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At least 577 records · Page 32

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↗

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↗

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↗

17beta-estradiol potently suppresses cAMP-induced insulin-like growth factor-I gene activation in primary rat osteoblast cultures

Insulin-like growth factor-I (IGF-I) is a key factor in bone remodeling. In osteoblasts, IGF-I synthesis is enhanced by parathyroid hormone and prostaglandin E2 (PGE2) through cAMP-activated protein kinase. In rats, estrogen loss after ovariectomy leads to a rise in serum IGF-I and an increase in bone remodeling, both of which are reversed by estrogen treatment. To examine estrogen-dependent regulation of IGF-I expression at the molecular level, primary fetal rat osteoblasts were co-transfected with the estrogen receptor (hER, to ensure active ER expression), and luciferase reporter plasmids controlled by promoter 1 of the rat IGF-I gene (IGF-I P1), used exclusively in these cells. As reported, 1 microM PGE2 increased IGF-I P1 activity by 5-fold. 17beta-Estradiol alone had no effect, but dose-dependently suppressed the stimulatory effect of PGE2 by up to 90% (ED50 approximately 0.1 nM). This occurred within 3 h, persisted for at least 16 h, required ER, and appeared specific, since 17alpha-estradiol was 100-300-fold less effective. By contrast, 17beta-estradiol stimulated estrogen response element (ERE)-dependent reporter expression by up to 10-fold. 17beta-Estradiol also suppressed an IGF-I P1 construct retaining only minimal promoter sequence required for cAMP-dependent gene activation, but did not affect the 60-fold increase in cAMP induced by PGE2. There is no consensus ERE in rat IGF-I P1, suggesting novel downstream interactions in the cAMP pathway that normally enhances IGF-I expression in skeletal cells. To explore this, nuclear extract from osteoblasts expressing hER were examined by electrophoretic mobility shift assay using the atypical cAMP response element in IGF-I P1. Estrogen alone did not cause DNA-protein binding, while PGE2 induced a characteristic gel shift complex. Co-treatment with both hormones caused a gel shift greatly diminished in intensity, consistent with their combined effects on IGF-I promoter activity. Nonetheless, hER did not bind IGF-I cAMP response element or any adjacent sequences. These results provide new molecular evidence that estrogen may temper the biological effects of hormones acting through cAMP to regulate skeletal IGF-I expression and activity.

Non-NASA Center↗

Alteration of mineral crystallinity and collagen cross-linking of bones in osteopetrotic toothless (tl/tl) rats and their improvement after treatment with colony stimulating factor-1

A common feature of various types of mammalian osteopetroses is a marked increase in bone mass accompanied by spontaneous bone fractures. The toothless (tl/tl) rat osteopetrotic mutation is characterized by drastically reduced bone resorption due to a profound deficiency of osteoclasts and their precursors. An altered bone morphology has also been observed. The mutants cannot be cured by bone marrow transplantation, but skeletal defects are greatly reduced after treatment with colony stimulating factor 1 (CSF-1). The objectives of this study were to characterize mineral and collagen matrices in cancellous and compact bone isolated from long bones of 6-week-old normal littermates, tl/tl osteopetrotic mutants and mutants (tl/tl) treated with CSF-1. There were no differences in bone mineral content, but a significant decrease in the crystallinity of mineral evaluated by the method based on electron paramagnetic resonance spectrometry was observed in all bones of tl/tl mutants as compared to that of controls. Within the collagen matrix, slight decreases in the labile cross-links, but significant increases in the content of the stable cross-links, pyridinoline, and deoxypyridinoline, were observed in both cancellous and compact bone of osteopetrotic mutants. In tl/tl mutants treated with human recombinant CSF-1, the normalization of the crystallinity of bone mineral as well as collagen cross-links was found. Our results indicate that remodeling of bone matrix in tl/tl mutants is highly suppressed, but that after treatment with CSF-1, this activity recovers significantly. Taken together, these data provide further support for the hypothesis that CSF-1 is an essential factor for normal osteoclast differentiation and bone remodelling.

NASA Discipline Musculoskeletal↗

Regulation of insulin-like growth factor I transcription by cyclic adenosine 3',5'-monophosphate (cAMP) in fetal rat bone cells through an element within exon 1: protein kinase A-dependent control without a consensus AMP response element

Insulin-like growth factor I (IGF-I) is a locally synthesized anabolic growth factor for bone. IGF-I synthesis by primary fetal rat osteoblasts (Ob) is stimulated by agents that increase the intracellular cAMP concentration, including prostaglandin E2 (PGE2). Previous studies with Ob cultures demonstrated that PGE2 enhanced IGF-I transcription through selective use of IGF-I promoter 1, with little effect on IGF-I messenger RNA half-life. Transient transfection of Ob cultures with an array of promoter 1-luciferase reporter fusion constructs has now allowed localization of a potential cis-acting promoter element(s) responsible for cAMP-stimulated gene expression to the 5'-untranslated region (5'-UTR) of IGF-I exon 1, within a segment lacking a consensus cAMP response element. Our evidence derives from three principal observations: 1) a transfection construct containing only 122 nucleotides (nt) of promoter 1 and 328 nt of the 5'-UTR retained full PGE2-stimulated reporter expression; 2) maximal PGE2-driven reporter expression required the presence of nt 196 to 328 of exon 1 when tested within the context of IGF-I promoter 1; 3) cotransfection of IGF-I promoter-luciferase-reporter constructs with a plasmid encoding the alpha-isoform of the catalytic subunit of murine cAMP-dependent protein kinase (PKA) produced results comparable to those seen with PGE2 treatment, whereas cotransfection with a plasmid encoding a mutant regulatory subunit of PKA that cannot bind cAMP blocked PGE2-induced reporter expression. Deoxyribonuclease I footprinting of the 5'-UTR of exon 1 demonstrated protected sequences at HS3A, HS3B, and HS3D, three of six DNA-protein binding sites previously characterized with rat liver nuclear extracts. Of these three regions, only the HS3D binding site is located within the functionally identified hormonally responsive segment of IGF-I exon 1. These results directly implicate PKA in the control of IGF-I gene transcription by PGE2 and identify a segment of IGF-I exon 1 as being essential for this hormonal regulation.

Non-NASA Center↗

Transcription factor IID in the Archaea: sequences in the Thermococcus celer genome would encode a product closely related to the TATA-binding protein of eukaryotes

The first step in transcription initiation in eukaryotes is mediated by the TATA-binding protein, a subunit of the transcription factor IID complex. We have cloned and sequenced the gene for a presumptive homolog of this eukaryotic protein from Thermococcus celer, a member of the Archaea (formerly archaebacteria). The protein encoded by the archaeal gene is a tandem repeat of a conserved domain, corresponding to the repeated domain in its eukaryotic counterparts. Molecular phylogenetic analyses of the two halves of the repeat are consistent with the duplication occurring before the divergence of the archael and eukaryotic domains. In conjunction with previous observations of similarity in RNA polymerase subunit composition and sequences and the finding of a transcription factor IIB-like sequence in Pyrococcus woesei (a relative of T. celer) it appears that major features of the eukaryotic transcription apparatus were well-established before the origin of eukaryotic cellular organization. The divergence between the two halves of the archael protein is less than that between the halves of the individual eukaryotic sequences, indicating that the average rate of sequence change in the archael protein has been less than in its eukaryotic counterparts. To the extent that this lower rate applies to the genome as a whole, a clearer picture of the early genes (and gene families) that gave rise to present-day genomes is more apt to emerge from the study of sequences from the Archaea than from the corresponding sequences from eukaryotes.

NASA Discipline Exobiology↗

Human factors in mission assurance

Space projects rely completely on people for development and implementation - but project-related risk list rarely include human factors as significant sources of risk. The paper notes mitigation techniques for risks associated with the human factors - readers are encouraged to come up with as many mitigation strategies as possible, and share them with each other.

human factors mission assurance risk management↗

Derivation of Sky-View Factors from LIDAR Data

The use of Lidar (Light Detection and Ranging), an active light-emitting instrument, is becoming increasingly common for a range of potential applications. Its ability to provide fine resolution spatial and vertical resolution elevation data makes it ideal for a wide range of studies. This paper demonstrates the capability of Lidar data to measure sky view factors (SVF). The Lidar data is used to generate a spatial map of SVFs which are then compared against photographically-derived SVF at selected point locations. At each location three near-surface elevations measurements were taken and compared with collocated Lidar-derived estimated. It was found that there was generally good agreement between the two methodologies, although with decreasing SVF the Lidar-derived technique tended to overestimate the SVF: this can be attributed in part to the spatial resolution of the Lidar sampling. Nevertheless, airborne Lidar systems can map sky view factors over a large area easily, improving the utility of such data in atmospheric and meteorological models.

spatial map↗

Human Factors of Remotely Piloted Aircraft

The civilian use of remotely piloted, or unmanned aircraft is expected to increase rapidly in the years ahead. Despite being referred to as unmanned some of the major challenges confronting this emerging sector relate to human factors. As unmanned aircraft systems (UAS) are introduced into civil airspace, a failure to adequately consider human factors could result in preventable accidents that may not only result in loss of life, but may also undermine public confidence in remotely piloted operations. Key issues include pilot situational awareness, collision avoidance in the absence of an out-the-window view, the effects of time delays in communication and control systems, control handovers, the challenges of very long duration flights, and the design of the control station. Problems have included poor physical layout of controls, non-intuitive automation interfaces, an over-reliance on text displays, and complicated sequences of menu selection to perform routine tasks. Some of the interface problems may have been prevented had an existing regulation or cockpit design principle been applied. In other cases, the design problems may indicate a lack of suitable guidance material.

unmanned aircraft systems↗

Martian Atmospheric Modeling of Scale Factors for MarsGRAM 2005 and the MAVEN Project

For spacecraft missions to Mars, especially the navigation of Martian orbiters and landers, an extensive knowledge of the Martian atmosphere is extremely important. The generally-accepted NASA standard for modeling (MarsGRAM), which was developed at Marshall Space Flight Center. MarsGRAM is useful for task such as aerobraking, performance analysis and operations planning for aerobraking, entry descent and landing, and aerocapture. Unfortunately, the densities for the Martian atmosphere in MarsGRAM are based on table look-up and not on an analytical algorithm. Also, these values can vary drastically from the densities actually experienced by the spacecraft. This does not have much of an impact on simple integrations but drastically affects its usefulness in other applications, especially those in navigation. For example, the navigation team for the Mars Atmosphere Volatile Environment (MAVEN) Project uses MarsGRAM to target the desired atmospheric density for the orbiter's pariapse passage, its closet approach to the planet. After the satellite's passage through pariapsis the computed density is compared to the MarsGRAM model and a scale factor is assigned to the model to account for the difference. Therefore, large variations in the atmosphere from the model can cause unexpected deviations from the spacecraft's planned trajectory. In order to account for this, an analytic stochastic model of the scale factor's behavior is desired. The development of this model will allow for the MAVEN navigation team to determine the probability of various Martian atmospheric variations and their effects on the spacecraft.

Martian atmosphere↗

Human Factors and Behavioral Performance Challenges for Lunar Surface Exploration

As the agency focuses on lunar missions, it is important to revisit the human factors and behavioral performance (HFBP) challenges for long duration exploration missions. We outline the important factors from the Apollo program, the long duration experience gained onboard International Space Station (ISS), and HFBP research applicable to exploration-class missions.

human factors performance↗

Comparing the Regional Variability of Emission Factors of Greenhouse Gases Over Different Landscape During FIREX-AQ Campaign

Biomass burning (wildfires, prescribed and agricultural burning) is one of the major sources of trace gases and particulate emissions and annual variability in growth rates. Biomass burning can impact local, regional, and global air quality, as well as climate. Measurements of emissions from biomass burning are crucial to a better understanding of how it influences and interacts with biogeochemical cycles. High resolution in-situ measurements were recorded onboard the NASA DC-8 aircraft during the FIREX-AQ (Fire Influence on Regional to Global Environments and Air Quality) airborne field campaign July-September, 2019, which was conducted over the continental U.S. Fire emission factors (EF) are essential input for emissions models used to develop biomass burning emission inventories. Here we present the Emission Ratio (ER), MCE (Modified Combustion Efficiency), and EF (Emission Factor) of CO2, CO, and CH4, which constitute the majority of carbon emitted from the wildland, prescribed, and agricultural fires. EFCO2, EFCO, and EFCH4 from the Wildland fires at Williams Flats, WA (primarily Douglas Fir, Ponderosa pine, wheatgrass: 50-75%), ranged from 1527 – 1820 g/kg (Avg. 1641±42), 6.5 – 174.1 g/kg (110.5±24.1), and 0.7 – 11.3 g/kg (6.2±1.9), respectively. EFs from the Arizona CASTLE fire, with somewhat different fuel sources (primarily Ponderosa pine, Douglas fir: 40-70%) ranged from 1266 – 1667 g/kg (1596±59), 99.5 – 344.5 g/kg (136.7±36.8), and 0.4 – 9.2 g/kg (7.2±1.7), respectively. Another primary driver of EFs is likely fire weather. Detailed variability of greenhouse gas EFs will be examined and presented in accordance with different fuels and fire conditions at burned areas, specifically within unique wildland and croplands, using the FCCS (Fuel Characteristic Classification System) 30m land cover identification and the Cropland Data Layer (CDL).

Biomass burning↗

Comparing the regional variability of emission factors of greenhouse gases over different landscape during FIREX-AQ campaign

Biomass burning (wildfires, prescribed and agricultural burning) is one of the major sources of trace gases and particulate emissions and annual variability in growth rates. Biomass burning can impact local, regional, and global air quality, as well as climate. Measurements of emissions from biomass burning are crucial to a better understanding of how it influences and interacts with biogeochemical cycles. High resolution in-situ measurements were recorded onboard the NASA DC-8 aircraft during the FIREX-AQ (Fire Influence on Regional to Global Environments and Air Quality) airborne field campaign July-September, 2019, which was conducted over the continental U.S. Fire emission factors (EF) are essential input for emissions models used to develop biomass burning emission inventories. Here we present the Emission Ratio (ER), MCE (Modified Combustion Efficiency), and EF (Emission Factor) of CO2, CO, and CH4, which constitute the majority of carbon emitted from the wildland, prescribed, and agricultural fires. EFCO2, EFCO, and EFCH4 from the Wildland fires at Williams Flats, WA (primarily Douglas Fir, Ponderosa pine, wheatgrass: 50-75%), ranged from 1527 – 1820 g/kg (Avg. 1641±42), 6.5 – 174.1 g/kg (110.5±24.1), and 0.7 – 11.3 g/kg (6.2±1.9), respectively. EFs from the Arizona CASTLE fire, with somewhat different fuel sources (primarily Ponderosa pine, Douglas fir: 40-70%) ranged from 1266 – 1667 g/kg (1596±59), 99.5 – 344.5 g/kg (136.7±36.8), and 0.4 – 9.2 g/kg (7.2±1.7), respectively. Another primary driver of EFs is likely fire weather. Detailed variability of greenhouse gas EFs will be examined and presented in accordance with different fuels and fire conditions at burned areas, specifically within unique wildland and croplands, using the FCCS (Fuel Characteristic Classification System) 30m land cover identification and the Cropland Data Layer (CDL).

Biomass burning↗

Factors that Influenced Airplane State Awareness Accidents and Incidents: CAST SE-210 Output 2: Report 2 of 6

This report is part of a series of reports that address flight deck design and evaluation, written as a response to loss of control accidents. In particular, this activity is directed at failures in airplane state awareness in which the pilot loses awareness of the airplane’s energy state or attitude and enters an upset condition. The Commercial Aviation Safety Team (CAST) created a team to analyze a set of incidents and accidents associated with the flight crew’s loss of awareness of aircraft attitude or energy state. The CAST activity focused on a set of 18 loss of control (LOC) accidents and incidents. In those events, the pilot seemed to lose awareness of the state of the airplane, especially related to its energy state or its attitude. To understand the roots of that loss of awareness, we analyzed the events in relation to a set of factors that were present in many of them. We show how these factors contributed to lost awareness. Then, we use that understanding to identify potentially useful changes to the flight deck interface and how those flight deck changes could be evaluated.

commercial aviation↗

A Remote Vehicle Operations Center’s Role in Collecting Human Factors Data

The National Aeronautics and Space Administration is supporting research to develop a prototype remote vehicle operations center at Langley Research Center to explore current and future advanced air mobility operations using small unmanned aerial systems vehicles as surrogates for future, larger-scale passenger carrying vehicles. Data collected within the Remote Operations for Autonomous Missions (ROAM) Unmanned Aerial Systems (UAS) Operations Center will be used to explore different roles and responsibilities of remote operators managing multiple autonomous vehicles, with the goal of exploring human-autonomy teaming concepts that enable m:N operations (i.e., m operators managing N vehicles). ROAM has developed into a world-class research, development, and technology (RD&T) environment that can support both the collection of human factors data and the command and control of remote vehicles in beyond visual line of sight conditions. Presented in this paper is an overview of ROAM, with a focus on the design components that support human factors data collection and a review of initial usability results of the facility.

Human factors↗

A Remote Vehicle Operations Center’s Role in Collecting Human Factors Data

The National Aeronautics and Space Administration is supporting research to develop a prototype remote vehicle operations center at Langley Research Center to explore current and future advanced air mobility operations using small unmanned aerial systems vehicles as surrogates for future, larger-scale passenger carrying vehicles. Data collected within the Remote Operations for Autonomous Missions (ROAM) Unmanned Aerial Systems (UAS) Operations Center will be used to explore different roles and responsibilities of remote operators managing multiple autonomous vehicles, with the goal of exploring human-autonomy teaming concepts that enable m:N operations (i.e., m operators managing N vehicles). ROAM has developed into a world-class research, development, and technology (RD&T) environment that can support both the collection of human factors data and the command and control of remote vehicles in beyond visual line of sight conditions. Presented in this paper is an overview of ROAM, with a focus on the design components that support human factors data collection and a review of initial usability results of the facility.

Human factors↗