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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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At least 325 records · Page 18
All sourcesNASA NTRSDOE OSTI
NASA NTRSDate not supplied

Impacts into a Strength‐Layered Target: The Time Evolution of the Excavation‐Stage Flow

Impact cratering has dominated the evolution and modification of planetary surfaces throughout the history of the solar system. Impact craters can serve as probes to understanding the details of a planetary subsurface; for example, Oberbeck and Quaide suggested that crater morphology can be used to estimate the thickness of a regolith layer on top of a more competent unit. Lunar craters show a morphological progression from a simple bowl shape to flat‐floored and concentric craters as diameter increases for a given regolith thickness. The final shape of the impact crater is a result of the subsurface flow‐field initiated as the projectile transfers its energy and momentum to the target surface at the moment of impact. Therefore, when a regolith layer is present over a stronger substrate, such as is the case on the lunar mare, the substrate modifies the flow‐field resulting in the distinctive final crater morphology. Here we report on a series of experimental impacts into targets composed of a thin (2 cm) layer of loose sand on top of a stronger substrate. We use the Ejection‐Velocity Measurement System (EVMS, Fig.1) developed by [3] to examine the ejecta kinematics at specific times during the formation of these craters in strength‐layered targets.

J. L. B. Anderson↗
DOE OSTI2024

Multi-layered heterochromatin interaction as a switch for DIM2-mediated DNA methylation

Functional crosstalk between DNA methylation, histone H3 lysine-9 trimethylation (H3K9me3) and heterochromatin protein 1 (HP1) is essential for proper heterochromatin assembly and genome stability. However, how repressive chromatin cues guide DNA methyltransferases for region-specific DNA methylation remains largely unknown. Here, we report structure-function characterizations of DNA methyltransferase Defective-In-Methylation-2 (DIM2) in Neurospora . The DNA methylation activity of DIM2 requires the presence of both H3K9me3 and HP1. Our structural study reveals a bipartite DIM2-HP1 interaction, leading to a disorder-to-order transition of the DIM2 target-recognition domain that is essential for substrate binding. Furthermore, the structure of DIM2-HP1-H3K9me3-DNA complex reveals a substrate-binding mechanism distinct from that for its mammalian orthologue DNMT1. In addition, the dual recognition of H3K9me3 peptide by the DIM2 RFTS and BAH1 domains allosterically impacts the DIM2-substrate binding, thereby controlling DIM2-mediated DNA methylation. Together, this study uncovers how multiple heterochromatin factors coordinately orchestrate an activity-switching mechanism for region-specific DNA methylation.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗
NASA NTRS1998

A role for cyclin-dependent kinase(s) in the modulation of fast anterograde axonal transport: effects defined by olomoucine and the APC tumor suppressor protein

Proteins that interact with both cytoskeletal and membrane components are candidates to modulate membrane trafficking. The tumor suppressor proteins neurofibromin (NF1) and adenomatous polyposis coli (APC) both bind to microtubules and interact with membrane-associated proteins. The effects of recombinant NF1 and APC fragments on vesicle motility were evaluated by measuring fast axonal transport along microtubules in axoplasm from squid giant axons. APC4 (amino acids 1034-2844) reduced only anterograde movements, whereas APC2 (aa 1034-2130) or APC3 (aa 2130-2844) reduced both anterograde and retrograde transport. NF1 had no effect on organelle movement in either direction. Because APC contains multiple cyclin-dependent kinase (CDK) consensus phosphorylation motifs, the kinase inhibitor olomoucine was examined. At concentrations in which olomoucine is specific for cyclin-dependent kinases (5 microM), it reduced only anterograde transport, whereas anterograde and retrograde movement were both affected at concentrations at which other kinases are inhibited as well (50 microM). Both anterograde and retrograde transport also were inhibited by histone H1 and KSPXK peptides, substrates for proline-directed kinases, including CDKs. Our data suggest that CDK-like axonal kinases modulate fast anterograde transport and that other axonal kinases may be involved in modulating retrograde transport. The specific effect of APC4 on anterograde transport suggests a model in which the binding of APC to microtubules may limit the activity of axonal CDK kinase or kinases in restricted domains, thereby affecting organelle transport.

Non-NASA Center↗
DOE OSTI2024

Evidence for autotrophic growth of purple sulfur bacteria using pyrite as electron and sulfur source

ABSTRACT Purple sulfur bacteria (PSB) are capable of anoxygenic photosynthesis via oxidizing reduced sulfur compounds and are considered key drivers of the sulfur cycle in a range of anoxic environments. In this study, we show that Allochromatium vinosum (a PSB species) is capable of autotrophic growth using pyrite as the electron and sulfur source. Comparative growth profile, substrate characterization, and transcriptomic sequencing data provided valuable insight into the molecular mechanisms underlying the bacterial utilization of pyrite and autotrophic growth. Specifically, the pyrite-supported cell cultures (“py”’) demonstrated robust but much slower growth rates and distinct patterns from their sodium sulfide-amended positive controls. Up to ~200-fold upregulation of genes encoding various c - and b -type cytochromes was observed in “py,” pointing to the high relevance of these molecules in scavenging and relaying electrons from pyrite to cytoplasmic metabolisms. Conversely, extensive downregulation of genes related to LH and RC complex components indicates that the electron source may have direct control over the bacterial cells’ photosynthetic activity. In terms of sulfur metabolism, genes encoding periplasmic or membrane-bound proteins (e.g., FccAB and SoxYZ) were largely upregulated, whereas those encoding cytoplasmic proteins (e.g., Dsr and Apr groups) are extensively suppressed. Other notable differentially expressed genes are related to flagella/fimbriae/pilin(+), metal efflux(+), ferrienterochelin(−), and [NiFe] hydrogenases(+). Characterization of the biologically reacted pyrite indicates the presence of polymeric sulfur. These results have, for the first time, put the interplay of PSB and transition metal sulfide chemistry under the spotlight, with the potential to advance multiple fields, including metal and sulfur biogeochemistry, bacterial extracellular electron transfer, and artificial photosynthesis. IMPORTANCE Microbial utilization of solid-phase substrates constitutes a critical area of focus in environmental microbiology, offering valuable insights into microbial metabolic processes and adaptability. Recent advancements in this field have profoundly deepened our knowledge of microbial physiology pertinent to these scenarios and spurred innovations in biosynthesis and energy production. Furthermore, research into interactions between microbes and solid-phase substrates has directly linked microbial activities to the surrounding mineralogical environments, thereby enhancing our understanding of the relevant biogeochemical cycles. Our study represents a significant step forward in this field by demonstrating, for the first time, the autotrophic growth of purple sulfur bacteria using insoluble pyrite (FeS2) as both the electron and sulfur source. The presented comparative growth profiles, substrate characterizations, and transcriptomic sequencing data shed light on the relationships between electron donor types, photosynthetic reaction center activities, and potential extracellular electron transfer in these organisms capable of anoxygenic photosynthesis. Furthermore, the findings of our study may provide new insights into early-Earth biogeochemical evolutions, offering valuable constraints for understanding the environmental conditions and microbial processes that shaped our planet’s history.

59 BASIC BIOLOGICAL SCIENCES↗
NASA NTRS2012

MgB2-Based Bolometer Array for Far Infra-Red Thermal Imaging and Fourier Transform Spectroscopy Applications

The mid-superconducting critical temperature (T(sub c) approximately 39 K) of the simple binary, intermetallic MgB, [1] makes it a very good candidate for the development of the next generation of electrooptical devices (e.g. [2]). In particular, recent advances in thin film deposition teclmiques to attain higb quality polycrystalline thin film MgB, deposited on SiN-Si substrates, with T(sub c) approximately 38K [3] coupled with the low voltage noise performance of the film [4] makes it higbly desirable for the development of moderately cooled bolometer arrays for integration into future space-bourne far infra-red (FIR) spectrometers and thermal mappers for studying the outer planets, their icy moons and other moons of interest in the 17-250 micrometer spectral wavelength range. Presently, commercially available pyroelectric detectors operating at 300 K have specific detectivity, D(*), around 7 x 10(exp 8) to 2 x 10(exp 9) centimeters square root of Hz/W. However, a MgB2 thin film based bolometer using a low-stress (less than 140 MPa) SiN membrane isolated from the substrate by a small thermal conductive link, operating at 38 K, promises to have two orders of magnitude higher specific detectivity [5][6].

Lakew, B.↗
DOE OSTI2026

Shrub and sedge rhizosphere communities display distinct affinities toward exudates and soil organic matter degradation: a quantitative stable isotope probing analysis

Warming temperatures are accelerating permafrost thaw and changing tundra vegetation, where woody shrubs are displacing sedges. Shrubs, such as Betula nana, and sedges, such as Eriophorum vaginatum, exhibit distinct life strategies including unique root-associated, or rhizosphere microbial communities. As permafrost thaws it unlocks previously unavailable carbon and nutrient sources resulting in deeper roots and a translocation of rhizosphere communities. Because permafrost microbial communities contain lower diversity and biomass than rhizosphere communities, the coalescence of rhizosphere and permafrost microbial communities could alter soil organic matter (SOM) degradation rates and increase greenhouse gas emissions. To identify metabolic strategies across distinct rhizosphere and permafrost microbial communities we conducted an isotope tracing incubation experiment. We inoculated thawed permafrost with shrub and sedge rhizosphere communities while adding exudates or water daily and compared this to an uninoculated control. After 46 days, we spiked samples with 18O enriched water or 13C enriched exudates and measured isotope incorporation into microbial DNA with quantitative stable isotope probing (qSIP). Our results indicate that exudate additions had little effect on uninoculated permafrost communities but the addition of exudates and rhizosphere inoculants had a compounding effect on respiration rates. We found that soils inoculated with shrub rhizosphere communities contained a mixture of exudate and SOM degraders while soils inoculated with sedge rhizosphere communities contained mainly SOM degraders. Finally, we found that individual microbial taxa exhibited maximum growth rates under specific combinations of microbial inoculant communities and exudate addition treatments. Our results reveal that microbial niches are strongly influenced by substrate preferences and community context, and suggest that a reduction in sedges and an expansion of shrubs may provide a mechanism by which permafrost carbon losses are mitigated through corresponding shifts in microbial communities and their substrate preferences.

Schaefer, Sean R [Natural Resources and Earth Syst↗
DOE OSTI2025

Enzymatic cleavage of model lignin dimers depends on pH, enzyme, and bond type

Lignin is composed of phenylpropanoid monomers linked by ether and carbon-carbon bonds to form a complex heterogeneous structure. Bond-specific studies of lignin-modifying enzymes (LMEs; e.g., laccases and peroxidases) are limited by the polymerization of model lignin substrates and repolymerization of cleavage products. Here we present a high throughput platform to screen LME activities on four tagged model lignin compounds that represent the β-O-4’, β-β’, 5–5’, and 4-O-5’ linkages in lignin. We utilized nanostructure-initiator mass spectrometry (NIMS) and model lignin compounds with tags containing perfluorinated and cationic moieties, which effectively limit polymerization and condensation of the substrates and their degrading products. Sub-microliter sample droplets were printed on the NIMS chip with a novel robotics method. This rapid platform enabled characterization of LMEs across a range of pH 3–10 and relative quantification of modified (typically oxidized), cleaved, and polymerized products. All tested enzymes oxidized the four substrates and cleaved the β-O-4’ and β-β’ substrates to monomeric products. We discovered that the active pH range depended on both the substrate and the enzyme type. This has important applications for biomass conversion to biofuels and bioproducts, where the relative percentages of different bond types in lignin varies depending on feedstock and chemical pretreatment methods.

59 BASIC BIOLOGICAL SCIENCES↗
NASA NTRS1981

InGaAsP/InP laser development for single-mode, high-data-rate communications

Materials studies as well as general and specific device development were carried out in the InGaAsP system. A comparison was made of three standard methods of evaluating substrate quality by means of dislocation studies. A cause of reduced yield of good wafers, the pullover of melt from one bin to the next, has been analyzed. Difficulties with reproducible zinc acceptor doping have been traced to segregation of zinc in the In/Zn alloy used for the doping source. Using EBIC measurments, the pn junction was shown to drift in location depending on factors not always under control. An analysis of contact structures by SIMS showed that the depth to which the sintered Au/Zn contact penetrates into the structure is typically 0.13 microns, or well within the cap layer and out of the p-type cladding and thus not deleterious to laser prformance. The problem of single-mode laser development was investigated and it was shown to be related to the growth habit over four different possible substrate configurations. The fabrication of constricted double heterojunctions, mesa stripe buried heterostructures, and buried heterostructures was discussed, and measurements were presented on the device properties of single-mode buried heterostructure lasers. Results include single spectral line emission at 3 mW and a threshold current of 60 mA.

Ladany, I.↗
NASA NTRS1995

High energy collimating fine grids

The objective of this project was to demonstrate the fabrication of extremely tight tolerance collimating grids using a high-Z material, specifically tungsten. The approach taken was to fabricate grids by a replication method involving the coating of a silicon grid substrate with tungsten by chemical vapor deposition (CVD). A negative of the desired grid structure was fabricated in silicon using highly wafering techniques developed for the semiconductor industry and capable of producing the required tolerances. Using diamond wafering blades, a network of accurately spaced slots was machined into a single-crystal silicon surface. These slots were then filled with tungsten by CVD, via the hydrogen reduction of tungsten hexafluoride. Following tungsten deposition, the silicon negative was etched away to leave the tungsten collimating grid structure. The project was divided into five tasks: (1) identify materials of construction for the replica and final collimating grid structures; (2) identify and implement a micromachining technique for manufacturing the negative collimator replicas (performed by NASA/JPL); (3) develop a CVD technique and processing parameters suitable for the complete tungsten densification of the collimator replicas; (4) develop a chemical etching technique for the removal of the collimator replicas after the tungsten deposition process; and (5) fabricate and deliver tungsten collimating grid specimens.

Arrieta, Victor M.↗
NASA NTRS2003

Thermal Modeling of Permafrost Melt by Overlying Lava Flows with Applications to Flow-associated Outflow Channel Volumes in the Cerberus Plains, Mars

The Cerberus region of Mars has numerous geologically recent fluvial and volcanic features superimposed spatially, with some of them using the same flow channels and apparent vent structures. Lava-water interaction landforms such as psuedocraters suggest some interaction of emplacing lava flows with underlying ground ice or water. This study investigates a related interaction type a region where the emplaced lava might have melted underlying ice in the regolith, as there are small outflow channel networks emerging from the flank flows of a lava shield over a portion of the Eastern Cerberus Rupes. Specifically, we use high-resolution Mars Orbiter Laser Altimeter (MOLA) topography to constrain channel and flow dimensions, and thus estimate the thermal pulse from the emplaced lava into the substrate and the resulting melting durations and refreezing intervals. These preliminary thermal models indicate that the observed flows could easily create thermal pulse(s) sufficient to melt enough ground ice to fill the observed fluvial small outflow channels. Depending on flow eruption timing and hydraulic recharge times, this system could easily have produced multiple thermal pulses and fluvial releases. This specific case suggests that regional small water releases from similar cases may be more common than suspected, and that there is a possibility for future fluvial releases if ground ices are currently present and future volcanic eruptions in this young region are possible.

Chase, Z. A. J.↗
NASA NTRS2013

Robust Platinum Resistor Thermometer (PRT) Sensors and Reliable Bonding for Space Missions

Platinum resistance thermometers (PRTs) provide accurate temperature measurements over a wide temperature range and are used extensively on space missions due to their simplicity and linearity. A standard on spacecraft, PRTs are used to provide precision temperature control and vehicle health assessment. This paper reviews the extensive reliability testing of platinum resistor thermometer sensors (PRTs) and bonding methods used on the Mars Science Laboratory (MSL) mission and for the upcoming Soil Moisture Active Passive (SMAP) mission. During the Mars Exploration Rover (MER) mission, several key, JPL-packaged PRTs failed on those rovers prior to and within 1-Sol of landing due to thermally induced stresses. Similar failures can be traced back to other JPL missions dating back thirty years. As a result, MSL sought out a PRT more forgiving to the packaging configurations used at JPL, and extensively tested the Honeywell HRTS-5760-B-U-0-12 sensor to successfully demonstrate suitable robustness to thermal cycling. Specifically, this PRT was cycled 2,000 times, simulating three Martian winters and summers. The PRTs were bonded to six substrate materials (Aluminum 7050, treated Magnesium AZ231-B, Stainless Steel 304, Albemet, Titanium 6AL4V, and G-10), using four different aerospace adhesives--two epoxies and two silicones--that conformed to MSL's low out-gassing requirements. An additional epoxy was tested in a shorter environmental cycling test, when the need for a different temperature range adhesive was necessary for mobility and actuator hardware late in the fabrication process. All of this testing, along with electrostatic discharge (ESD) and destructive part analyses, demonstrate that this PRT is highly robust, and not subject to the failure of PRTs on previous missions. While there were two PRTs that failed during fabrication, to date there have been no in-flight PRT failures on MSL, including those on the Curiosity rover. Since MSL, the sensor has gone through a change in construction such that the manufacturer significantly restricts the minimum temperature. However, significant subsequent testing was performed with this new version of the part to show that it indeed is still robust to at least Mars minimum temperatures of -135(sup o)C. The additional completed testing will be described. This work has resulted in a successful sensor package qualification and a reliable bonding method suitable for use over large temperature extremes.

dectector↗
NASA NTRS2013

Robust Platinum Resistor Thermometer (PRT) Sensors and Reliable Bonding for Space Missions

Platinum resistance thermometers (PRTs) provide accurate temperature measurements over a wide temperature range and are used extensively on space missions due to their simplicity and linearity. A standard on spacecraft, PRTs are used to provide precision temperature control and vehicle health assessment. This paper reviews the extensive reliability testing of platinum resistor thermometer sensors (PRTs) and bonding methods used on the Mars Science Laboratory (MSL) mission and for the upcoming Soil Moisture Active Passive (SMAP) mission. During the Mars Exploration Rover (MER) mission, several key, JPL-packaged PRTs failed on those rovers prior to and within 1-Sol of landing due to thermally induced stresses. Similar failures can be traced back to other JPL missions dating back thirty years. As a result, MSL sought out a PRT more forgiving to the packaging configurations used at JPL, and extensively tested the Honeywell HRTS-5760-B-U-0-12 sensor to successfully demonstrate suitable robustness to thermal cycling. Specifically, this PRT was cycled 2,000 times, simulating three Martian winters and summers. The PRTs were bonded to six substrate materials (Aluminum 7050, treated Magnesium AZ231-B, Stainless Steel 304, Albemet, Titanium 6AL4V, and G-10), using four different aerospace adhesives--two epoxies and two silicones--that conformed to MSL's low out-gassing requirements. An additional epoxy was tested in a shorter environmental cycling test, when the need for a different temperature range adhesive was necessary for mobility and actuator hardware late in the fabrication process. All of this testing, along with electrostatic discharge (ESD) and destructive part analyses, demonstrate that this PRT is highly robust, and not subject to the failure of PRTs on previous missions. While there were two PRTs that failed during fabrication, to date there have been no in-flight PRT failures on MSL, including those on the Curiosity rover. Since MSL, the sensor has gone through a change in construction such that the manufacturer significantly restricts the minimum temperature. However, significant subsequent testing was performed with this new version of the part to show that it indeed is still robust to at least Mars minimum temperatures of -135 degrees Centigrade. The additional completed testing will be described. This work has resulted in a successful sensor package qualification and a reliable bonding method suitable for use over large temperature extremes

Platinum Resistor Thermometer (PRT)↗
NASA NTRS1990

Compound-specific isotopic analyses: a novel tool for reconstruction of ancient biogeochemical processes

Patterns of isotopic fractionation in biogeochemical processes are reviewed and it is suggested that isotopic fractionations will be small when substrates are large. If so, isotopic compositions of biomarkers will reflect those of their biosynthetic precursors. This prediction is tested by consideration of results of analyses of geoporphyrins and geolipids from the Greenhorn Formation (Cretaceous, Western Interior Seaway of North America) and the Messel Shale (Eocene, lacustrine, southern Germany). It is shown (i) that isotopic compositions of porphyrins that are related to a common source, but which have been altered structurally, cluster tightly and (ii) that isotopic differences between geolipids and porphyrins related to a common source are equal to those observed in modern biosynthetic products. Both of these observations are consistent with preservation of biologically controlled isotopic compositions during diagenesis. Isotopic compositions of individual compounds can thus be interpreted in terms of biogeochemical processes in ancient depositional environments. In the Cretaceous samples, isotopic compositions of n-alkanes are covariant with those of total organic carbon, while delta values for pristane and phytane are covariant with those of porphyrins. In this unit representing an open marine environment, the preserved acyclic polyisoprenoids apparently derive mainly from primary material, while the extractable, n-alkanes derive mainly from lower levels of the food chain. In the Messel Shale, isotopic compositions of individual biomarkers range from -20.9 to -73.4% vs PDB. Isotopic compositions of specific compounds can be interpreted in terms of origin from methylotrophic, chemautotrophic, and chemolithotrophic microorganisms as well as from primary producers that lived in the water column and sediments of this ancient lake.

Non-NASA Center↗
NASA NTRSDate not supplied

Optical Spectroscopy of Venus Aerosol Analogs and Substrate Survivability

Aerosol Rapid Analysis Combined Entry Probe/Sonde Technology (AERACEPT) is a dual descent probe and in-situ sampler of cloud and aerosol particles, used as part of the Nephele mission concept to study Venus cloud layers. Various optical spectroscopic characterization methods, including Raman spectroscopy and Surface Enhanced Raman Spectroscopy (SERS), Laser induced Breakdown Spectroscopy (LIBS), and absorbance and fluorescence spectroscopy are being assessed for viability for compatibility with AERACEPT. Specifically, the detection limits, sensitivity, specificity, and analysis cadence of these techniques for a set of Venus aerosol analogs and their mixtures are tested. We report on preliminary optical spectroscopy results of the Venus aerosol analogs, as well as optical substrate survivability in heated and acidic conditions, substrate physical robustness, and analyte wettability on substrates.

Venus↗
DOE OSTI2026

Enhanced quantum efficiency from optical interference in alkali antimonide photocathodes: Modeling and experimental results

We present measurements of enhanced quantum efficiency (QE) in thin film alkali antimonide photocathodes from optical interference in the cathode-substrate multilayer. Modulations in the spectral response are observed over a range of visible wavelengths and are shown to increase the QE by more than a factor of two at specific wavelengths. We present a model describing the QE modulations based on the three step photoemission process incorporating cases of both constant density of states and density functional theory-derived density of states and show that the calculated results are in good agreement with the measurements. Model predictions demonstrate that QE can be enhanced by more than a factor of 5 by optimization of cathode and substrate layer thicknesses. Additionally, these calculations reveal that optical interference can yield higher quantum efficiencies in thin films compared to thick, optically dense films. We model the QE vs excitation wavelength of multiple alkali antimonide compounds at different thicknesses. We then discuss the advantages of this interference effect for electron accelerators.

73 NUCLEAR PHYSICS AND RADIATION PHYSICS↗
NASA NTRS1978

Automated solar-cell-array assembly machine

Continuous-feeding machine automatically bonds solar cells to printed-circuit substrate. In completed machine, cells move to test station where electrical characteristics could be checked. If performance of cell is below specifications, that cell is marked and removed. All machine functions are synchronized by electronics located within unit. It may help to lower costs in future solar-cell production.

Costogue, E. N.↗
NASA NTRS1992

On the Stereoselective Synthesis of (+)-Pinoresinol in Forsythia Suspensa from its Achiral Precursor, Coniferyl Alcohol

The residue from Forsythia suspensa stems, upon removal of soluble enzymes, has provided the first evidence for a stereoselective coupling enzyme in lignan biosynthesis. This preparation catalyses the preferred formation (ca 65%) of (+)-[8,8'- C-14] pinoresinol from [8-C-14]coniferyl alcohol in the absence of exogenously provided cofactors; addition of H2O2 had little effect on enantiomeric composition. However, when NAD and malate were supplied, the stereoselectivity of the coupling reaction was significantly enhanced and pinoresinol consisting of ca 80% of the (+)-antipode was obtained. Clearly, the insoluble residue contains a specific coupling enzyme which catalyses (+)-pinoresinol formation from coniferyl alcohol. By contrast, when [8- C-14] sinapyl alcohol was employed as substrate, only racemic syringaresinols were formed: this non-stereoselective peroxidase-catalysed coupling reaction presumably accounts for the low levels of (-)-pinoresinol encountered in this system when coniferyl alcohol is used as a substrate.

Davin, Laurence B.↗
NASA NTRS2002

Influence of Unweighting on Insulin Signal Transduction in Muscle

Unweighting of the juvenile soleus muscle is characterized by an increased binding capacity for insulin relative to muscle mass due to sparing of the receptors during atrophy. Although carbohydrate metabolism and protein degradation in the unweighted muscle develop increased sensitivity to insulin in vivo, protein synthesis in vivo and system A amino acid transport in vitro do not appear to develop such an enhanced response. The long-term goal is to identify the precise nature of this apparent resistance in the insulin signal transduction pathway and to consider how reduced weight-bearing may elicit this effect, by evaluating specific components of the insulin signalling pathway. Because the insulin-signalling pathway has components in common with the signal transduction pathway for insulin-like growth factor (IGF-1) and potentially other growth factors, the study could have important implications in the role of weight-bearing function on muscle growth and development. Since the insulin signalling pathway diverges following activation of insulin receptor tyrosine kinase, the immediate specific aims will be to study the receptor tyrosine kinase (IRTK) and those branches, which lead to phosphorylation of insulin receptor substrate-1 (IRS-1) and of Shc protein. To achieve these broader objectives, we will test in situ, by intramuscular injection, the responses of glucose transport, system A amino acid transport and protein synthesis to insulin analogues for which the receptor has either a weaker or much stronger binding affinity compared to insulin. Studies will include: (1) estimation of the ED(sub 50) for each analogue for these three processes; (2) the effect of duration (one to four days) of unweighting on the response of each process to all analogues tested; (3) the effect of unweighting and the analogues on IRTK activity; and (4) the comparative effects of unweighting and analogue binding on the tyrosine phosphorylation of IRTK, IRS-1, and Shc protein.

Tischler, Marc E.↗