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Results for “Stress Response Signaling”

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 145 records · Page 8
All sourcesNASA NTRSDOE OSTI
NASA NTRS2018

Redox Signaling and Its Impact on Skeletal and Vascular Responses to Spaceflight

Spaceflight entails exposure to numerous environmental challenges with the potential to contribute to both musculoskeletal and vascular dysfunction. The purpose of this review is to describe current understanding of microgravity and radiation impacts on the mammalian skeleton and associated vasculature at the level of the whole organism. Recent experiments from spaceflight and groundbased models have provided fresh insights into how these environmental stresses influence mechanisms that are related to redox signaling, oxidative stress, and tissue dysfunction. Emerging mechanistic knowledge on cellular defenses to radiation and other environmental stressors, including microgravity, are useful for both screening and developing interventions against spaceflight-induced deficits in bone and vascular function.

redox siggnalin↗
DOE OSTI2023

Information theory and machine learning illuminate large‐scale metabolomic responses of Brachypodium distachyon to environmental change

SUMMARY Plant responses to environmental change are mediated via changes in cellular metabolomes. However, <5% of signals obtained from liquid chromatography tandem mass spectrometry (LC‐MS/MS) can be identified, limiting our understanding of how metabolomes change under biotic/abiotic stress. To address this challenge, we performed untargeted LC‐MS/MS of leaves, roots, and other organs of Brachypodium distachyon (Poaceae) under 17 organ–condition combinations, including copper deficiency, heat stress, low phosphate, and arbuscular mycorrhizal symbiosis. We found that both leaf and root metabolomes were significantly affected by the growth medium. Leaf metabolomes were more diverse than root metabolomes, but the latter were more specialized and more responsive to environmental change. We found that 1 week of copper deficiency shielded the root, but not the leaf metabolome, from perturbation due to heat stress. Machine learning (ML)‐based analysis annotated approximately 81% of the fragmented peaks versus approximately 6% using spectral matches alone. We performed one of the most extensive validations of ML‐based peak annotations in plants using thousands of authentic standards, and analyzed approximately 37% of the annotated peaks based on these assessments. Analyzing responsiveness of each predicted metabolite class to environmental change revealed significant perturbations of glycerophospholipids, sphingolipids, and flavonoids. Co‐accumulation analysis further identified condition‐specific biomarkers. To make these results accessible, we developed a visualization platform on the Bio‐Analytic Resource for Plant Biology website ( https://bar.utoronto.ca/efp_brachypodium_metabolites/cgi‐bin/efpWeb.cgi ), where perturbed metabolite classes can be readily visualized. Overall, our study illustrates how emerging chemoinformatic methods can be applied to reveal novel insights into the dynamic plant metabolome and stress adaptation.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2023

Super-Resolution Imaging of Plant Receptor-Like Kinases Uncovers Their Colocalization and Coordination with Nanometer Resolution

Plant cell signaling often relies on the cellular organization of receptor-like kinases (RLKs) within membrane nanodomains to enhance signaling specificity and efficiency. Thus, nanometer-scale quantitative analysis of spatial organizations of RLKs could provide new understanding of mechanisms underlying plant responses to environmental stress. Here, we used stochastic optical reconstruction fluorescence microscopy (STORM) to quantify the colocalization of the flagellin-sensitive-2 (FLS2) receptor and the nanodomain marker, remorin, within Arabidopsis thaliana root hair cells. We found that recovery of FLS2 and remorin in the plasma membrane, following ligand-induced internalization by bacterial-flagellin-peptide (flg22), reached ~85% of their original membrane density after ~90 min. The pairs colocalized at the membrane at greater frequencies, compared with simulated randomly distributed pairs, except for directly after recovery, suggesting initial uncoordinated recovery followed by remorin and FLS2 pairing in the membrane. The purinergic receptor, P2K1, colocalized with remorin at similar frequencies as FLS2, while FLS2 and P2K1 colocalization occurred at significantly lower frequencies, suggesting that these RLKs mostly occupy distinct nanodomains. The chitin elicitor receptor, CERK1, colocalized with FLS2 and remorin at much lower frequencies, suggesting little coordination between CERK1 and FLS2. These findings emphasize STORM’s capacity to observe distinct nanodomains and degrees of coordination between plant cell receptors, and their respective immune pathways.

59 BASIC BIOLOGICAL SCIENCES↗
NASA NTRSDate not supplied

Deep Space Radiation Affects Neurovascular Functions in Human Organ-on-a-Chip Models

A major health risk for human deep space exploration is central nervous system (CNS) damage by galactic cosmic ray radiation. Simulated galactic cosmic rays or their components, especially the high- linear energy transfer (LET) particles such as 56 Fe ions, cause CNS damage, neuroinflammation and cognitive dysfunction in rodent models, but their effects on human CNS remain to be investigated. CNS damage from any insult, including ionizing radiation, is partially mediated by the blood-brain barrier (BBB), which regulates the interactions between CNS and the rest of the body. The main cellular regulators of BBB permeability are astrocytes, which also modulate neuronal health and neuroinflammation. However, there have been few studies on BBB and astrocyte functions in regulating CNS responses, especially in human tissue/organ analogs. Therefore, we utilized a high-throughput human 3D organ-on-a-chip system, seeded with induced pluripotent stem cell-derived endothelial cells, astrocytes and neurons, to study human neurovascular responses to simulated deep space radiation. We investigated BBB permeability, oxidative stress, cellular and tissue damage, and secreted factors over the time period of 24 hours-1 week after irradiation with 0.25-0.5 Gy 5-ion simplified simulated galactic cosmic rays and 0.3-0.8 Gy high-LET 600MeV/n 56 Fe particles, and compared the outcomes to low-LET irradiation with 0.1-1 Gy doses of X-rays and gamma rays. Both high and low-LET radiation increased neurovascular permeability, caused oxidative stress, damaged endothelial cells and tight junctions, and altered expression of inflammatory cytokines. Ionizing radiation- induced neurovascular permeability and oxidative stress peaked at 3 days after irradiation and were further exacerbated by the presence of astrocytes. Furthermore, in response to particle irradiation, astrocytes stimulated interleukin-1 signaling by inhibiting the expression of interleukin-1 receptor antagonist. Thus, we also evaluated interleukin-1 receptor antagonist as a potential countermeasure against particle radiation. Ultimately, our results may help develop countermeasures to mitigate human CNS damage in deep space exploration.

Sonali D Verma↗
DOE OSTI2020

Medium amplitude parallel superposition (MAPS) rheology. Part 2: Experimental protocols and data analysis

An experimental protocol is developed to directly measure the new material functions revealed by medium amplitude parallel superposition (MAPS) rheology. This protocol measures the medium amplitude response of a material to a simple shear deformation composed of three sine waves at different frequencies, revealing a rich dataset consisting of up to 19 measurements of the third-order complex modulus at distinct three-frequency coordinates. We discuss how the choice of input frequencies influences the features of the MAPS domain studied by the experiment. A polynomial interpolation method for reducing the bias of measured values from spectral leakage and reducing variance due to noise is discussed, including a derivation of the optimal range of amplitudes for the input signal. This leads to the conclusion that conducting the experiment in a stress-controlled fashion possesses a distinct advantage to the strain-controlled mode. The experimental protocol is demonstrated through measurements of the MAPS response of a model complex fluid: a surfactant solution of wormlike micelles. The resulting dataset is indeed large and feature-rich, while still acquired in a time comparable to similar medium amplitude oscillatory shear (MAOS) experiments. We demonstrate that the data represent measurements of an intrinsic material function by studying its internal consistency, compatibility with low-frequency predictions for Coleman–Noll simple fluids, and agreement with data obtained via MAOS amplitude sweeps. Finally, the data are compared to predictions from the corotational Maxwell model to demonstrate the power of MAPS rheology in determining whether a constitutive model is consistent with a material’s time-dependent response.

Lennon, Kyle R. (ORCID:0000000212515461)↗
DOE OSTI2021

Gene co-expression network analysis in zebrafish reveals chemical class specific modules

Zebrafish is a popular animal model used for high-throughput screening of chemical hazards, however, investigations of transcriptomic mechanisms of toxicity are still needed. Here, our goal was to identify genes and biological pathways that Aryl Hydrocarbon Receptor 2 (AHR2) Activators and flame retardant chemicals (FRCs) alter in developing zebrafish. Taking advantage of a compendium of phenotypically-anchored RNA sequencing data collected from 48-h post fertilization (hpf) zebrafish, we inferred a co-expression network that grouped genes based on their transcriptional response. Genes responding to the FRCs and AHR2 Activators localized to distinct regions of the network, with FRCs inducing a broader response related to neurobehavior. AHR2 Activators centered in one region related to chemical stress responses. We also discovered several highly co-expressed genes in this module, including cyp1a, and we subsequently show that these genes are definitively within the AHR2 signaling pathway. Systematic removal of the two chemical types from the data, and analysis of network changes identified neurogenesis associated with FRCs, and regulation of vascular development associated with both chemical classes. We also identified highly connected genes responding specifically to each class that are potential biomarkers of exposure. Overall, we created the first zebrafish chemical-specific gene co-expression network illuminating how chemicals alter the transcriptome relative to each other. In addition to our conclusions regarding FRCs and AHR2 Activators, our network can be leveraged by other studies investigating chemical mechanisms of toxicity.

59 BASIC BIOLOGICAL SCIENCES↗
NASA NTRS2002

Mechanical signaling and the cellular response to extracellular matrix in angiogenesis and cardiovascular physiology

Great advances have been made in the identification of the soluble angiogenic factors, insoluble extracellular matrix (ECM) molecules, and receptor signaling pathways that mediate control of angiogenesis--the growth of blood capillaries. This review focuses on work that explores how endothelial cells integrate these chemical signals with mechanical cues from their local tissue microenvironment so as to produce functional capillary networks that exhibit specialized form as well as function. These studies have revealed that ECM governs whether an endothelial cell will switch between growth, differentiation, motility, or apoptosis programs in response to a soluble stimulus based on its ability to mechanically resist cell tractional forces and thereby produce cell and cytoskeletal distortion. Transmembrane integrin receptors play a key role in this mechanochemical transduction process because they both organize a cytoskeletal signaling complex within the focal adhesion and preferentially focus mechanical forces on this site. Molecular filaments within the internal cytoskeleton--microfilaments, microtubules, and intermediate filaments--also contribute to the cell's structural and functional response to mechanical stress through their role as discrete support elements within a tensegrity-stabilized cytoskeletal array. Importantly, a similar form of mechanical control also has been shown to be involved in the regulation of contractility in vascular smooth muscle cells and cardiac myocytes. Thus, the mechanism by which cells perform mechanochemical transduction and the implications of these findings for morphogenetic control are discussed in the wider context of vascular development and cardiovascular physiology.

Non-NASA Center↗
NASA NTRS2000

Cell signaling by reactive nitrogen and oxygen species in atherosclerosis

The production of reactive oxygen and nitrogen species has been implicated in atherosclerosis principally as means of damaging low-density lipoprotein that in turn initiates the accumulation of cholesterol in macrophages. The diversity of novel oxidative modifications to lipids and proteins recently identified in atherosclerotic lesions has revealed surprising complexity in the mechanisms of oxidative damage and their potential role in atherosclerosis. Oxidative or nitrosative stress does not completely consume intracellular antioxidants leading to cell death as previously thought. Rather, oxidative and nitrosative stress have a more subtle impact on the atherogenic process by modulating intracellular signaling pathways in vascular tissues to affect inflammatory cell adhesion, migration, proliferation, and differentiation. Furthermore, cellular responses can affect the production of nitric oxide, which in turn can strongly influence the nature of oxidative modifications occurring in atherosclerosis. The dynamic interactions between endogenous low concentrations of oxidants or reactive nitrogen species with intracellular signaling pathways may have a general role in processes affecting wound healing to apoptosis, which can provide novel insights into the pathogenesis of atherosclerosis.

Review, Tutorial↗
NASA NTRS1999

Tensegrity and mechanoregulation: from skeleton to cytoskeleton

OBJECTIVE: To elucidate how mechanical stresses that are applied to the whole organism are transmitted to individual cells and transduced into a biochemical response. DESIGN: In this article, we describe fundamental design principles that are used to stabilize the musculoskeletal system at many different size scales and show that these design features are embodied in one particular form of architecture that is known as tensegrity. RESULTS: Tensegrity structures are characterized by use of continuous tension and local compression; architecture, prestress (internal stress prior to application of external force), and triangulation play the most critical roles in terms of determining their mechanical stability. In living organisms, use of a hierarchy of tensegrity networks both optimizes structural efficiency and provides a mechanism to mechanically couple the parts with the whole: mechanical stresses applied at the macroscale result in structural rearrangements at the cell and molecular level. CONCLUSION: Due to use of tensegrity architecture, mechanical stress is concentrated and focused on signal transducing molecules that physically associate with cell surface molecules that anchor cells to extracellular matrix, such as integrins, and with load-bearing elements within the internal cytoskeleton and nucleus. Mechanochemical transduction may then proceed through local stress-dependent changes in molecular mechanics, thermodynamics, and kinetics within the cell. In this manner, the entire cellular response to stress may be orchestrated and tuned by altering the prestress in the cell, just as changing muscular tone can alter mechanical stability and structural coordination throughout the whole musculoskeletal system.

NASA Discipline Cell Biology↗
NASA NTRS2011

A Hypothesis on Biological Protection from Space Radiation Through the Use of New Therapeutic Gases

Radiation exposure to astronauts could be a significant obstacle for long duration manned space exploration because of current uncertainties regarding the extent of biological effects. Furthermore, concepts for protective shielding also pose a technically challenging issue due to the nature of cosmic radiation and current mass and power constraints with modern exploration technology. The concern regarding exposure to cosmic radiation is the biological damage it induces. As damage is associated with increased oxidative stress, it is important and would be enabling to mitigate and/or prevent oxidative stress prior to the development of clinical symptoms and disease. This paper hypothesizes a "systems biology" approach in which a combination of chemical and biological mitigation techniques are used conjunctively. It proposes using new, therapeutic, medical gases as both chemical radioprotectors for radical scavenging and biological signaling molecules for management of the body s response to exposure. From reviewing radiochemistry of water, biological effects of CO, H2, NO, and H2S gas, and mechanisms of radiation biology, it is concluded that this approach may have great therapeutic potential for radiation exposure. Furthermore, it also appears to have similar potential for curtailing the pathogenesis of other diseases in which oxidative stress has been implicated including, cardiovascular disease, cancer, chronic inflammatory disease, hypertension, ischemia/reperfusion injury, acute respiratory distress syndrome, parkinson s and alzheimer s disease, cataracts, and aging

Schoenfeld, Michael P.↗
NASA NTRS2012

A Hypothesis on Biological Protection from Space Radiation Through the Use of New Therapeutic Gases as Medical Counter Measures

Radiation exposure to astronauts could be a significant obstacle for long duration manned space exploration because of current uncertainties regarding the extent of biological effects. Furthermore, concepts for protective shielding also pose a technically challenging issue due to the nature of cosmic radiation and current mass and power constraints with modern exploration technology. The concern regarding exposure to cosmic radiation is the biological damage it induces. As damage is associated with increased oxidative stress, it is important and would be enabling to mitigate and/or prevent oxidative stress prior to the development of clinical symptoms and disease. This paper hypothesizes a "systems biology" approach in which a combination of chemical and biological mitigation techniques are used conjunctively. It proposes using new, therapeutic, medical gases as both chemical radioprotectors for radical scavenging and biological signaling molecules for management of the body s response to exposure. From reviewing radiochemistry of water, biological effects of CO, H2, NO, and H2S gas, and mechanisms of radiation biology, it is concluded that this approach may have great therapeutic potential for radiation exposure. Furthermore, it also appears to have similar potential for curtailing the pathogenesis of other diseases in which oxidative stress has been implicated including cardiovascular disease, cancer, chronic inflammatory disease, hypertension, ischemia/reperfusion injury, acute respiratory distress syndrome, Parkinson s and Alzheimer s disease, cataracts, and aging.

Schoenfeld, Michael P.↗
NASA NTRS2011

A Hypothesis on Biological Protection from Space Radiation Through the Use of New Therapeutic Gases

Radiation exposure to astronauts could be a significant obstacle for long duration manned space exploration because of current uncertainties regarding the extent of biological effects. Furthermore, concepts for protective shielding also pose a technically challenging issue due to the nature of cosmic radiation and current mass and power constraints with modern exploration technology. The concern regarding exposure to cosmic radiation is the biological damage it induces. As damage is associated with increased oxidative stress, it is important and would be enabling to mitigate and/or prevent oxidative stress prior to the development of clinical symptoms and disease. This paper hypothesizes a "systems biology" approach in which a combination of chemical and biological mitigation techniques are used conjunctively. It proposes using new, therapeutic, medical gases as both chemical radioprotectors for radical scavenging and biological signaling molecules for management of the body s response to exposure. From reviewing radiochemistry of water, biological effects of CO, H2, NO, and H2S gas, and mechanisms of radiation biology, it is concluded that this approach may have great therapeutic potential for radiation exposure. Furthermore, it also appears to have similar potential for curtailing the pathogenesis of other diseases in which oxidative stress has been implicated including cardiovascular disease, cancer, chronic inflammatory disease, hypertension, ischemia/reperfusion injury, acute respiratory distress syndrome, Parkinson s and Alzheimer s disease, cataracts, and aging.

Schoenfeld, Michael P.↗
NASA NTRS1999

Differences In Early T-Cell Signaling In Cultures Grown In a Rotating Clinostat vs. Static Controls

Altered gravity has previously been demonstrated to be a stress that can influence components of the immune system. Specifically, T-cell activation has been shown to be affected by changes in gravity, exhibiting a decrease in proliferative response to in vitro stimulation in microgravity. Subsequent ground based studies utilizing a rotating clinostat to model some of the effects of microgravity have been consistent with earlier flight based experiments. These ground and flight experiments have examined T-cell activation by measuring various responses including production of cytokines, DNA synthesis and the production of various cell surface activation markers. These indicators of T-cell activation were measured anywhere from 4 to 72 hours after stimulation. Prior to the work described here, the initial signaling events in T-cell activation had not been directly examined. The goal of this project was to determine how the process of early signal transduction was affected by growth in a rotating clinostat. Here we directly show a defect in signaling from TCR to MAPK in purified peripheral T-cells activated in the clinostat by OKT3/antiCD28 coated microbeads as compared to static controls.

Alexamder. M.↗
NASA NTRS2002

Remote sensing of gene expression in Planta: transgenic plants as monitors of exogenous stress perception in extraterrestrial environments

Transgenic arabidopsis plants containing the alcohol dehydrogenase (Adh) gene promoter fused to the green fluorescent protein (GFP) reporter gene were developed as biological sensors for monitoring physiological responses to unique environments. Plants were monitored in vivo during exposure to hypoxia, high salt, cold, and abcissic acid in experiments designed to characterize the utility and responses of the Adh/GFP biosensors. Plants in the presence of environmental stimuli that induced the Adh promoter responded by expressing GFP, which in turn generated a detectable fluorescent signal. The GFP signal degraded when the inducing stimulus was removed. Digital imaging of the Adh/GFP plants exposed to each of the exogenous stresses demonstrated that the stress-induced gene expression could be followed in real time. The experimental results established the feasibility of using a digital monitoring system for collecting gene expression data in real time from Transgenic Arabidopsis Gene Expression System (TAGES) biosensor plants during space exploration experiments.

NASA Discipline Plant Biology↗
DOE OSTI2024

Integrative Multi-PTM Proteomics Reveals Dynamic Global, Redox, Phosphorylation, and Acetylation Regulation in Cytokine-treated Pancreatic Beta Cells

Studying regulation of protein function at a systems level necessitates an understanding of the interplay among diverse post-translational modifications (PTMs). A variety of proteomics sample processing workflows are currently used to study specific PTMs but rarely characterize multiple types of PTMs from the same sample inputs. Method incompatibilities and laborious sample preparation steps complicate large-scale physiological investigations and can lead to variations in results. The single-pot, solid-phase-enhanced sample preparation (SP3) method for sample cleanup is compatible with different lysis buffers and amenable to automation, making it attractive for high-throughput multi-PTM profiling. Herein, we describe an integrative SP3 workflow for multiplexed quantification of protein abundance, cysteine thiol oxidation, phosphorylation, and acetylation. The broad applicability of this approach is demonstrated using cell and tissue samples, and its utility for studying interacting regulatory networks is highlighted in a time-course experiment of cytokine-treated ß-cells. We observed a swift response in global regulation of protein abundances consistent with rapid activation of JAK-STAT and NF-?B signaling pathways. Regulators of these pathways as well as proteins involved in their target processes displayed multi-PTM dynamics indicative of a complex cellular response stages: acute, adaptation, and chronic (prolonged stress). PARP14, a negative regulator of JAK-STAT, had multiple co-localized PTMs that may be involved in intraprotein regulatory crosstalk. Our workflow provides a high-throughput platform that can profile multi-PTMomes from the same sample set, which is valuable in unraveling the functional roles of PTMs and their co-regulation.

proteomics, PTM, automation, SP3, cysteine thiol o↗
NASA NTRS1967

Cardiotachometer with linear beat-to-beat frequency response

Cardiotachometer detects and displays the human heart rate during physiological studies. It provides linear response to the heart rate, records heart rate during rest and under heavy stress, provides a beat-to-beat indication of changes in heart rate, and is relatively free of interfering signals from activities other than the heart rate.

Deboo, G. J.↗
NASA NTRS2004

Mechanotransduction through Integrins

The goal of this project was to characterize the molecular mechanism by which cells recognize and respond to physical forces in their local environment. The project was based on the working hypothesis that cells sense mechanical stresses through cell surface integrin receptors and through their interconnections with the underlying cytoskeleton. Work completed and published in past funding period had provided direct support for this hypothesis. In particular, we demonstrated that application of mechanical stresses to activated integrin receptors (but not inactive integrins or other control transmembrane receptors) resulted in stress-dependent activation of the CAMP signaling pathway leading to gene transcription. We also showed that this form of mechanotransduction requires activation of heterotrimeric G proteins. In this grant, our specific aims included: 1) to characterize the signal processing capabilities of different integrins and other cell surface receptors, 2) to identify heterotrimeric G proteins that mediate CAMP signaling by stresses applied to integrins, 3) to identify molecules that mediate transmembrane mechanochemical coupling between integrins and G proteins, and 4) to use genome-wide gene expression profiling techniques to identify other genes and signaling pathways that are activated by mechanical forces transmitted over specific cell surface receptors. Elucidation of the mechanism by which cells sense mechanical stresses through integrins and translate them into a biochemical response should help us to understand the molecular basis of the cellular response to gravity as well as many other forms of mechanosensation and tissue regulation.

Ingber, Donald↗
DOE OSTI2024

Phytohormones in a universe of regulatory metabolites: lessons from jasmonate

Small-molecule phytohormones exert control over plant growth, development, and stress responses by coordinating the patterns of gene expression within and between cells. Increasing evidence indicates that currently recognized plant hormones are part of a larger group of regulatory metabolites that have acquired signaling properties during the evolution of land plants. This rich assortment of chemical signals reflects the tremendous diversity of plant secondary metabolism, which offers evolutionary solutions to the daunting challenges of sessility and other unique aspects of plant biology. A major gap in our current understanding of plant regulatory metabolites is the lack of insight into the direct targets of these compounds. Here, we illustrate the blurred distinction between classical phytohormones and other bioactive metabolites by highlighting the major scientific advances that transformed the view of jasmonate from an interesting floral scent to a potent transcriptional regulator. Lessons from jasmonate research generally apply to other phytohormones and thus may help provide a broad understanding of regulatory metabolite–protein interactions. In providing a framework that links small-molecule diversity to transcriptional plasticity, we hope to stimulate future research to explore the evolution, functions, and mechanisms of perception of a broad range of plant regulatory metabolites.

59 BASIC BIOLOGICAL SCIENCES↗