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At least 433 records · Page 24
All sourcesNASA NTRSDOE OSTI
NASA NTRS2023

Measurement Report :Emission Factors of NH3 and NHx for Wildfires and Agricultural Fires in the United States

During the 2019 Fire Influence on Regional to Global Environments and Air Quality (FIREX-AQ) study, the NASA DC-8 carried out in situ chemical measurements in smoke plumes emitted from wildfires and agricultural fires in the contiguous United States. The DC-8 payload included a modified proton-transfer-reaction time-of-flight mass spectrometer (PTR-ToF-MS) for the fast measurement of gaseous ammonia (NH 3 ) and a high-resolution time-of-flight aerosol mass spectrometer (AMS) for the fast measurement of submicron particulate ammonium (NH 4 + ). We herein report data collected in smoke plumes emitted from 6 wildfires in the Western United States, 2 prescribed grassland fires in the Central United States, 1 prescribed forest fire in the Southern United States, and 66 small agricultural fires in the Southeastern United States. Smoke plumes contained double to triple digit ppb levels of NH 3 . In the wildfire plumes, a significant fraction of NH 3 had already been converted to NH 4 + at the time of sampling (≥2 h after emission). Substantial amounts of NH 4 + were also detected in freshly emitted smoke from corn and rice field fires. We herein present a comprehensive set of emission factors of NH 3 and NH x , with NH x = NH 3 + NH 4 + . Average NH 3 and NH x emission factors for wildfires in the Western United States were 1.86±0.75 g kg −1 and 2.47±0.80 g kg −1 of fuel burned, respectively. Average NH 3 and NH x emission factors for agricultural fires in the Southeastern United States were 0.89±0.58 and 1.74±0.92 g kg −1 , respectively. Our data show no clear inverse correlation between modified combustion efficiency (MCE) and NH 3 emissions. The observed NH 3 emissions were significantly higher than measured in previous laboratory experiments in the FIREX FireLab 2016 study.

Laura Tomsche↗
NASA NTRSDate not supplied

Transition Modeling Based on the Dual N-factor Method for the CRM-NLF Wind Tunnel Configuration

The dual N-factor method is used to model the boundary-layer transition over the common research model with natural laminar flow (CRM-NLF) aircraft configuration. The flow conditions match selected test conditions from a wind tunnel experiment in the National Transonic Facility at the NASA Langley Research Center. The paper presents a systematic methodology for transition prediction in the presence of a dual shock system and extends the prior capability for iteratively coupled computational fluid dynamics (CFD) predictions to incorporate three-dimensional, transonic wings. The method employs stability computations based on the linear parabolized stability equations (PSE), along with a dual N-factor criterion. The iterative process begins with the fully turbulent Reynolds-averaged-Navier-Stokes (RANS) mean flow solution. For the first iteration, a mean flow solution is calculated with an imposed transition front that aligns with the shock front from the fully turbulent solution. Subsequently, stability computations are performed along a set of streamlines across the wing to calculate the amplification of planar Tollmien-Schlichting (TS) and stationary crossflow (CF) modes. The transition criterion based on the dual N-factor method is used to infer the updated transition front and the process is successively repeated until convergence of the solution. Within three iterations, the predicted fronts for angles of attack of 1.45, 1.98, 2.46 and 2.94 degrees and a mean-aerodynamic-chord Reynolds number equal to 15 million, approach visual convergence in most regions of the studied cases, and the resulting predictions are in good agreement with the transition fronts deduced from measurements of temperature-sensitive paint. Even though surface pressure measurements based on fully-turbulent flow agree well with the measured pressure coefficient distributions, strong viscous-inviscid interaction effects cause significant shifts in the shock locations based on the imposed transition front, underscoring the intrusive nature of static pressure measurements using surface mounted ports on the CRM-NLF configuration.

Boundary Layer Transition↗
NASA NTRSDate not supplied

Bayesian Symbolic Regression: Addressing Challenges in Estimating Fractional Bayes Factors and Application to Fatigue Crack Growth Modeling

This research pioneers advancements in computational mechanics by integrating Bayesian-based uncertainty quantification into symbolic regression, specifically focusing on the critical task of accurately estimating the fractional Bayes factor for selecting arbitrary equations. In our exploration, we rigorously study two prominent methods—sequential Monte Carlo and the Laplace approximation—employed for computing the fractional Bayes factor. Our findings underscore the limitations of the Laplace approximation, revealing its diminished accuracy in nonlinear and multimodal scenarios. Specifically, the Laplace approximation is shown to underpredict fractional Bayes factor on a wide set of equations associated with a symbolic regression benchmark. This comparative analysis sheds light on the nuanced performance of these techniques, guiding researchers toward more informed choices in uncertainty quantification within symbolic regression. Furthermore, we showcase the practical utility of these enhanced symbolic regression tools through their application to a real-world problem in fatigue crack growth modeling, emphasizing their efficacy in capturing the complexities of mechanical systems.

Geoffrey Bomarito↗
NASA NTRS2024

Córdoba Wildland Fires: Assessing Fire Risk Factors in Córdoba, Argentina using Earth Observations

In recent years, Córdoba, Argentina has experienced intensified wildfire activity, with fires in 2020 alone scorching over 300,000 hectares within the province. Potential causes for the increased burn area include climate change, the expanding wildland-urban interface (WUI), and inadequate fire management practices. Previous studies have produced fire frequency maps for the region, but gaps remain in understanding the environmental parameters influencing fire behavior and growth. We partnered with the Instituto Nacional de Tecnología Agropecuaria (INTA) to address these gaps by utilizing NASA Earth observing data to analyze key wildfire risk factors. Using a combination of data inputs from Soil Moisture Active Passive (SMAP), Shuttle Radar Topography Mission (SRTM), Global Precipitation Measurement (GPM) Integrated Multi-satellite Retrievals for GPM (IMERG), and Aqua/Terra Moderate Resolution Imaging Spectroradiometer (MODIS), we created a ten-year baseline using environmental variables to determine anomalies that influenced the fires of 2020. Baseline data were used to calculate the statistical significance of the environmental factors as precursors to wildfires. We found that the normalized difference vegetation index (NDVI) and precipitation were the strongest indicators for the September 2020 wildfires. Using the environmental risk factors, we created a wildfire risk map for the province of Córdoba, which can be used to enhance our partner’s fire management strategies and decision-making processes.

wildland fires↗
NASA NTRSDate not supplied

Risk Characterization Research for Artemis II: Human Factors and Behavioral Performance

BACKGROUND Artemis II will be the first time NASA astronauts go beyond low-Earth orbit (LEO) since the Apollo era, and the first astronauts heading into space in the Orion vehicle. As such, it provides a critical opportunity to refine our understanding of the likelihood and consequences associated with the Behavioral Medicine (BMed), Team, Human System Integration Architecture (HSIA), and Sleep Risks, and prepare for future Moon and Mars missions. However, Artemis II research efforts are uniquely shaped by in-mission data collection constraints. There is currently no in-mission crew time available to complete measures. In-mission data will need to be collected unobtrusively from available data streams (e.g., audiovisual, existing records such as schedules, and actigraphy). Accordingly, the overarching goal of our research is to utilize Artemis II data to further define the likelihood and consequences of these risks, and to create an unobtrusive research infrastructure that can be expanded to include future Artemis missions. This goal spans four aims across three research phases: (1) identify and operationally define key performances metrics and constructs across the four aforementioned risks, (2) develop an unobtrusive methodology and coding scheme for in-mission data collection, (3) characterize performance decrements due to Bmed, Team, HSIA, and Sleep Risks, and (4) develop a data infrastructure for future Artemis missions. The following details results of Phase I efforts in which we address Aims 1 and 2 to develop an unobtrusive measurement plan and coding scheme to capture key constructs, contributing factors, and performance decrements across each risk area. METHOD As part of Phase I, we conducted an interdisciplinary literature review and consulted with SMEs to identify unobtrusive methodologies that leverage text, audio, and/or video data as well as conceptualize key performance metrics, contributing factors, and BMed, Team, HSIA, and Sleep risk constructs related to performance decrements. The Phase I effort resulted in a finalized pre- and post-mission protocol for Artemis II, along with a measurement and coding scheme for in-mission Artemis II data. Phase II will involve data collection from the upcoming Artemis II mission. Phase III will include data processing, coding, depiction, analysis, and report writing of the Artemis II data. RESULTS & DISCUSSION To date, we have completed Phase I efforts. Specifically, we identified BMed, Team, HSIA, and Sleep risk constructs related to performance metrics, summarized how these constructs can be measured using audiovisual data collected during the mission, and worked with NASA’s HFBP Element to finalize a data collection protocol that leverages audiovisual input from the Orion spacecraft system. Our protocol includes novel unobtrusive methodologies that adhere to in-mission data streams and subsequent constraints (e.g., limited storage space on GoPro cameras, ambient noise impeding audio files) to best capture in-mission phenomena across each risk area. We will present our results from Phase I efforts, namely best practices for unobtrusive measurement as identified through literature reviews and SME consultation as well as codebook excerpts for use in Artemis II. We will include a description of planned work as we prepare for Phase II and Phase III of this research plan and the Artemis II mission itself. SUMMARY We describe progress on our Human Factors and Behavioral Performance Research for Artemis II study.

behavioral health↗
NASA NTRS2025

Habitability and Human Factors Assessment (iSHORT, SHAQ, and SHU)

BACKGROUND As long-duration off-planet habitats become a reality, a consideration of habitability and human factors (HF) is crucial. The habitat is more than just a place to live and work. It is also the crew’s perception of the space, and the psychological impacts of size, layout, and usage over time; all of which can support or strain behavioral health and performance (BHP). A previous International Space Station (ISS) habitability study used the iSHORT (Space Habitability Observation Reporting Tool) to collect detailed data about habitability and human factors and inform NASA Standards. Of the previous iSHORT study, only one of the six ISS subjects had a duration of one year; all other ISS and ground analog subjects had shorter mission durations from one week to six months. It is necessary to collect new data with a focus on long-duration exploration missions of > 6 months and on planetary surface habitat design. New data is also needed to compare the iSHORT to other habitability measures. One measure, the SHAQ (Subjective Habitability and Acceptability Questionnaire), assesses the intersection of psychology and habitability. Another complementary measure, the Scale for Habitat Usability (SHU), is a brief subjective scale that captures how habitat design impacts perceived usability of the built environment in relation to task performance. OBJECTIVE Our study aims to (1) understand how individual well-being and team dynamics may relate to HF concerns over time, (2) capture how habitability and HF change over time, (3) compare the three habitability measures (iSHORT, SHAQ, SHU), (4) assess habitats to capture HF design concerns and related BHP impacts of a planetary habitat, and (5) inform future standards for HF design. METHOD Data are being collected on crews living and working in long-duration spaceflight analogs. Individual-level data collections are repeated at regular intervals throughout the missions on several habitat areas, activities, and key equipment (i.e., points of interest). These points of interest (POIs) include the kitchen/galley, crew quarters, and other work and living areas. Assessments include evaluations of privacy, comfort, convenience, control, efficiency, and social density through the lens of subsequent outcomes like sleep, individual performance, group activities performance, stress, mood, and social interactions. Pre- and post-mission evaluations will also allow comparison with homes, pre- and post-mission hotels, and a retrospective reflection of living and working in a long-duration analog. INITIAL DATA COLLECTIONS In this poster, we will describe the measures and data yield. Since the research protocol was designed, the study team has collected iSHORT Standalone four times, nine collections of SHAQ, and three collections of iSHORT with SHAQ. Data collection is ongoing. SUMMARY A novel assessment suite has been developed to further aid the comparison and complementary understanding of the habitability and human factors measures, which will allow for efficient deployment of these measures in analogs and/or spaceflight in near-term research as well as support well-being and performance through design.

J C W Miller↗
NASA NTRSDate not supplied

Exemplifying the Usability of NASA Earth Observations to Analyze Potential Risk Factors that Predispose Wildfires in the Rural-Urban Areas of Córdoba, Argentina

In recent years, Córdoba, Argentina has experienced intensified wildfire activity, with fires in 2020 alone scorching over 300,000 hectares within the province. Potential causes for the increased burn area include climate change, the expanding wildland-urban interface, and inadequate fire management practices. Previous studies have produced fire frequency maps for the region, but gaps remain in understanding the parameters influencing fire behavior and growth. This project partnered with the Instituto Nacional de Tecnología Agropecuaria to address these gaps by utilizing NASA’s remote sensing capabilities to analyze key wildfire risk factors. Using a combination of data inputs from Soil Moisture Active Passive (SMAP), Shuttle Radar Topography Mission (SRTM), Global Precipitation Measurement (GPM) Integrated Multi-satellite Retrievals for GPM (IMERG), and Aqua/Terra Moderate Resolution Imaging Spectroradiometer (MODIS), a ten-year baseline was created using environmental variables to determine anomalies that influenced the fires of 2020. Of these anomalies, the baseline data were used to calculate the statistical significance of the environmental factors to the wildfires. This study found that the normalized difference vegetation index (NDVI) and precipitation were the strongest indicators for the September 2020 wildfires. Using the environmental risk factors, this project created a wildfire risk map for the province of Córdoba, which can be used to enhance partner’s fire management strategies and decision-making processes.

Chassety Raines↗
NASA NTRS1993

Extracellular matrix and growth factors in branching morphogenesis

The unifying hypothesis of the NSCORT in gravitational biology postulates that the ECM and growth factors are key interrelated components of a macromolecular regulatory system. The ECM is known to be important in growth and branching morphogenesis of embryonic organs. Growth factors have been detected in the developing embryo, and often the pattern of localization is associated with areas undergoing epithelial-mesenchymal interactions. Causal relationships between these components may be of fundamental importance in control of branching morphogenesis.

Non-NASA Center↗
NASA NTRS2001

Selected Contribution: Skeletal muscle focal adhesion kinase, paxillin, and serum response factor are loading dependent

This investigation examined the effect of mechanical loading state on focal adhesion kinase (FAK), paxillin, and serum response factor (SRF) in rat skeletal muscle. We found that FAK concentration and tyrosine phosphorylation, paxillin concentration, and SRF concentration are all lower in the lesser load-bearing fast-twitch plantaris and gastrocnemius muscles compared with the greater load-bearing slow-twitch soleus muscle. Of these three muscles, 7 days of mechanical unloading via tail suspension elicited a decrease in FAK tyrosine phosphorylation only in the soleus muscle and decreases in FAK and paxillin concentrations only in the plantaris and gastrocnemius muscles. Unloading decreased SRF concentration in all three muscles. Mechanical overloading (via bilateral gastrocnemius ablation) for 1 or 8 days increased FAK and paxillin concentrations in the soleus and plantaris muscles. Additionally, whereas FAK tyrosine phosphorylation and SRF concentration were increased by < or =1 day of overloading in the soleus muscle, these increases did not occur until somewhere between 1 and 8 days of overloading in the plantaris muscle. These data indicate that, in the skeletal muscles of rats, the focal adhesion complex proteins FAK and paxillin and the transcription factor SRF are generally modulated in association with the mechanical loading state of the muscle. However, the somewhat different patterns of adaptation of these proteins to altered loading in slow- vs. fast-twitch skeletal muscles indicate that the mechanisms and time course of adaptation may partly depend on the prior loading state of the muscle.

NASA Discipline Musculoskeletal↗
NASA NTRS1994

Skeletal unloading induces resistance to insulin-like growth factor I

In previous studies with a hindlimb elevation model, we demonstrated that skeletal unloading transiently inhibits bone formation. This effect is limited to the unloaded bones (the normally loaded humerus does not cease growing), suggesting that local factors are of prime importance. IGF-I is one such factor; it is produced in bone and stimulates bone formation. To determine the impact of skeletal unloading on IGF-I production and function, we assessed the mRNA levels of IGF-I and its receptor (IGF-IR) in the proximal tibia and distal femur of growing rats during 2 weeks of hindlimb elevation. The mRNA levels for IGF-I and IGF-IR rose during hindlimb elevation, returning toward control values during recovery. This was accompanied by a 77% increase in IGF-I levels in the bone, peaking at day 10 of unloading. Changes in IGF binding protein levels were not observed. Infusion of IGF-I (200 micrograms/day) during 1 week of hindlimb elevation doubled the increase in bone mass of the control animals but failed to reverse the cessation of bone growth in the hindlimb-elevated animals. We conclude that skeletal unloading induces resistance to IGF-I, which may result secondarily in increased local production of IGF-I.

NASA Center ARC↗
NASA NTRS2025

Mechanics of Preloaded Bolt Tensile Loading With Focus on Load Introduction Factor

The bolt tensile and joint separation loads are directly influenced by the locations at which the external loads enter the clamped members of a preloaded bolted joint (PBJ) and the associated load-paths through the joint. This physical load introduction mechanism affecting the bolt tensile loading is typically represented in the bolt tensile load equation, in part, by a load introduction factor (LIF), which was shown by H.M. Lee of Marshall Spaceflight Center to be a natural product of the bolt tensile load equation using a linear spring stiffness model. This LIF, being a function of load-path stiffness, has subsequently been denoted as the stiffness-based LIF (SBLIF), providing a framework to calculate the LIF using whatever load-path stiffness approximations are appropriate. Expanding upon the work of Lee, it is shown that the SBLIF and the joint stiffness factor are functions of the stiffnesses of the same load-paths and regions within a PBJ, and thus they should not be treated as independent variables. Mathematical expressions for the SBLIF are presented. Comparisons are shown between the analytically calculated SBLIF, the analytically calculated geometric LIF (GLIF), which is a simple clamped-member thickness ratio, the experimentally derived LIF, and the LIF determined by finite element analysis (FEA). Using experiment and FEA as a benchmark, the SBLIF, using traditional load-path stiffness approximations, enables a more accurate prediction of bolt tensile loading than the GLIF, although it can be unconservative near joint separation. The GLIF generally attributes more of the externally applied tensile load to the bolt than does the SBLIF, potentially resulting in heavier and/or more costly bolted joints. Mathematical relationships between the SBLIF and the GLIF are developed. Supplemental material is provided in the appendixes where the historical practice of using the joint compressive stiffness in place of the joint tensile stiffness is evaluated. The appendixes include step-by-step examples demonstrating the calculation of the SBLIF using traditional stiffness approximations and conclude with the development of the joint diagram in terms of the SBLIF, culminating into formulas for the key features of a joint diagram, which is useful for programming.

Load Path↗
NASA NTRS1964

Biomedical and Human Factors Requirements for a Manned Earth Orbiting Station

This report is the result of a study conducted by Republic Aviation Corporation in conjunction with Spacelabs, Inc.,in a team effort in which Republic Aviation Corporation was prime contractor. In order to determine the realistic engineering design requirements associated with the medical and human factors problems of a manned space station, an interdisciplinary team of personnel from the Research and Space Divisions was organized. This team included engineers, physicians, physiologists, psychologists, and physicists. Recognizing that the value of the study is dependent upon medical judgments as well as more quantifiable factors (such as design parameters) a group of highly qualified medical consultants participated in working sessions to determine which medical measurements are required to meet the objectives of the study. In addition, various Life Sciences personnel from NASA (Headquarters, Langley, MSC) participated in monthly review sessions. The organization, team members, consultants, and some of the part-time contributors are shown in Figure 1. This final report embodies contributions from all of these participants.

EARTH ORBIT↗
NASA NTRS1987

The preservation of urine samples for determination of renal stone risk factors

A preservation technique for urine specimens before determination of stone risk factors was evaluated. The purpose of these experiments was to prove the effectiveness of the preservatives used to prevent changes in the concentrations of those constituents measured. Measured concentrations in fresh specimens were compared with those in the same specimens after storage with the preservatives. Refrigeration at 4 degrees C up to five days was appropriate in a laboratory setting, as no significant changes in urinary concentrations occurred. Refrigeration, however, did not offer a convenient method for shipping. Chemical preservation was found to be an effective alternative to refrigeration. Thymol prevented changes in concentration of pH, citrate, uric acid, sulfate, sodium, potassium, and cyclic AMP, while a mixture of hydrochloric (HCl) acid and boric acid prevented changes in calcium, magnesium, phosphorus, oxalate, ammonium, and creatinine. Thus, the addition of thymol or HCl/boric acid to urine specimens will prevent significant changes in the concentrations of stone risk factors.

Non-NASA Center↗
NASA NTRS1991

Seasonal variations in urinary risk factors among patients with nephrolithiasis

Twenty-four hour urine specimens from 5,677 stone-forming patients throughout the United States were analyzed for seasonal variations in urinary risk factors for nephrolithiasis. Determinations were performed for urine volume, pH, calcium, oxalate, phosphorus, sodium, magnesium, citrate, sulfate, uric acid, and the relative supersaturation (RS) of calcium oxalate, brushite, monosodium urate, and uric acid. Criteria for significant seasonal variation included a significant difference in monthly means of risk factors, seasonal grouping of the data by the Student-Newman-Keuls multiple range test, consistent year-to-year trends and a physiologically significant range. Minimum urine volume of 1.54 +/- 0.70 SD L/day occurred in October while a maximum urine volume of 1.76 +/- 0.78 SD L/day was observed during February. Minimum urine pH of 5.94 +/- 0.64 SD was observed during July and August while a maximum pH of 6.18 +/- 0.61 SD was observed during February. Daily urinary excretion of sodium was lowest during August, 158 +/- 74 SD mEq/day and highest during February 177 +/- 70 SD mEq/day. The RS of brushite and uric acid were found to display significant pH-dependent seasonal variation with a maximum RS of uric acid 2.26 +/- 1.98 SD in June and a low of 1.48 +/- 1.30 SD in February. Maximum RS of brushite 2.75 +/- 2.58 was observed during February. Minimum RS of brushite 1.93 +/- 1.70 SD was observed in June. Phosphorus excretion displayed seasonal variation about a spring-fall axis with a maximum value 1042 +/- 373 SD mg/day in April and a minimum value of 895 +/- 289 SD mg/day. Urine volume, sodium, and pH were significantly lower during the summer (June, July, August) than in the winter (December, January, February). The RS of uric acid was higher, but that of brushite and monosodium urate was lower in the summer than in the winter. The seasonal changes observed in urine volume, pH, sodium, and the RS of brushite and uric acid are consistent with summertime sweating and increased physical activity. Seasonal variations in phosphorus excretion are probably dietary in origin. The summertime was characterized by an increased propensity for the crystallization of uric acid but not of calcium oxalate or calcium phosphate.

NASA Discipline Regulatory Physiology↗
NASA NTRS2000

Insulin-like growth factor-I extends in vitro replicative life span of skeletal muscle satellite cells by enhancing G1/S cell cycle progression via the activation of phosphatidylinositol 3'-kinase/Akt signaling pathway

Interest is growing in methods to extend replicative life span of non-immortalized stem cells. Using the insulin-like growth factor I (IGF-I) transgenic mouse in which the IGF-I transgene is expressed during skeletal muscle development and maturation prior to isolation and during culture of satellite cells (the myogenic stem cells of mature skeletal muscle fibers) as a model system, we elucidated the underlying molecular mechanisms of IGF-I-mediated enhancement of proliferative potential of these cells. Satellite cells from IGF-I transgenic muscles achieved at least five additional population doublings above the maximum that was attained by wild type satellite cells. This IGF-I-induced increase in proliferative potential was mediated via activation of the phosphatidylinositol 3'-kinase/Akt pathway, independent of mitogen-activated protein kinase activity, facilitating G(1)/S cell cycle progression via a down-regulation of p27(Kip1). Adenovirally mediated ectopic overexpression of p27(Kip1) in exponentially growing IGF-I transgenic satellite cells reversed the increase in cyclin E-cdk2 kinase activity, pRb phosphorylation, and cyclin A protein abundance, thereby implicating an important role for p27(Kip1) in promoting satellite cell senescence. These observations provide a more complete dissection of molecular events by which increased local expression of a growth factor in mature skeletal muscle fibers extends replicative life span of primary stem cells than previously known.

NASA Discipline Musculoskeletal↗
NASA NTRS1998

Role of insulin-like growth factor-I in the regulation of skeletal muscle adaptation to increased loading

Adaptations in muscle mass stimulated by changes in muscle loading state entail alternations in the synthesis and degradation of myofiber proteins and the modulation of myonuclear number such that the ratio between the number of myonuclei and the size of the myofibers remains relatively constant. As depicted schematically in Figure 2.6, the literature regarding the role of IGF-in mediating muscle adaptation to alterations in loading state suggests the following conclusions: During periods of increased loading, myofibers upregulate the expression and secretion of IGF-I. Acting as an autocrine and/or paracrine growth factor, IGF-I stimulates myofiber anabolic processes. Acting as a paracrine growth factor, IGF-I also stimulates adjacent satellite cells to enter the cell cycle and proliferate. Continued myofiber production of IGF-I stimulates some satellite cells to differentiate and then fuse with myofibers, thus providing additional myonuclei in order to maintain or reestablish the myonucleus to myofiber size ratios of the enlarged myofibers.

Review, Academic↗
NASA NTRS1998

Fibronectin is a survival factor for differentiated osteoblasts

The skeletal extracellular matrix produced by osteoblasts contains the glycoprotein fibronectin, which regulates the adhesion, differentiation and function of various adherent cells. Interactions with fibronectin are required for osteoblast differentiation in vitro, since fibronectin antagonists added to cultures of immature fetal calvarial osteoblasts inhibit their progressive differentiation. To determine if fibronectin plays a unique role in fully differentiated osteoblasts, cultures that had already formed mineralized nodules in vitro were treated with fibronectin antagonists. Fibronectin antibodies caused >95% of the cells in the mature cultures to display characteristic features of apoptosis (nuclear condensation, apoptotic body formation, DNA laddering) within 24 hours. Cells appeared to acquire sensitivity to fibronectin antibody-induced apoptosis as a consequence of differentiation, since antibodies failed to kill immature cells and the first cells killed were those associated with mature nodules. Intact plasma fibronectin, as well as fragments corresponding to the amino-terminal, cell-binding, and carboxy-terminal domains of fibronectin, independently induced apoptosis of mature (day-13), but not immature (day-4), osteoblasts. Finally, transforming growth factor-beta1 partially protected cells from the apoptotic effects of fibronectin antagonists. Thus, in the course of maturation cultured osteoblasts switch from depending on fibronectin for differentiation to depending on fibronectin for survival. These data suggest that fibronectin, together with transforming growth factor-beta1, may affect bone formation, in part by regulating the survival of osteoblasts.

NASA Center ARC↗
NASA NTRS1997

CCAAT/enhancer-binding protein delta activates insulin-like growth factor-I gene transcription in osteoblasts. Identification of a novel cyclic AMP signaling pathway in bone

Insulin-like growth factor-I (IGF-I) plays a key role in skeletal growth by stimulating bone cell replication and differentiation. We previously showed that prostaglandin E2 (PGE2) and other cAMP-activating agents enhanced IGF-I gene transcription in cultured primary rat osteoblasts through promoter 1, the major IGF-I promoter, and identified a short segment of the promoter, termed HS3D, that was essential for hormonal regulation of IGF-I gene expression. We now demonstrate that CCAAT/enhancer-binding protein (C/EBP) delta is a major component of a PGE2-stimulated DNA-protein complex involving HS3D and find that C/EBPdelta transactivates IGF-I promoter 1 through this site. Competition gel shift studies first indicated that a core C/EBP half-site (GCAAT) was required for binding of a labeled HS3D oligomer to osteoblast nuclear proteins. Southwestern blotting and UV-cross-linking studies showed that the HS3D probe recognized a approximately 35-kDa nuclear protein, and antibody supershift assays indicated that C/EBPdelta comprised most of the PGE2-activated gel-shifted complex. C/EBPdelta was detected by Western immunoblotting in osteoblast nuclear extracts after treatment of cells with PGE2. An HS3D oligonucleotide competed effectively with a high affinity C/EBP site from the rat albumin gene for binding to osteoblast nuclear proteins. Co-transfection of osteoblast cell cultures with a C/EBPdelta expression plasmid enhanced basal and PGE2-activated IGF-I promoter 1-luciferase activity but did not stimulate a reporter gene lacking an HS3D site. By contrast, an expression plasmid for the related protein, C/EBPbeta, did not alter basal IGF-I gene activity but did increase the response to PGE2. In osteoblasts and in COS-7 cells, C/EBPdelta, but not C/EBPbeta, transactivated a reporter gene containing four tandem copies of HS3D fused to a minimal promoter; neither transcription factor stimulated a gene with four copies of an HS3D mutant that was unable to bind osteoblast nuclear proteins. These results identify C/EBPdelta as a hormonally activated inducer of IGF-I gene transcription in osteoblasts and show that the HS3D element within IGF-I promoter 1 is a high affinity binding site for this protein.

NASA Discipline Musculoskeletal↗