the BioSensor, BioSentinel’s biology experiments occurred at three locations -- deep space, ISS and ground. The payload contained 18 microfluidic cards, each featuring 16 growth wells (a total of 288 growth wells). Each well was loaded before launch with desiccated yeast. In space, liquid culture medium (nutrients) was automatically introduced to batches of wells at a time to initiate a series of biology experiments. Temperature was maintained by thin film heaters on both sides of each card. Each well was equipped with three LEDs emitting at 570 nm, 630 nm, and 850 nm, paired with photodetectors to measure cell concentration and the alamarBlue (metabolic indicator dye) color transition from blue to pink. Phenotypic parameters like cell viability, metabolic rate, and generation time can be derived from these measurements. The sequence and timing of fluid fills, optical measurements, and thermal control were stored onboard, but could be updated asynchronously via ground communication. LEIA: LEIA is slated for launch no earlier than 2026 on a CLPS lander. BioSentinel’s BioSensor has been modified for use in LEIA. These improvements include: (a) storage for multiple culture medium types, (b) additional LED color (465 nm) for a new biological assay for antioxidant (carotenoid) production, (c) housing modifications for later biology load before launch, (d) improved isolation between electronic and fluidic components, and (e) improved humidity control for prolonged organism viability in case of post-load launch delay. Future Prospects: The consistent and successful demonstration of complex fluidics platforms alongside reliable instrument operations in a space environment is poised to create strong momentum for BioSensor-based biological experiment payloads. Planned future developments with the BioSensor include extending compatibility to a broader range of organisms and assays. Preliminary work has already demonstrated successful growth of Arabidopsis seedlings in fluidic cards. With a few modifications to the optical assembly, the setup could easily measure photosynthetic traits in plants and cyanobacteria. The addition of fluorescence measurements and generation of novel luminescent assays will elevate BioSensor’s functionality further. Beyond the BioSensor’s potential uses on free-flyer missions, ISS and Gateway, and CLPS landers, deploying the BioSensor to the lunar surface or in an artificial habitat on crewed missions could enable pioneering research on both how life responds to lunar conditions and future bioproduction capabilities making the BioSensor an indispensable tool for future space biology research.

Chinmayee Govinda Raj↗

NASA NTRSDate not supplied

Impact of the ISS Environment on CNS in Drosophila Melanogaster

Altered gravity and elevated carbon dioxide (CO 2 ) levels as experienced on the ISS can adversely affect human health across various organ systems, especially the Central Nervous System (CNS). Investigating these changes is essential for understanding the long-term effects of spaceflight on human physiology to ensure crew health. Ground-based analogs provide an efficient method to evaluate alterations induced by chronic spaceflight on a larger scale. This study focuses on CNS changes in response to hypergravity (HG) and elevated CO 2 levels via a ground-based analog using the well-established model organism, Drosophila melanogaster. We hypothesize behavior and physiological changes immediately post exposure to HG+CO 2 , along with chronic effects up to 25 days post-exposure. Adult male and female flies were exposed to varying gravity loads (1g, 1.2g, and 3g) and elevated CO 2 levels (~4000 ppm, mimicking CO 2 levels on the ISS) for 15 days and were assessed immediately and at 5-, 10-, and 25-days post-exposure, mirroring astronauts’ post-return profiling. The flies were assessed for neurobehavioral changes, including longevity and negative geotaxis; brain morphological changes, such as dopaminergic neuron count, apoptosis, and glial cell density; and bioenergetic changes in the brain, including mitochondrial abundance and membrane potential. Longevity remained unchanged under hypergravity, even with the addition of elevated CO 2 as a stressor. However, despite the stable lifespan, quality of life appeared to be affected, as shown by negative geotaxis and neuroanatomical changes. Negative geotaxis testing revealed a reduction in motor ability at R0 across all conditions, which correlated with a decrease in dopaminergic (DA) neuron count. Additional observations suggested further systemic alterations, including a decrease in glial cell count, an increase in apoptosis, and notable bioenergetic changes. Collectively, these findings contribute to our understanding of the long-term effects of spaceflight on the CNS.

spaceflight↗

NASA NTRSDate not supplied

Yeast strain development to test in-space bioproduction in the Lunar Explorer Instrument for space biology Applications (LEIA) mission

The Lunar Explorer Instrument for space biology Applications (LEIA) is investigating the effects of lunar radiation and gravity on yeast viability, growth, and metabolism. LEIA is part of the CP-22 Commercial Lunar Payload Services (CLPS) surface mission to the south polar region of the Moon. The biological payload will test genetic factors that are likely to influence the tolerance of yeast for deep space and lunar surface radiation. LEIA is also investigating in-space production of β-carotene in bioengineered yeast. This carotenoid is both an antioxidant and pro-vitamin A- an essential human micronutrient. We report progress on engineering carotenoid-expressing strains to test the impacts of strain background and specific genetic variants on growth and production of β-carotene. To test for enhanced sensitivity to the LEIA mission environment, we generated gene knockouts for the RAD51 DNA damage repair locus as well as the SOD1, SOD2, and TSA1 reactive oxygen species (ROS) defense enzymes. We are also generating strains expected to increase tolerance to abiotic stressors and ROS. To be included in the biology payload, each strain needs to satisfy a series of requirements to be compatible with the mission concept of operations. The LEIA mission will conduct experiments using an autonomous light emitting diode optical detection system and microfluidics incubator to quantify growth, metabolism, and carotenoid production. Strains must produce sufficient carotenoids for bioproduction to be detectable with this optical system. Cells will be loaded into microfluidics cards, desiccated, and stored for 8-12 months prior to the initiation of lunar surface operations. The CLPS lander will operate for one lunar day, and strains will need to grow to stationary phase within 96 hours to ensure that telemetry of LEIA data to Earth can be completed. Genetic variants also need to display expected phenotypes within these optical detection, storage, and growth cycle constraints.

Yeast Engineering↗

NASA NTRSDate not supplied

Evaluating the Efficacy of Conditional Variational Autoencoders in Generating Synthetic Single Nuclei RNA-Seq Data for Space Biology Research

Astronauts are subject to unique stressors during spaceflight, leading to changes in their cellular function. However, neither astronauts nor model organisms respond the same to spaceflight, and research implicates a contribution of omics components in differential responses. Understanding how gene expression affects astronaut health is critical for the success of long-term space missions, prompting interest in developing personalized predictive models leveraging artificial intelligence (AI) and machine learning (ML) techniques. Developing such models requires extensive data, which is challenging to obtain and share. This study explores the use of conditional variational autoencoders (CVAEs) to synthetically generate single-nuclei RNA-seq (snRNA-seq) data. CVAEs build on standard variational autoencoders (VAEs) by conditioning data generation on covariates like sample identity and mission parameters, enhancing the relevance of generated data for specific contexts. For our work, we built two CVAEs with varying degrees of sparsity to optimize both interpretability and generative power. We train and validate models on existing snRNA-seq data collected from the brain tissue of mice subjected to spaceflight conditions and their ground control counterparts. We evaluate model performance using statistical tests and visualizations to compare synthetic data to real data. We aim to demonstrate that these prototype CVAE architectures could be used in future space biology work and that this is a method worth further exploring.

Sarah Golts↗

NASA NTRSDate not supplied

Exploration Medical Integrated Product Team Clinical Decision Support Market Survey

NASA’s Exploration Medical Integrated Product Team (XMIPT) has identified Clinical Decision Support (CDS) technology as a critical need for future human space exploration. Such technology will support real time diagnosis, monitoring, and treatment of spaceflight medical conditions. The need for such tools and support systems is critical for in-mission clinical decision-making, especially when Earth-based support is unavailable due to communication delays or blackouts. Supporting technologies may or may not involve Artificial Intelligence (AI), and would support astronaut crew with minimal clinical training, or even those with advanced training if they are, for example, in need of a refresher, experiencing multiple stressors, or temporarily overloaded with tasking. This need traces to the Development of Earth Independent Operations Technologies for NASA’s Mars Campaign Office. The CDS Market Survey purpose, methods, outcomes thus far, and near-term steps will be discussed.

Decision support↗

NASA NTRSDate not supplied

CIPHER: Egress Fitness

The transition between gravity environments will involve one of the most complex, high-risk phases of exploration missions. The reduced functional capacity caused by physiological deconditioning adaptations in microgravity coupled with the stressors of re-entry into partial gravity environments will increase risks to crew, even with rigorous adherence to inflight countermeasures. Specifically, two high-risk scenarios may be required to be performed soon after gravity transitions: 1) nominal and/or emergency unassisted capsule egress task after return to Earth, and 2) planetary extravehicular activity (EVA) soon after landing on Mars or the Moon. Quantification of crewmember’s functional performance after long-duration spaceflight is necessary to inform concepts of operations for future exploration missions. The overarching aim of this study is to quantify post-landing functional performance with deconditioning after long-duration ISS missions. This study is broken down into two phases. Phase 1 includes a pilot study to assess the overall feasibility and demonstrate the capability to perform mission-like tasks shortly after landing. Phase 2, the Egress Fitness study, which is part of the Complement of Integrated Protocols for Human Exploration Research (CIPHER), uses a task-based approach to characterize functional performance in long-duration ISS crewmembers before flight and shortly after return to Earth. The pilot and full Egress Fitness study includes pre-flight and post-flight testing of simulated emergency egress out of a functional capsule mockup and a Mars gravity EVA simulation at the Active Response Gravity Offload System (ARGOS) facility. The EVA simulation tasks include suit donning, hatch egress, ladder descent, task board cable operations, baggage transfer over sand/rocky regolith, alignment with a rear entry port, and suit egress. The post-flight simulated capsule egress test occurs 1–4 h after landing and the planetary EVA simulation occurs 18–36 h after landing. The full CIPHER Egress Fitness study has additional pre-flight sessions, longer EVA tasks that include traverse and geology sampling, and post-flight sessions on R+1, 4, and 8 to characterize the timeframe of recovery. Pilot Egress Fitness has completed baseline and post-flight testing on four crewmembers. That study remains open. Originally this was to cover the Boeing CFT mission, but now also includes private astronauts on commercial spaceflights. CIPHER study data collection is ongoing with 2 subjects completed and 4 additional subjects consented. This study will quantify post-landing functional performance in operationally relevant simulations to help inform fitness for duty standards and future planetary concepts of operations shortly after landing.

Jason Norcross↗

NASA NTRS2017

Cross-Disciplinarity in the Advance of Antarctic Ecosystem Research

The biodiversity, ecosystem services and climate variability of the Antarctic continent, and the Southern Ocean are major components of the whole Earth system. Antarctic ecosystems are driven more strongly by the physical environment than many other marine and terrestrial ecosystems. As a consequence, to understand ecological functioning, cross-disciplinary studies are especially important in Antarctic research. The conceptual study presented here is based on a workshop initiated by the Research Programme Antarctic Thresholds - Ecosystem Resilience and Adaption of the Scientific Committee on Antarctic Research, which focused on challenges in identifying and applying cross-disciplinary approaches in the Antarctic. Novel ideas, and first steps in their implementation, were clustered into eight themes, ranging from scale problems, risk maps, organism and ecosystem responses to multiple environmental changes, to evolutionary processes. Scaling models and data across different spatial and temporal scales were identified as an overarching challenge. Approaches to bridge gaps in the research programmes included multi-disciplinary monitoring, linking biomolecular findings and simulated physical environments, as well as integrative ecological modelling. New strategies in academic education are proposed. The results of advanced cross-disciplinary approaches can contribute significantly to our knowledge of ecosystem functioning, the consequences of climate change, and to global assessments that ultimately benefit humankind.

Scaling↗

NASA NTRSDate not supplied

Altered Immune Differentials Between Male and Female Mice Independent of Ionizing Irradiation

As upcoming exploratory missions to the Lunar surface and Mars during the Artemis Program will send both female and male crewmembers, studies identifying sex-specific effects are necessary. It is well-documented that the immune system engages different responses between females and males following exposures to infectious challenge, tumors surveillance, and autoimmune development. Yet, the immune effects of spaceflight-like exposures between the sexes are limited. Therefore, this study sought to address the effects of spaceflight-like conditions on immune differentials in female and male mice. We hypothesized that the spaceflight factor, ionizing radiation, will have sex-specific effects on immune differentials. To test this, singly-housed, 12-month old female and male wildtype (Wt) mice were exposed to acute ionizing gamma irradiation (50 cGy), followed by retro-orbital blood collections at 7-days post-irradiation. Leukocytes were analyzed by flow cytometry characterizing, granulocytes, monocytes, lymphocytes (cytotoxic/helper T cells and B cells), neutrophils, eosinophils, and NK/NKT cells. Briefly, minimal sex-specific effects were observed across the cell types listed at this time point, including changes in granulocyte and lymphocyte populations. The results revealed females displayed elevated granulocytes and reduced lymphocytes compared to their male counterparts, independent of irradiation exposure. These results suggest female mice may be more capable to produce innate inflammatory mediators but may be adaptively immune compromised. In brief, this study provides insight into the sex-specific immune risks following ionizing radiation that may be experienced during spaceflight, which is relevant for future countermeasure development.

spaceflight stressors↗

NASA NTRSDate not supplied

Altered Immune Differentials Between Male and Female Mice Independent of Ionizing Irradiation

spaceflight stressors↗

NASA NTRS2021

Advancing Space Life Science Research Using Drosophila Melanogaster

As we embark on exploring deep space, it is imperative to unravel the impacts of such unique and dynamic environments on biological systems. Multiple studies using D. melanogaster, a well-established spaceflight model, have paved the way towards our understanding of spaceflight-associated health risks. Further, Drosophila quantitative genomic experiments along with improved automated hardware systems will enable efficient and effective identification of the underlying genetic and molecular determinants capable of physiological adaptation to endure harsh space environments.

Quantitative genomics↗

NASA NTRSDate not supplied

Impact of Simulated Galactic Cosmic Radiation and Hindlimb Unloading on the Mouse Adrenal Gland Morphology and Histology

Stress related impact of Galactic Cosmic Radiation (GCR) combined with microgravity in space are concerns for astronauts going beyond the Van Allen belts on their way to the Moon and Mars. The adrenal gland is the central endocrine tissue involved in stress management, adrenal hormones regulate the immune system, cellular and tissue metabolism, and glucose and sodium balances. Adult (6 m old) female (n=18) and male (n=18) C57BL/6J mice were divided evenly into 6 treatment groups (control, hindlimb unloading (HU), irradiated (IR), HU+IR, group house control, and group house IR). Adrenals were dissected and fixed for 24 h in 4% paraformaldehyde, followed by transfer to 70% EtOH, and shipment to KUMC. Adrenals were then embedded in paraffin and serial sectioned and 4 central sections from each were stained with H&E, prior to imaging on a Nikon 80i microscope. Whole adrenal cross section area, medullary area, and cortex area were determined. General adrenal gland morphology and histology did not appear to be affected by hindlimb unloading or GCR exposure. Total cross-sectional area, medullary region, and cortex of the adrenal were not different across treatment groups. Male adrenal cross-sectional areas are half the size of the female adrenals, due to a difference in cortex area. In conclusion, simulated microgravity and GCR did not dramatically affect the adrenal gland histology or size. Support from Accelerate Cancer Education Internship Program (KUCC) and KINBRE Summer Scholars Program (KUMC) and NASA Human Research Program (HRP) Human Factors Behavioral Performance Element Grant 18 18FLAG 2 0028

radiation↗