Results for “Activation” — Page 11

DOE OSTI2024

Metatranscriptomic analysis reveals dissimilarity in viral community activity between an ice-free and ice-covered winter in Lake Erie

Winter is a relatively under-studied season in freshwater ecology. The paucity of wintertime surveys has led to a lack of knowledge regarding microbial community activity during the winter in Lake Erie, a North American Great Lake. Viruses shape microbial communities and regulate biogeochemical cycles by acting as top-down controls, yet very few efforts have been made to examine active virus populations during the winter in Lake Erie. Furthermore, climate change-driven declines in seasonal ice cover have been shown to influence microbial community structure, but no studies have compared viral community activity between different ice cover conditions. We surveyed surface water metatranscriptomes for viral hallmark genes as a proxy for active virus populations and compared activity metrics between ice-covered and ice-free conditions from two sampled winters. Transcriptionally active viral communities were detected in both winters, spanning diverse phylogenetic clades of putative bacteriophage (Caudoviricetes), giant viruses (Nucleocytoviricota, or NCLDV), and RNA viruses (Orthornavirae). However, viral community activity metrics revealed pronounced differences between the ice-covered and ice-free winters. Viral community composition was distinct between winters and viral hallmark gene richness was reduced in the ice-covered relative to the ice-free conditions. In addition, the observed differences in viral communities correlated with microbial community activity metrics. Overall, these findings contribute to our understanding of the viral populations that are active during the winter in Lake Erie and suggest that viral community activity may be associated with ice cover extent.

59 BASIC BIOLOGICAL SCIENCES↗

DOE OSTI2026

Perspective on “Active Brownian particles moving in a random Lorentz gas”

Self-propelled active matter can exhibit vastly different behavior than systems with purely Brownian motion. In Eur. Phys. J. E 40, 23 (2017), Zeitz, Wolf, and Stark compared an active matter particle with a Brownian particle moving in a random obstacle array. They showed that near the obstacle percolation density, both Brownian and active particles exhibit the same subdiffusive behavior, but the active particle reaches a steady state more rapidly. They also found that for high activity, the active particle has a lower effective diffusion than the Brownian particle due to the increased self-trapping effect generated by the activity. This result opens new directions for the study of active matter in disordered media, including bacteria in porous media, active colloids on quenched disorder, and active particles in crowded environments.

36 MATERIALS SCIENCE↗

NASA NTRS1986

Delta-configurations - Flare activity and magnetic-field structure

Complex sunspots in four active regions of April and May 1980, all exhibiting regions of magnetic classification delta, were studied using data from the NASA Marshall Space Flight Center vector magnetograph. The vector magnetic field structure in the vicinity of each delta was determined, and the location of the deltas in each active region was correlated with the locations and types of flare activity for the regions. Two types of delta-configuration were found to exist, active and inactive, as defined by the relationships between magnetic field structure and activity. The active delta exhibited high flare activity, strong horizontal gradients of the longitudinal (line-of-sight) magnetic field component, a strong transverse (perpendicular to line-of-sight) component, and a highly nonpotential orientation of the photospheric magnetic field, all indications of a highly sheared magnetic field. The inactive delta, on the other hand, exhibited little or no flare production, weaker horizontal gradients of the longitudinal component, weaker transverse components, and a nearly potential, nonsheared orientation of the magnetic field. It is concluded that the presence of such sheared fields is the primary signature by which the active delta may be distinguished, and that it is this shear which produces the flare activity of the active delta.

Patty, S. R.↗

NASA NTRS2009

The Active Oxidation of Silicon Carbide

The high temperature oxidation of silicon carbide occurs in two very different modes. Passive oxidation forms a protective oxide film which limits further attack of the SiC: SiC(s) + 3/2 O2(g) = SiO2(s) + CO(g) Active oxidation forms a volatile oxide and may lead to extensive attack of the SiC: SiC(s) + O2(g) = SiO(g) + CO(g) Generally passive oxidation occurs at higher oxidant pressures and active oxidation occurs at lower oxidant pressures and elevated temperatures. Active oxidation is a concern for reentry, where the flight trajectory involves the latter conditions. Thus the transition points and rates of active oxidation are a major concern. Passive/active transitions have been studied by a number of investigators. An examination of the literature indicates many questions remain regarding the effect of impurity, the hysteresis of the transition (i.e. the difference between active-to-passive and passive-toactive), and the effect of total pressure. In this study we systematically investigate each of these effects. Experiments were done in both an alumina furnace tube and a quartz furnace tube. It is known that alumina tubes release impurities such as sodium and increase the kinetics in the passive region [1]. We have observed that the active-to-passive transition occurs at a lower oxygen pressure when the experiment is conducted in alumina tubes and the resultant passive silica scale contains sodium. Thus the tests in this study are conducted in quartz tubes. The hysteresis of the transition has been discussed in the detail in the original theoretical treatise of this problem for pure silicon by Wagner [2], yet there is little mention of it in subsequent literature. Essentially Wagner points out that the active-to-passive transition is governed by the criterion for a stable Si/SiO2 equilibria and the passive-to-active transition is governed by the decomposition of the SiO2 film. A series of experiments were conducted for active-to-passive and passive-to-active transitions by increasing and decreasing oxygen pressure, respectively. For pure silicon a dramatic difference was found; whereas for SiC the difference was not as great. This may be due to the oxidation of the carbon in SiC which may break down the scale [3]. The third area is the effect of total pressure. In the literature, low oxygen potentials are achieved via either low total pressure or low oxygen pressure in an O2/Ar mixture. Both types of experiments are done in this study and the differences are discussed with regard to the presence or absence of a boundary layer.

Jacobson, Nathan S.↗

NASA NTRS2014

MAG4 Versus Alternative Techniques for Forecasting Active-Region Flare Productivity

MAG4 is a technique of forecasting an active region's rate of production of major flares in the coming few days from a free-magnetic-energy proxy. We present a statistical method of measuring the difference in performance between MAG4 and comparable alternative techniques that forecast an active region's major-flare productivity from alternative observed aspects of the active region. We demonstrate the method by measuring the difference in performance between the "Present MAG4" technique and each of three alternative techniques, called "McIntosh Active-Region Class," "Total Magnetic Flux," and "Next MAG4." We do this by using (1) the MAG4 database of magnetograms and major-flare histories of sunspot active regions, (2) the NOAA table of the major-flare productivity of each of 60 McIntosh active-region classes of sunspot active regions, and (3) five technique-performance metrics (Heidke Skill Score, True Skill Score, Percent Correct, Probability of Detection, and False Alarm Rate) evaluated from 2000 random two-by-two contingency tables obtained from the databases. We find that (1) Present MAG4 far outperforms both McIntosh Active-Region Class and Total Magnetic Flux, (2) Next MAG4 significantly outperforms Present MAG4, (3) the performance of Next MAG4 is insensitive to the forward and backward temporal windows used, in the range of one to a few days, and (4) forecasting from the free-energy proxy in combination with either any broad category of McIntosh active-region classes or any Mount Wilson active-region class gives no significant performance improvement over forecasting from the free-energy proxy alone (Present MAG4).

Falconer, David A.↗

NASA NTRS2014

Aeromechanical Evaluation of Smart-Twisting Active Rotor

An investigation of Smart-Twisting Active Rotor (STAR) was made to assess potential benefits of the current active twist rotor concept for performance improvement, vibration reduction, and noise alleviation. The STAR rotor is a 40% Mach-scaled, Bo105 rotor with an articulated flap-lag hinge at 3.5%R and no pre-cone. The 0-5 per rev active twist harmonic inputs were applied for various flight conditions including hover, descent, moderate to high speed level flights, and slowed rotor high advance ratio. For the analysis, the STAR partners used multiple codes including CAMRAD II, S4, HOST, rFlow3D, elsA, and their associated software. At the high thrust level in hover, the 0 per rev active twist with 80% amplitude increased figure of merit (FM) by 0.01-0.02 relative to the baseline. In descent, the largest BVI noise reduction was on the order of 2 to 5 dB at the 3 per rev active twist. In the high speed case (mu = 0.35), the 2 per rev actuation was found to be the most effective in achieving a power reduction as well as a vibration reduction. At the 2 per rev active twist, total power was reduced by 0.65% at the 60 deg active twist phase, and vibration was reduced by 47.6% at the 45 deg active twist phase. The use of the 2 per rev active twist appears effective for vibration reduction. In the high advance ratio case (mu = 0.70), the 0 per rev actuation appeared to have negligible impact on performance improvement. In summary, computational simulations successfully demonstrated that the current active twist concept provided a significant reduction of the maximum BVI noise in descent, a significant reduction of the vibration in the high speed case, a small improvement on rotor performance in hover, and a negligible impact on rotor performance in forward flight.

Lim, Joon W.↗

NASA NTRS2015

Increased Brain Activation for Foot Movement During 70-Day 6 Deg Head-Down Bed Rest (HDBR): Evidence from Functional Magnetic Resonance Imaging (fMRI)

Bed rest has been widely used as a simulation of weightlessness in studying the effects of microgravity exposure on human physiology and cognition. Changes in muscle function and functional mobility have been reported to be associated with bed rest. Understanding the effect of bed rest on neural control of movement would provide helpful information for spaceflight. In the current study, we evaluated how the brain activation for foot movement changed as a function of bed rest. Eighteen healthy men (aged 25 to 39 years) participated in this HDBR study. They remained continuously in the 6deg head‐down tilt position for 70 days. Functional MRI was acquired during 1‐Hz right foot tapping, and repeated at 7 time points: 12 days pre‐, 8 days pre‐, 7 days in‐, 50 days in‐, 70 days in‐, 8 days post‐, and 12 days post‐ HDBR. In all 7 sessions, we observed increased activation in the left motor cortex, right cerebellum and right occipital cortex during foot movement blocks compared to rest. Compared to the pre‐HDBR baseline (1st and 2nd sessions), foot movement‐induced activation in the left hippocampus increased during HDBR. This increase emerged in the 4th session, enlarged in the 5th session, and remained significant in the 6th and 7th sessions. Furthermore, increased activation relative to the baseline in left precuneus was observed in the 5th, 6th and 7th sessions. In addition, in comparison with baseline, increased activation in the left cerebellum was found in the 4th and 5th sessions, whereas increased activation in the right cerebellum was observed in the 4th, 6th and 7th sessions. No brain region exhibited decreased activation during bed rest compared to baseline. The increase of foot movement related brain activation during HDBR suggests that in a long‐term head‐down position, more neural control is needed to accomplish foot movements. This change required a couple of weeks to develop in HDBR (between 3rd and 4th sessions), and did not return to baseline even 12 days after HDBR. The observed effect of bed rest on brain activation during a foot tapping task could be linked to HDBR related changes in brain structure that we have recently reported. The relationship between pre‐ and post‐ HDBR changes in brain activation and performance in a functional mobility test will also be presented.

Yuan, P.↗

NASA NTRS2014

MAG4 Versus Alternative Techniques for Forecasting Active-Region Flare Productivity

MAG4 is a technique of forecasting an active region's rate of production of major flares in the coming few days from a free-magnetic-energy proxy. We present a statistical method of measuring the difference in performance between MAG4 and comparable alternative techniques that forecast an active region's major-flare productivity from alternative observed aspects of the active region. We demonstrate the method by measuring the difference in performance between the "Present MAG4" technique and each of three alternative techniques, called "McIntosh Active-Region Class," "Total Magnetic Flux," and "Next MAG4." We do this by using (1) the MAG4 database of magnetograms and major-flare histories of sunspot active regions, (2) the NOAA table of the major-flare productivity of each of 60 McIntosh active-region classes of sunspot active regions, and (3) five technique-performance metrics (Heidke Skill Score, True Skill Score, Percent Correct, Probability of Detection, and False Alarm Rate) evaluated from 2000 random two-by-two contingency tables obtained from the databases. We find that (1) Present MAG4 far outperforms both McIntosh Active-Region Class and Total Magnetic Flux, (2) Next MAG4 significantly outperforms Present MAG4, (3) the performance of Next MAG4 is insensitive to the forward and backward temporal windows used, in the range of one to a few days, and (4) forecasting from the free-energy proxy in combination with either any broad category of McIntosh active-region classes or any Mount Wilson active-region class gives no significant performance improvement over forecasting from the free-energy proxy alone (Present MAG4).

Falconer, David A.↗

NASA NTRSDate not supplied

Role of PIEZO1 in T Cell Activation Under Simulated Microgravity

True and simulated microgravity conditions have been well documented to cause the inhibition of T cell activation by mitogens. Although several studies aimed at exploring the mechanisms for such a phenomenon have been published, how this is occurring remains unresolved. PIEZO1 is a known mechanosensing gene and has been shown to be critically involved in human T cell activation. In our analysis of transcriptomics changes in peripheral mononuclear cells (PBMC) collected from the ISS crewmembers in space, the expression of PIEZO1 was downregulated. To investigate the role of the PIEZO1 gene in T cell activation in microgravity, we used rotating wall vessels (RWV), which simulate microgravity on the ground and are known to inhibit T cell activation. In this pilot study, PBMC cultured in RWV and in the static 1g condition were stimulated with Human T-Activator CD3/CD28 beads. The cells were also treated with and without Yoda1, a chemical agonist that activates PIEZO1 independent of mechanical cues or any other cellular component. After culturing for 24 hours, the cells were stained for activation markers and the PIEZO1 antibody, then were analyzed by flow cytometry. Our results indicate reduced T cell activation with mitogen under simulated microgravity, but no changes of the PIEZO1 signals were detected. In addition, the reduced activation was not restored in cells cultured with Yoda1. Taken together, our results suggest that PIEZO1 may play a minimal role in the inhibition of T cell activation in space.

Honglu Wu↗

NASA NTRSDate not supplied

Role of PIEZO1 in T Cell Activation Under Simulated Microgravity

True and simulated microgravity conditions have been well documented to cause the inhibition of T cell activation by mitogens. Although several studies aimed at exploring the mechanisms for such a phenomenon have been published, how this is occurring remains unresolved. PIEZO1 is a known mechanosensing gene and has been shown to be critically involved in human T cell activation. In our analysis of transcriptomics changes in peripheral mononuclear cells (PBMC) collected from the ISS crewmembers in space, the expression of PIEZO1 was downregulated. To investigate the role of the PIEZO1 gene in T cell activation in microgravity, we used rotating wall vessels (RWV), which simulate microgravity on the ground and are known to inhibit T cell activation. In this pilot study, PBMC cultured in RWV and in the static 1g condition were stimulated with Human T-Activator CD3/CD28 beads. The cells were also treated with and without Yoda1, a chemical agonist that activates PIEZO1 independent of mechanical cues or any other cellular component. After culturing for 24 hours, the cells were stained for activation markers and the PIEZO1 antibody, then were analyzed by flow cytometry. Our results indicate reduced T cell activation with mitogen under simulated microgravity, but no changes of the PIEZO1 signals were detected. In addition, the reduced activation was not restored in cells cultured with Yoda1. Taken together, our results suggest that PIEZO1 may play a minimal role in the inhibition of T cell activation in space.

Honglu Wu↗

NASA NTRSDate not supplied

Role of PIEZO1 in T Cell Activation Under Simulated Microgravity

True and simulated microgravity conditions have been well documented to cause the inhibition of T cell activation by mitogens. Although several studies aimed at exploring the mechanisms for such a phenomenon have been published, how this is occurring remains unresolved. PIEZO1 is a known mechanosensing gene and has been shown to be critically involved in human T cell activation. In our analysis of transcriptomics changes in peripheral mononuclear cells (PBMC) collected from the ISS crewmembers in space, the expression of PIEZO1 was downregulated. To investigate the role of the PIEZO1 gene in T cell activation in microgravity, we used rotating wall vessels (RWV), which simulate microgravity on the ground and are known to inhibit T cell activation. In this pilot study, PBMC cultured in RWV and in the static 1g condition were stimulated with Human T-Activator CD3/CD28 beads. The cells were also treated with and without Yoda1, a chemical agonist that activates PIEZO1 independent of mechanical cues or any other cellular component. After culturing for 24 hours, the cells were stained for activation markers and the PIEZO1 antibody, then were analyzed by flow cytometry. Our results indicate reduced T cell activation with mitogen under simulated microgravity, but no changes of the PIEZO1 signals were detected. In addition, the reduced activation was not restored in cells cultured with Yoda1. Taken together, our results suggest that PIEZO1 may play a minimal role in the inhibition of T cell activation in space.

Honglu Wu↗

NASA NTRS2024

The Active Volcanoes of Kamchatka as Suitable Terrestrial Analogs Within the AVENGERS Initiative: An Opportunity for In-Situ Operational Tests for Future Landing Venus Missions

The next decade will see the return to Venus thanks to a number of missions which have been recently selected and proposed for launch. The Roscosmos Venera-D mission, along with the NASA DAVINCI, NASA VERITAS, ESA EnVision, the ISRO Shukrayaan-1, and the CNSA VOICE missions will open a new era for the exploration of the Earth’s hellish twin planet. The next missions to Venus should be able to shed new light on the science questions such as: a) whether the volcanic activity on this planet is locally constrained, or volcanism acts on a global scale, b) the rate of the present-day volcanic activity, and c) the style of volcanism on Venus, whether it is predominantly effusive, or the occurrence of local episodes of pyroclastic volcanism is also possible. In preparation for the future missions to Venus, the Analogs for VENus’ Geologically Recent Surfaces (AVENGERS) initiative will select and analyze a number of active terrestrial volcanoes as suitable analogs for the identification and analysis of active volcanism on Venus. Among the future missions to Venus, the Roscosmos Venera-D is the only one to be equipped with a lander which will analyze the elemental and mineralogical composition of the surface. As the young topographic rises (areas characterized by recent volcano-tectonic activity) on Venus are being proposed as one of the possible terrain types for the Venera-D landing, it is crucial to look for volcanic areas on Earth where to perform operational tests such as surface drilling and in-situ elemental composition analysis. To this regard, we propose here the analysis of the active volcanoes of the Kamchatka Peninsula in Russia as a very suitable analog for the Venera-D mission, as well as for the analysis of surface change detection due to ongoing eruptions. The Kamchatka Peninsula is located on the eastern margin of the Eurasia plate, in proximity of the Kuril-Kamchatka subduction zone. The volcanoes of the Kamchatka Peninsula are among the most active volcanoes of the world, making them a suitable terrestrial analog in the search for active volcanism on Venus. Moreover, the volcanoes of Kamchatka are characterized by pyroclastic activity. Since the previous Soviet Venera and Vega missions landed over areas which elemental composition was most likely consistent with that of tholeiitic basalts, performing operational tests over areas characterized by pyroclastic activity also offers the unique opportunity to provide us the tools to potentially interpret the diverse output given by landing over portions of the surface of Venus possibly characterized by explosive volcanic products. Finally, the frequent eruptions characterizing the volcanoes of the Kamchatka Peninsula make them also a suitable terrestrial analog for the possible detection of ongoing eruptions on Venus by future missions, which can be achieved by comparing two (or more) radar images of the same volcano (and its surroundings) in two (or more) different moments of time.

Planetary Geology↗

DOE OSTI2025

Active-noise-induced dynamic clustering of passive colloidal particles

Active fluids generate spontaneous, often chaotic mesoscale flows. Harnessing these flows to drive soft materials embedded within an active fluid into structures with controlled length scales and lifetimes is a key challenge at the interface between the fields of active matter and nonequilibrium self-assembly. Here, we present a simple and efficient computational approach to model soft materials advected by active fluids, by simulating particles moving in a spatiotemporally correlated noise field. To illustrate our approach, we simulate the dynamical self-organization of repulsive colloids within such an active noise field. The colloids form structures whose sizes and dynamics can be tuned by the correlation time and length of the active fluid, and range from small rotating droplets to clusters with internal flows and system-spanning sizes that vastly exceed the active correlation length. Our results explain how the interplay between active fluid time and length scales and emergent driven assembly can be used to rationally design functional assemblies. More broadly, our approach can be used to efficiently simulate diverse active fluids and other systems with spatiotemporally correlated noise.

Brownian dynamics↗

NASA NTRS2000

Intramolecular activation of a Ca(2+)-dependent protein kinase is disrupted by insertions in the tether that connects the calmodulin-like domain to the kinase

Ca(2+)-dependent protein kinases (CDPK) have a calmodulin-like domain (CaM-LD) tethered to the C-terminal end of the kinase. Activation is proposed to involve intramolecular binding of the CaM-LD to a junction sequence that connects the CaM-LD to the kinase domain. Consistent with this model, a truncated CDPK (DeltaNC) in which the CaM-LD has been deleted can be activated in a bimolecular interaction with an isolated CaM-LD or calmodulin, similar to the activation of a calmodulin-dependent protein kinase (CaMK) by calmodulin. Here we provide genetic evidence that this bimolecular activation requires a nine-residue binding segment from F436 to I444 (numbers correspond to CPK-1 accession number L14771). Two mutations at either end of this core segment (F436/A and VI444/AA) severely disrupted bimolecular activation, whereas flanking mutations had only minor effects. Intramolecular activation of a full-length kinase was also disrupted by a VI444/AA mutation, but surprisingly not by a F436/A mutation (at the N-terminal end of the binding site). Interestingly, intramolecular but not bimolecular activation was disrupted by insertion mutations placed immediately downstream of I444. To show that mutant enzymes were not misfolded, latent kinase activity was stimulated through binding of an antijunction antibody. Results here support a model of intramolecular activation in which the tether (A445 to G455) that connects the CaM-LD to the kinase provides an important structural constraint and is not just a simple flexible connection.

NASA Discipline Plant Biology↗

DOE OSTI2025

Direct root contact among neighboring plants influences activity of soil extracellular enzymes

Composition and diversity of vegetation systems can influence soil microbial activity and extracellular enzyme (EE) dynamics, which are crucial for soil carbon (C) accrual and nutrient cycling. Yet, the impact of plant interactions and competition on EE activities remains a notable knowledge gap. This study examines how direct root contact and neighboring plant identity affect the activity and spatial distribution of four key soil EEs: β-glucosidase (BGlu), chitinase, acid phosphatase (AcidP), and alkaline phosphatase (AlkP). Using three-compartment rhizoboxes with switchgrass (Panicum virgatum L.) grown alongside bush clover (Lespedeza capitata Michx.), and black-eyed Susan (Rudbeckia hirta L.), we assessed enzyme activities using zymography under conditions that either allowed or restricted direct root contact by root barriers. Results show that root proliferation and species interactions significantly influenced EE activity. While BGlu and AcidP activities were strongly correlated with root biomass, AlkP activity was consistently higher in the absence of root barriers, indicating a pronounced microbial response to plant interactions via direct/close root contacts. Additionally, soil phosphorus availability modulated enzyme activity, with higher phosphatase activities in low-P soils. Furthermore, these findings highlight the importance of root-root interactions and plant species composition in shaping soil biochemical processes.

enyzme activity↗

DOE OSTI2025

Active Fluids Form System-Spanning Filamentary Networks

Recent experimental realizations of liquid-liquid phase separation of active liquid crystals have offered an insight into the interaction between phase separation, ubiquitous in soft matter and biology, and chaotic active flows. Here, in this Letter, we use continuum theory to examine phase separation of an active liquid crystal and a passive fluid and report two new results. First, we provide an analytical derivation of the activity-induced suppression of the phase boundary of the coexistence region—a result first reported in simulations and experiments. We show that the shift in the critical point is a result of the balance between self-stirring active flows and phase-separating diffusive fluxes. Second, we show that this same balance is responsible for dramatically changing the morphology of the phase separated state, resulting in the emergence of a new mixed active phase consisting of a dynamical filamentous active network that invades the entire system area, trapping droplets of passive material. This structure exists even for very low volume fractions of active material. Our work provides an important step towards the goal of understanding how to use activity as a new handle for sculpting interfaces.

active nematics↗

NASA NTRS2001

Endothelial NOS-dependent activation of c-Jun NH(2)- terminal kinase by oxidized low-density lipoprotein

Oxidized low-density lipoprotein (oxLDL) is known to activate a number of signal transduction pathways in endothelial cells. Among these are the c-Jun NH(2)-terminal kinase (JNK), also known as stress-activated protein kinase, and extracellular signal-regulated kinase (ERK). These mitogen-activated protein kinases (MAP kinase) determine cell survival in response to environmental stress. Interestingly, JNK signaling involves redox-sensitive mechanisms and is activated by reactive oxygen and nitrogen species derived from both NADPH oxidases, nitric oxide synthases (NOS), peroxides, and oxidized low-density lipoprotein (oxLDL). The role of endothelial NOS (eNOS) in the activation of JNK in response to oxLDL has not been examined. Herein, we show that on exposure of endothelial cells to oxLDL, both ERK and JNK are activated through independent signal transduction pathways. A key role of eNOS activation through a phosphatidylinositol-3-kinase-dependent mechanism leading to phosphorylation of eNOS is demonstrated for oxLDL-dependent activation of JNK. Moreover, we show that activation of ERK by oxLDL is critical in protection against the cytotoxicity of oxLDL.

Non-NASA Center↗

NASA NTRS2001

YC-1 activation of human soluble guanylyl cyclase has both heme-dependent and heme-independent components

YC-1 [3-(5'-hydroxymethyl-2'furyl)-1-benzyl indazole] is an allosteric activator of soluble guanylyl cyclase (sGC). YC-1 increases the catalytic rate of the enzyme and sensitizes the enzyme toward its gaseous activators nitric oxide or carbon monoxide. In other studies the administration of YC-1 to experimental animals resulted in the inhibition of the platelet-rich thrombosis and a decrease of the mean arterial pressure, which correlated with increased cGMP levels. However, details of YC-1 interaction with sGC and enzyme activation are incomplete. Although evidence in the literature indicates that YC-1 activation of sGC is strictly heme-dependent, this report presents evidence for both heme-dependent and heme-independent activation of sGC by YC-1. The oxidation of the sGC heme by 1H-(1,2,4)oxadiazole(4,3-a)quinoxalin-1-one completely inhibited the response to NO, but only partially attenuated activation by YC-1. We also observed activation by YC-1 of a mutant sGC, which lacks heme. These findings indicate that YC-1 activation of sGC can occur independently of heme, but that activation is substantially increased when the heme moiety is present in the enzyme.

NASA Discipline Cardiopulmonary↗