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Results for “Stress Response Signaling”

Search indexed NASA NTRS and DOE OSTI research on propulsion, heat transfer, battery materials and energy systems. Follow report and document links to the original sources.

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All sourcesNASA NTRSDOE OSTI
NASA NTRS1999

The Effects of Partial Mechanical Loading and Ibandronate on Skeletal Tissues in the Adult Rat Hindquarter Suspension Model for Microgravity

We report initial data from a suspended rat model that quantitatively relates chronic partial weightbearing to bone loss. Chronic partial weightbearing is our simulation of the effect of limited artificial gravity aboard spacecraft or reduced planetary gravity. Preliminary analysis of bone by PQCT, histomorphometry, mechanical testing and biochemistry suggest that chronic exposure to half of Earth gravity is insufficient to prevent severe bone loss. The effect of episodic full weightbearing activity (Earth Gravity) on rats otherwise at 50% weightbearing was also explored. This has similarity to treatment by an Earth G-rated centrifuge on a spacecraft that normally maintained artificial gravity at half of Earth G. Our preliminary evidence, using the above techniques to analyze bone, indicate that 2 hours daily of full weightbearing was insufficient to prevent the bone loss observed in 50% weightbearing animals. The effectiveness of partial weightbearing and episodic full weightbearing as potential countermeasures to bone loss in spaceflight was compared with treatment by ibandronate. Ibandronate, a long-acting potent bisphosphonate proved more effective in preventing bone loss and associated functionality based upon structure than our first efforts at mechanical countermeasures. The effectiveness of ibandronate was notable by each of the testing methods we used to study bone from gross structure and strength to tissue and biochemistry. These results appear to be independent of generalized systemic stress imposed by the suspension paradigm. Preliminary evidence does not suggest that blood levels of vitamin D were affected by our countermeasures. Despite the modest theraputic benefit of mechanical countermeasures of partial weightbearing and episodic full weightbearing, we know that some appropriate mechanical signal maintains bone mass in Earth gravity. Moreover, the only mechanism that correctly assigns bone mass and strength to oppose regionally specific force applied to bone is mechanical, a process based upon bone strain. Substantial evidence indicates that the specifics of dynamic loading i.e. time-varying forces are critical. Bone strain history is a predictor of the effect that mechanical conditions have on bone structure mass and strength. Using servo-controlled force plates on suspended rats with implanted strain gauges we manipulated impact forces of ambulation in the frequency (Fourier) domain. Our results indicate that high frequency components of impact forces are particularly potent in producing bone strain independent of the magnitude of the peak force or peak energy applied to the leg. Because a servo-system responds to forces produced by the rat's own muscle activity during ambulation, the direction of ground-reaction loads act on bone through the rat's own musculature. This is in distinction to passive vibration of the floor where forces reach bone through the natural filters of soft tissue and joints. Passive vibration may also be effective, but it may or may not increase bone in the appropriate architectural pattern to oppose the forces of normal ambulatory activity. Effectiveness of high frequency mechanical stimulation in producing regional (muscle directed) bone response will be limited by 1. the sensitivity of bone to a particular range of frequencies and 2. the inertia of the muscles, limiting their response to external forces by increasing tension along insertions. We have begun mathematical modeling of normal ambulatory activity. Effectiveness of high frequency mechanical stimulation in producing regional (muscle directed) bone response will be limited by 1. the sensitivity of bone to a particular range of frequencies and 2. the inertia of the muscles, limiting their response to external forces by increasing tension along insertions. We have begun mathematical modeling of the rat forelimb as a transfer function between impact force and bone strain to predict optimal dynamic loading conditions for this system. We plan additional studies of mechanical counter-measures that incorporate improved dynamic loading, features relevant to anticipated evaluation of artificial gravity, exercise regimens and exposure to Martian gravity, The combination of mechanical countermeasures with ibandronate will also be investigated for signs of synergy.

Schultheis, Lester W.↗
NASA NTRS1999

Mechanically induced c-fos expression is mediated by cAMP in MC3T3-E1 osteoblasts

In serum-deprived MC3T3-E1 osteoblasts, mechanical stimulation caused by mild (287 x g) centrifugation induced a 10-fold increase in mRNA levels of the proto-oncogene, c-fos. Induction of c-fos was abolished by the cAMP-dependent protein kinase inhibitor H-89, suggesting that the transient c-fos mRNA increase is mediated by cAMP. Down-regulation of protein kinase C (PKC) activity by chronic TPA treatment failed to significantly reduce c-fos induction, suggesting that TPA-sensitive isoforms of PKC are not responsible for c-fos up-regulation. In addition, 287 x g centrifugation increased intracellular prostaglandin E2 (PGE2) levels 2.8-fold (P<0. 005). Since we have previously shown that prostaglandin E2 (PGE2) can induce c-fos expression via a cAMP-mediated mechanism, we asked whether the increase in c-fos mRNA was due to centrifugation-induced PGE2 release. Pretreatment with the cyclooxygenase inhibitors indomethacin and flurbiprofen did not hinder the early induction of c-fos by mechanical stimulation. We conclude that c-fos expression induced by mild mechanical loading is dependent primarily on cAMP, not PKC, and initial induction of c-fos is not necessarily dependent on the action of newly synthesized PGE2.

Non-NASA Center↗
NASA NTRS2012

Multi-Sensors Observations of Pre-Earthquake Signals. What We Learned from the Great Tohoku Earthquake?

The lessons learned from the Great Tohoku EQ (Japan, 2011) will affect our future observations and an analysis is the main focus of this presentation. Multi-sensors observations and multidisciplinary research is presented in our study of the phenomena preceding major earthquakes Our approach is based on a systematic analysis of several physical and environmental parameters, which been reported by others in connections with earthquake processes: thermal infrared radiation; temperature; concentration of electrons in the ionosphere; radon/ion activities; and atmospheric temperature/humidity [Ouzounov et al, 2011]. We used the Lithosphere-Atmosphere-Ionosphere Coupling (LAIC) model, one of several possible paradigms [Pulinets and Ouzounov, 2011] to interpret our observations. We retrospectively analyzed the temporal and spatial variations of three different physical parameters characterizing the state of the atmosphere, ionosphere the ground surface several days before the March 11, 2011 M9 Tohoku earthquake Namely: (i) Outgoing Long wave Radiation (OLR) measured at the top of the atmosphere; (ii) Anomalous variations of ionospheric parameters revealed by multi-sensors observations; and (iii) The change in the foreshock sequence (rate, space and time); Our results show that on March 8th, 2011 a rapid increase of emitted infrared radiation was observed and an anomaly developed near the epicenter with largest value occurring on March 11 at 07.30 LT. The GPS/TEC data indicate an increase and variation in electron density reaching a maximum value on March 8. Starting from this day in the lower ionosphere there was also observed an abnormal TEC variation over the epicenter. From March 3 to 11 a large increase in electron concentration was recorded at all four Japanese ground-based ionosondes, which returned to normal after the main earthquake. We use the Japanese GPS network stations and method of Radio Tomography to study the spatiotemporal structure of ionospheric perturbations, and to distinguish ionospheric responses to processes of EQ preparation against the effects of other factors. The 2-D snapshots of the electron density over Japan showed abnormal increase over the maximum stress during the night, a few hours before the main shock. Our results from recording atmospheric and ionospheric conditions during the earthquake indicate the presence of anomalies in the atmosphere and ionospheres occurring consistently over regions of maximum stress near the epicenter. Due to their long duration (hours and days) and spatial appearance (only over the Sendai region) these results do not appear to be caused by meteorological or magnetic activity. They reveal the existence of atmospheric and ionospheric phenomena occurring prior to the earthquake, which indicates new evidence of a distinct coupling between the lithosphere and atmosphere/ionosphere. Similar results have been reported before the catastrophic events in Chile (M8.8, 2010), Italy (M6.3, 2009) and Sumatra (M9.3, 2004).

Ouzonounov, D.↗
NASA NTRS1999

The Effect of Gravity Fields on Cellular Gene Expression

Early theoretical analysis predicted that microgravity effects on the isolated cell would be minuscule at the subcellular level; however, these speculations have not proven true in the real world. Astronauts experience a significant bone and muscle loss in as little as 2 weeks of spaceflight and changes are seen at the cellular level soon after exposure to microgravity. Changes in biological systems may be primarily due to the lack of gravity and the resulting loss of mechanical stress on tissues and cells. Recent ground and flight studies examining the effects of gravity or mechanical stress on cells demonstrate marked changes in gene expression when relatively small changes in mechanical forces or gravity fields were made. Several immediate early genes (IEG) like c-fos and c-myc are induced by mechanical stimulation within minutes. In contrast, several investigators report that the absence of mechanical forces during space flight result in decreased sera response element (SRE) activity and attenuation of expression of IEGs such as c-fos, c-jun and cox-2 mRNAs. Clearly, these early changes in gene expression may have long term consequences on mechanically sensitive cells. In our early studies on STS-56, we reported four major changes in the osteoblast; 1) prostaglandin synthesis in flight, 2) changes in cellular morphology, 3) altered actin cytoskeleton and 4) reduced osteoblast growth after four days exposure to microgravity. Initially, it was believed that changes in fibronectin (FN) RNA, FN protein synthesis or subsequent FN matrix formation might account for the changes in cytoskeleton and/ or reduction of growth. However our recent studies on Biorack (STS-76, STS-81 and STS-84), using ground and in-flight 1-G controls, demonstrated that fibronectin synthesis and matrix formation were normal in microgravity. In addition, in our most recent Biorack paper, our laboratory has documented that relative protein synthesis and mRNA synthesis are not changed after 24 hours exposure to microgravity. We did, however, find significant changes in osteoblast gene expression of IEGs, c-fos and cox-2 in microgravity exposure as compared to ground and in-flight 1-G controls. Subsequent ground studies suggest that the molecular mechanism underlying these changes may involve prostaglandin c-AMP receptors (EPs) and/or subsequent alteration of intracellular signaling in the absence of gravity.

Hughes-Fulford, Millie↗
NASA NTRS1999

Seasonal-to-Interannual Variability in Antarctic Sea-Ice Dynamics, and Its Impact on Surface Fluxes and Water Mass Production

Strong seasonal and interannual signals in Antarctic bottom-water outflow remain unexplained yet are highly correlated with anomalies in net sea-ice growth in coastal polynyas. The mechanisms responsible for driving salination and replenishment and rejuvenation of the dense shelf "source" waters likely also generate pulses of bottom water outflow. The objective of this research is to investigate time-scales of variability in the dynamics of sea-ice in the Southern Ocean in order to determine the primary sites for production of dense shelf waters. We are using a merged satellite/buoy sea-ice motion data set for the period 1978-present day to compute the dynamics of opening and closing of coastal polynyas over the continental shelf. The Ocean Circulation and Climate Advanced Model (OCCAM) ocean general circulation model with coupled sea-ice dynamics is presently forced using National Center for Environmental Prediction (NCEP) data to simulate fluxes and the salination impact of the ocean shelf regions. This work is relevant in the context of measuring the influence of polar sea-ice dynamics upon polar ocean characteristics, and thereby upon global thermohaline ocean circulation. Interannual variability in simulated net freezing rate in the Southern Weddell Sea is shown for the period 1986-1993. There is a pronounced maximum of ice production in 1988 and minimum in 1991 in response to anomalies in equatorward meridional wind velocity. This follows a similar approximate 8-year interannual cycle in Sea Surface Temperature (SST) and satellite-derived ice-edge anomalies reported elsewhere as the "Antarctic Circumpolar Wave." The amplitude of interannual fluctuations in annual net ice production are about 40% of the mean value, implying significant interannual variance in brine rejection and upper ocean heat loss. Southward anomalies in wind stress induce negative anomalies in open water production, which are observed in passive microwave satellite images. Thus, cycles of enhanced poleward wind stress reduce ice growth by compacting the ice along the coastline and closing open water in leads and polynyas. Model simulations confirm that years of low ice production, such as 1991, coincide with years of lower than normal bottom water outflow. Future plans include the assimilation of satellite ice concentrations and ice drift dynamics to more accurately constrain boundary conditions in the model.

Drinkwater, Mark R.↗
NASA NTRS1995

Probing transmembrane mechanical coupling and cytomechanics using magnetic twisting cytometry

We recently developed a magnetic twisting cytometry technique that allows us to apply controlled mechanical stresses to specific cell surface receptors using ligand-coated ferromagnetic microbeads and to simultaneously measure the mechanical response in living cells. Using this technique, we have previously shown the following: (i) beta 1 integrin receptors mediate mechanical force transfer across the cell surface and to the cytoskeleton, whereas other transmembrane receptors (e.g., scavenger receptors) do not; (ii) cytoskeletal stiffness increases in direct proportion to the level of stress applied to integrins; and (iii) the slope of this linear stiffening response differs depending on the shape of the cell. We now show that different integrins (beta 1, alpha V beta 3, alpha V, alpha 5, alpha 2) and other transmembrane receptors (scavenger receptor, platelet endothelial cell adhesion molecule) differ in their ability to mediate force transfer across the cell surface. In addition, the linear stiffening behavior previously observed in endothelial cells was found to be shared by other cell types. Finally, we demonstrate that dynamic changes in cell shape that occur during both cell spreading and retraction are accompanied by coordinate changes in cytoskeletal stiffness. Taken together, these results suggest that the magnetic twisting cytometry technique may be a powerful and versatile tool for studies analyzing the molecular basis of transmembrane mechanical coupling to the cytoskeleton as well as dynamic relations between changes in cytoskeletal structure and alterations in cell form and function.

NASA Discipline Number 40-20↗
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 NTRS1995

Human osteoblast-like cells respond to mechanical strain with increased bone matrix protein production independent of hormonal regulation

Exposure of osteosarcoma cell lines to chronic intermittent strain increases the activity of mechano-sensitive cation (SA-cat) channels. The impact of mechano-transduction on osteoblast function has not been well studied. We analyzed the expression and production of bone matrix proteins in human osteoblast-like osteosarcoma cells, OHS-4, in response to chronic intermittent mechanical strain. The OHS-4 cells exhibit type I collagen production, 1,25-Dihydroxyvitamin D-inducible osteocalcin, and mineralization of the extracellular matrix. The matrix protein message level was determined from total RNA isolated from cells exposed to 1-4 days of chronic intermittent strain. Northern analysis for type I collagen indicated that strain increased collagen message after 48 h. Immunofluorescent labeling of type I collagen demonstrated that secretion was also enhanced with mechanical strain. Osteopontin message levels were increased several-fold by the application of mechanical load in the absence of vitamin D, and the two stimuli together produced an additive effect. Osteocalcin secretion was also increased with cyclic strain. Osteocalcin levels were not detectable in vitamin D-untreated control cells. However, after 4 days of induced load, significant levels of osteocalcin were observed in the medium. With vitamin D present, osteocalcin levels were 4 times higher in the medium of strained cells compared to nonstrained controls. We conclude that mechanical strain of osteoblast-like cells is sufficient to increase the transcription and secretion of matrix proteins via mechano-transduction without hormonal induction.

NASA Discipline Number 40-40↗