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At least 523 records · Page 29

Histological and Transcriptomic Analysis of Spaceflight-Induced Ocular Changes in the Mouse Retina

Anatomical changes have been observed in astronauts’ eyes after long duration spaceflight missions. These alterations can lead to visual impairment which in part constitutes the spaceflight-associated neuroocular syndrome (SANS), one of the top risk priorities for deep space missions. The HRP Systems Biology (SysBio) Translation Project will apply systems biology approaches utilizing current human physiological spaceflight data, molecular results from rodents, and future research with a multi-level, multi-system, and multi-species perspective to augment the existing research plan to resolve the SANS risk. Not much is known about SANS at the cellular and molecular level, but studies in mice and rats have recently begun to determine how spaceflight might affect the biology of the eye. Preliminary studies of mice that flew on the Space Shuttle, and more recently the International Space Station (ISS), have shown changes in retinal physiology as assessed by histology and gene expression analysis. The study presented here obtained samples from the CASIS sponsored Rodent Research 8 Experiment delivered to the ISS by SpaceX CRS-16 on 12/08/2018. Female BALB/cAnNTac mice flew on the ISS for 45 days, while ground controls were housed in a standard vivarium or animal enclosure module. Sacrifice and sample acquisition occurred once mice returned to Earth, possibly allowing for readaptation affecting retinal homeostasis. We applied standard transcriptomic (RNAseq) and histological approaches to characterize genes and pathways in the mouse retina affected by spaceflight or age. The differentially expressed gene (DEG) data was analyzed using Galaxy (GeneLab) and Ingenuity Pathway Analysis. Significant DEGs between flight and ground samples were relatively few but biologically meaningful. Pathways identified related to neuronal differentiation, cellular transport/movement, and wound healing. Age effects were detected between the young (10–12 weeks) and old (32 weeks) groups and between the baseline and end of experiment (~46 days). The biological relevance of specific DEGs were confirmed through immunohistochemical evaluation using fixed histological sections of the eye from four flight group mice and four habitat control mice. Staining was performed specific for synaptophysin, glial fibrillary acidic protein (GFAP), and neurofilament in the retinal periphery, equator, and peripapillary regions. For synaptophysin staining, the innerplexiform and outerplexiform layers were scored; for GFAP staining, Mueller cells and perivascular astrocytes were scored. Results show flight samples typically had more staining of GFAP and neurofilament while, conversely, the habitat control group had more staining of synaptophysin.

C. Perez↗

Controlled ecological life support system higher plant flight experiments

Requirements for spaceflight experments which involve higher plants were determined. The plants are studied for use in controlled ecological life support systems (CELSS). Two categories of research requirements are discussed: (1) the physical needs which include nutrient, water and gas exchange requirements; (2) the biological and physiological functions which affect plants in zero gravity environments. Physical problems studies are given the priority since they affect all biological experiments.

Tibbitts, T. W.↗

Novel Receptor-Based Countermeasures to Microgravity-Induced Bone Loss

The biological actions mediated by the estrogen receptor (ER), vitamin D receptor (VDR) and Ca(sup 2+) (sub o) -sensing receptor (CaR) play key roles in the normal control of bone growth and skeletal turnover that is necessary for skeletal health. These receptors act by controlling the differentiation and/or function of osteoblasts and osteoclasts, and other cell types within the bone and bone marrow microenvironment. The appropriate use of selective ER modulators (SERMS) which target bone, vitamin D analogs that favor bone formation relative to resorption, and CaR agonists may both stimulate osteoblastogenesis and inhibit osteoclastogenesis and the function of mature osteoclasts, should make it possible to prevent the reduction in bone formation and increase in bone resorption that normally contribute to the bone loss induced by weightlessness. Indeed, there may be synergistic interactions among these receptors that enhance the actions of any one used alone. Therefore, we proposed to: 1) assess the in vitro ability of novel ER, VDR and CaR agonists, alone or in combination, to modulate osteoblastogenesis and mature osteoblast function under conditions of 1g and simulated microgravity; 2) assess the in vitro ability of novel ER, VDR and CaR agonists, alone or in combination, to modulate osteoclastogenesis and bone resorption under conditions of lg and simulated microgravity; and 3) carry out baseline studies on the skeletal localization of the CaR in normal rat bone as well as the in vivo actions of our novel ER- and VDR-based therapeutics in the rat in preparation for their use, alone or in combination, in well-established ground-based models of microgravity and eventually in space flight.

OMalley, Bert W.↗

The mammalian retina as a clock

Many physiological, cellular, and biochemical parameters in the retina of vertebrates show daily rhythms that, in many cases, also persist under constant conditions. This demonstrates that they are driven by a circadian pacemaker. The presence of an autonomous circadian clock in the retina of vertebrates was first demonstrated in Xenopus laevis and then, several years later, in mammals. In X. laevis and in chicken, the retinal circadian pacemaker has been localized in the photoreceptor layer, whereas in mammals, such information is not yet available. Recent advances in molecular techniques have led to the identification of a group of genes that are believed to constitute the molecular core of the circadian clock. These genes are expressed in the retina, although with a slightly different 24-h profile from that observed in the central circadian pacemaker. This result suggests that some difference (at the molecular level) may exist between the retinal clock and the clock located in the suprachiasmatic nuclei of hypothalamus. The present review will focus on the current knowledge of the retinal rhythmicity and the mechanisms responsible for its control.

Review Literature↗

Composting on Mars or the Moon: I. Comparative evaluation of process design alternatives

As a candidate technology for treating solid wastes and recovering resources in bioregenerative Advanced Life Support, composting potentially offers such advantages as compactness, low mass, near ambient reactor temperatures and pressures, reliability, flexibility, simplicity, and forgiveness of operational error or neglect. Importantly, the interactions among the physical, chemical, and biological factors that govern composting system behavior are well understood. This article comparatively evaluates five Generic Systems that describe the basic alternatives to composting facility design and control. These are: 1) passive aeration; 2) passive aeration abetted by mechanical agitation; 3) forced aeration--O2 feedback control; 4) forced aeration--temperature feedback control; 5) forced aeration--integrated O2 and temperature feedback control. Each of the five has a distinctive pattern of behavior and process performance characteristics. Only Systems 4 and 5 are judged to be viable candidates for ALS on alien worlds, though which is better suited in this application is yet to be determined.

Review↗

Contemplating the plasmalemmal control center model

An abundant epidermal mechanosensory calcium-selective ion channel appears able not only to detect mechanical stimuli such as those that initiate gravitropism but also to detect thermal, electrical, and various chemical stimuli. Because it responds to multimodal input with a second messenger output, this channel system seems likely to be an integrator that can engage in feedbacks with many other systems of the cell--and feedback is the hallmark of regulation. In general, the mechanical tension required for channel activation is likely transmitted from the relatively rigid cell wall to the plasma membrane system via linkage or adhesion sites that display antigenicities recognized by antibodies to animal beta-1 integrin, vitronectin, and fibronectin and which have mechanical connections to the cytoskeleton. Thus, functionally, leverage exerted against any given adhesion site will tend to control channels within a surrounding domain. Reactions initiated by passage of calcium ions through the channels could presumably be more effectively regulated if channels within the domains were somewhat clustered and if appropriate receptors, kinases, porters, pumps, and some key cytoskeletal anchoring sites were in turn clustered about them. Accumulating evidence suggests not only that activity of clusters of channels may contribute to control of cytoskeletal architecture and of regulatory protein function within their domain, but also that both a variety of regulatory proteins and components of the cortical cytoskeleton may contribute to control of channel activity. The emerging capabilities of electronic optical microscopy are well suited for resolving the spatial distributions of many of these cytoskeletal and regulatory molecules in living cells, and for following some of their behaviors as channels are stimulated to open and cytosolic calcium builds in their vicinity. Such microscopy, coupled with biochemical and physiological probing, should help to establish the nature of the feedback loops putatively controlled by the linkage sites and their channel domains.

Review↗

Traction in smooth muscle cells varies with cell spreading

Changes in cell shape regulate cell growth, differentiation, and apoptosis. It has been suggested that the regulation of cell function by the cell shape is a result of the tension in the cytoskeleton and the distortion of the cell. Here we explore the association between cell-generated mechanical forces and the cell morphology. We hypothesized that the cell contractile force is associated with the degree of cell spreading, in particular with the cell length. We measured traction fields of single human airway smooth muscle cells plated on a polyacrylamide gel, in which fluorescent microbeads were embedded to serve as markers of gel deformation. The traction exerted by the cells at the cell-substrate interface was determined from the measured deformation of the gel. The traction was measured before and after treatment with the contractile agonist histamine, or the relaxing agonist isoproterenol. The relative increase in traction induced by histamine was negatively correlated with the baseline traction. On the contrary, the relative decrease in traction due to isoproterenol was independent of the baseline traction, but it was associated with cell shape: traction decreased more in elongated than in round cells. Maximum cell width, mean cell width, and projected area of the cell were the parameters most tightly coupled to both baseline and histamine-induced traction in this study. Wide and well-spread cells exerted larger traction than slim cells. These results suggest that cell contractility is controlled by cell spreading.

Non-NASA Center↗

Low Temperature Performance of High-Speed Neural Network Circuits

Artificial neural networks, derived from their biological counterparts, offer a new and enabling computing paradigm specially suitable for such tasks as image and signal processing with feature classification/object recognition, global optimization, and adaptive control. When implemented in fully parallel electronic hardware, it offers orders of magnitude speed advantage. Basic building blocks of the new architecture are the processing elements called neurons implemented as nonlinear operational amplifiers with sigmoidal transfer function, interconnected through weighted connections called synapses implemented using circuitry for weight storage and multiply functions either in an analog, digital, or hybrid scheme.

artificial neural networks image processing signal↗

NASA Thesaurus Data File

The NASA Thesaurus contains the authorized NASA subject terms used to index and retrieve materials in the NASA Aeronautics and Space Database (NA&SD) and NASA Technical Reports Server (NTRS). The scope of this controlled vocabulary includes not only aerospace engineering, but all supporting areas of engineering and physics, the natural space sciences (astronomy, astrophysics, planetary science), Earth sciences, and the biological sciences. The NASA Thesaurus Data File contains all valid terms and hierarchical relationships, USE references, and related terms in machine-readable form. The Data File is available in the following formats: RDF/SKOS, RDF/OWL, ZThes-1.0, and CSV/TXT.

Source record↗

Importance of Sulfur for Phosphorus Mobility on the Martian Surface

Sulfur and phosphorus were mobile on the martian surface, and we present evidence that sulfate was likely a control on phosphate mobility. Mobility of the two elements on the martian surface is crucial for the habitability of Mars because their availability for biochemical reactions and biological structures is a major constraint on life. In the sedimentary rocks of Gale crater, the rover Curiosity has discovered evidence of mobile S and P with the alpha particle X-ray spectrometer (APXS). Sulfur-rich fluids are evident in ubiquitous Ca-sulfate veins that crosscut the bedrock. Compelling evidence of P mobility is in nodules, veins, crusts, and haloes with P2O5 enrichments (1.5-7.5 wt%) relative to the median bedrock (0.9-1.2 wt%) and average basaltic crust (~0.9 wt%). We have investigated phosphorus mobility in Hawaiian analogues, where the primary P2O5 (0.2-2.1 wt%) is contained in Ca-apatite. Four relevant processes have emerged: (1) In open-system, circumneutral regolith weathering profiles, we found up to 40% of the P was leached over 10s-100s ka. (2) Natural acid-sulfate alteration at the Maunakea summit resulted in the dissolution of apatite and mobilization of phosphate 10s-1000s µm to rock surfaces where it formed Al-phosphates and substituted into crystalline sulfates (alunite and jarosite). (3) Experimental results indicate that basaltic sediment chemisorbs phosphate (pH < 7). (4) In experimental systems containing water, basaltic sediment, and a starting pH = 2-7, phosphate has higher solubility in chloride-rich fluids, but significantly lower solubility in sulfate-rich fluids. For example, in water doped with phosphate (~100-500 mg/L), ~60-80% of the PO43- was removed from the sulfate-rich fluid, whereas ~20% of the PO43- was removed from the Cl-rich and pure water fluids (likely via adsorption). Gypsum precipitated from the sulfate-rich fluids; the fate of phosphate in the solid residue is unconfirmed. The potential for phosphate incorporation in martian sulfates is reflected in the enrichment of P2O5 in Gale Ca-sulfate veins, based on preliminary analyses of APXS data. Models for the mobility of phosphorus in Gale crater should consider these conflicting P characteristics: (1) P solubility may have been inhibited by sulfate and (2) P¬ is enriched in diagenetic features and was therefore mobile.

Jeff A. Berger↗

System development and early biological tests in NASA's biomass production chamber

The Biomass Production Chamber at Kennedy Space Center was constructed to conduct large scale plant growth studies for NASA's CELSS program. Over the past four years, physical systems and computer control software have been continually upgraded and the degree of atmospheric leakage from the chamber has decreased from about 40 to 5 percent of the total volume per day. Early tests conducted with a limited degree of closure showed that total crop (wheat) growth from the best trays was within 80 percent of reported optimal yields for similar light levels. Yields from subsequent tests under more tightly closed conditions have not been as good--up to only 65 percent of optimal yields. Yields appear to have decreased with increasing closure, yet potential problems exist in cultural techniques and further studies are warranted. With the ability to tightly seal the chamber, quantitative data were gathered on CO2 and water exchange rates. Results showed that stand photosynthesis and transpiration reached a peak near 25 days after planting, soon after full vegetative ground cover was established. In the final phase of testing when atmospheric closure was the highest, ethylene gas levels in the chamber rose from about 10 to nearly 120 ppb. Evidence suggests that the ethylene originated from the wheat plants themselves and may have caused an epinastic rolling of the leaves, but no apparent detrimental effects on whole plant function.

Wheeler, R. M.↗

Human System Risk Management for Space Flight

This brief abstract reviews the development of the current day approach to human system risk management for space flight and the development of the critical components of this process over the past few years. The human system risk management process now provides a comprehensive assessment of each human system risk by design reference mission (DRM) and is evaluated not only for mission success but also for long‐term health impacts for the astronauts. The discipline of bioastronautics is the study of the biological and medical effects of space flight on humans. In 1997, the Space Life Sciences Directorate (SLSD) initiated the Bioastronautics Roadmap (Roadmap) as the "Critical Path Roadmap", and in 1998 participation in the roadmap was expanded to include the National Space Biomedical Research Institute (NSBRI) and the external community. A total of 55 risks and 250 questions were identified and prioritized and in 2000, the Roadmap was base-lined and put under configuration control. The Roadmap took into account several major advisory committee reviews including the Institute of Medicine (IOM) "Safe Passage: Astronaut care for Exploration Missions", 2001. Subsequently, three collaborating organizations at NASA HQ (Chief Health and Medical Officer, Office of Space Flight and Office of Biological & Physical Research), published the Bioastronautics Strategy in 2003, that identified the human as a "critical subsystem of space flight" and noted that "tolerance limits and safe operating bands must be established" to enable human space flight. These offices also requested a review by the IOM of the Roadmap and that review was published in October 2005 as "A Risk Reduction Strategy for Human Exploration of Space: A Review of NASA's Bioastronautics Roadmap", that noted several strengths and weaknesses of the Roadmap and made several recommendations. In parallel with the development of the Roadmap, the Office of the Chief Health and Medical Officer (OCHMO) began a process in 2004 of evaluating the tolerance limits and safe operating bands called for in the Bioastronautics Strategy. Over the next several years, the concept of the "operating bands" were turned into Space Flight Human System Standards (SFHSS), developed by the technical resources of the SLSD at the NASA Johnson Space Center (JSC). These standards were developed and reviewed at the SLSD and then presented to the OCHMO for acceptance. The first set of standards was published in 2007 as the NASA‐STD‐3001, Volume 1, Crew Health that elaborated standards for several physiological areas such as cardiovascular, musculoskeletal, radiation exposure and nutrition. Volume 2, Human Factors, Habitability and Human Health was published in 2011, along with development guidance in the Human Integration Design Handbook (HIDH). Taken together, the SFHSS Volumes 1 and 2, and the HIDH replaced the NASA‐STD‐3000 with new standards and revisions of the older document. Three other changes were also taking place that facilitated the development of the human system risk management approach. In 2005, the life sciences research and development portfolio underwent a comprehensive review through the Exploration Systems Architecture Study (ESAS) that resulted in the reformulation of the Bioastronautics Program into Human Research Program (HRP) that was focused on appropriate mitigation results for high priority human health risks. The baseline HRP budget was established in August 2005. In addition, the OCHMO formulated the Health and Medical Technical Authority (HMTA) in 2006 that established the position of the Chief Medical Officer (CMO) at the NASA JSC along with other key technical disciplines, and the OCHMO became the responsible office for the SFHSS as noted above. The final change was the establishment in 2008 of the Human System Risk Board (HSRB), chaired by the CMO with representation from the HRP, SLSD management and technical experts. The HSRB then began to review all human system risks, established a comprehensive risk management and configuration management plan and data sharing policy. These major developments of standards, the HRP, the HMTA and a forum for review of human system risks (HSRB) facilitated the integration of human research, medical operations, systems engineering and many other disciplines in the comprehensive review of human system risks. The HSRB began a comprehensive review of all potential inflight medical conditions and events and over the course of several reviews consolidated the number of human system risks to 30 where the greatest emphasis is placed for investing program dollars for risk mitigation. The HSRB considers all available evidence from human research, medical operations and occupational surveillance in assessing the risks for appropriate mitigation and future work. All applicable DRMs (low earth orbit 6 and 12 months, deep space sortie for 30 days and 1 year, a one year lunar mission, and a planetary mission for 3 years) are considered as human system risks are modified by the hazards associated with space flight such as microgravity, exposure to radiation, distance from the earth, isolation and a closed environment. Each risk has a summary assessment representing the state of knowledge/evidence base for that risk, the available risk mitigations, traceability to the SFHSS and program requirements, and future work required. These data then can drive coordinated budgets across the HRP, the International Space Station, Crew Health and Safety and Advanced Exploration System budgets. These risk assessments were completed for 6 DRMs in December of 2014 and serve as the baseline for which subsequent research and technology development and crew health care portfolios can be assessed. The HSRB will review each risk at least annually and especially when new information is available that must be considered for effective risk mitigation. The current status of each risk can be reported to program management for operations, budget reviews and general oversight of the human system risk management program.

Davis, Jeffrey↗

Space Algae: Understanding the Genomic Impacts on Microalgae After Growth in the International Space Station

Plants and microbes can be used for biological support of crewed space missions. The radiation and microgravity environment of spaceflight is expected to increase genetic mutation of all organisms. It is essential to understand how spaceflight impacts mutation rates in photosynthetic organisms to enable appropriate countermeasures and ensure productivity during long duration and deep space missions. The Space Algae flight experiments to the International Space Station (ISS) are studying the genomic stability of microalgae that could potentially be used in biological life support systems. Space Algae-1 grew ultraviolet light mutagenized Chlamydomonas reinhardtii in the VEGGIE plant growth chamber for approximately 40 mitotic generations over one month on the ISS. Whole genome sequencing from pooled cell samples every 10 generations revealed that spaceflight cultures had an ~50% increase in DNA polymorphisms relative to ground controls. These mutations had a novel base substitution signature and suggested a risk that microalgae may be unstable for long-term production in space. Space Algae-2 is focusing on the edible cyanobacterium Arthrospira platensis, commonly known as Spirulina. This experiment seeks to grow serial cultures to allow the organism to evolve in long-term spaceflight. Biological responses of the cells to spaceflight will be assessed with multi-omics analyses to determine mutation load, gene/protein expression, metabolic/nutritional composition, and cell morphology.

Algae↗

Space Algae: Understanding the Genomic Impacts on Microalgae After Growth in the International Space Station

Plants and microbes can be used for biological support of crewed space missions. The radiation and microgravity environment of spaceflight is expected to increase genetic mutation of all organisms. It is essential to understand how spaceflight impacts mutation rates in photosynthetic organisms to enable appropriate countermeasures and ensure productivity during long duration and deep space missions. The Space Algae flight experiments to the International Space Station (ISS) are studying the genomic stability of microalgae that could potentially be used in biological life support systems. Space Algae-1 grew ultraviolet light mutagenized Chlamydomonas reinhardtii in the VEGGIE plant growth chamber for approximately 40 mitotic generations over one month on the ISS. Whole genome sequencing from pooled cell samples every 10 generations revealed that spaceflight cultures had an ~50% increase in DNA polymorphisms relative to ground controls. These mutations had a novel base substitution signature and suggested a risk that microalgae may be unstable for long-term production in space. Space Algae-2 is focusing on the edible cyanobacterium Arthrospira platensis, commonly known as Spirulina. This experiment seeks to grow serial cultures to allow the organism to evolve in long-term spaceflight. Biological responses of the cells to spaceflight will be assessed with multi-omics analyses to determine mutation load, gene/protein expression, metabolic/nutritional composition, and cell morphology.

Algae↗

Investigating Biological Responses to Space-like Radiation using the yeast Saccharomyces cerevisiae

As we plan crewed missions to the Moon, Mars, and beyond, it is essential to understand how persistent exposure to space radiation affects biology. Unlike on the International Space Station, where crew support and sample return are possible, experiments for long-duration missions require autonomous systems with no sample return. Human cells would be ideal biosensors, but limitations in culture methods, extended prelaunch storage, and long flight durations make it very difficult to keep human cells alive. Unlike other model systems, yeast can survive the constraints of long-duration spaceflight. Despite a billion years of evolution separating yeast from humans, we share homology in hundreds of genes important for basic cell function, including responses to DNA damage. Thus, yeast are excellent biosensors for detecting types/extent of damage induced by space radiation. BioSentinel is NASA’s latest biological CubeSat, and first interplanetary space bioscience mission. BioSentinel is manifested on Artemis 1, the first test flight of NASA’s Space Launch System, in the coming year. The BioSensor payload within BioSentinel contains two yeast strains. The wild type serves as a control for health and “normal” DNA damage repair (DDR). The rad51 deletion mutant is defective for DDR and will undergo alterations to growth and metabolism as it accumulates radiation damage. Changes in growth and metabolic activity will be measured using a 3-color LED detection system and the metabolic redox dye alamarBlue®. Preliminary tests indicate a significant change in alamarBlue response to space-like, low-dose ionizing radiation. We will discuss these findings in four parts – Introduction to biological CubeSats and the BioSentinel mission (presented by Sergio Santa Maria), preliminary responses to space-like ionizing radiation (presented here), a deeper dive into tracking metabolic changes after exposure to ionizing radiation (presented by Diana Gentry), and a look into methods for correcting flight optical data (presented by Abbey Kim). This work is funded by NASA’s Advanced Exploration Systems.

CubeSat↗

Biological life-support systems

The establishment of human living environments by biologic methods, utilizing the appropriate functions of autotrophic and heterotrophic organisms is examined. Natural biologic systems discussed in terms of modeling biologic life support systems (BLSS), the structure of biologic life support systems, and the development of individual functional links in biologic life support systems are among the factors considered. Experimental modeling of BLSS in order to determine functional characteristics, mechanisms by which stability is maintained, and principles underlying control and regulation is also discussed.

Shepelev, Y. Y.↗

Initial MPTS study results: Design considerations and issues

One of the key issues identified during investigations of microwave power transmission systems from 1965 to 1976 was the need to assure that the billions of diodes on ground-based rectennas are sufficiently reliable to support long life times of approximately 30 years. Major systems studies conducted focused on waveguides; radio frequency interference and biological considerations; the relationship between performance, weight, and cost; risk assessment; crossed field directional amplifier noise; a 48 kW klystron; effects of the environment on propagation and phase control; rectenna technology; a rationale for the ground power density region; alternate technologies for orbital assembly; ionospheric effects and phase control; and reception conversion (rf to dc collector/converter).

Maynard, O. E.↗