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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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912 records · Page 51
All sourcesNASA NTRSDOE OSTI
DOE OSTI2026

EXCHANGE Campaign 2 - Microbial Biomass Collapse (EC2-MBC): Carbon Availability Under Prolonged Flooding in Mid-Atlantic and Great Lakes Coastal Ecosystems

Our collective research focus is on investigating the interaction between carbon availability and microbial demands during prolonged flooding. Through laboratory experiments utilizing freshly collected soil samples from diverse transition zone environments, we aim to simulate flooding and understand the mechanisms governing carbon cycling under anoxic conditions. Our primary objective is to elucidate how carbon becomes available to microbes and how they utilize it, discerning between maintenance and investment processes. By examining soils from regions with differing native redox conditions, our aim is to gain comprehensive insights into carbon dynamics across various soil types. Future data types will be added to the ESS-DIVE data package as they are completed and will be version-controlled in the Change History section of EC2_MBC_README.pdf. This data package includes: EC2_MBC_README.pdf flmd.csv dd.csv EC2_SampleIdentificationKey.csv EC2_SoilMoistureKey.csv Processed_GHGFlux_Entisols.csv Processed_GHGFlux_Inceptisols.csv Processed_GHGFlux_Ultisols.csv Processed_Porewater_Iron_II.csv Processed_Porewater_Nutrients.csv Processed_Porewater_Sulfate.csv Processed_Probe_Measurements.csv Processed_Soil_HydrolyticEnzymes.csv Processed_Soil_MicrobialCN.csv Processed_Soil_NPOC_TN_SaltExtracted.csv Processed_Soil_NPOC_TN_WaterExtracted.csv Processed_Soil_Nutrients_OlsenPExtracted.csv Processed_Soil_Nutrients_SaltExtracted.csv Processed_Soil_Nutrients_WaterExtracted.csv Processed_DO_Probe.zip Processed_Temperature_Probe.zip

Carbon Cycling↗
DOE OSTI2022

Mechanistic assessment of tolerance to iron deficiency mediated by Trichoderma harzianum in soybean roots

Abstract Aims Iron (Fe) deficiency in soil is a continuing problem for soybean (Glycine max L.) production, partly as a result of continuing climate change. This study elucidates how Trichoderma harzianum strain T22 (TH) mitigates growth retardation associated with Fe-deficiency in a highly sensitive soybean cultivar. Methods and Results Soil TH supplementation led to mycelial colonization and the presence of UAOX1 gene in roots that caused substantial improvement in chlorophyll score, photosynthetic efficiency and morphological parameters, indicating a positive influence on soybean health. Although rhizosphere acidification was found to be a common feature of Fe-deficient soybean, the upregulation of Fe-reductase activity (GmFRO2) and total phenol secretion were two of the mechanisms that substantially increased the Fe availability by TH. Heat-killed TH applied to soil caused no improvement in photosynthetic attributes and Fe-reductase activity, confirming the active role of TH in mitigating Fe-deficiency. Consistent increases in tissue Fe content and increased Fe-transporter (GmIRT1, GmNRAMP2a, GmNRAMP2b and GmNRAMP7) mRNA levels in roots following TH supplementation were observed only under Fe-deprivation. Root cell death, electrolyte leakage, superoxide (O2•–) and hydrogen peroxide (H2O2) substantially declined due to TH in Fe-deprived plants. Further, the elevation of citrate and malate concentration along with the expression of citrate synthase (GmCs) and malate synthase (GmMs) caused by TH suggest improved chelation of Fe in Fe-deficient plants. Results also suggest that TH has a role in triggering antioxidant defence by increasing the activity of glutathione reductase (GR) along with elevated S-metabolites (glutathione and methionine) to stabilize redox status under Fe-deficiency. Conclusions TH increases the availability and mobilization of Fe by inducing Fe-uptake pathways, which appears to help provide resistance to oxidative stress associated with Fe-shortage in soybean. Significance and Impact of the Study These findings indicate that while Fe deficiency does not affect the rate or degree of TH hyphal association in soybean roots, the beneficial effects of TH alone may be Fe deficiency-dependent.

59 BASIC BIOLOGICAL SCIENCES↗
NASA NTRS2002

Impaired pulmonary artery contractile responses in a rat model of microgravity: role of nitric oxide

Vascular contractile hyporesponsiveness is an important mechanism underlying orthostatic intolerance after microgravity. Baroreceptor reflexes can modulate both pulmonary resistance and capacitance function and thus cardiac output. We hypothesized, therefore, that pulmonary vasoreactivity is impaired in the hindlimb-unweighted (HLU) rat model of microgravity. Pulmonary artery (PA) contractile responses to phenylephrine (PE) and U-46619 (U4) were significantly decreased in the PAs from HLU vs. control (C) animals. N(G)-nitro-L-arginine methyl ester (10(-5) M) enhanced the contractile responses in the PA rings from both C and HLU animals and completely abolished the differential responses to PE and U4 in HLU vs. C animals. Vasorelaxant responses to ACh were significantly enhanced in PA rings from HLU rats compared with C. Moreover, vasorelaxant responses to sodium nitroprusside were also significantly enhanced. Endothelial nitric oxide synthase (eNOS) and soluble guanlyl cyclase expression were significantly enhanced in PA and lung tissue from HLU rats. In marked contrast, the expression of inducible nitric oxide synthase was unchanged in lung tissue. These data support the hypothesis that vascular contractile responsiveness is attenuated in PAs from HLU rats and that this hyporesponsiveness is due at least in part to increased nitric oxide synthase activity resulting from enhanced eNOS expression. These findings may have important implications for blood volume distribution and attenuated stroke volume responses to orthostatic stress after microgravity exposure.

Non-NASA Center↗
NASA NTRS1998

Role of nitric oxide in adenosine-induced vasodilation in humans

Vasodilation is one of the most prominent effects of adenosine and one of the first to be recognized, but its mechanism of action is not completely understood. In particular, there is conflicting information about the potential contribution of endothelial factors. The purpose of this study was to explore the role of nitric oxide in the vasodilatory effect of adenosine. Forearm blood flow responses to intrabrachial adenosine infusion (125 microg/min) were assessed with venous occlusion plethysmography during intrabrachial infusion of saline or the nitric oxide synthase inhibitor NG-monomethyl-L-arginine (L-NMMA) (12.5 mg/min). Intrabrachial infusions of acetylcholine (50 microg/min) and nitroprusside (3 microg/min) were used as a positive and negative control, respectively. These doses were chosen to produce comparable levels of vasodilation. In a separate study, a second saline infusion was administered instead of L-NMMA to rule out time-related effects. As expected, pretreatment with L-NMMA reduced acetylcholine-induced vasodilation; 50 microg/min acetylcholine increased forearm blood flow by 150+/-43% and 51+/-12% during saline and L-NMMA infusion, respectively (P<.01, n=6). In contrast, L-NMMA did not affect the increase in forearm blood flow produced by 3 microg/min nitroprusside (165+/-30% and 248+/-41% during saline and L-NMMA, respectively) or adenosine (173+/-48% and 270+/-75% during saline and L-NMMA, respectively). On the basis of our observations, we conclude that adenosine-induced vasodilation is not mediated by nitric oxide in the human forearm.

Non-NASA Center↗
NASA NTRS1995

Modeling of a possible conformational change associated with the catalytic mechanism in the hammerhead ribozyme

Here we describe a possible model of the cleavage mechanism in the hammerhead ribozyme. In this model, the 2' hydroxyl of C17 is moved into an appropriate orientation for an in-line attack on the G1.1 phosphate through a change in its sugar pucker from C3' endo to C2' endo. This conformational change in the active site is caused by a change in the uridine turn placing the N2 and N3 atoms of G5 of the conserved core in hydrogen bonding geometry with the N3 and N2 atoms on the conserved G16.2 residue. The observed conformational change in the uridine turn suggests an explanation for the conservation of G5. In the crystal structure of H.M. Pley et al., Nature 372, 68-74 (1994), G5 is situated 5.3A away from G16.2. However, the uridine turn is sufficiently flexible to allow this conformational change with relatively modest changes in the backbone torsion angles (average change of 14.2 degrees). Two magnesium ions were modeled into the active site with positions analogous to those described in the functionally similar Klenow fragment 3'-5' exonuclease (L.S. Beese and T.A. Steitz, EMBO J. 10, 25-33 (1991)), the Group I intron (T.A. Steitz and J.A. Steitz, P.N.A.S. U.S.A. 90, 6498-6502 (1993); R.F. Setlik et al., J. Biomol. Str. Dyn. 10, 945-972 (1993)) and other phosphotransferases. Comparison of this model with one in which the uridine turn conformation was not changed showed that although the changes in the C17 sugar pucker could be modeled, insufficient space existed for the magnesium ions in the active site.

Non-NASA Center↗
DOE OSTI2021

Growth differentiation factor-15 promotes immune escape of ovarian cancer via targeting CD44 in dendritic cells

Immune escape is the main cause of the low response rate to immunotherapy for cancer, including ovarian cancer. Growth differentiation factor-15 (GDF-15) inhibits immune cell function. However, only few reports described the mechanism. Therefore, the aim of this study was to investigate the mechanism of immune escape regulated by GDF-15 in ovarian cancer. Ovarian cancer patients and healthy women were enrolled in this study. Immunohistochemistry and ELISA were performed to measure GDF-15 expression. Immunoprecipitation combined with mass spectrometry, surface plasmon resonance, and co-immunoprecipitation assay were used to evaluate the interaction between GDF-15 and the surface molecules of DCs. Immunofluorescence analysis, flow cytometry and transwell assay were used to evaluate additional effects of GDF-15 on DCs. The results showed that GDF-15 expression was higher in the ovarian cancer patients compared to that in the healthy women. The TIMER algorithm revealed that highly GDF-15 expression is associated with immune DC infiltration in immunoreactive high-grade serous carcinoma. A further study showed that GDF-15 suppressed DCs maturation, as well as IL-12p40 and TNF-α secretion, the length and number of protrusions and the migration. More importantly, CD44 in the surface of DCs interacted with GDF-15. The overexpression of CD44 in DCs resulted in the suppression of the inhibitory effect of GDF-15 on the length and number of DC synapses. In DCs overexpressing CD44 the inhibition of GDF-15 on the expression of CD11c, CD83 and CD86 was decreased, while in DCs with a knockdown of CD44 the inhibition was further enhanced. Knockdown of CD44 in DCs enhanced the inhibitory effect of GDF-15 on DC migration, while the overexpression of CD44 inhibited the inhibitory effect of GDF-15 on DC migration. In conclusion, the present study suggested that GDF-15 might facilitate ovarian cancer immune escape by interacting with CD44 in DCs to inhibit their function.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2022

C6 Hydroxymethyl-Substituted Carbapenem MA-1-206 Inhibits the Major Acinetobacter baumannii Carbapenemase OXA-23 by Impeding Deacylation

Acinetobacter baumannii has become a major nosocomial pathogen, as it is often multidrug-resistant, which results in infections characterized by high mortality rates. The bacterium achieves high levels of resistance to β-lactam antibiotics by producing β-lactamases, enzymes which destroy these valuable agents. Historically, the carbapenem family of b-lactam antibiotics have been the drugs of choice for treating A. baumannii infections. However, their effectiveness has been significantly diminished due to the pathogen’s production of carbapenem-hydrolyzing class D β-lactamases (CHDLs); thus, new antibiotics and inhibitors of these enzymes are urgently needed. Here, we describe a new carbapenem antibiotic, MA-1-206, in which the canonical C6 hydroxyethyl group has been replaced with hydroxymethyl. The antimicrobial susceptibility studies presented here demonstrated that this compound is more potent than meropenem and imipenem against A. baumannii producing OXA-23, the most prevalent CHDL of this pathogen, and also against strains producing the CHDL OXA-24/40 and the class B metallo-β-lactamase VIM-2. Our kinetic and mass spectrometry studies revealed that this drug is a reversible inhibitor of OXA-23, where inhibition takes place through a branched pathway. X-ray crystallographic studies, molecular docking, and molecular dynamics simulations of the OXA-23-MA-1-206 complex show that the C6 hydroxymethyl group forms a hydrogen bond with the carboxylated catalytic lysine of OXA-23, effectively preventing deacylation. These results provide a promising strategy for designing a new generation of CHDL-resistant carbapenems to restore their efficacy against deadly A. baumannii infections. Carbapenem antibiotics are the drugs of choice for treatment of deadly infections caused by Gram-negative bacteria. However, their efficacy is severely compromised by the wide spread of carbapenem-hydrolyzing class D β-lactamases (CHDLs). The importance of this research is the discovery that substitution of the canonical hydroxyethyl group of carbapenems by a hydroxymethyl significantly enhances stability against inactivation by the major CHDL of Acinetobacter baumannii, OXA-23. These results provide a novel strategy for designing next-generation, carbapenemase-stable carbapenems to fight multidrug-resistant infections caused by Gram-negative pathogens

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2025

Toward a Unified Kinetic Model of Nitrogenase Catalysis

The microbial enzyme nitrogenase catalyzes the MgATP-dependent reduction of N 2 to 2NH 3 , a transformation central to the global nitrogen cycle. While the canonical Thorneley−Lowe (TL) kinetic model has long served as a mechanistic framework, it does not incorporate several recent insights. Here, we present an updated kinetic model for Monitrogenase that incorporates these new findings. A significant insight is that electron transfer (ET) from the reduced Fe protein to the FeMo-cofactor is gated by MgATP-dependent conformational transitions and can be described as a probabilistic event that is dependent on the ligand bound to the active-site metallocofactor. The updated kinetic model quantitatively reproduces steady-state product formation rates across a broad range of experimental conditions, yielding revised estimates for key rate constants. It is demonstrated that under N 2 turnover, the probability of productive ET to the active site decreases by ∼60%, resulting in a significant fraction of Fe protein cycles that are unproductive for electron delivery. This mechanistic feature explains the observed rate limitation in N 2 reduction and implies a revised minimum energetic cost of approximately 25 MgATP per N 2 reduced. Integrating these new features into the revised kinetic model provides a more complete and usable foundation for understanding nitrogenase catalysis.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗
NASA NTRS2003

Modeling beta-adrenergic control of cardiac myocyte contractility in silico

The beta-adrenergic signaling pathway regulates cardiac myocyte contractility through a combination of feedforward and feedback mechanisms. We used systems analysis to investigate how the components and topology of this signaling network permit neurohormonal control of excitation-contraction coupling in the rat ventricular myocyte. A kinetic model integrating beta-adrenergic signaling with excitation-contraction coupling was formulated, and each subsystem was validated with independent biochemical and physiological measurements. Model analysis was used to investigate quantitatively the effects of specific molecular perturbations. 3-Fold overexpression of adenylyl cyclase in the model allowed an 85% higher rate of cyclic AMP synthesis than an equivalent overexpression of beta 1-adrenergic receptor, and manipulating the affinity of Gs alpha for adenylyl cyclase was a more potent regulator of cyclic AMP production. The model predicted that less than 40% of adenylyl cyclase molecules may be stimulated under maximal receptor activation, and an experimental protocol is suggested for validating this prediction. The model also predicted that the endogenous heat-stable protein kinase inhibitor may enhance basal cyclic AMP buffering by 68% and increasing the apparent Hill coefficient of protein kinase A activation from 1.0 to 2.0. Finally, phosphorylation of the L-type calcium channel and phospholamban were found sufficient to predict the dominant changes in myocyte contractility, including a 2.6x increase in systolic calcium (inotropy) and a 28% decrease in calcium half-relaxation time (lusitropy). By performing systems analysis, the consequences of molecular perturbations in the beta-adrenergic signaling network may be understood within the context of integrative cellular physiology.

Non-NASA Center↗
NASA NTRS2003

Arginase reciprocally regulates nitric oxide synthase activity and contributes to endothelial dysfunction in aging blood vessels

BACKGROUND: Although abnormal L-arginine NO signaling contributes to endothelial dysfunction in the aging cardiovascular system, the biochemical mechanisms remain controversial. L-arginine, the NO synthase (NOS) precursor, is also a substrate for arginase. We tested the hypotheses that arginase reciprocally regulates NOS by modulating L-arginine bioavailability and that arginase is upregulated in aging vasculature, contributing to depressed endothelial function. METHODS AND RESULTS: Inhibition of arginase with (S)-(2-boronoethyl)-L-cysteine, HCl (BEC) produced vasodilation in aortic rings from young (Y) adult rats (maximum effect, 46.4+/-9.4% at 10(-5) mol/L, P<0.01). Similar vasorelaxation was elicited with the additional arginase inhibitors N-hydroxy-nor-L-arginine (nor-NOHA) and difluoromethylornithine (DFMO). This effect required intact endothelium and was prevented by 1H-oxadiazole quinoxalin-1-one (P<0.05 and P<0.001, respectively), a soluble guanylyl cyclase inhibitor. DFMO-elicited vasodilation was greater in old (O) compared with Y rat aortic rings (60+/-6% versus 39+/-6%, P<0.05). In addition, BEC restored depressed L-arginine (10(-4) mol/L)-dependent vasorelaxant responses in O rings to those of Y. Arginase activity and expression were increased in O rings, whereas NOS activity and cyclic GMP levels were decreased. BEC and DFMO suppressed arginase activity and restored NOS activity and cyclic GMP levels in O vessels to those of Y. CONCLUSIONS: These findings demonstrate that arginase modulates NOS activity, likely by regulating intracellular L-arginine availability. Arginase upregulation contributes to endothelial dysfunction of aging and may therefore be a therapeutic target.

Non-NASA Center↗