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All sourcesNASA NTRSDOE OSTI
NASA NTRS2014

Transgenic Mouse Model for Reducing Oxidative Damage in Bone

Exposure to musculoskeletal disuse and radiation result in bone loss; we hypothesized that these catabolic treatments cause excess reactive oxygen species (ROS), and thereby alter the tight balance between bone resorption by osteoclasts and bone formation by osteoblasts, culminating in bone loss. To test this, we used transgenic mice which over-express the human gene for catalase, targeted to mitochondria (MCAT). Catalase is an anti-oxidant that converts the ROS hydrogen peroxide into water and oxygen. MCAT mice were shown previously to display reduced mitochondrial oxidative stress and radiosensitivity of the CNS compared to wild type controls (WT). As expected, MCAT mice expressed the transgene in skeletal tissue, and in marrow-derived osteoblasts and osteoclast precursors cultured ex vivo, and also showed greater catalase activity compared to wildtype (WT) mice (3-6 fold). Colony expansion in marrow cells cultured under osteoblastogenic conditions was 2-fold greater in the MCAT mice compared to WT mice, while the extent of mineralization was unaffected. MCAT mice had slightly longer tibiae than WT mice (2%, P less than 0.01), although cortical bone area was slightly lower in MCAT mice than WT mice (10%, p=0.09). To challenge the skeletal system, mice were treated by exposure to combined disuse (2 wk Hindlimb Unloading) and total body irradiation Cs(137) (2 Gy, 0.8 Gy/min), then bone parameters were analyzed by 2-factor ANOVA to detect possible interaction effects. Treatment caused a 2-fold increase (p=0.015) in malondialdehyde levels of bone tissue (ELISA) in WT mice, but had no effect in MCAT mice. These findings indicate that the transgene conferred protection from oxidative damage caused by treatment. Unexpected differences between WT and MCAT mice emerged in skeletal responses to treatment.. In WT mice, treatment did not alter osteoblastogenesis, cortical bone area, moment of inertia, or bone perimeter, whereas in MCAT mice, treatment increased these parameters. Taken together, this typically catabolic treatment (disuse and irradiation) appeared to stimulate cortical expansion in MCAT mice but not WT mice. In conclusion, these results reveal the importance of mitochondrial ROS generation in skeletal remodeling and show that MCAT mice provide a useful animal model for bone studies.

trandgenic↗
NASA NTRS2017

Pulmonary Inflammatory Responses to Acute Meteorite Dust Exposures - to Acute Meteorite Dust Exposures - Exploration

New initiatives to begin lunar and martian colonization within the next few decades are illustrative of the resurgence of interest in space travel. One of NASA's major concerns with extended human space exploration is the inadvertent and repeated exposure to unknown dust. This highly interdisciplinary study evaluates both the geochemical reactivity (e.g. iron solubility and acellular reactive oxygen species (ROS) generation) and the relative toxicity (e.g. in vitro and in vivo pulmonary inflammation) of six meteorite samples representing either basalt or regolith breccia on the surface of the Moon, Mars, and Asteroid 4Vesta. Terrestrial mid-ocean ridge basalt (MORB) is also used for comparison. The MORB demonstrated higher geochemical reactivity than most of the meteorite samples but caused the lowest acute pulmonary inflammation (API). Notably, the two martian meteorites generated some of the highest API but only the basaltic sample is significantly reactive geochemically. Furthermore, while there is a correlation between a meteorite's soluble iron content and its ability to generate acellular ROS, there is no direct correlation between a particle's ability to generate ROS acellularly and its ability to generate API. However, assorted in vivo API markers did demonstrate strong positive correlations with increasing bulk Fenton metal content. In summary, this comprehensive dataset allows for not only the toxicological evaluation of astromaterials but also clarifies important correlations between geochemistry and health.

Harrington, A. D.↗
NASA NTRS2018

Aging and Spaceflight: Catalase Targeted to Mitochondria Alters Skeletal Structure and Responses to Musculoskeletal Disuse

Microgravity and ionizing radiation in the spaceflight environment pose multiple challenges to homeostasis and may contribute to cellular stress. Effects may include increased generation of reactive oxygen species (ROS), DNA damage and repair error, cell cycle arrest, cell senescence or death. Our central hypothesis is that prolonged exposure to the spaceflight environment leads to excess production of ROS and oxidative damage, culminating in accelerated tissue degeneration which resembles aging. The main goal of this project is to determine the importance of cellular redox defense for physiological adaptations and tissue degeneration in the space environment. To accomplish this, we will use both wildtype (WT) mice and a well-established, genetically-engineered animal model (mCAT mice) which displays extended lifespan (Schriner et al. 2005). The animal model selected to test these ideas is engineered to quench ROS in mitochondria by targeted over-expression of the human catalase gene to the mitochondrial matrix. We showed previously that mCAT mice express the catalase transgene in skeletal tissues, bone forming osteoblasts, and bone resorbing osteoclasts. In addition, mCAT mice also display increased catalase activity in bone. Our findings revealed that exposure of adult, male, C57Bl/6J mice to simulated spaceflight (hindlimb unloading and gamma radiation) led to an increase in markers of oxidative damage (malondialdehyde, 4-hydroxynonenol) in skeletal tissue of WT mice but not mCAT mice. To extend our hypothesis to other, spaceflight-relevant tissues, we are performing a ground-based study simulating 30 days of spaceflight by hindlimb unloading to determine potential protective effects of mitochondrial catalase activity on aging of multiple tissues (cardiovascular, nervous and skeletal).

transgenic mice↗
NASA NTRS2019

Simulated Microgravity Affects Behavior and Cytokine Expression in the Hippocampus of Adult Mice: Influence of Mitochondrial Reactive Oxygen Species

The effects of microgravity, and social isolation on the CNS are poorly understood. We hypothesize that mitochondrial reactive oxygen species (ROS) play an important role in this process. Since mice are social animals, our lab developed a novel social model of hindlimb unloading (HU), enabling us to determine the effects of both social isolation and simulated microgravity. Responses to 30d of HU were compared in wildtype or transgenic MCAT mice who over-express human catalase in mitochondria. Abundance of 4-Hydroxynonenal, Park7 (a redox-sensitive chaperone and sensor of oxidative stress) and corticosterone were measured by ELISA. Cytokines related to inflammation in the hippocampus and in plasma were analyzed by a protein array. Behavioral data was collected over a 24-hour period.Socially housed HU mice were more active and conducted at least two times more exploratory activities, compared to normally loaded mice. Correlation analysis revealed that specific brain and plasma cytokines correspond with specific behaviors. Simulated microgravity and/or social isolation caused changes in cytokine patterns in the hippocampus and in plasma, with significant interaction effects of HU and genotype in expression levels of five cytokines (out of 35). Interestingly, elevation of these generally pro-inflammatory cytokines by HU in WT mice was mitigated in MCAT mice, suggesting a role for mitochondrial ROS signaling in inflammatory CNS responses to microgravity. Interestingly, socially housed mice had also lower level of 4HNE and higher level of Park7 in the hippocampus compared to singly housed animals. The cytokine responses to social isolation were more extensive in brain vs plasma. Further, there was no overlap in the cytokine repertoire regulated in response to microgravity versus, isolation suggesting divergent mechanisms or downstream signaling. These findings implicate a potentially important role for mitochondrial ROS in CNS responses to the challenges posed both by prolonged missions in space and bedrest on Earth

Guttmann, Linda↗
NASA NTRSDate not supplied

Behavioral consequences of low dose radiation and sex differences in MCAT mouse model

Our study used 1-year old C57BL/6NJ male and female mice (astronaut-relevant age) that underwent exposure to 0.5 gray of gamma radiation and were euthanized 12 weeks after. In this study, we used an MCAT mouse model for mitochondrial ROS quenching, which overexpress human catalase. MCAT mice were shown to live longer and age better. Hence, in this study we determined whether quenching ROS in the mitochondria will mitigate the adverse effects of ionizing radiation exposure on spaceflight-relevant tissues. As part of the analysis, we have completed 5 different behavioral tests which focus on memory, physical stance, stress, anxiety, and other mission relevant behaviors. In the Neuro-score battery, performed after both 1and 8 weeks post IR we saw that all female groups had significantly higher scores compared to males. When comparing the baseline vs 8 weeks of radiation, we saw that all the male groups (including the sham) had lower neuro-score, pointing out to aging effect in addition to IR. In the female groups only the female IR group had lower neuro-score and the MCAT group was protected from this effect. In the Nestlet building test we saw similarly that only females were affected by radiation, having lower scores and this effect was mitigated in the MCAT animals as well. In the Catwalk test we saw that females were faster, had higher swing speed and stride length in all four paws. Males had higher stand, step cycle and max contact area. Aging is associated with slowing of gait speed, swing speed and shortening of stride length which we see in males, this is consistent with physical appearance where males look markedly older. In the Light-Dark Box test we saw that females were more frequently present in the light side and altered zones more frequently, pointing out to a more exploratory and less anxious pattern of behavior. Similarly, to what was detected in the Nest building and Neuro-score test, in the Barnes maze test, during the acquisition phase (learning) we saw that IR affected more the females who did not do better in the maze after 4 days. On the other hand, during the probe phase of the test (spatial memory) the females visited the target hole and the box quadrant more often, but also had more errors vs males, which points out to possible serial escape vs spatial escape strategy. Overall, we see that older females look physically better are faster and perform better almost in all behavioral tests compared to their male counterparts. On the other hand, they are more sensitive to low dose radiation in many cases, in some cases this effect was mitigated in the MCAT model pointing out to the importance of ROS in these stressors. In the near future we will focus on corelating these behavioral tests with molecular findings such as for example brain IHC, plasma and hippocampal cytokines in order to find specific biomarkers for behavioral deficits.

radiation↗
NASA NTRSDate not supplied

VIPER: Volatiles Investigating Polar Exploration Rover

We will review the technical components of the NASA lunar rover mission, VIPER, with a focus on software components that rely on ROS 2 and Gazebo. We’ll start with an overview of the hardware and software components. Next, we’ll explore some of the custom Gazebo plugins for simulating the rover and the lunar surface. We’ll describe a fault injection framework that was built on ROS 2 parameters and how it is used to simulate hardware faults. Finally, we’ll see how ROS 2 is used as part of the rover ground software.

Jacob Michael Perron↗
NASA NTRSDate not supplied

Autonomous Ocean World Exploration: Advancement of a Virtual Testbed

The search for life (extinct or extant) and potentially habitable bodies in our solar system and beyond is one of the 12 priority science questions outlined in the National Acadamies’ 2022 decadal survey [5]. Extraterrestrial destinations containing liquid water present an opportunity to search for life as we know it, and in recent years an increasing number of such locations have been discovered within our solar system. Several Jovian moons—Europa, Ganymede, and Callisto [10]—and the Saturnian moons Enceladus [8] and Titan [9] are known or suspected to harbor massive subsurface oceans. Of these "ocean worlds", Europa is the focus of at least one planned NASA orbiter mission, Europa Clipper [4], and an early lander mission concept, the Europa Lander [2, 3]. Whereas most robotic missions to the Moon and Mars (e.g. orbiters, rovers, landers) to date have had ground controllers on Earth tightly involved in mission operations, missions to more distant worlds will require a high degree of onboard autonomy due to long communication lags and blackouts, harsh environments (radiation, cold), and more limited battery and hardware life. The past decade has seen great advances in both AI technologies and computing scalability and performance that offer promising solutions for spacecraft autonomy and motivate the software system and research programs described in this paper. The Ocean Worlds Autonomy Testbed for Exploration, Research, and Simulation (OceanWATERS) [1], which has been in development at the NASA Ames Research Center since 2018, is a virtual environment for testing lander autonomy solutions. It is built on the Robot Operating System (ROS), runs on consumer-grade Linux workstations, and was released as open source in 2020. OceanWATERS provides a physical and visual simulation of a prototypical lander in a Europa-like environment (Figure 1). The lander was modeled after requirements and specifications made in JPL’s Europa Lander Study of 2016 [3]. Simulated lander systems include stereo cameras and spotlights mounted on an antenna mast that pans and tilts, a 6 degrees of freedom (DoF) robotic arm with a force-torque sensor and two interchangeable end effectors, and a battery pack power system. The environment consists of multiple terrain models including a highly detailed model sourced from the FROST dataset [11], simulation of surrounding planetary bodies based on an ephemeris model, and lighting from the sun with associated surface illumination, reflectance, and shadows. Operations supported by OceanWATERS include panoramic and directed imaging of the environment and lander workspace, Cartesian and joint-level arm commanding, grinding of the terrain surface (e.g. digging a trench), and scooping of ground material (Figure 2) which can be discarded or collected as science samples in a receptacle that can be emptied (science operations themselves are not simulated). These operations are realized as ROS Actions and are complimented by a wide selection of telemetry that is continually produced by each lander subsystem. The power system model is driven by the open-source Generic Software Architecture for Prognostics (GSAP) [11] that predicts the battery’s remaining useful life and other characteristics. As a testbed for high-level autonomy, OceanWATERS provides an execution framework based on PLEXIL [12], an open-source plan specification language and execution engine developed largely at Ames. NASA's initial development of OceanWATERS, as well the Ocean Worlds Lander Autonomy Testbed (OWLAT) [6], a complimentary physical testbed developed at JPL, was the first step in a plan for realizing candidate onboard autonomy solutions for such planetary landers. In 2020 NASA solicited applications for its Autonomous Robotics Research for Ocean Worlds (ARROW) program, and in 2021 the similar Concepts for Ocean worlds Life Detection Technology (COLDTech) program. Collectively six research teams, based in universities and companies across the United States, were awarded grants to develop and demonstrate autonomy solutions on OceanWATERS and OWLAT. These 1–2-year projects have now finished or are nearing completion, and a wide variety of autonomy challenges in ocean world surface missions were addressed. Prototyped and demonstrated solutions have included autonomous discovery, response and adaptation to system faults and unexpected environmental events, world model synthesis through perception, plan synthesis using learned models, methods to optimize sample target selection and prioritize science data transmission, extension of PLEXIL for stochastic decision-making, and an integration of a model of JPL’s mission-ready COLDArm [7]. Technologies used in these projects include many forms of machine learning, causal reasoning, automated planning, Markov decision processes, formal methods, and other advanced techniques. A more detailed summary of the ARROW and COLDTech projects is given herein. OceanWATERS has had significant enhancements since its open-source release in 2020. Many of its new features were driven or shaped by feedback from the ARROW and COLDTech teams and requirements of their projects. In support of enabling autonomous adaptation to spacecraft faults (a specific capability solicited by both programs), a fault injection and detection framework was developed that supports a wide and growing range of fault types such as locked joints, image loss, and battery failures. The power system model was completed and integrated into the simulator, starting as a single-cell battery model and later upgraded to a multi-cell model with associated faults such as cell disconnection. Arm/terrain interaction was improved by adding a force-torque sensor and associated faults, and an analytic dig force model based on the Balovnev bucket force equations. Environment fidelity was increased by modeling terrain deformation resulting from digging and scooping; visual improvements were made in textures, lighting, and shadows. To facilitate interoperation with OWLAT, a unified command and telemetry interface between the testbeds was developed at the ROS level, along with a PLEXIL interface. The number of lander operations was greatly expanded (e.g. with Cartesian-based arm and antenna movement), and a framework was designed for users to build their own lander actions. A GUI for PLEXIL plan selection was created (Figure 3), and an expansive set of plans were added, such as those that illustrate patterns for fault handling. This paper provides a self-contained high-level description of OceanWATERS, focusing on more detailed coverage of the aforementioned enhancements. It provides a high-level summary of the projects undertaken by participants in the ARROW and COLDTech programs and how these efforts have helped shape OceanWATERS. Finally, potential future work and directions for the testbed are listed, as likely informed by the recent planetary science decadal survey [5].

K Michael Dalal↗
NASA NTRS1994

A phyllosilicate-sulfide vein in Kaidun

A fragment of a carbonaceous chondrite (#53.12, maximal dimension about 2 mm) containing a phyllosilicate-sulfide vein was found during an inspection of small pieces of the Kaidun meteorite. Phyllosilicate veins are apparently rare in carbonaceous chondrites and have so far only been reported from the Y82162 CI chondrite. In hand sample the vein was visible on two perpendicular faces. The polished section prepared from one side displays a complex structure. A single vein, 150 microns in width, bifurcates, and each branch narrows toward a large rounded object (RO). The section contains abundant ROs, most of them less than or equal to 100 microns in diameter. The vein has sharp contacts to the surrounding matrix, whereas the RO contacts are diffuse. The phyllosilicate in the main vein has a massive texture along the contact, which becomes platy toward the vein center where the crystals protrude into an open space. The texture of the largest RO resembles that of a barred olivine (BO) chondrule. Some of the smaller ROs also texturally resemble chondrules. The BO chondrule contains rounded sulfide-silicate objects and small metal grains covered by oxides. Phyllosilicates of the main vein consist mainly of serpentine. The phyllosilicate near the contact with the matrix has low contents of minor elements and a high Mg/Fe ratio. The composition changes in a regular manner toward the center: Al, Na, Ca, Ni, and S increase, indicating increasing amounts of sulfates admixed. The phyllosilicate vein could only have formed after a substantial rock was formed. Mechanical stress probably opened a crack that was subsequently filled by phyllosilicate, pyrrhotite, and finally by a (Fe,Mg)-sulfate. The source of the matter mobilized to form the vein could have been within the rock itself or outside. No compositional or mineralogical zoning is apparent at the vein-rock contacts. The nature of the transporting agent (liquid H2O or vapor) must also remain an enigma. M. Zolensky has recently observed similar phyllosilicate-filled veins in dark, wet clasts in the Al Rais CR chondrite.

Ivanov, A. V.↗
NASA NTRS2003

Hydrogen peroxide stimulates ubiquitin-conjugating activity and expression of genes for specific E2 and E3 proteins in skeletal muscle myotubes

Reactive oxygen species (ROS) are thought to promote muscle atrophy in chronic wasting diseases, but the underlying mechanism has not been determined. Here we show that H2O2 stimulates ubiquitin conjugation to muscle proteins through transcriptional regulation of the enzymes (E2 and E3 proteins) that conjugate ubiquitin to muscle proteins. Incubation of C2C12 myotubes with 100 microM H2O2 increased the rate of 125I-labeled ubiquitin conjugation to muscle proteins in whole cell extracts. This response required at least 4-h exposure to H2O2 and persisted for at least 24 h. Preincubating myotubes with cycloheximide or actinomycin D blocked H2O2 stimulation of ubiquitin-conjugating activity, suggesting that gene transcription is required. Northern blot analyses revealed that H2O2 upregulates expression of specific E3 and E2 proteins that are thought to regulate muscle catabolism, including atrogin1/MAFbx, MuRF1, and E214k. These results suggest that ROS stimulate protein catabolism in skeletal muscle by upregulating the ubiquitin conjugation system.

Non-NASA Center↗
NASA NTRS2005

Activation of nuclear transcription factor-kappaB in mouse brain induced by a simulated microgravity environment

Microgravity induces inflammatory responses and modulates immune functions that may increase oxidative stress. Exposure to a microgravity environment induces adverse neurological effects; however, there is little research exploring the etiology of these effects resulting from exposure to such an environment. It is also known that spaceflight is associated with increase in oxidative stress; however, this phenomenon has not been reproduced in land-based simulated microgravity models. In this study, an attempt has been made to show the induction of reactive oxygen species (ROS) in mice brain, using ground-based microgravity simulator. Increased ROS was observed in brain stem and frontal cortex with concomitant decrease in glutathione, on exposing mice to simulated microgravity for 7 d. Oxidative stress-induced activation of nuclear factor-kappaB was observed in all the regions of the brain. Moreover, mitogen-activated protein kinase kinase was phosphorylated equally in all regions of the brain exposed to simulated microgravity. These results suggest that exposure of brain to simulated microgravity can induce expression of certain transcription factors, and these have been earlier argued to be oxidative stress dependent.

Non-NASA Center↗
NASA NTRS2007

Anti-radiation vaccine: Immunologically-based Prophylaxis of Acute Toxic Radiation Syndromes Associated with Long-term Space Flight

Protecting crew from ionizing radiation is a key life sciences problem for long-duration space missions. The three major sources/types of radiation are found in space: galactic cosmic rays, trapped Van Allen belt radiation, and solar particle events. All present varying degrees of hazard to crews; however, exposure to high doses of any of these types of radiation ultimately induce both acute and long-term biological effects. High doses of space radiation can lead to the development of toxicity associated with the acute radiation syndrome (ARS) which could have significant mission impact, and even render the crew incapable of performing flight duties. The creation of efficient radiation protection technologies is considered an important target in space radiobiology, immunology, biochemistry and pharmacology. Two major mechanisms of cellular, organelle, and molecular destruction as a result of radiation exposure have been identified: 1) damage induced directly by incident radiation on the macromolecules they encounter and 2) radiolysis of water and generation of secondary free radicals and reactive oxygen species (ROS), which induce chemical bond breakage, molecular substitutions, and damage to biological molecules and membranes. Free-radical scavengers and antioxidants, which neutralize the damaging activities of ROS, are effective in reducing the impact of small to moderate doses of radiation. In the case of high doses of radiation, antioxidants alone may be inadequate as a radioprotective therapy. However, it remains a valuable component of a more holistic strategy of prophylaxis and therapy. High doses of radiation directly damage biological molecules and modify chemical bond, resulting in the main pathological processes that drive the development of acute radiation syndromes (ARS). Which of two types of radiation-induced cellular lethality that ultimately develops, apoptosis or necrosis, depends on the spectrum of incident radiation, dose, dose rate, and functional conditions of impacted cells/organisms. The administration of an experimental anti-radiation vaccine may provide an immunologically based, adjunct method of prevention or prophylaxis against clinical ARS. The administration of experimental anti-radiation serum (ARS) and the use of the blood dialysis methods, such as immune plasma-sorption, may assist in the clearance of radiation-specific toxins and may enhance established strategies for the mitigation of the biological effects leading to ARS, and should be evaluated for use on exploration-class space missions.

Popov, Dmitri↗
NASA NTRS2010

Iron Homeostasis in Yellowstone National Park Hot Spring Microbial Communities

It has been postulated that life may have originated on Earth, and possibly on Mars, in association with hydrothermal activity and high concentrations of ferrous iron. However, it is not clear how an iron-rich thermal hydrosphere could be hospitable to microbes, since reduced iron appears to stimulate oxidative stress in all domains of life and particularly in oxygenic phototrophs. Therefore, the study of microbial diversity in iron-depositing hot springs (IDHS) and the mechanisms of iron homeostasis and suppression of oxidative stress may help elucidate how Precambrian organisms could withstand the extremely high concentrations of reactive oxygen species (ROS) produced by interaction between environmental Fe(2+) and O2. Proteins and clusters of orthologous groups (COGs) involved in the maintenance of Fe homeostasis found in cyanobacteria (CB) inhabiting environments with high and low [Fe] were main target of this analysis. Preliminary results of the analysis suggest that the Chocolate Pots (CP) microbial community is heavily dominated by phototrophs from the cyanobacteria (CB), Chloroflexi and Chlorobi phyla, while the Mushroom Spring (MS) effluent channel harbors a more diverse community in which Chloroflexi are the dominant phototrophs. It is speculated that CB inhabiting IDHS have an increased tolerance to both high concentrations of Fe(2+) and ROS produced in the Fenton reaction. This hypothesis was explored via a comparative analysis of the diversity of proteins and COGs involved in Fe and redox homeostasis in the CP and MS microbiomes.

Brown, I.↗
NASA NTRS2016

Electromagnetic Basis of Metabolism and Heredity

Living organisms control their cellular biological clocks to maintain functional oscillation of the redox cycle, also called the "metabolic cycle" or "respiratory cycle". Organization of cellular processes requires parallel processing on a synchronized time-base. These clocks coordinate the timing of all biochemical processes in the cell, including energy production, DNA replication, and RNA transcription. When this universal time keeping function is perturbed by exogenous induction of reactive oxygen species (ROS), the rate of metabolism changes. This causes oxidative stress, aging and mutations. Therefore, good temporal coordination of the redox cycle not only actively prevents chemical conflict between the reductive and oxidative partial reactions; it also maintains genome integrity and lifespan. Moreover, this universal biochemical rhythm can be disrupted by ROS induction in vivo. This in turn can be achieved by blocking the electron transport chain either endogenously or exogenously by various metabolites, e.g. hydrogen sulfide (H2S), highly diffusible drugs, and carbon monoxide (CO). Alternatively, the electron transport in vivo can be attenuated via a coherent or interfering transfer of energy from exogenous ultralow frequency (ULF) and extremely low frequency (ELF) electromagnetic (EM) fields, suggesting that-on Earth-such ambient fields are an omnipresent (and probably crucially important) factor for the time-setting basis of universal biochemical reactions in living cells. Our work demonstrated previously un-described evidence for quantum effects in biology by electromagnetic coupling below thermal noise at the universal electron transport chain (ETC) in vivo.

Electromagnetic↗
NASA NTRS2014

Role of Oxidative Damage in Radiation-Induced Bone Loss

During prolonged spaceflight, astronauts are exposed to both microgravity and space radiation, and are at risk for increased skeletal fragility due to bone loss. Evidence from rodent experiments demonstrates that both microgravity and ionizing radiation can cause bone loss due to increased bone-resorbing osteoclasts and decreased bone-forming osteoblasts, although the underlying molecular mechanisms for these changes are not fully understood. We hypothesized that excess reactive oxidative species (ROS), produced by conditions that simulate spaceflight, alter the tight balance between osteoclast and osteoblast activities, leading to accelerated skeletal remodeling and culminating in bone loss. To test this, we used the MCAT mouse model; these transgenic mice over-express the human catalase gene targeted to mitochondria, the major organelle contributing free radicals. Catalase is an anti-oxidant that converts reactive species, hydrogen peroxide into water and oxygen. This animal model was selected as it displays extended lifespan, reduced cardiovascular disease and reduced central nervous system radio-sensitivity, consistent with elevated anti-oxidant activity conferred by the transgene. We reasoned that mice overexpressing catalase in mitochondria of osteoblast and osteoclast lineage cells would be protected from the bone loss caused by simulated spaceflight. Over-expression of human catalase localized to mitochondria caused various skeletal phenotypic changes compared to WT mice; this includes greater bone length, decreased cortical bone area and moment of inertia, and indications of altered microarchitecture. These findings indicate mitochondrial ROS are important for normal bone-remodeling and skeletal integrity. Catalase over-expression did not fully protect skeletal tissue from structural decrements caused by simulated spaceflight; however there was significant protection in terms of cellular oxidative damage (MDA levels) to the skeletal tissue. Furthermore, we used an array of countermeasures (Antioxidant diets and injections) to prevent the radiation-induced bone loss, although these did not prevent bone loss, analysis is ongoing to determine if these countermeasure protected radiation-induced damage to other tissues.

oxidative damage↗
NASA NTRS2017

Role of Mitochondrial Oxidative Stress in Spaceflight-Induced Tissue Degeneration

Microgravity and ionizing radiation in the spaceflight environment poses multiple challenges to homeostasis and may contribute to cellular stress. Effects may include increased generation of reactive oxygen species (ROS), DNA damage and repair error, cell cycle arrest, cell senescence or death. Our central hypothesis is that prolonged exposure to the spaceflight environment leads to the excess production of ROS and oxidative damage, culminating in accelerated tissue degeneration. The main goal of this project is to determine the importance of cellular redox defense for physiological adaptations and tissue degeneration in the space environment.

transgenic mic↗
NASA NTRS2019

Planetary Rover Simulation for Lunar Exploration Missions

When planning planetary rover missions it is useful to develop intuition and skills driving in, quite literally, alien environments before incurring the cost of reaching said locales. Simulators make it possible to operate in environments that have the physical characteristics of target locations without the expense and overhead of extensive physical tests. To that end, NASA Ames and Open Robotics collaborated on a Lunar rover driving simulator based on the open source Gazebo simulation platform and leveraging ROS (Robotic Operating System) components. The simulator was integrated with research and mission software for rover driving, system monitoring, and science instrument simulation to constitute an end-to-end Lunar mission simulation capability. Although we expect our simulator to be applicable to arbitrary Lunar regions, we designed to a reference mission of prospecting in polar regions. The harsh lighting and low illumination angles at the Lunar poles combine with the unique reflectance properties of Lunar regolith to present a challenging visual environment for both human and computer perception. Our simulator placed an emphasis on high fidelity visual simulation in order to produce synthetic imagery suitable for evaluating human rover drivers with navigation tasks, as well as providing test data for computer vision software development.In this paper, we describe the software used to construct the simulated Lunar environment and the components of the driving simulation. Our synthetic terrain generation software artificially increases the resolution of Lunar digital elevation maps by fractal synthesis and inserts craters and rocks based on Lunar size-frequency distribution models. We describe the necessary enhancements to import large scale, high resolution terrains into Gazebo, as well as our approach to modeling the visual environment of the Lunar surface. An overview of the mission software system is provided, along with how ROS was used to emulate flight software components that had not been developed yet. Finally, we discuss the effect of using the high-fidelity synthetic Lunar images for visual odometry. We also characterize the wheel slip model, and find some inconsistencies in the produced wheel slip behaviour.

Allan, Mark↗
NASA NTRS2019

Reduced Gravity Contributes to Neutrophil to Lymphocyte Ratio Shifting and Promotion of the Oxidative Stress Response

Spaceflight can cause immune system dysfunction, such as elevated white blood cells (WBC) and polymorphonuclear neutrophils (PMN), along with unchanged or reduced lymphocyte counts. A high PMN to lymphocyte ratio (NLR) can acts as a poor prognosis in cancer and a biomarker for subclinical inflammation however, the NLR has not been identified as a predictor of astronaut health during spaceflight. CBC data collected on board the International Space Station (ISS) was repurposed to determine the granulocyte to lymphocyte ratio (GLR) in humans and the NLR in rodents. The results displayed a progressive increase in GLR and NLR during spaceflight and at landing. The mechanism for increased NLR was assessed in vitro using the microgravity-analog, rotating wall vessel (RWV), with human WBCs. The results indicated that simulated microgravity led to increased GLR and NLR profiles, and production of reactive oxygen species (ROS) and myeloperoxidase (MPO). Interestingly, simulated microgravity increased the number of matured PMNs that showed impaired phagocytic function, while treatment with tert-Butyl hydroperoxide (TBHP), also reduced PMN phagocytosis. In addition, 30-days of simulated microgravity (hindlimb unloading) in mice, indicated an increased NLR and MPO gene expression, which were mitigated in mitochondrial catalase overexpressing transgenic mice, suggesting ROS scavenging is essential for maintaining homeostatic immunity. Collectively, we propose that the health status of astronauts during future short- and long-term space missions can be monitored by their NLR profile, in addition to utilizing this measurement as a tool for oxidative stress response countermeasure development to restore homeostatic immunity.

Paul, Amber M.↗
NASA NTRS2019

Modeled Microgravity Induces Neutrophil Extracellular Trap (NET)osis Formation and Reduced Phagocytosis of Polymorphonuclear Neutrophils

Spaceflight can dysregulate immunity, by way of increasing granulocytes numbers with impaired function. Polymorphonuclear neutrophils (PMN) are granulocytes that are first responders to infection or injury, and consist of the largest pool of immune cells in humans. PMNs function during innate immunity, through phagocytosis and promotion of inflammation, via the release of reactive oxygen species (ROS) mediators and granule-containing enzymes, such as myeloperoxidase (MPO) and NADPH oxidase-2 (NOX-2). In addition, neutrophil extracellular trap (NET) formation is another mechanism of PMN surveillance that works independently of engulfment phagocytosis, and is a last resort function that can induce NETosis or PMN-specific cell death. Previous studies in our lab have identified increased mature neutrophils, ROS and MPO production, and reduced phagocytosis in granulocytes in simulated microgravity (sug) models of hindlimb unloading (HU) in adult mice and leukocytes cultured in high-aspect rotating wall vessels (HARV-RWV). Since sug impaired phagocytosis, but improved enzymatic mediator production of MPO and redox molecules, we sought to address the third known function of PMNs, NETosis. For this, PMNs were culture in the presence or absence of the anti-oxidant N-acetyl cysteine (NAC), which rescued impaired phagocytosis that was present in sug without NAC treatment. Further, NETosis was induced in sug that was no different in the presence of NAC, suggesting NAC targets independent functions of PMNs under sug. Collectively, these results suggest modeled microgravity induced NETosis, which opens a new avenue for spaceflight studies in immune dysfunction.

Paul, Amber M.↗