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51 records · Page 3

Limitations to the study of man in space in the U.S. space program

Research on humans conducted during spaceflight is fraught both with great opportunities and great obstacles. The purpose of this paper is to review some of the limitations to research in space in the United States with hope that an informed scientific community may lead to more rapid and efficient solution of these problems. Limitations arise because opportunities to study the same astronauts in well-controlled situations on repeated spaceflights are practically non-existent. Human research opportunities are further limited by the necessity of avoiding simultaneous mutually-interfering experiments. Environmental factors, including diet and other physiological perturbations concomitant with spaceflight, also complicate research design and interpretation. Technical limitations to research methods and opportunities further restrict the development of the knowledge base. Finally, Earth analogues of space travel all suffer from inadequacies. Though all of these obstacles will eventually be overcome, creativity, diligence, and persistence are required to further our knowledge of humans in space.

Bishop, Phillip A.↗

Advancing Translational Space Research Through Biospecimen Sharing: Amplifying the Impact of Ground-Based Studies

Biospecimen Sharing Programs (BSPs) have been organized by NASA Ames Research Center since the 1960s with the goal of maximizing utilization and scientific return from rare, complex and costly spaceflight experiments. BSPs involve acquiring otherwise unused biological specimens from primary space research experiments for distribution to secondary experiments. Here we describe a collaboration leveraging Ames expertise in biospecimen sharing to magnify the scientific impact of research informing astronaut health funded by the NASA Human Research Program (HRP) Human Health Countermeasures (HHC) Element. The concept expands biospecimen sharing to one-off ground-based studies utilizing analogue space platforms (e.g., Hind limb Unloading (HLU), Artificial Gravity) for rodent experiments, thereby significantly broadening the range of research opportunities with translational relevance for protecting human health in space and on Earth. In this presentation, we will report on biospecimens currently being acquired from HHC Award Head-Down Tilt as a Model for Intracranial and Intraocular Pressures, and Retinal Changes during Spaceflight, and their availability. The BSP add-on to the project described herein has already yielded for HHC-funded investigators more than 4,700 additional tissues that would otherwise have been discarded as waste, with additional tissues available for analysis. Young (3-mo old) male and female rats and Older (9-mo old) male rats are being exposed to HLU for either 7, 14, 28, or 90 days. Additional groups are exposed to 90 days of unloading followed by either 7, 14, 28 days or 90 days of recovery (normal loading). Comparisons are made with non-suspended controls. Unused tissues are: Skin, Lungs, Thymus, Adrenals, Kidneys, Spleen, Hindlimb Muscles (Soleus, Extensor Digitorum Longus, Tibialis Anterior, Plantaris Gastrocnemius), Fat Pads, Reproductive Organs, and Intestines. Tissues are harvested, weighed, preserved then archived (with metadata) using a sample tracking system (CryoTrack). Preservation techniques include snap-freezing and RNALatersnap-freezing. Specimens were weighed at the time of dissection, and organ mass: body mass ratios analyzed to determine unloading effects across conditions and durations. The results corroborate previously reported effects of short-term exposure to microgravity or unloading exposure on various organs, and provide new insights into adaptation to long-duration unloading relevant to sustained spaceflight exposures on ISS. Supported by the Human Research Program (HRP) Human Health Countermeasures (HHC) Element and NASA Grant NNX13AD94G (CAF).

rodent↗

Behavioral health in Antarctica: implications for long-duration space missions

Ideally, evidence from long-duration spaceflight should be used to predict likely occurrences of behavioral health events and for planning management strategies for such events. With small numbers of space travelers, and limited long-duration missions of a year or more, Earth analogues and simulations must be used as the evidence base, despite such analogues lacking microgravity, radiation, rapidly altering photoperiodicity, and fidelity to space. Antarctic health data are reviewed and an assessment made of the likely frequency of behavioral health events. Based on the Antarctic evidence, the likelihood of behavioral health problems in space is low. However, such cases may be serious and of high consequence, placing considerable demands on the mission crew and ground support to achieve a successful outcome, given the availability of pharmaceuticals and resources.

Review↗

The Use of Microgravity Simulators for Space Research

The spaceflight environment is known to influence biological processes ranging from stimulation of cellular metabolism to possible impacts on cellular damage repair, suppression of immune functions, and bone loss in astronauts. Microgravity is one of the most significant stress factors experienced by living organisms during spaceflight, and therefore, understanding cellular responses to altered gravity at the physiological and molecular level is critical for expanding our knowledge of life in space. Since opportunities to conduct experiments in space are scarce, various microgravity simulators and analogues have been widely used in space biology ground studies. Even though simulated microgravity conditions have produced some, but not all of the biological effects observed in the true microgravity environment, they provide test beds that are effective, affordable, and readily available to facilitate microgravity research. A Micro-g Simulator Center is being developed at Kennedy Space Center (KSC) to offer a variety of microgravity simulators and platforms for Space Biology investigators. Assistance will be provided by both KSC and external experts in molecular biology, microgravity simulation, and engineering. Comparisons between the physical differences in microgravity simulators, examples of experiments using the simulators, and scientific questions regarding the use of microgravity simulators will be discussed.

Simulation↗

The Use of Microgravity Simulators for Space Research

The spaceflight environment is known to influence biological processes ranging from stimulation of cellular metabolism to possible impacts on cellular damage repair, suppression of immune functions, and bone loss in astronauts. Microgravity is one of the most significant stress factors experienced by living organisms during spaceflight, and therefore, understanding cellular responses to altered gravity at the physiological and molecular level is critical for expanding our knowledge of life in space. Since opportunities to conduct experiments in space are scarce, various microgravity simulators and analogues have been widely used in space biology ground studies. Even though simulated microgravity conditions have produced some, but not all of the biological effects observed in the true microgravity environment, they provide test beds that are effective, affordable, and readily available to facilitate microgravity research. Kennedy Space Center (KSC) provides ground microgravity simulator support to offer a variety of microgravity simulators and platforms for Space Biology investigators. Assistance will be provided by both KSC and external experts in molecular biology, microgravity simulation, and engineering. Comparisons between the physical differences in microgravity simulators, examples of experiments using the simulators, and scientific questions regarding the use of microgravity simulators will be discussed.

Simulation↗

Exercise Effects on the Course of Gray Matter Changes Over 70 Days of Bed Rest

Long duration spaceflight affects posture control, locomotion, and manual control. The microgravity environment is an important causal factor for spaceflight induced sensorimotor changes through direct effects on peripheral changes that result from reduced vestibular stimulation and body unloading. Effects of microgravity on sensorimotor function have been investigated on earth using bed rest studies. Long duration bed rest serves as a space-flight analogue because it mimics microgravity in body unloading and bodily fluid shifts. It has been hypothesized that the cephalad fluid shift that has been observed in microgravity could potentially affect central nervous system function and structure, and thereby indirectly affect sensorimotor or cognitive functioning. Preliminary results of one of our ongoing studies indeed showed that 70 days of long duration head down-tilt bed rest results in focal changes in gray matter volume from pre-bed rest to various time points during bed rest. These gray matter changes that could reflect fluid shifts as well as neuroplasticity were related to decrements in motor skills such as maintenance of equilibrium. In consideration of the health and performance of crewmembers both inand post-flight we are currently conducting a study that investigates the potential preventive effects of exercise on gray matter and motor performance changes that we observed over the course of bed rest. Numerous studies have shown beneficial effects of aerobic exercise on brain structure and cognitive performance in healthy and demented subjects over a large age range. We therefore hypothesized that an exercise intervention in bed rest could potentially mitigate or prevent the effects of bed rest on the central nervous system. Here we present preliminary outcomes of our study.

Koppelmans, V.↗

Menstrual Cycle Control in Female Astronauts and the Associated Risk of Venous Thromboembolism

Venous thromboembolism (VTE) is a common and serious condition affecting approximately 1‐2 per 1000 people in the USA every year. There have been no documented case reports of VTE in female astronauts during spaceflight in the published literature. Some female astronauts use hormonal contraception to control their menstrual cycles and it is currently unknown how this affects their risk of VTE. Current terrestrial risk prediction models do not account for the spaceflight environment and the physiological changes associated with it. We therefore aim to estimate a specific risk score for female astronauts who are taking hormonal contraception for menstrual cycle control, to deduce whether they are at an elevated risk of VTE. A systematic review of the literature was conducted in order to identify and quantify known terrestrial risk factors for VTE. Studies involving analogues for the female astronaut population were also reviewed, for example, military personnel who use the oral contraceptive pill for menstrual suppression. Well known terrestrial risk factors, for example, obesity or smoking would not be applicable to our study population as these candidates would have been excluded during astronaut selection processes. Other risk factors for VTE include hormonal therapy, lower limb paralysis, physical inactivity, hyperhomocysteinemia, low methylfolate levels and minor injuries, all of which potentially apply to crew members LSAH data will be assessed to identify which of these risk factors are applicable to our astronaut population. Using known terrestrial risk data, an overall estimated risk of VTE for female astronauts using menstrual cycle control methods will therefore be calculated. We predict this will be higher than the general population but not significantly higher requiring thromboprophylaxis. This study attempts to delineate what is assumed to be true of our astronaut population, for example, they are known to be a healthy fit cohort of individuals, and combine physiological impacts of spaceflight (cephalic fluid shifts, lower limb inactivity) to understand specific risks associated with hormonal contraception.

Jain, Varsha↗

Effect of +Gz Acceleration on the Oxygen Uptake-Excercise Load Relationship during Lower Extremity Ergometer Excercise

Long term spaceflight and habitation of a space station and/or the moon require that astronauts be provided with sufficient environmental and physiological support so that they can not only function in microgravity but be returned to earth safely. As the duration of habitation in microgravity increase the effects of the concomitant deconditioning of body systems becomes a concern for added exercise in space and for reentry to Earth gravity. Many countermeasures have been proposed to maintain proper functioning of the body, but none have proved sufficient, especially when the cost of crew time spent in these activities is considered. The issue of appropriate countermeasures remains unresolved. Spaceflight deconditioning decreases tolerance to +Gz acceleration, head to foot, the direction which is experienced during reentry; the result is that the crew member is more prone to becoming pre-syncopal or syncopal, thus exacerbating the orthostatic intolerance. All ground-based research using microgravity analogues has produced this same lowered G tolerance. When intermittent exposure to +1 to +4 Gz acceleration training was used, some alleviation of orthosatic intolerance and negative physiological effects of deconditioning occurred. Exercise alone was not as effective; but the added G force was. The physiological responses to acceleration added to exercise training have not been clearly shown. We will test the hypothesis that there will be no difference in the exercise oxygen uptake-exercise load relationship with added +Gz acceleration. We wi also compare oxygen uptake during graded exercise-acceleration loads in the human-powered short arm centrifuge with those from normal supine exercise loads. The human-powered short arm centrifuge was built by NASA engineers at Ames Research Center.

Jackson, Catherine G. R.↗

Development and Evaluation of the Habitat Demonstration Unit Medical Operations Workstation and Opportunities for Future Research

As NASA develops missions to leave Earth orbit and explore distant destinations (Mars, Moon, Asteroids) it is necessary to rethink human spaceflight paradigms in the life sciences. Standards developed for low earth orbit human spaceflight may not be fully applicable and in-space research may be required to develop new standards. Preventative and emergency medical care may require new capabilities never before used in space. Due to spacecraft volume limitations, this work area may also be shared with various animal and plant life science research. This paper explores the prototype Medical Operations Workstation within the NASA Habitat Demonstration Unit and discusses some of the lessons learned from field analogue missions involving the workstation. Keywords: Exploration, medical, health, crew, injury emergency, biology, animal, plant, science, preventative, emergency.

Howard, Robert L., Jr.↗

Large Scale Transcriptional Analysis of Legacy Spaceflight Tissues from the NASA Institutional Scientific Collection

The NASA Institutional Scientific Collection (ISC) has amassed a collection of valuable space biology samples spanning from early Space Shuttle missions to recent missions on the International Space Station (ISS). However, the full potential of this archive has not been realized, with many samples having been stored for decades without being re-accessed. Given the pace of analytical advancement since the ISC began accumulating samples, we undertook a systematic transcriptional analysis of these samples to reveal additional patterns that may have been missed during the original investigations. We selected 93 mouse and rat samples from 5 separate Space Shuttle, ISS and ground-analogue studies with a focus on muscle, spleen and thymus tissues to allow identification of important changes related to musculoskeletal unloading and immune function. RNA extracted from these tissues was consistently of a quality and we are now generating transcriptional profiling data from sample set. This resulting data will be immediately released through the GeneLab data systems for open analysis by the space biology community. While this study will stand on its own, it will also serve as a model for future, comprehensive, analyses of the ISC.

Rodent↗

Large Scale Transcriptional Analysis of Legacy Spaceflight Tissues From the Nasa Biological Institutional Science Collection

The NASA Biological Institutional Science Collection (NBISC) has amassed a collection of valuable space biology samples spanning from early Space Shuttle missions to recent missions on the International Space Station (ISS). However, the full potential of this archive has not been realized, with many samples having been stored for decades without being re-accessed. Given the pace of analytical advancement since NBISC began accumulating samples, we initiated a pilot study to reveal additional patterns that may have been missed during the original investigations and provide technical robustness and scientific value for a cost-effective sequencing approach. We selected 84 mouse and rat samples spanning four separate Space Shuttle, ISS and ground-analogue studies with a focus on muscle, spleen and thymus tissues to allow identification of important changes related to musculoskeletal unloading and immune function. High quality RNA from these tissues was extracted and used to generate transcriptional profiling data using a cost-effective Tag-seq approach and immediately released it on GeneLab. The released datasets included gastrocnemius tissues from rats during the 1991 Space Shuttle mission (GLDS-422) and a ground analogue study in 2019 (GLDS-418), and mice from the 2014 ISS mission (GLDS-419). Also released were two thymus datasets, one from rats flown on the 1993 Space Shuttle (GLDS-423) and another from mice flown on the 2017 ISS (GLDS-421) missions, along with one mouse spleen dataset from a 2017 ISS mission (GLDS-420). These data will serve as a pilot of a much larger and comprehensive study which would generate similar data from thousands of NBISC samples, enabling the discovery and validation of molecular networks influenced by space conditions.

Lovorka Degoricija↗

Exercise Countermeasures Demonstration Project During the Lunar-Mars Life Support Test Project Phase 2A

This demonstration project assessed the crew members' compliance to a portion of the exercise countermeasures planned for use onboard the International Space Station (ISS) and the outcomes of their performing these countermeasures. Although these countermeasures have been used separately in other projects and investigations, this was the first time they'd been used together for an extended period (60 days) in an investigation of this nature. Crew members exercised every day for six days, alternating every other day between aerobic and resistive exercise, and rested on the seventh day. On the aerobic exercise days, subjects exercised on an electronically braked cycle ergometer using a protocol that has been previously shown to maintain aerobic capacity in subjects exposed to a space flight analogue. On the resistive exercise days, crew members performed five major multijoint resistive exercises in a concentric mode, targeting those muscle groups and bones we believe are most severely affected by space flight. The subjects favorably tolerated both exercise protocols, with a 98% compliance to aerobic exercise prescription and a 91% adherence to the resistive exercise protocol. After 60 days, the crew members improved their peak aerobic capacity by an average 7%, and strength gains were noted in all subjects. These results suggest that these exercise protocols can be performed during ISS, lunar, and Mars missions, although we anticipate more frequent bouts with both protocols for long-duration spaceflight. Future projects should investigate the impact of increased exercise duration and frequency on subject compliance, and the efficacy of such exercise prescriptions.

Lee, Stuart M. C.↗

Effects of 2G on Gene Expression of Stress-Related Hormones in Rat Placenta

Understanding the effects of spaceflight on mammalian reproductive and developmental physiology is important to future human space exploration and permanent settlement beyond Earth orbit. Fetal developmental programming, including modulation of the HPA axis, is thought to originate at the placental-uterine interface, where both transfer of maternal hormones to the fetus and synthesis of endogenous hormones occurs. In healthy rats, fetal corticosterone levels are kept significantly lower by 11BetaHSD-2, which inactivates corticosterone by conversion into cortisone. Placental tissues express endogenous HPA axis-associated hormones including corticotropin-releasing hormone (CRH), pre-opiomelanocortin (POMC), and vasopressin, which may contribute to fetal programming alongside maternal hormones. DNA methylase 3A, 11BetaHSD-2, and 11BetaHSD-1, which are involved in the regulation of maternal cortisol transfer and modulation of the HPA axis, are also expressed in placental tissues along with glucocorticoid receptor and may be affected by differential gravity exposure during pregnancy. Fetuses may respond differently to maternal glucocorticoid exposure during gestation through sexually dimorphic expression of corticosterone-modulating hormones. To elucidate effects of altered gravity on placental gene expression, here we present a ground-based analogue study involving continuous centrifugation to produce 2g hypergravity. We hypothesized that exposure to 2g would induce a decrease in 11BetaHSD-2 expression through the downregulation of DNA methylase 3a and GC receptor, along with concurrent upregulation in endogenous CRH, POMC, and vasopressin expression. Timed pregnant female rats were exposed to 2G from Gestational day 6 to Gestational day 20, and comparisons made with Stationary Control (SC) and Vivarium Control (VC) dams at 1G. Dams were euthanized and placentas harvested on G20. We homogenized placental tissues, extracted and purified RNA, synthesized cDNA, and quantified the expression levels of the genes of interest relative to the GAPDH housekeeping gene, using RT-qPCR and gene-specific cDNA probes. Elucidation of glucocorticoid transfer and synthesis in the placenta can provide new insights into the unique dynamics of mammalian development in microgravity and guide future multi-generational studies in space.

Benson, S.↗

A New Representative for Small-Body Gravity Estimation

One of the options proposed in the 2009 Review of the U. S. Human Spaceflight Plans Committee calls for the consideration of robotic and human missions to asteroids. Beginning in 2000, the NEAR Shoemaker spacecraft inserted into orbit about the asteroid 433 Eros, and studied it for a year before landing. The Hayabusa satellite journeyed to 25143 Itokawa, and operated in a proximity of the asteroid for several months before landing to collect a return sample. Additionally, the DAWN satellite, which was launched in 2007, will explore the dwarf-planet Ceres and the asteroid 4 Vesta in the next three years. These are just several examples of current interests in exploring asteroids. In this paper, we explore an alternative for estimating the gravity field of a small body using observations of an orbiting satellite. Our approach uses two new mathematical tools, the quadratures (on a sphere) invariant under the icosahedral group, and a multiresolution representation of the gravity potential. With the near optimal quadratures on the sphere, we minimize the number of parameters needed to recover a function. Also, instead of estimating the coefficients of the spherical harmonics, the new quadratures allow us to estimate directly the values of the gravity field since they offer an analogue of the Lagrange-type interpolation.

Jones, Brandon A.↗

Improvement in the control aspect of laser frequency stabilization for SUNLITE project

Flight Electronics Division of Langley Research Center is developing a spaceflight experiment called the Stanford University and NASA Laser In-Space Technology (SUNLITE). The objective of the project is to explore the fundamental limits on frequency stability using an FM laser locking technique on a Nd:YAG non-planar ring (free-running linewidth of 5 KHz) oscillator in the vibration free, microgravity environment of space. Compact and automated actively stabilized terahertz laser oscillators will operate in space with an expected linewidth of less than 3 Hz. To implement and verify this experiment, NASA engineers have designed and built a state of the art, space qualified high speed data acquisition system for measuring the linewidth and stability limits of a laser oscillator. In order to achieve greater stability and better performance, an active frequency control scheme requiring the use of a feedback control loop has been applied. In the summer of 1991, the application of control theory in active frequency control as a frequency stabilization technique was investigated. The results and findings were presented in 1992 at the American Control Conference in Chicago, and have been published in Conference Proceedings. The main focus was to seek further improvement in the overall performance of the system by replacing the analogue controller by a digital algorithm.

Zia, Omar↗