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Aging and Oxidative Stress: Insights from Spaceflight

Long-term spaceflight leads to profound changes in multiple organs systems attributable to unloading and fluid shifts in microgravity. Future space explorations beyond low earth orbit will expose astronauts to space radiation, which may result in additional deficits that are not yet fully understood.The Space Life Sciences Research and Applications Division is hosting a lunch and learn briefing by Dr. Ruth Globus of the Ames Research Center. The topic is how living in space causes changes in the human body that resemble age-related diseases on earth (like osteoporosis), and how we experimentally explore coping responses.modulating the responses of bone to the challenges of spaceflight. This presentation will highlight how knowledge from studies on fundamental bone biology can inform the design of intervention strategies against spaceflight-induced bone loss.

bone↗

Successful Validation of RNA Purification and Quantitative Real-Time PCR Analysis of Gene Expression on the International Space Station

The NASA Ames WetLab-2 system was developed to offer new on-orbit gene expression analysis capabilities to ISS researchers and can be used to conduct on-orbit RNA isolation and quantitative real time PCR (RT-qPCR) analysis of gene expression from a wide range of biological samples ranging from microbes to mammalian tissues. On orbit validation included three quantitative PCR (qPCR) runs using an E. coli genomic DNA template pre-loaded at three different concentrations. The flight Ct values for the DNA standards showed no statistically significant differences relative to ground controls although there was increased noise in Ct curves, likely due to microgravity-related bubble retention in the optical windows. RNA was successfully purified from both E. coli and mouse liver samples and successfully generated singleplex, duplex and triplex data although with higher standard deviations than ground controls, also likely due to bubbles. Using volunteer science activities, a potential bubble reduction strategy was tested and resulted in smooth amplification curves and tighter Cts between replicates. The WetLab-2 validation experiment demonstrates a novel molecular biology workbench on ISS which allows scientists to purify and stabilize RNA, and to conduct RT-qPCR analyses on-orbit with rapid results. This novel ability is an important step towards utilizing ISS as a National Laboratory facility with the capability to conduct and adjust science experiments in real time without sample return, and opens new possibilities for rapid medical diagnostics and biological environmental monitoring on ISS.

microgravity↗

Advances in Rodent Research Missions on the International Space Station

A Research platform for rodent experiment on the ISS is an essential tool for advancing biomedical research in space. The Rodent Research allows for experiments of much longer duration that experiments on the Shuttle. NASA’s Rodent Research (RR)-1 mission was successfully completed, including post-flight analysis and achieved a number of objectives including validation of flight hardware, on-orbit operations, and science capabilities that were developed at the NASA Ames Research Center. Briefly, twenty C57BL/6J adult female mice were launched on the SpX4 Dragon vehicle, which thrived for up to 37 days in microgravity. Daily health checks of the mice were performed during the mission via downlinked video; all animals were healthy and displayed normal behavior without any significant signs of stress. Behavioral analysis demonstrated that Flight and Ground Control mice exhibited the same range of behaviors, including eating, drinking, exploratory behavior, self- and allo-grooming, and social interactions indicative of healthy animals. The animals were euthanized and select tissues were collected from some of the mice on orbit to assess the long-term sample storage capabilities of the ISS. The data obtained from the flight mice were comparable to those from the 3 groups of control mice (baseline, vivarium and ground controls), suggesting that the ISS has adequate capability to support long-duration rodent experimentations. We recovered over 35 tissues from 40 RR1 frozen carcasses, yielded over 3200 aliquots of tissues, and distributed to the scientific community, including NASA’s GeneLab and scientists in the U.S. through Biospecimen Sharing Program via Ames Life Science Data Archive. Tissues were also distributed to Russian research colleagues at the Institute for Biomedical Problems. The expression levels of select genes including albumin, catalase, GAPDH, HMGCoA Reductase, and IGF1 were determined using RNA isolated from the livers by qPCR and no significant differences by one factor ANOVA were found between flight and ground control groups. In addition, some of the liver samples were subject to transcriptomics, epigenomics and proteomics. The data are now available to the scientific community through GeneLab’s open science data website. Since the RR1 mission, another long duration mission (Rodent Research-2) was completed on the ISS in 2015 in which 20 female C57 BL/6J mice were successfully maintained on the ISS for varying time points, with the last group of 5 animals being on-orbit for 54 days. This second Rodent Research flight expanded the program’s capabilities with the introduction of new technologies including blood collection and separation and bone densitometry scanning. Furthermore, we have continued to expand the ISS’s capabilities by running a series of ground-based verification testing using male mice. Our next step is to fly male mice for Rodent Research-4 on SpaceX-10 to study the effects of microgravity on bone healing and regeneration. It will be the first long-duration mission using male mice using Rodent Hardware. In addition, the number of mice will increase from 20 mice (on RR-1 and RR-2) to 40 for RR-4. When samples return to Earth, a number of tissues will be dissected from the frozen carcasses and select tissue samples will become available to the scientific community via BSP. Altogether, we have continued to expand our capabilities for performing long-duration missions on the ISS as emphasized in the National Research Council’s Decadal Survey released in 2011 and to maximize science return from each mission.

Choi, S.↗

Levitation Technology in International Space Station Research

The International Space Station (ISS) is a unique multidisciplinary orbiting laboratory for science and technology research, enabling discoveries that benefit life on Earth and exploration of the universe. ISS facilities for containerless sample processing in Materials Science experiments include levitation devices with specimen positioning control while reducing containment vessel contamination. For example, ESA's EML (ElectroMagnetic Levitator), is used for melting and solidification of conductive metals, alloys, or semiconductors in ultra-high vacuum, or in high-purity gaseous atmospheres. Sample heating and positioning are accomplished through electromagnetic fields generated by a coil system. EML applications cover investigation of solidification and microstructural formation, evaluation of thermophysical properties of highly reactive metals (whose properties can be very sensitive to contamination), and examination of undercooled liquid metals to understand metastable phase convection and influence convection on structural changes. MSL utilization includes development of novel light-weight, high-performance materials. Another facility, JAXA's ELF (Electrostatic Levitation Furnace), is used to perform high temperature melting while avoiding chemical reactions with crucibles by levitating a sample through Coulomb force. ELF is capable of measuring density, surface tension, and viscosity of samples at high temperatures. One of the initial ELF investigations, Interfacial Energy-1, is aimed at clarification of interfacial phenomena between molten steels and oxide melts with industrial applications in control processes for liquid mixing. In addition to these Materials Science facilities, other ISS investigations that involve levitation employ it for biological research. For example, NASA's "Magnetic 3D Culturing and Bioprinting" investigation uses magnetic levitation for three-dimensional culturing and positioning of magnetized cells to generate spheroid assemblies for biomedical applications. Levitation is also used as a modeled microgravity ground analog in the NASA OsteoOmics ISS investigation, which tests whether magnetic levitation accurately simulates microgravity conditions by studying gravitational regulation of osteoblast and osteoclast genomics and metabolism. Elucidating the cellular mechanisms of bone loss in microgravity contributes to the understanding of bone loss in medical disorders on Earth, which may lead to development of preventive or therapeutic countermeasures. Thus, the ISS state-of-the-art laboratory offers various levitation capability platforms with applications for innovative research in Materials and Life Sciences disciplines, with benefits for humanity.

Guinart-Ramirez, Y.↗

LifeSat - Program overview

LifeSat is a reusable reentry satellite for use by NASA and the international space life sciences community. It will be employed beginning in late 1994, to understand the effects of the space environment (i.e., high energy space radiation and microgravity) on biological systems. This paper describes the program for LifeSat.

Gilbreath, William P.↗

The Biological Flight Research Facility

NASA Ames Research Center is building a research facility, the Biological Flight Research Facility (BFRF), to meet the needs of life scientists to study the long-term effects of variable gravity on living systems. The facility will be housed on Space Station Freedom and is anticipated to operate for the lifetime of the station, approximately 30 years. It will allow plant and animal biologists to study the role of gravity, or its absence, at varying gravity intensities for varying periods of time and with various organisms. The principal difference between current Spacelab missions and those on Space Station Freedom, other than length of mission, will be the capability to perform on-orbit science procedures and the capability to simulate earth gravity. Initially, the facility will house plants and rodents in habitats which can be maintained at microgravity or can be placed on a 2.5-m diam centrifuge. However, the facility is also being designed to accommodate future habitats for small primates, avian, and aquatic specimens. The centrifuge will provide 1 g for controls and will also be able to provide gravity from 0.01 to 2.0 g for threshold gravity studies as well as hypergravity studies. The BFRF will provide the means to conduct basic experiments to gain an understanding of the effects of microgravity on the structure and function of plants and animals, as well as investigate the role of gravity as a potential countermeasure for the physiological changes observed in microgravity.

Johnson, Catherine C.↗

Neuromuscular aspects in development of exercise countermeasures

The paper reviews data obtained at the Human Life Sciences Research Program at the Kennedy Space Center on the structural and functional characteristics of the human muscle and on the effects of simulated microgravity (head-down bed rest) and exercise on the muscle. It is shown that prolonged exposure to microgravity induced ultrastructural abnormalities and the atrophy of muscle and impaired muscle functioning (especially upon return to terrestrial gravity) and that ground-based models can be effectively used to study these changes. Results indicate that the incorporation of resistive exercise with a strong emphasis on the use of eccentric muscle action, in addition to concentric action, may provide a very effective countermeasure against muscle atrophy and dysfunction caused by long-duration exposures to microgravity.

Convertino, Victor A.↗

Rotational speed control

Viewgraphs on rotational speed control are presented. The Centrifuge Facility Systems Study - 2.5 m centrifuge is shown. A life sciences centrifuge is scheduled to fly aboard Space Station Freedom. Live animal and plant specimens will be carried on the rotor and compared with microgravity specimens in racks.

Bastin, Paul↗

The Biological Flight Research Facility

NASA Ames Research Center (ARC) is building a research facility, the Biological Flight Research Facility (BFRF), to meet the needs of life scientists to study the long-term effects of variable gravity on living systems. The facility will be housed on Space Station Freedom and is anticipated to operate for the lifetime of the station, approximately thirty years. It will allow plant and animal biologists to study the role of gravity, or its absence, at varying gravity intensities for varying periods of time and with various organisms. The principal difference between current Spacelab missions and those on Space Station Freedom, other than length of mission, will be the capability to perform on-orbit science procedures and the capability to simulate earth gravity. Initially the facility will house plants and rodents in habitats which can be maintained at microgravity or can be placed on a 2.5 meter diameter centrifuge. However, the facility is also being designed to accommodate future habitats for small primates, avian, and aquatic specimens. The centrifuge will provide 1 g for controls and will also be able to provide gravity from 0.01 to 2.0 g for threshold gravity studies as well as hypergravity studies. Included in the facility are a service unit for providing clean chambers for the specimens and a glovebox for manipulating the plant and animal specimens and for performing experimental protocols. The BFRF will provide the means to conduct basic experiments to gain an understanding of the effects of microgravity on the structure and function of plants and animals, as well as investigate the role of gravity as a potential countermeasure for the physiological changes observed in microgravity.

Johnson, Catherine C.↗

Quench Module Insert Capabilities and Development Test Results

The Quench Module Insert is a directional solidification furnace that will operate in the Materials Science Research Rack (MSRR) on the International Space Station. It will provide high thermal gradient and quench capabilities for processing metals and alloys in microgravity. Numerical analyses and breadboard testing conducted to date show that the QMI can produce an axial temperature gradient approaching 150 C per centimeter in a 1 centimeter diameter aluminum sample with a maximum molten sample temperature of 1100 C. Breadboard testing and analysis have also shown that the quench capabilities of the furnace are sufficient to rapidly solidify at least a 5mm axial portion of a 1 centimeter diameter molten aluminum sample in significantly less than the required 2 seconds and prevent significant backmelt. This paper presents the furnace requirements and capabilities and a status of the associated development testing and analyses.

Carswell, William E.↗

Materials science and engineering in space

The influences of gravitational forces on processes used in the preparation of materials employed in earth-based applications are addressed and the benefits which may be derived from the microgravity environment of space in improving on such constraints are considered. Attention is given to the fact that Materials Processing in Space is directed toward the utilization of the unique space environment as a tool to establish a scientific characterization of materials processes for technological exploitation in the public benefit. In the context of enhancement to earth-based technology or implementation of space-based processes for specialized, low volume, high value materials, the thrust of the Materials Processing in Space program is surveyed.

Zoller, L. K.↗

Expanded Benefits for Humanity from the International Space Station

In 2012, the International Space Station (ISS) partnership published the updated International Space Station Benefits for Humanity, 2nd edition, a compilation of stories about the many benefits being realized in the areas of human health, Earth observations and disaster response, and global education. This compilation has recently been revised to include updated statistics on the impacts of the benefits, and new benefits that have developed since the first publication. Two new sections have also been added to the book, economic development of space and innovative technology. This paper will summarize the updates on behalf of the ISS Program Science Forum, made up of senior science representatives across the international partnership. The new section on "Economic Development of Space" highlights case studies from public-private partnerships that are leading to a new economy in low earth orbit (LEO). Businesses provide both transportation to the ISS as well as some research facilities and services. These relationships promote a paradigm shift of government-funded, contractor-provided goods and services to commercially-provided goods purchased by government agencies. Other examples include commercial firms spending research and development dollars to conduct investigations on ISS and commercial service providers selling services directly to ISS users. This section provides examples of ISS as a test bed for new business relationships, and illustrates successful partnerships. The second new section, Innovative Technology, merges technology demonstration and physical science findings that promise to return Earth benefits through continued research. Robotic refueling concepts for life extensions of costly satellites in geo-synchronous orbit have applications to robotics in industry on Earth. Flame behavior experiments reveal insight into how fuel burns in microgravity leading to the possibility of improving engine efficiency on Earth. Nanostructures and smart fluids are examples of materials improvements that are being developed using data from ISS. The publication also expands the benefits of research results in human health, environmental change and disaster response and in education activities developed to capture student imaginations in support of science, technology, engineering and mathematics, or STEM, education internationally. Applications to human health of the knowledge gained on ISS continues to grow and improve healthcare technologies and our understanding of human physiology. Distinct benefits return to Earth from the only orbiting multi-disciplinary laboratory of its kind. The ISS is a stepping stone for future space exploration by providing findings that develop LEO and improve life on our planet.

Rai, Amelia↗

Exposure to Microgravity for 30 Days Onboard Bion M1 Caused Muscle Atrophy and Decreased Regeneration in the Mouse Femoral Quadriceps

Mechanical unloading of muscle during spaceflight in microgravity is known to cause muscular atrophy, changes in muscle fiber type composition, gene expression, and reductions in regenerative muscle growth. Although limited data exists for long-term effects of microgravity in human muscle, these processes have mostly been studied in rodents for short periods of time. Here we report on how 30-day, long-term, mechanical unloading in microgravity affects mouse muscle of the femoral Quadriceps group. To conduct these studies we used muscle tissue from 6 mice from the NASA Biospecimen Sharing Program conducted in collaboration with the Institute for Biomedical Problems of the Russian Academy of Sciences, during the Russian Bion M1 biosatellite mission in 2013. Muscle morphology observed in histological sections shows signs of extensive atrophy and regenerative hypoplasia. Specifically, we observed a two-fold decrease in the number of myonuclei, their central location, low density of myofibers and myofibrils, in fragmentation and swelling of myofibers. Despite obvious atrophy, muscle regeneration nevertheless appears to have continued after 30 days in microgravity as evidenced by thin and short newly formed myofibers. Many of them however showed evidence of apoptotic, TUNEL positive cells and myofibrils degradation, suggesting long-term unloading in microgravity affects late stages of myofiber differentiation. Ground asynchronous and vivarium control animals showed normal, well-developed tissue structure with sufficient blood and nerve supply and evidence of regenerative formation of new myofibers free of apoptotic nuclei. Myonuclei stress response in spaceflight animals was detected by positive nuclear immunolocalization of c-jun and c-myc proteins. Regenerative activity of satellite cells in muscles is detected in mice of all animal groups, by pax7, MyoD, and myogenin immunostaining and myogenin PCR analysis. In summary, long-term spaceflight in microgravity causes significant atrophy and degeneration of the femoral Quadriceps muscle group, and it may interfere with muscle regenerative processes by inducing apoptosis in newly-formed myofibrils during their differentiation phase.

Grigoryan, E. N.↗

Health monitoring of Japanese payload specialist: Autonomic nervous and cardiovascular responses under reduced gravity condition (L-0)

In addition to health monitoring of the Japanese Payload Specialists (PS) during the flight, this investigation also focuses on the changes of cardiovascular hemodynamics during flight which will be conducted under the science collaboration with the Lower Body Negative Pressure (LBNP) Experiment of NASA. For the Japanese, this is an opportunity to examine firsthand the effects of microgravity of human physiology. We are particularly interested in the adaption process and how it relates to space motion sickness and cardiovascular deconditioning. By comparing data from our own experiment to data collected by others, we hope to understand the processes involved and find ways to avoid these problems for future Japanese astronauts onboard Space Station Freedom and other Japanese space ventures. The primary objective of this experiment is to monitor the health condition of Japanese Payload Specialists to maintain a good health status during and after space flight. The second purpose is to investigate the autonomic nervous system's response to space motion sickness. To achieve this, the function of the autonomic nervous system will be monitored using non-invasive techniques. Data obtained will be employed to evaluate the role of autonomic nervous system in space motion sickness and to predict susceptibility to space motion sickness. The third objective is evaluation of the adaption process of the cardiovascular system to microgravity. By observation of the hemodynamics using an echocardiogram we will gain insight on cardiovascular deconditioning. The last objective is to create a data base for use in the health care of Japanese astronauts by obtaining control data in experiment L-O in the SL-J mission.

Sekiguchi, Chiharu↗

The Application of Advanced Cultivation Techniques in the Long Term Maintenance of Space Flight Plant Biological Systems

The development of the International Space Station (ISS) presents extensive opportunities for the implementation of long duration space life sciences studies. Continued attention has been placed in the development of plant growth chamber facilities capable of supporting the cultivation of plants in space flight microgravity conditions. The success of these facilities is largely dependent on their capacity to support the various growth requirements of test plant species. The cultivation requirements for higher plant species are generally complex, requiring specific levels of illumination, temperature, humidity, water, nutrients, and gas composition in order to achieve normal physiological growth and development. The supply of water, nutrients, and oxygen to the plant root system is a factor, which has proven to be particularly challenging in a microgravity space flight environment. The resolution of this issue is particularly important for the more intensive crop cultivation of plants envisaged in Nasa's advanced life support initiative. BioServe Space Technologies is a NASA, Research Partnership Center (RPC) at the University of Colorado, Boulder. BioServe has designed and operated various space flight plant habitat systems, and placed specific emphasis on the development and enhanced performance of subsystem components such as water and nutrient delivery, illumination, gas exchange and atmosphere control, temperature and humidity control. The further development and application of these subsystems to next generation habitats is of significant benefit and contribution towards the development of both the Space Plant biology and the Advanced Life Support Programs. The cooperative agreement between NASA Ames Research center and BioServe was established to support the further implementation of advanced cultivation techniques and protocols to plant habitat systems being coordinated at NASA Ames Research Center. Emphasis was placed on the implementation of passive-based water and nutrient support systems and techniques, which can be used to minimize demands on power, mass, and operational complexity in space flight studies. This effort has direct application to the development of next-generation space flight plant chambers such as the Plant Research Unit (PRU). Work was also directed at the development of in-flight plant preservation techniques and protocols consistent with the interest in applying recent developments in gene chip micro array technologies. Cultivation technologies and protocols were evaluated in a 55 day space flight plant growth study, conducted on the ISS, mission 9A (10/7/02 - 12/7/02).

Heyenga, A. G.↗

Innovative Robot Archetypes for In-Space Construction and Maintenance

The space environment presents unique challenges and opportunities in the assembly, inspection and maintenance of orbital and transit spaceflight systems. While conventional Extra-Vehicular Activity (EVA) technology, out of necessity, addresses each of the challenges, relatively few of the opportunities have been exploited due to crew safety and reliability considerations. Extra-Vehicular Robotics (EVR) is one of the least-explored design spaces but offers many exciting innovations transcending the crane-like Space Shuttle and International Space Station Remote Manipulator System (RMS) robots used for berthing, coarse positioning and stabilization. Microgravity environments can support new robotic archetypes with locomotion and manipulation capabilities analogous to undersea creatures. Such diversification could enable the next generation of space science platforms and vehicles that are too large and fragile to launch and deploy as self-contained payloads. Sinuous manipulators for minimally invasive inspection and repair in confined spaces, soft-stepping climbers with expansive leg reach envelopes and free-flying nanosatellite cameras can access EVA worksites generally not accessible to humans in spacesuits. These and other novel robotic archetypes are presented along with functionality concepts

Rehnmark, Fredrik↗

RadLab and the Environmental Data Application Dashboard: Graphical and Programming Interfaces for Interrogation of Space Telemetry Data

Sensors on the International Space Station (ISS) and multiple spacecraft elsewhere in Earth orbit and in deep space continuously monitor and collect environmental data, transmitting this information back to Earth. These data include ionizing radiation and, on the ISS, CO2, relative humidity levels, and temperature, and are of great importance to space biology research. Ionizing radiation in particular has been established in ground-based experiments as being correlated with increased risk of carcinogenesis and cardiovascular and neurological effects. Looking ahead to future long duration crewed missions beyond low Earth orbit, the ability to study how factors including CO2 levels, light cycle, temperature modulate the response to ionizing radiation and microgravity is essential. To date, access to these data has been fragmented across space agencies, spacecraft, and databases. To address this issue, NASA’s Open Science Data Repository (osdr.nasa.gov) has developed two Web applications: the Environmental Data Application (EDA) and a radiation-specific RadLab. Each consists of an API (application programming interface) and an associated GUI (graphical user interface) that provide single points of access to the data. To date, OSDR has focused on the sensors from payloads and radiation detectors located on the ISS. The Web applications process telemetry information and associated data, such as spacecraft location and orientation, from multiple international databases. The applications’ request syntax enables users to interrogate these data by craft, sensor type, time range, radiation type (galactic cosmic rays, solar particle events, the contribution of the South Atlantic Anomaly), facilitating arbitrary comparisons of original source data at varying time resolutions. The applications provide programmatic access for use in computational pipelines and GUIs for data visualization and exploration, making these data FAIR (Findable, Accessible, Interoperable, and Reusable), complementing the biological data contained in OSDR, and providing the space science community with a valuable resource for scientific analyses.

radiation↗

The Environmental Data Application for Analysis of Space Telemetry Data

Sensors on the International Space Station (ISS) and multiple spacecraft elsewhere in Earth orbit and in deep space continuously monitor and collect environmental data, transmitting this information back to Earth. These data include ionizing radiation and, on the ISS and spacecrafts, CO2, relative humidity levels, and temperature, and are of great importance to space biology research. Looking ahead to future long duration crewed missions beyond low Earth orbit, the ability to study how factors including CO2 levels, light cycle, temperature modulate the response to ionizing radiation and microgravity is essential. To date, access to these data has been fragmented across space agencies, spacecraft, and databases. To address this issue, NASA’s Open Science Data Repository (OSDR) has developed a user interface for interrogation of telemetry data: the Environmental Data Application (EDA). The EDA provides the capability to visualize telemetry and radiation data collected on the International Space Station and corresponding ground platforms during the Rodent Research missions. Telemetry data includes temperature, relative humidity, and CO2 levels. Radiation data includes galactic cosmic rays, the contribution of the South Atlantic Anomaly, total radiation dose rate, and accumulated radiation dose. The application allows users to view single missions, compare multiple missions, and view and download summary or full data tables. In summary, the EDA provides GUIs for data visualization and exploration, as well as means for data export, making these data FAIR (Findable, Accessible, Interoperable, and Reusable), complementing the biological data contained in OSDR, and providing the space science community with a valuable resource for scientific analyses.

telemetry↗