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At least 811 records · Page 45
All sourcesNASA NTRSDOE OSTI
NASA NTRS2000

Cell movement is guided by the rigidity of the substrate

Directional cell locomotion is critical in many physiological processes, including morphogenesis, the immune response, and wound healing. It is well known that in these processes cell movements can be guided by gradients of various chemical signals. In this study, we demonstrate that cell movement can also be guided by purely physical interactions at the cell-substrate interface. We cultured National Institutes of Health 3T3 fibroblasts on flexible polyacrylamide sheets coated with type I collagen. A transition in rigidity was introduced in the central region of the sheet by a discontinuity in the concentration of the bis-acrylamide cross-linker. Cells approaching the transition region from the soft side could easily migrate across the boundary, with a concurrent increase in spreading area and traction forces. In contrast, cells migrating from the stiff side turned around or retracted as they reached the boundary. We call this apparent preference for a stiff substrate "durotaxis." In addition to substrate rigidity, we discovered that cell movement could also be guided by manipulating the flexible substrate to produce mechanical strains in the front or rear of a polarized cell. We conclude that changes in tissue rigidity and strain could play an important controlling role in a number of normal and pathological processes involving cell locomotion.

NASA Discipline Cell Biology↗
NASA NTRS2000

Response of soybean rhizosphere communities to human hygiene water addition as determined by community level physiological profiling (CLPP) and terminal restriction fragment length polymorphism (TRFLP) analysis

In this report, we describe an experiment conducted at Kennedy Space Center in the biomass production chamber (BPC) using soybean plants for purification and processing of human hygiene water. Specifically, we tested whether it was possible to detect changes in the root-associated bacterial assemblage of the plants and ultimately to identify the specific microorganism(s) which differed when plants were exposed to hygiene water and other hydroponic media. Plants were grown in hydroponics media corresponding to four different treatments: control (Hoagland's solution), artificial gray water (Hoagland's+surfactant), filtered gray water collected from human subjects on site, and unfiltered gray water. Differences in rhizosphere microbial populations in all experimental treatments were observed when compared to the control treatment using both community level physiological profiles (BIOLOG) and molecular fingerprinting of 16S rRNA genes by terminal restriction fragment length polymorphism analysis (TRFLP). Furthermore, screening of a clonal library of 16S rRNA genes by TRFLP yielded nearly full length SSU genes associated with the various treatments. Most 16S rRNA genes were affiliated with the Klebsiella, Pseudomonas, Variovorax, Burkholderia, Bordetella and Isosphaera groups. This molecular approach demonstrated the ability to rapidly detect and identify microorganisms unique to experimental treatments and provides a means to fingerprint microbial communities in the biosystems being developed at NASA for optimizing advanced life support operations.

NASA Discipline Life Support Systems↗
NASA NTRS1997

Vagal and sympathetic mechanisms in patients with orthostatic vasovagal syncope

BACKGROUND: Autonomic and particularly sympathetic mechanisms play a central role in the pathophysiology of vasovagal syncope. We report direct measurements of muscle sympathetic nerve activity in patients with orthostatic vasovagal syncope. METHODS AND RESULTS: We studied 53 otherwise healthy patients with orthostatic syncope. We measured RR intervals and finger arterial pressures and in 15 patients, peroneal nerve muscle sympathetic activity before and during passive 60 degree head-up tilt, with low-dose intravenous isoproterenol if presyncope did not develop by 15 minutes. We measured baroreflex gain before tilt with regression of RR intervals or sympathetic bursts on systolic or diastolic pressures after sequential injections of nitroprusside and phenylephrine. Orthostatic vasovagal reactions occurred in 21 patients, including 7 microneurography patients. Presyncopal and nonsyncopal patients had similar baseline RR intervals, arterial pressure, and muscle sympathetic nerve activity. Vagal baroreflex responses were significantly impaired at arterial pressures below (but not above) baseline levels in presyncopal patients. Initial responses to tilt were comparable; however, during the final 200 seconds of tilt, presyncopal patients had lower RR intervals and diastolic pressures than nonsyncopal patients and gradual reduction of arterial pressure and sympathetic activity. Frank presyncope began abruptly with precipitous reduction of arterial pressure, disappearance of muscle sympathetic nerve activity, and RR interval lengthening. CONCLUSIONS: Patients with orthostatic vasovagal reactions have impaired vagal baroreflex responses to arterial pressure changes below resting levels but normal initial responses to upright tilt. Subtle vasovagal physiology begins before overt presyncope. The final trigger of human orthostatic vasovagal reactions appears to be the abrupt disappearance of muscle sympathetic nerve activity.

Non-NASA Center↗
NASA NTRS2015

The Twins Study: NASA's First Foray into 21st Century Omics Research

The full array of 21st century omics-based research methods should be intelligently employed to reduce the health and performance risks that astronauts will be exposed to during exploration missions beyond low Earth Orbit. In March of 2015, US Astronaut Scott Kelly will launch to the International Space Station for a one year mission while his twin brother, Mark Kelly, a retired US Astronaut, remains on the ground. This situation presents an extremely rare flight opportunity to perform an integrated omics-based demonstration pilot study involving identical twin astronauts. A group of 10 principal investigators has been competitively selected, funded, and teamed together to form the Twins Study. A very broad range of biological function are being examined including the genome, epigenome, transcriptome, proteome, metabolome, gut microbiome, immunological response to vaccinations, indicators of atherosclerosis, physiological fluid shifts, and cognition. The plans for the Twins Study and an overview of initial results will be described as well as the technological and ethical issues raised for such spaceflight studies. An anticipated outcome of the Twins Study is that it will place NASA on a trajectory of using omics-based information to develop precision countermeasures for individual astronauts.

Kundrot, C. E.↗
NASA NTRS2015

Research from the NASA Twins Study and Omics in Support of Mars Missions

The NASA Twins Study, NASA's first foray into integrated omic studies in humans, illustrates how an integrated omics approach can be brought to bear on the challenges to human health and performance on a Mars mission. The NASA Twins Study involves US Astronaut Scott Kelly and his identical twin brother, Mark Kelly, a retired US Astronaut. No other opportunity to study a twin pair for a prolonged period with one subject in space and one on the ground is available for the foreseeable future. A team of 10 principal investigators are conducting the Twins Study, examining a very broad range of biological functions including the genome, epigenome, transcriptome, proteome, metabolome, gut microbiome, immunological response to vaccinations, indicators of atherosclerosis, physiological fluid shifts, and cognition. A novel aspect of the study is the integrated study of molecular, physiological, cognitive, and microbiological properties. Major sample and data collection from both subjects for this study began approximately six months before Scott Kelly's one year mission on the ISS, continue while Scott Kelly is in flight and will conclude approximately six months after his return to Earth. Mark Kelly will remain on Earth during this study, in a lifestyle unconstrained by this study, thereby providing a measure of normal variation in the properties being studied. An overview of initial results and the future plans will be described as well as the technological and ethical issues raised for spaceflight studies involving omics.

Kundrot, C.↗
NASA NTRS2016

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↗
NASA NTRS2016

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↗
NASA NTRS2017

The Effects of CDKN1a/p21 on Oxidative Stress and Mitochondrial Function During Long Duration Spaceflight

Spaceflight factors, such as microgravity and space radiation, are known to put astronauts at risk for negative effects to their tissue regeneration and degenerative conditions. On our previous spaceflight research, we found that long duration spaceflight produced increased oxidative stress and activation of the inflammatory response as a major contributor to physiological changes, including alterations to the cardiovascular and musculoskeletal systems, metabolism, and the liver. Proliferation, apoptosis, and ion-channel remodeling of vascular smooth muscle cells, as well as endothelial inflammation, and nitric oxide synthase-nitric oxide system regulation have been shown by spaceflight and simulated spaceflight projects. CDKN1ap21 is a regulatory gene for tissue regeneration and also plays an important role in upregulating oxidative stress caused by radiation. In further research, we have also determined CDKN1ap21 to be overexpressed during spaceflight. When knocked out in mice, however, it protects against unloading-induced changes to the morphology and physiology of carotid arteries. In this proposal, we seek to test a potential dietary countermeasure to down-regulate CDKN1ap21 in the mice and protect against oxidative stress in the rodents. Specifically, we will expose both Wildtype and CDKN1ap21-null mice to hydrogen peroxide to induce oxidative stress and observe the molecular mechanisms in which a dietary supplement protects vascular smooth muscle cells against the consequences of the apoptotic environment within Wildtype mice versus the, hypothetically, sound physiology of CDKN1ap21-null mice. The successful completion of this experiment will conclusively determine accuracy of a dietary supplement as a CDKN1ap21 suppressor. This will provide a new perspective on the problem of increased oxidative stress developing into cardiovascular disease as a result of long-term space flight. This research will address the Human Research Plan Roadmaps Risk of Cardiac Rhythm Problems including CV-8, the Risk of Cardiovascular Disease and Other Degenerative Tissue Effects from Radiation Exposure including Degen-6 and Degen-7, and the Risk of Adverse Health Event from Radiation Exposure including IM-8. Additionally, this research will address Space Biology Research Plans questions SBP CMB-1, SBP CMB-3, and SB AN-2.

Oxidative Stress↗
NASA NTRS2001

Asthenia--does it exist in space?

OBJECTIVE: First popularized as neurasthenia in the late 1800s by American George Beard, asthenia has been viewed by Russian psychologists and flight surgeons as a major problem that affects cosmonauts participating in long-duration space missions. However, there is some controversy about whether this syndrome exists in space; this controversy is attributable in part to the fact that it is not recognized in the current American psychiatric diagnostic system. METHODS: To address this issue empirically, we retrospectively examined the data from our 4 1/2-year, NASA-funded study of crew member and mission control interactions during the Shuttle/Mir space program. Three of the authors identified eight items of stage 1 asthenia from one of our measures, the Profile of Mood States (POMS). Scores on these items from 13 Russian and American crew members were compared with scores derived from the opinions of six Russian space experts. RESULTS: Crew members' scores in space were significantly lower than the experts' scores on seven of the eight items, and they generally were in the "not at all" to "a little" range of the item scales. There were no differences in mean scores before and after launch or across the four quarters of the missions. There were no differences in response between Russian and American crew members. CONCLUSIONS: We could not demonstrate the presence of asthenia in space as operationally defined using the POMS. However, the POMS addresses only emotional and not physiological aspects of the syndrome, and the subject responses in our study generally were skewed toward the positive end of the scales. Further research on this syndrome needs to be done and should include physiological measures and measures that are specific to asthenia.

Non-NASA Center↗
NASA NTRS2002

Transcription profiling of the early gravitropic response in Arabidopsis using high-density oligonucleotide probe microarrays

Studies of plant tropisms, the directed growth toward or away from external stimuli such as light and gravity, began more than a century ago. Yet biochemical, physiological, and especially molecular mechanisms of plant tropic responses remain for the most part unclear. We examined expression of 8,300 genes during early stages of the gravitropic response using high-density oligonucleotide probe microarrays. Approximately 1.7% of the genes represented on the array exhibited significant expression changes within the first 30 min of gravity stimulation. Among gravity-induced genes were a number of genes previously implicated to be involved in gravitropism. However, a much larger number of the identified genes have not been previously associated with gravitropism. Because reorientation of plants may also expose plants to mechanical perturbations, we also compared the effects of a gentle mechanical perturbation on mRNA levels during the gravity response. It was found that approximately 39% of apparently gravity-regulated genes were also regulated by the mechanical perturbation caused by plant reorientation. Our study revealed the induction of complex gene expression patterns as a consequence of gravitropic reorientation and points to an interplay between the gravitropic and mechanical responses and to the extreme sensitivity of plants to even very gentle mechanical perturbations.

NASA Discipline Plant Biology↗
DOE OSTI2023

Starch depletion in the xylem and phloem ray parenchyma of grapevine stems under drought

Abstract While nonstructural carbohydrate (NSC) storage can support long-lived woody plants during abiotic stress, the timing and extent of their use are less understood, as are the thresholds for cell mortality as NSCs and water supplies are consumed. Here, we combine physiological and imaging tools to study the response of Vitis riparia to a 6-week experimental drought. We focused on the spatial and temporal dynamics of starch consumption and cell viability in the xylem and phloem of the stem. Starch dynamics were further corroborated with enzymatic starch digestion and X-ray microcomputed tomography imaging. Starch depletion in the stems of droughted plants was detected after 2 weeks and continued over time. We observed distinct differences in starch content and cell viability in the xylem and phloem. By the end of the drought, nearly all the starch was consumed in the phloem ray parenchyma (98 % decrease), and there were almost no metabolically active cells in the phloem. In contrast, less starch was consumed in the xylem ray parenchyma (30 % decrease), and metabolically active cells remained in the ray and vessel-associated parenchyma in the xylem. Our data suggest that the higher proportion of living cells in the phloem and cambium, combined with smaller potential NSC storage area, rapidly depleted starch, which led to cell death. In contrast, the larger cross-sectional area of the xylem ray parenchyma with higher NSC storage and lower metabolically active cell populations depleted starch at a slower pace. Why NSC source-sink relationships between xylem and phloem do not allow for a more uniform depletion of starch in ray parenchyma over time is unclear. Our data help to pinpoint the proximate and ultimate causes of plant death during prolonged drought exposure and highlight the need to consider the influence of within-organ starch dynamics and cell mortality on abiotic stress response.

59 BASIC BIOLOGICAL SCIENCES↗
NASA NTRS1977

Comparative orthostatic responses - Standing vs. head-up tilt

In both physiologic and clinical studies, standing is often loosely equated with head-up tilt (HUT) although the cardiovascular effects of these variants of orthostasis have not been formally compared, except for heart rate. The effects of HUT and standing were measured noninvasively in male volunteers satisfying identical criteria for age and normal status. In both postures, there were significant increases in heart rate, pre-ejection period, isovolumic contraction time, and the ratio of pre-ejection to ejection period, and significant decreases in ejection period and ejection time index. All of these changes were greater for standing than for tilt. Pulse transmission time changed significantly (-14%) only with tilt. We conclude that head-up tilt and standing are rather comparable but not physiologically identical forms of orthostasis.

Spodick, D. H.↗
NASA NTRS1991

An overview of gravitational physiology

The focus of this review is on the response of humans and animals to the effects of the near weightless condition occurring aboard orbiting spacecraft. Gravity is an omnipresent force that has been a constant part of our lives and of the evolution of all living species. Emphasis is placed on the general mechanisms of adaptation to altered gravitational fields and vectors, i.e., both hypo- and hypergravity. A broad literature review of gravitational biology was conducted and the general state of our knowledge in this area is discussed. The review is specifically targeted at newcomers to the exciting and relatively new area of space and gravitational biology.

Miquel, Jaime↗
NASA NTRS1998

2-deoxy-D-glucose-induced metabolic stress enhances resistance to Listeria monocytogenes infection in mice

Exposure to different forms of psychological and physiological stress can elicit a host stress response, which alters normal parameters of neuroendocrine homeostasis. The present study evaluated the influence of the metabolic stressor 2-deoxy-D-glucose (2-DG; a glucose analog, which when administered to rodents, induces acute periods of metabolic stress) on the capacity of mice to resist infection with the facultative intracellular bacterial pathogen Listeria monocytogenes. Female BDF1 mice were injected with 2-DG (500 mg/kg b. wt.) once every 48 h prior to, concurrent with, or after the onset of a sublethal dose of virulent L. monocytogenes. Kinetics of bacterial growth in mice were not altered if 2-DG was applied concurrently or after the start of the infection. In contrast, mice exposed to 2-DG prior to infection demonstrated an enhanced resistance to the listeria challenge. The enhanced bacterial clearance in vivo could not be explained by 2-DG exerting a toxic effect on the listeria, based on the results of two experiments. First, 2-DG did not inhibit listeria replication in trypticase soy broth. Second, replication of L. monocytogenes was not inhibited in bone marrow-derived macrophage cultures exposed to 2-DG. Production of neopterin and lysozyme, indicators of macrophage activation, were enhanced following exposure to 2-DG, which correlated with the increased resistance to L. monocytogenes. These results support the contention that the host response to 2-DG-induced metabolic stress can influence the capacity of the immune system to resist infection by certain classes of microbial pathogens.

Non-NASA Center↗
NASA NTRSDate not supplied

Translational Line of Sight: a multi-omics longitudinal study of the murine retinal response to spaceflight hazard analogs

The space environment includes unique hazards like radiation and microgravity which adversely affect physiology and behavior of humans and rodent models. To better characterize the retinal response to spaceflight, we assessed a multi-omics NASA GeneLab dataset where 6-month-old female mice were gamma irradiated and/or hindlimb unloaded for 21 days followed by whole transcriptome shotgun sequencing (RNA-Seq) and reduced representation bisulfite sequencing (RRBS) of retina samples collected at 7 days, 1 month or 4 months post-exposure. We compared time-matched epigenomic and transcriptomic retinal profiles revealing a total of 4,178 differentially methylated loci or regions, and 457 differentially expressed genes. Highest correlation in methylation differences was seen across different conditions at the same time point (e.g., between radiation exposure and hindlimb unloaded at 7 days). Biological processes related to nucleotide metabolism were enriched in all groups with activation at 1 month and suppression at 7 days and 4 months. Genes and processes related to Notch and Wnt signaling showed alterations 4 months post-exposure. Interestingly, Notch3 and Lrg1 showed differential patterns in the NASA Twins Study in-flight samples and in response to stressors in the murine retina in the current study. A total of 23 genes were both differentially methylated and expressed, including genes involved in retinal disease or cataract development (Crybb3, Fgfr1, Pitpnm3, Sipa1l3, Sox9) and inflammatory response (B4galt6, Ppm1a, Sphk1). To our knowledge, the current multi-omics analysis is the first multi-omics study to interrogate the epigenomic and transcriptomic impacts of radiation and hindlimb unloading on the retina in isolation and in combination. The results provide an insight into the retinal response to individual spaceflight hazard analogs and their interplay at different post-exposure stages and contributes towards a mechanistic understanding of spaceflight-induced vision impairment using ground-based models.

Prachi Kothiyal↗
NASA NTRS1972

The foundations of space biology and medicine. Volume 2: Ecological and physiological bases of space biology and medicine. Part 3: Effect on the organism of dynamic flight factors. Chapter 1: Principles of gravitational biology

The physical principles of gravitation are discussed, such as gravitational and intertial forces, weight and mass, weightlessness, size and scale effects, scale limits of gravitational effects, and gravity as a biogenic factor. The behavior of the accelerative force gravitation, is described. This law proposes and quantifies the mutual gravitational attraction existing between all bodies of matter, the force being proportional to the product of masses, and inversely related to the square of the distance separating them. Gravity orientation, chronic acceleration, and hematology are examined. Systematic responses, such as circulation and renal functions, are also considered, along with animal response to a decreased acceleration field and physiology of hyper- and hypodynamic fields.

Smith, A. H.↗
DOE OSTI2023

Balancing growth amidst salt stress – lifestyle perspectives from the extremophyte model Schrenkiella parvula

Schrenkiella parvula, a leading extremophyte model in Brassicaceae, can grow and complete its lifecycle under multiple environmental stresses, including high salinity. Yet, the key physiological and structural traits underlying its stress-adapted lifestyle are unknown along with trade-offs when surviving salt stress at the expense of growth and reproduction. We aimed to identify the influential adaptive trait responses that lead to stress-resilient and uncompromised growth across developmental stages when treated with salt at levels known to inhibit growth in Arabidopsis and most crops. Its resilient growth was promoted by traits that synergistically allowed primary root growth in seedlings, the expansion of xylem vessels across the root-shoot continuum, and a high capacity to maintain tissue water levels by developing thicker succulent leaves while enabling photosynthesis during salt stress. A successful transition from vegetative to reproductive phase was initiated by salt-induced early flowering, resulting in viable seeds. Self-fertilization in salt-induced early flowering was dependent upon filament elongation in flowers otherwise aborted in the absence of salt during comparable plant ages. Furthermore, the maintenance of leaf water status promoting growth, and early flowering to ensure reproductive success in a changing environment, were among the most influential traits that contributed to the extremophytic lifestyle of S. parvula.

59 BASIC BIOLOGICAL SCIENCES↗
NASA NTRS2004

Biophotonics and Bone Biology

One of the more serious side effects of extended space flight is an accelerated bone loss. Rates of bone loss are highest in the weight-bearing bones of the hip and spine regions, and the average rate of bone loss as measured by bone mineral density measurements is around 1.2% per month for persons in a microgravity environment. It is well known that bone remodeling responds to mechanical forces. We are developing two-photon microscopy techniques to study bone tissue and bone cell cultures to better understand the fundamental response mechanism in bone remodeling. Osteoblast and osteoclast cell cultures are being studied, and the goal is to use molecular biology techniques in conjunction with Fluorescence Lifetime Imaging Microscopy (FLIM) to study the physiology of in-vitro cell cultures in response to various stimuli, such as fluid flow induced shear stress and mechanical stress. We have constructed a two-photon fluorescence microscope for these studies, and are currently incorporating FLIM detection. Current progress will be reviewed. This work is supported by the NASA John Glenn Biomedical Engineering Consortium.

Zimmerli, Gregory↗