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Gemini spacecraft and launch vehicle development and performance, flight operations, mission results, and physical science and biomedical experiments - Gemini midprogram conference
Animal models, particularly rodents, are the foundation of pre-clinical research to understand human diseases and evaluate new therapeutics, and play a key role in advancing biomedical discoveries both on Earth and in space. The National Research Councils Decadal survey emphasized the importance of expanding NASAs life sciences research to perform long duration, rodent experiments on the International Space Station (ISS). To accomplish this objective, flight hardware, operations, and science capabilities were developed at NASA Ames Research Center (ARC) to enhance science return for both commercial (CASIS) and government-sponsored rodent research. The Rodent Research program at NASA ARC has pioneered a new research capability on the International Space Station and has progressed toward translating research to the ISS utilizing commercial rockets, collaborating with academia and science industry, while training crewmembers to assist in performing research on orbit. Throughout phases of these missions, our practices, hardware and operations have evolved from tested to developed standards, and we are able to modify and customize our procedure and operations for mission specific requirements. The Rodent Research Habitat is capable of providing a living environment for animals on ISS according to standard animal welfare requirements. Using the cameras in the Habitat, the Rodent Research team has the ability to perform daily health checks on animals, and further analyze the collected videos for behavioral studies. A recent development of the Rodent Research hardware is inclusion of enrichment, to provide the animals the ability to rest and huddle. The Enrichment Hut is designed carefully for adult mice (up to 35 week old) within animal welfare, engineering, and operations constraints. The Hut is made out of the same stainless steel mesh as the cage interior, it has an ingress and an egress to allow animals move freely, and a hinge door to allow crewmembers remove the animals easily. The Rodent Research team has also developed Live Animal Return (LAR) capability, which will be implemented during Rodent Research-5 mission for the first time. The animals will be transported from the Habitat to a Transporter, which will return on the Dragon capsule and splashes down in the Pacific Ocean. Once SpaceX retrieves the Dragon, all powered payloads will be transferred to a SeaVan and transferred to the Long Beach pier. The NASA team then receives the transporter and delivers to a PI-designated laboratory within 120 mile radius of Long Beach. This is a significant improvement allowing researchers to examine animals within 72 hrs. of reentry or to conduct recovery experiments. Together, the hardware improvements and experience that the Rodent Research team has gained working with principal investigators and ISS crew to conduct complex experiments on orbit are expanding capabilities for long duration rodent research on the ISS to achieve both basic science and biomedical objectives.
Animal models, particularly rodents, are the foundation of pre-clinical research to understand human diseases and evaluate new therapeutics, and play a key role in advancing biomedical discoveries both on Earth and in space. The National Research Councils Decadal survey emphasized the importance of expanding NASA's life sciences research to perform long duration, rodent experiments on the International Space Station (ISS) to study effects of the space environment on the musculoskeletal and neurological systems of mice as model organisms of human health and disease, particularly in areas of muscle atrophy, bone loss, and fracture healing. To accomplish this objective, flight hardware, operations, and science capabilities were developed at NASA Ames Research Center (ARC) to enhance science return for both commercial (CASIS) and government-sponsored rodent research. The Rodent Research Project at NASA ARC has pioneered a new research capability on the International Space Station and has progressed toward translating research to the ISS utilizing commercial rockets, collaborating with academia and science industry, while training crewmembers to assist in performing research on orbit. The Rodent Research Habitat provides a living environment for animals on ISS according to standard animal welfare requirements, and daily health checks can be performed using the habitats camera system. Results from these studies contribute to the science community via both the primary investigation and banked samples that are shared in publicly available data repository such as GeneLab. Following each flight, through the Biospecimen Sharing Program (BSP), numerous tissues and thousands of samples will be harvested, and distributed from the Space Life and Physical Sciences (SLPS) to Principal Investigators (PIs) through the Ames Life Science Data Archive (ALSDA). Every completed mission sets a foundation to build and design greater complexity into future research and answer questions about common human diseases. Together, the hardware improvements (enrichment, telemetry sensors, cameras), new capabilities (live animal return), and experience that the Rodent Research team has gained working with principal investigator teams and ISS crew to conduct complex experiments on orbit are expanding capabilities for long duration rodent research on the ISS to achieve both basic science and biomedical research objectives.
Rodent research has played a key role in advancing biomedical discoveries both on Earth and in space. The National Research Counsel’s Decadal survey(1) emphasized the importance of expanding NASAs life sciences research to perform long duration, rodent experiments on the International Space Station (ISS). To accomplish this objective, flight hardware, operations, and science capabilities were developed at NASA ARC to support both commercial and government-sponsored rodent research.Rodent Research-1 (RR-1) was the first mission in which animals were delivered and maintained in the ISS for a long duration mission in modified Animal Enclosure Module hardware. Both RR validation and commercial science objectives were pursued on the RR-1 mission. Adult female mice (20 total Flight, FLT) were launched Sept 21, 2014 in RR hardware within a Dragon Capsule (SpaceX4), then after 4 days in transit, were transferred for habitation on the ISS for 17 days (commercial) or 33 days (validation), when animals were euthanized and select tissues recovered on orbit. Various controls groups consisted of: 1) Basal mice from the same cohorts as FLT mice, but tissues were recovered at time of launch, 2) Vivarium (VIV) were housed in standard cages 3) Ground Controls (GC) were housed in flight hardware within an environmental chamber at Kennedy Space Center. The health and behavior of all mice on the ISS were monitored by video feed on a daily basis. Mice were euthanized by injection of Euthasol, then either fast frozen intact or dissected to preserve livers (fast frozen) and spleens (RNAlater). Samples were stored at ≤ -80˚C until their return to Earth for later analyses.Hardware performed nominally throughout the mission and the planned in-flight science operations were completed successfully. FLT mice appeared generally more physically active on orbit than respective GC groups. After 33 days on the ISS, mean body weights of FLT mice did not differ from GC, with both groups showing a 6% rise compared to time of launch, while VIV mice showed an 8% rise over the same period. Importantly, there were no significant differences in body weights between groups at the end of 33 days on the ISS, providing an indication that the RR hardware supported the health of the mice both on Earth and in space. Based on the preliminary data obtained from the livers and spleens of mice after 17 days on the ISS, purified RNA was of high quality (RIN values of spleen: FLT=9.48 +0.40, GC=9.28 +0.44, n=5/group); therefore, RNA quality from samples retrieved on orbit was acceptable for even the most demanding transcriptomic analyses. In addition, liver enzyme activity levels (units/mg protein) of FLT mice (after 17d on ISS) and all control mice were similar in magnitude to samples that were optimally prepared by freezing in liquid nitrogen in the laboratory (enzymes analyzed included catalase, glutathione reductase and glyceraldehyde-3-phosphate dehydrogenase). Validation analyses still in progress include behavior and tissue biochemistries, as well as optimization of science return by post-flight recovery of tissues for biospecimen sharing and global expression analyses.Together, these preliminary findings demonstrate new capability for supporting long duration rodent research on the ISS to achieve both basic science and biomedical objectives.
The advent of X-ray multi-contrast imaging methods, providing absorption, phase, and dark-field images, holds tremendous promise for complementary and non-destructive visualization of inner structures within materials and bio-samples. However, the low efficiency in measuring and analyzing X-ray modulated patterns has hindered their application in high-resolution in situ imaging. In this work, the Enhanced Scanning Pattern-based Imaging Neural Network (ESPINNet) is introduced as a powerful tool for achieving high-speed, high-resolution quantitative imaging. ESPINNet is faster than correlation-based speckle tracking methods such as XSVT and UMPA, and provides a balanced performance in terms of resolution and speed for data collection by using fewer scanning images. In comparison with our previously developed neural network, ESPINNet introduces the capability to generate dark-field images, further enhancing its versatility. By leveraging scanning patterns, ESPINNet significantly improves resolution and measurement precision. Furthermore, its adaptability to various modulation patterns, including those produced by sandpaper, coded masks, or gratings, ensures broad applicability. These features enable real-time 2D and 3D multi-contrast imaging, positioning ESPINNet as a transformative solution for applications in materials science and biomedical research, particularly for high-speed and in situ measurements.
Research using rodents is an essential tool for advancing biomedical research on Earth and in space. Prior rodent experiments on the Shuttle were limited by the short flight duration. The International Space Station (ISS) provides a new platform for conducting rodent experiments under long duration conditions. Rodent Research (RR)-1 was conducted to validate flight hardware, operations, and science capabilities that were developed at the NASA Ames Research Center. Twenty C57BL6J adult female mice were launched on Sept 21, 2014 in a Dragon Capsule (SpaceX-4), then transferred to the ISS for a total time of 21-22 days (10 commercial mice) or 37 days (10 validation mice). Tissues collected on-orbit were either rapidly frozen or preserved in RNAlater at -80C (n2group) until their return to Earth. Remaining carcasses on-orbit were rapidly frozen for dissection post-flight. The three controls groups at Kennedy Space Center consisted of: Basal mice euthanized at the time of launch, Vivarium controls housed in standard cages, and Ground Controls (GC) housed in flight hardware within an environmental chamber. Upon return to Earth, there were no differences in body weights between Flight (FLT) and GC at the end of the 37 days in space. Liver enzyme activity levels of FLT mice and all control mice were similar in magnitude to those of the samples that were processed under optimal conditions in the laboratory. Liver samples dissected on-orbit yielded high quality RNA (RIN8.99+-0.59, n7). Liver samples dissected post-flight from the intact, frozen FLT carcasses yielded RIN of 7.27 +- 0.52 (n6). Additionally, wet weights of various tissues were measured. Adrenal glands and spleen showed no significant differences in FLT compared to GC although thymus and livers weights were significantly greater in FLT compared to GC. Over 3,000 tissue aliquots collected post-flight from the four groups of mice were deposited into the Ames Life Science Data Archives for future Biospecimen Sharing Program. Together, the RR validation flight successfully demonstrates the capability to support long-duration experimentation on the ISS to achieve both basic science and biomedical objectives.
During microbial infection, mammalian hosts reduce the availability of free metals such as zinc in a process known as nutritional immunity. Pathogens counteract nutritional immunity by expressing gene products that enhance growth in metal-limited conditions. One of the most transcriptionally induced genes in zinc-limited Neisseria gonorrhoeae , ngo1049, encodes a DUF4198 family protein we have named Zcp. This family of proteins is widely distributed in Gram-negative bacteria. Here, we provide the first structural, biochemical, and functional characterization of a DUF4198 protein. Zcp is a periplasmic, homodimeric substrate-binding protein (SBP), which binds one zinc ion per subunit with submicromolar affinity. We identified a zinc binding pocket in each subunit, composed of three histidine residues. Zcp enables maximal growth of N. gonorrhoeae in zinc-limited conditions but is dispensable for zinc uptake, in contrast to the cluster A-I SBP ZnuA, which is required for zinc import. The growth defect of zcp mutant N. gonorrhoeae is rescued by zinc supplementation. Zcp associates with proteins with roles in maintaining cell envelope integrity, and N. gonorrhoeae lacking zcp is more sensitive to envelope-targeting antimicrobials. Zcp enables infectivity of human epithelial cells and neutrophils by zinc-limited N. gonorrhoeae . We conclude that N. gonorrhoeae produces Zcp to buffer periplasmic zinc, which enables ZnuA to balance import of different metals and ensures the bioavailability of zinc for extracytoplasmic zinc-requiring proteins, as part of the coordinated response to host-imposed nutritional immunity.
For this work, atomistic molecular dynamics (MD) simulations coupled with potential of mean force (PMF) calculations were employed to investigate the interactions between PVC polymer chains containing 6–20 repeating units and various plasticizers, with the goal of identifying potential replacements for the toxic plasticizer di(2-ethylhexyl)phthalate (DEHP) used in blood bags. The selected plasticizers belong to various chemical families, such as orthophthalates, citrates, adipates, and the terephthalate DEHT. Both the polymer and the plasticizers lack ionizable groups, and their interactions are primarily governed by van der Waals and electrostatic forces. A model correlating PMF profiles with interaction forces was developed and validated across polyvinyl chloride (PVC) polymers of different lengths and all investigated plasticizers. This model provides insight into how structural variations in plasticizers influence their respective PMF values. The study ranks the investigated plasticizers based on binding affinity, identifying TOTM (tris(2-ethylhexyl) trimellitate, TEHTM), BTHC (butyryl trihexyl citrate, Citroflex B-6), ATHC (acetyl trihexyl citrate, Citroflex A-6, CA-6), and DEHT (bis(2-ethylhexyl)terephthalate, DOTP/DEHTP) as promising alternatives for further investigation. This comprehensive study encompasses PVC polymers of four different lengths and 14 plasticizers, with all data averaged over 30 independent simulations. The approach provides a deeper understanding of molecular interactions, enabling the tailoring of polymer–plasticizer systems for diverse applications, including extractables and leachables, with relevance spanning materials science to biomedical engineering, and also serves as a basis for developing coarse-grained simulation protocols. Overall, this study provides valuable insights for designing safer and more efficient plasticizer substitutes and is well supported by other studies.
To evaluate the impact of individual sugar catabolic pathways on the physiology of A. niger when using plant biomass as a carbon source, key pathways converting plant biomass derived monomers were blocked. The resulting deletion mutants were analyzed using wheat bran and sugar beet pulp as substrates. On both substrates, the strongest affected single-pathway mutants were the pentose catabolic pathway (PCP) (Δ xkiA ) and glycolysis (Δ hxkA Δ glkA ) deficient mutants. On wheat bran, which is rich in pentose sugars, blocking the PCP by deletion of xkiA strongly impacted both growth and gene expression. However, the effect was even stronger in Δ hxkA Δ glkA and similar to a strain in which all pathways were blocked, highlighting the crucial role of glycolysis and/or carbon catabolite repression in A. niger physiology. These results demonstrate the complexity of A. niger metabolism during growth on plant biomass and provide insights into aspects to consider during metabolic engineering to obtain fungal cell factories.
Biomedical, physical science, and engineering experiments initiated by mercury project
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The emerging field of Translational Research aims to coalesce interdisciplinary findings from basic science for biomedical applications. To complement spaceflight research using human subjects, translational studies can be designed to address aspects of space-related human health risks and help develop countermeasures to prevent or mitigate them, with therapeutical benefits for analogous conditions experienced on Earth. Translational research with cells and model organisms is being conducted onboard the International Space Station (ISS) in connection with various human systems impacted by spaceflight, such as the cardiovascular, musculoskeletal, and immune systems. Examples of recent cell-based translational investigations on the ISS include the following. The JAXA investigation Cell Mechanosensing seeks to identify gravity sensors in skeletal muscle cells to develop muscle atrophy countermeasures by analyzing tension fluctuations in the plasma membrane, which changes the expression of key proteins and genes. Earth applications of this study include therapeutic approaches for some forms of muscular dystrophy, which appear to parallel aspects of muscle wasting in space. Spheroids is an ESA investigation examining the system of endothelial cells lining the inner surface of all blood vessels in terms of vessel formation, cellular proliferation, and programmed cell death, because injury to the endothelium has been implicated as underpinning various cardiovascular and musculoskeletal problems arising during spaceflight. Since endothelial cells are involved in the functional integrity of the vascular wall, this research has applications to Earth diseases such as atherosclerosis, diabetes, and hypertension. The goal of the T-Cell Activation in Aging NASA investigation is to understand human immune system depression in microgravity by identifying gene expression patterns of candidate molecular regulators, which will provide further insight into factors that may play a critical role in immune function loss during aging. In addition, Omics investigations with cells have synergistic applications ranging from the evaluation of pharmacological countermeasures to drug discovery. Thus, cell-based translational research onboard the ISS is bidirectionally bridging cutting-edge cellular and molecular approaches with space bioastronautics and human health methodologies on Earth.
The identification and solution of research and clinical problems in cardiovascular medicine which were investigated by means of biomedical data transfer are reported. The following are sample areas that were focused upon by the Stanford University Biomedical Technology Transfer Team: electrodes for hemiplegia research; vectorcardiogram computer analysis; respiration and phonation electrodes; radiotelemetry of intracranial pressure; and audiotransformation of the electrocardiographic signal. It is concluded that this biomedical technology transfer is significantly aiding present research in cardiovascular medicine.
Lower body negative pressure testing in cardiac patients has been completed as well as the design and construction of a new leg negative unit for evaluating heart patients. This technology is based on NASA research, using vacuum chambers to stress the cardiovascular system during space flight. Additional laboratory tests of an intracranial pressure transducer, have been conducted. Three new biomedical problems to which NASA technology is applicable are also identified. These are: a communication device for the speech impaired, the NASA development liquid-cooled garment, and miniature force transducers for heart research.
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Ongoing projects described address: (1) intracranial pressure monitoring; (2) versatile portable speech prosthesis; (3) cardiovascular magnetic measurements; (4) improved EMG biotelemetry for pediatrics; (5) ultrasonic kidney stone disintegration; (6) pediatric roentgen densitometry; (7) X-ray spatial frequency multiplexing; (8) mechanical impedance determination of bone strength; (9) visual-to-tactile mobility aid for the blind; (10) Purkinje image eyetracker and stabilized photocoalqulator; (11) neurological applications of NASA-SRI eyetracker; (12) ICU synthesized speech alarm; (13) NANOPHOR: microelectrophoresis instrument; (14) WRISTCOM: tactile communication system for the deaf-blind; (15) medical applications of NASA liquid-circulating garments; and (16) hip prosthesis with biotelemetry. Potential transfer projects include a person-portable versatile speech prosthesis, a critical care transport sytem, a clinical information system for cardiology, a programmable biofeedback orthosis for scoliosis a pediatric long-bone reconstruction, and spinal immobilization apparatus.
The National Space Biomedical Research Institute (NSBRI) encourages open involvement by scientists and the public at large in the Institute's activities. Through its Education and Public Outreach Program, the Institute is supporting national efforts to improve Kindergarten through grade twelve (K-12) and undergraduate education and to communicate knowledge generated by space life science research to lay audiences. Three academic institution Baylor College of Medicine, Morehouse School of Medicine and Texas A&M University are designing, producing, field-testing, and disseminating a comprehensive array of programs and products to achieve this goal. The objectives of the NSBRI Education and Public Outreach program are to: promote systemic change in elementary and secondary science education; attract undergraduate students--especially those from underrepresented groups--to careers in space life sciences, engineering and technology-based fields; increase scientific literacy; and to develop public and private sector partnerships that enhance and expand NSBRI efforts to reach students and families. c 2001. Elsevier Science Ltd. All rights reserved.
Biomedical research objectives for future Shuttle and/or Space Station missions are discussed, with a focus on experiments exploring the physiological effects of microgravity. Experience up to the present is found to indicate that molecular-level processes are not much affected by the space environment, so that future experiments should concentrate on larger-scale phenomena. Areas considered include cardiovascular, respiratory, skeletal, and muscular physiology; metabolism; neurophysiology; and behavior. Radiation effects are seen as well as understood on the basis of ground-based data, with the possible exception of HZE-particle radiation. The need for carefully constructed ground research to prepare for space experiments is stressed.