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NASA NTRSDate not supplied

Open Science for Plants in Space: Data Sharing, Standards, and Informatics for Reuse and Knowledge Discovery

Upcoming deep space missions rely on plants and crops for crew and ecosystem health. Access to space plant data enables scientists to gain a deeper understanding of biological responses to ionizing radiation, altered gravity, low atmospheric pressure, elevated CO2, and altered photoperiods. Open Science is the practice of making research available to all, while respecting diverse cultures, fostering collaborations with equity. 2023 is the ‘Year of Open Science’, and NASA has a 5-year Transform to Open Science (TOPS) mission designed to rapidly transform the agency toward an inclusive culture of open science. NASA’s Open Science Data Repository (OSDR) developed by NASA’s Biological and Physical Sciences Division provides access to data from space-relevant biological experiments. OSDR combines two databases, GeneLab and Ames Life Sciences Data Archive (ALSDA) to maximize access to standardized ‘omics (e.g., transcriptomics, proteomics) and phenotypic data (e.g., microscopy, biomass), respectively. OSDR started in 2014 with the creation of the first space-relevant FAIR (Findable, Accessible, Interoperable, Reusable) biological ‘omics repository (GeneLab), providing detailed metadata on investigation, sample, and assay levels. Today, GeneLab hosts 62 plant datasets which have led to 5 published peer-reviewed meta-analysis publications. Most of these publications were collaboration efforts under the OSDR Analysis Working Groups (AWGs). AWGs provide great opportunities for investigators to collaborate and set new standards for space-relevant data and metadata. The AWGs are welcoming any ASPB members interested in providing plant expertise for space biology. The addition of ALSDA to OSDR is also expanding analysis capability beyond ‘omics. Now is the time to get involved as a Subject Matter Expert as we establish the framework for modern plant data archiving through the AWGs. Investigators are invited to submit their space-relevant plant datasets to OSDR and visit the site to learn about the tools OSDR has to offer (osdr.nasa.gov/bio).

FAIR↗
NASA NTRS1979

Gravity as a biochemical determinant

The existence of obvious morphological and physiological changes in living systems exposed to altered gravity immediately informs us that prior changes have taken place in the chemistry of exposed cells, tissues and organs. These changes include transients that return more or less promptly to the norm when the system is restored to the terrestrial g-field. For example, altered serum hormone and electrolyte levels in man, which appear to reflect successful adaptation to the conditions of orbital weightlessness, disappear shortly after return to Earth. Other changes--in mineral and protein constituents of the skeletal system in man, and cell wall composition in plants--are more persistent or even permanent. Hypogravitational departures from the norm include not only "weightlessness" as achieved in orbit, but also experimental modes of compensation, on the clinostat or by flotation. These techniques are useful in the study of hypogravity but cannot replace fully the weightless environment. Plant ethylene and peroxidase both increase under orbital, clinostat and/or flotation conditions whereas 3-phosphoglyceraldehyde-dehydrogenase increases under orbital but not clinostat conditions; cytochrome reductase and malic dehydrogenase levels are affected by the clinostat, but not by actual weightless conditions. How do the altered organismal biochemistries induced by the centrifuge and the clinostat relate to one another? Does gravity operate on living systems as a continuous variable from 0 to superterrestrial values, or do deviations from g(earth) generate non-uniform, discontinuous stress responses, irrespective of sign? In plants, measurements of wall lignin content and peroxidase activity yield opposite answers. Given the limited data so far available we will consider the meaning of these contradictions.

Review↗
NASA NTRS2001

Neurophysiology Summary

The terrestrial gravitational field serves as an important orientation reference for human perception and movement, being continually monitored by sensory receptors in the skin, muscles, joints, and vestibular otolith organs. Cues from these graviceptors are used by the brain to estimate spatial orientation and to control balance and movement. Changes in these cues associated with the tonic changes in gravity (gravito-inertial force),during the launch and entry phases of space flight missions result in altered perceptions, degraded motor control performance, and in some cases, "motion" sickness during, and for a period of time after, the g-transitions. In response to these transitions, however, physiological and behavioral response mechanisms are triggered to compensate for altered graviceptor cues and/or to adapt to the new sensory environment. Basic research in the neurophysiology discipline is focused on understanding the characteristic features of and the underlying mechanisms for the normal human response to tonic changes in the gravito-inertial force environment. These studies address fundamental questions regarding the role of graviceptors in orientation and movement in the terrestrial environment, as well as the capacity, specificity, and modes for neural plasticity in the sensory-motor and perceptual systems of the brain. At the 2001 workshop basic research studies were presented addressing: neuroanatomical responses to altered gravity environments, the neural mechanisms for resolving the ambiguity between tilting and translational stimuli in otolith organ sensory input, interactions between the vestibular system and the autonomic nervous system , the roles of haptic and visual cues in spatial orientation, mechanisms for training environment-appropriate sensorimotor responses triggered by environment-specific context cues, and studies of sensori-motor control of posture and locomotion in the terrestrial environment with and without recent exposure to space flight. Building on these basic research studies are more applied studies focused on the development of countermeasures to the untoward neurophysiological responses to space flight. At the 2001 workshop, applied research studies were presented addressing issues related to the use of rotational artificial gravity (centripetal acceleration) as a multisystem (bone, muscle, cardiovascular, and, perhaps, neurovestibular) countermeasure. Also presented was a clinical study reporting on a new rating system for clinical evaluation of postflight functional neurological status.

Paloski, William H.↗
NASA NTRS1993

Centrifuges in gravitational physiology research

Data from space flight and ground based experiments have clearly demonstrated the importance of Earth gravity for normal physiological function in man and animals. Gravitational Physiology is concerned with the role and influence of gravity on physiological systems. Research in this field examines how we perceive and respond to gravity and the mechanisms underlying these responses. Inherent in our search for answers to these questions is the ability to alter gravity, which is not physically possible without leaving Earth. However, useful experimental paradigms have been to modify the perceived force of gravity by changing either the orientation of subjects to the gravity vector (i.e., postural changes) or by applying inertial forces to augment the magnitude of the gravity vector. The later technique has commonly been used by applying centripetal force via centrifugation.

Ballard, Rodney W.↗
NASA NTRS1987

Femur-bending properties as influenced by gravity. V - Strength vs. calcium and gravity in rats exposed for 2 weeks

The dependence of gravitationally related changes in femur bone strength on the comparable changes in calcium content was investigated in rats exposed to chronic simulations of altered gravity from the 28th to 42nd day of age. Zero G was simulated by harness suspension and 3 G by centrifugation. Bone strength (S) was determined by bending (using modified quasi-static cantilever bending methods and equipment described by Wunder et al., 1977 and 1979) and Ca content (C, by mass pct) determined by atomic absorption spectrometry; results were compared with data obtained on both normal and harnessed control animals at 1 G. Multiple regression showed significant dependence of S upon earth's gravity, independent from C, for which there was no significant coefficient of partial regression. It is suggested that the lack of S/C correlation might have been due to the fact that considerable fraction of the calcium in these young, developing bones has not yet crystallized into the hydroxyapatite which provides strength.

Wunder, Charles C.↗
NASA NTRS1998

Behavioral and Physiological Effects of Hindlimb Unloading in Rats

The overarching objective of this project was to identify changes in neural and biochemical systems of the central and peripheral nervous systems (the CNS and PNS) that are related to disruptions of functional motor responses, or motor control. The identification of neural and biochemical changes that are related to sensory-motor adaptation elicited as animals react to changes in the gravitational field was of particular interest. Thus, the major objective of this work was to study disruptions of motor responses that arise after (sic. due to) chronic exposure to altered gravity (G). To do this, parallel studies investigating changes in neural, sensory, and neuromuscular systems were conducted after animals (rats) experienced chronic exposure to conditions of altered-G. Conditions of altered-G included hyper-G produced by centrifugation, micro-G produced by orbital flight, and simulated micro-G produced by hind limb suspension. A second major interest was to examine the contribution of putative changes in sensory systems to disruptions of motor responses. To do this, motor responses and reflexes of rats were studied following chronic treatment with streptomycin sulfate (STP, an ototoxic chemical) to damage the vestibular hair cells.

Fox, Robert A.↗
NASA NTRS2017

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.↗
NASA NTRS2002

Evidence for vestibular regulation of autonomic functions in a mouse genetic model

Physiological responses to changes in the gravitational field and body position, as well as symptoms of patients with anxiety-related disorders, have indicated an interrelationship between vestibular function and stress responses. However, the relative significance of cochlear and vestibular information in autonomic regulation remains unresolved because of the difficulties in distinguishing the relative contributions of other proprioceptive and interoceptive inputs, including vagal and somatic information. To investigate the role of cochlear and vestibular function in central and physiological responses, we have examined the effects of increased gravity in wild-type mice and mice lacking the POU homeodomain transcription factor Brn-3.1 (Brn-3bPou4f3). The only known phenotype of the Brn-3.1(-/-) mouse is related to hearing and balance functions, owing to the failure of cochlear and vestibular hair cells to differentiate properly. Here, we show that normal physiological responses to increased gravity (2G exposure), such as a dramatic drop in body temperature and concomitant circadian adjustment, were completely absent in Brn-3.1(-/-) mice. In line with the lack of autonomic responses, the massive increase in neuronal activity after 2G exposure normally detected in wild-type mice was virtually abolished in Brn-3.1(-/-) mice. Our results suggest that cochlear and vestibular hair cells are the primary regulators of autonomic responses to altered gravity and provide genetic evidence that these cells are sufficient to alter neural activity in regions involved in autonomic and neuroendocrine control.

Non-NASA Center↗
NASA NTRS2003

Hypergravity-Induced Changes in Hematological and Lymphocyte Function Parameters in a Mouse Model

The purpose of this study was to quantify hypergravity-induced changes in hematological and lymphocyte characteristics. Mice were subjected to 1, 2, and 3G and euthanized on days 1 , 4, 7, 10, and 21. The data show that increased gravitational force resulted in persistent hypothermia. Red blood cell (RBC) counts, hematocrit, and hemoglobin were reduced by day 21, whereas hemoglobin and RBC volume were low at most times of measurement. A transient increase was noted in platelet numbers in the 3G group. Fluctuations in spontaneous blastogenesis of lymphocytes were dependent upon centrifugation time and not gravity. Changes in splenocyte responses to T and B cell mitogens due to gravity were also noted. Cytokine production was primarily affected during the first week; IL-2, IL-4 and TNF-alpha were increased, whereas IFN-gamma was decreased. These findings indicate that altered gravity can influence both hematological and functional variables that may translate into serious health consequences.

Gridley, Daila S.↗
NASA NTRSDate not supplied

Impact of the ISS Environment on CNS in Drosophila Melanogaster

Altered gravity and elevated carbon dioxide (CO 2 ) levels as experienced on the ISS can adversely affect human health across various organ systems, especially the Central Nervous System (CNS). Investigating these changes is essential for understanding the long-term effects of spaceflight on human physiology to ensure crew health. Ground-based analogs provide an efficient method to evaluate alterations induced by chronic spaceflight on a larger scale. This study focuses on CNS changes in response to hypergravity (HG) and elevated CO 2 levels via a ground-based analog using the well-established model organism, Drosophila melanogaster. We hypothesize behavior and physiological changes immediately post exposure to HG+CO 2 , along with chronic effects up to 25 days post-exposure. Adult male and female flies were exposed to varying gravity loads (1g, 1.2g, and 3g) and elevated CO 2 levels (~4000 ppm, mimicking CO 2 levels on the ISS) for 15 days and were assessed immediately and at 5-, 10-, and 25-days post-exposure, mirroring astronauts’ post-return profiling. The flies were assessed for neurobehavioral changes, including longevity and negative geotaxis; brain morphological changes, such as dopaminergic neuron count, apoptosis, and glial cell density; and bioenergetic changes in the brain, including mitochondrial abundance and membrane potential. Longevity remained unchanged under hypergravity, even with the addition of elevated CO 2 as a stressor. However, despite the stable lifespan, quality of life appeared to be affected, as shown by negative geotaxis and neuroanatomical changes. Negative geotaxis testing revealed a reduction in motor ability at R0 across all conditions, which correlated with a decrease in dopaminergic (DA) neuron count. Additional observations suggested further systemic alterations, including a decrease in glial cell count, an increase in apoptosis, and notable bioenergetic changes. Collectively, these findings contribute to our understanding of the long-term effects of spaceflight on the CNS.

spaceflight↗
NASA NTRS1998

Effect of gravity on vestibular neural development

The timing, molecular basis, and morphophysiological and behavioral consequences of the interaction between external environment and the internal genetic pool that shapes the nervous system over a lifetime remain important questions in basic neuroscientific research. Space station offers the opportunity to study this interaction over several life cycles in a variety of organisms. This short review considers past work in altered gravity, particularly on the vestibular system, as the basis for proposing future research on space station, and discusses the equipment necessary to achieve goals. It is stressed that, in keeping with the international investment being made in this research endeavor, both the questions asked and the technologies to be developed should be bold. Advantage must be taken of this unique research environment to expand the frontiers of neuroscience. Copyright 1998 Published by Elsevier Science B.V.

NASA Discipline Neuroscience↗
NASA NTRS2014

2014 SRP Integration Transcript

HRP's mission is to reduce the risks to human health and performance during long-duration spaceflight. The HRP Integrated Research Plan (IRP) contains the research plans for the 32 risks that require research to characterize and mitigate. From its inception the "integrate" aspect of the IRP has denoted the integrated nature of risks to human health and performance. Even though each risk in the IRP has its own research plan and is tracked separately, the interrelated nature of health and performance requires that they be addressed in an integrative or holistic fashion so that the connectedness of physiological systems within the human body and the integrated response to spaceflight can be addressed. Common characteristics of the spaceflight environment include altered gravity, atmospheres, and light/dark cycles; space radiation; isolation; noise; and periods of high or low workload. Long-term exposure to this unique environment produces a suite of physiological effects such as stress; vision, neurocognitive, and anthropometric changes; circadian misalignment; fluid shifts; cardiovascular deconditioning; immune dysregulation; and altered nutritional requirements. Expanding cross-disciplinary integrative approaches that synthesize concepts or data from two or more disciplines would improve the identification and characterization risk factors, and enable the development of countermeasures relevant to multiple risks. Cross-disciplinary approaches might also help to illuminate problem areas that may arise when a countermeasure adversely impacts risks other than those which it was developed to mitigate, or to identify groupings of physiological changes that are likely to occur that may impact the overall risk posture. In 2014 HRP embarked on a pilot study that combined four SRPs (and 12 HRP risks) - Behavioral Health, Sensorimotor, Cardiovascular, and Bone/Muscle - specifically to discuss cross-disciplinary integration. The points outlined below were suggested to seed the discussion, within the bounding constraint that research plans must be feasible and relevant to the HRP mission. While these were suggested starting points, the overall guiding principle was to allow free discussion from panel members on any aspect of integrated research that they felt was important, Existing cross-disciplinary integration as documented in the IRP (HRR), Existing or needed integration already identified by HRP, but not yet well defined within the IRP, Areas of integration that are missing.

Steinberg, Susan↗
NASA NTRS2000

Centrifugation of Cultured Osteoblasts And Macrophages as a Model To Study How Gravity Regulates The Function of Skeletal Cells

Mechanical loading helps define the architecture of weight-bearing bone via the tightly regulated process of skeletal turnover. Turnover occurs by the concerted activity of osteoblasts, responsible for bone formation. and osteoclasts, responsible for bone resorption. Osteoclasts are specialized megakaryon macrophages, which differentiate from monocytes in response to resorption stimuli, such as reduced weight-bearing. Habitation in space dramatically alters musculoskeletal loading, which modulates both cell function and bone structure. Our long-term objective is to define the molecular and cellular mechanisms that mediate skeletal adaptations to altered gravity environments. Our experimental approach is to apply hypergravity loads by centrifugation to rodents and cultured cells. As a first step, we examined the influence of centrifugation on the structure of cancellous bone in rats to test the ability of hypergravity to change skeletal architecture. Since cancellous bone undergoes rapid turnover we expected the most dramatic structural changes to occur in the shape of trabeculae of weight-bearing, cancellous bone. To define the cellular responses to hypergravity loads, we exposed cultured osteoblasts and macrophages to centrifugation. The intraosseous and intramedullary pressures within long bones in vivo reportedly range from 12-40 mm Hg, which would correspond to 18-59 gravity (g) in our cultures. We assumed that hydrostatic pressure from the medium above the cell layer is at least one major component of the mechanical load generated by centrifuging cultured cells. and therefore we exposed the cells to 10-50g. In osteoblasts, we examined the structure of their actin and microtubule networks, production of prostaglandin E2 (PGE2), and cell survival. Analysis of the shape of the cytoskeletal networks provides evidence for the ability of centrifugation to affect cell structure, while the production of PGE2 serves as a convenient marker for mechanical stimulation. We examined cell survival, reasoning that osteoblasts might mold skeletal structure in a hypergravity environment in part by regulating apoptosis and thus the duration of osteoblast productivity. Finally, we tested the influence of centrifugation on microbial activation of a macrophage cell line (RAW264.7). In response to the appropriate hormonal stimulation, this cell line is reportedly capable of undergoing differentiation to express osteoclast markers. In addition, a component of the cell wall of gram-negative bacteria, lipopolysaccaride (LPS), stimulates the formation of osteoclasts in vivo. Thus we tested the influence on centrifugation on RAW264.7 cells stimulated with LPS to provide an index of the function of osteoclast precursors.

Globus, Ruth K.↗
NASA NTRS1990

Definition of experiments to investigate fire suppressants in microgravity

Defined and justified here are the conceptual design and operation of a critical set of experiments expected to yield information on suppressants and on suppressant delivery systems under realistic spacecraft-fire conditions (smoldering). Specific experiment parameters are provided on the solid fuel (carbon), oxidants (habitable spacecraft atmospheres), fuel/oxidant supply, mixing mode, and rate (quiescent and finite; ventilated and replenishable), ignition mode, event, and reignition tendency, fire-zone size, fire conditions, lifetime, and consequences (toxicity), suppressants (CO2, H2O, N2) and suppressant delivery systems, and diagnostics. Candidate suppressants were identified after an analysis of how reduced gravity alters combustion, and how these alterations may influence the modes, mechanisms, and capacities of terrestrial agents to suppress unwanted combustion, or fire. Preferred spacecraft suppression concepts included the local, near-quiescent application of a gas, vapor, or mist that has thermophysical fire-suppression activity and is chemically inert under terrestrial (normal gravity) combustion conditions. The scale, number, and duration (about 1 hour) of the proposed low-gravity experiments were estimated using data not only on the limitations imposed by spacecraft-carrier (Shuttle or Space Station Freedom) accommodations, but also data on the details and experience of standardized smolder-suppression experiments at normal gravity. Deliberately incorporated into the conceptual design was sufficient interchangeability for the prototype experimental package to fly either on Shuttle now or Freedom later. This flexibility is provided by the design concept of up to 25 modular fuel canisters within a containment vessel, which permits both integration into existing low-gravity in-space combustion experiments and simultaneous testing of separate experiments to conserve utilities and time.

Reuther, James J.↗
NASA NTRS1972

Gravity as a factor in the animal environment.

Review of current knowledge, research, and research planning on the influence of gravity upon living organisms. Discussed factors affecting the adaptability of animals to increased acceleration fields include age, sex, posture, and body size. Affected functions and aspects reviewed cover growth and mature body size, body composition, maintenance feed requirements, and feed utilization efficiency. It is expected that research involving the exposure of animals to altered gravity states will lead to new biological concepts of very broad importance.

Smith, A. H.↗
NASA NTRS1998

Development of a noninvasive technique for the measurement of intracranial pressure

Intracranial pressure (ICP) dynamics are important for understanding adjustments to altered gravity. Previous flight observations document significant facial edema during exposure to microgravity, which suggests that ICP is elevated during microgravity. However, there are no experimental results obtained during space flight, primarily due to the invasiveness of currently available techniques. We have developed and refined a noninvasive technique to measure intracranial pressure noninvasively. The technique is based upon detecting skull movements of a few micrometers in association with altered intracranial pressure. We reported that the PPLL technique has enough sensitivity to detect changes in cranial distance associated with the pulsation of ICP in cadavera. In normal operations, however, we place a transducer on the scalp. Thus, we cannot rule out the possibility that the PPLL technique picks up cutaneous pulsation. The purpose of the present study was therefore to show that the PPLL technique has enough sensitivity to detect changes in cranial distance associated with cardiac cycles in vivo.

NASA Center ARC↗
NASA NTRS1998

Gravity of Living Systems: May the Force Be With You

Gravity, the force which shapes the architecture of organisms from single cells to dinosaurs, has been the most constant environmental factor during the evolution of species on Earth. With long-duration space flight, an understanding of how gravity affects living systems gains greater urgency in order to maintain the health and performance of crews who will explore the solar system. For example, the cardiovascular and musculoskeletal systems are normally exposed to gravitational gradients of blood pressure and weight on Earth. Such gradients increase blood pressure and tissue weight in dependent tissues of the body. Thus, from a physiologic standpoint, these systems are greatly affected by altered gravity. Exposure to actual and simulated microgravity causes blood and tissue fluid to shift from the legs to the head. Studies of humans in space have documented facial edema, space adaptation syndrome, decreased plasma volume, muscle atrophy, and loss of bone strength. Return of astronauts to Earth is accompanied by orthostatic intolerance, decreased neuromuscular coordination, and reduced exercise capacity. These factors decrease performance during descent from orbit and increase risk during emergency egress from the space craft. Models of simulated microgravity include 60 head-down tilt, immersion, and prolonged horizontal bedrest. Head-down tilt and dry immersion are the most accepted models and studies using these models of up to one year have been performed in Russia. Sensitive animal models which offer clear insights into the role of gravity on structure and function include the developing giraffe and snakes from various habitats. Finally, possible countermeasures to speed readaptation of astronauts to gravity after prolonged space flight include exercise, lower body negative pressure, and centrifugation.

Hargens, Alan R.↗
NASA NTRS1992

Clinostats and Centrifuges: Their Use, Value, and Limitations in Gravitational Biological Research

The present volume addresses physical phenomena and effects associated with clinostat and centrifuge operations as well as their physiological effects. Particular attention is given to the simulation of the gravity conditions on the ground, the internal dynamics of slowly rotating biological systems, and qualitative and quantitative aspects of the fast-rotating clinostat as a research tool. Also discussed are the development and use of centrifuges in gravitational biology, the use of centrifuges in plant gravitational biology and a comparison of ground-based and flight experiment results, the ability of clinostat to mimic the effect of microgravity on plant cells and organs, and the impact of altered gravity conditions on early EGF-induced signal transduction in human epidermal A431 cells.

Halstead, Thora W.↗