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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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45 records · Page 3
All sourcesNASA NTRSDOE OSTI
DOE OSTI2021

Altered Cardiac Energetics and Mitochondrial Dysfunction in Hypertrophic Cardiomyopathy

Background: Hypertrophic cardiomyopathy (HCM) is a complex disease partly explained by the effects of individual gene variants on sarcomeric protein biomechanics. At the cellular level, HCM mutations most commonly enhance force production, leading to higher energy demands. Despite significant advances in elucidating sarcomeric structure–function relationships, there is still much to be learned about the mechanisms that link altered cardiac energetics to HCM phenotypes. Here, we test the hypothesis that changes in cardiac energetics represent a common pathophysiologic pathway in HCM. Methods: We performed a comprehensive multiomics profile of the molecular (transcripts, metabolites, and complex lipids), ultrastructural, and functional components of HCM energetics using myocardial samples from 27 HCM patients and 13 normal controls (donor hearts). Results: Integrated omics analysis revealed alterations in a wide array of biochemical pathways with major dysregulation in fatty acid metabolism, reduction of acylcarnitines, and accumulation of free fatty acids. HCM hearts showed evidence of global energetic decompensation manifested by a decrease in high energy phosphate metabolites (ATP, ADP, and phosphocreatine) and a reduction in mitochondrial genes involved in creatine kinase and ATP synthesis. Accompanying these metabolic derangements, electron microscopy showed an increased fraction of severely damaged mitochondria with reduced cristae density, coinciding with reduced citrate synthase activity and mitochondrial oxidative respiration. These mitochondrial abnormalities were associated with elevated reactive oxygen species and reduced antioxidant defenses. However, despite significant mitochondrial injury, HCM hearts failed to upregulate mitophagic clearance. Conclusions: Overall, our findings suggest that perturbed metabolic signaling and mitochondrial dysfunction are common pathogenic mechanisms in patients with HCM. These results highlight potential new drug targets for attenuation of the clinical disease through improving metabolic function and reducing mitochondrial injury.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2021

The core autophagy machinery is not required for chloroplast singlet oxygen-mediated cell death in the Arabidopsis thaliana plastid ferrochelatase two mutant

Chloroplasts respond to stress and changes in the environment by producing reactive oxygen species (ROS) that have specific signaling abilities. The ROS singlet oxygen ( 1 O 2 ) is unique in that it can signal to initiate cellular degradation including the selective degradation of damaged chloroplasts. This chloroplast quality control pathway can be monitored in the Arabidopsis thaliana mutant plastid ferrochelatase two ( fc2 ) that conditionally accumulates chloroplast 1 O 2 under diurnal light cycling conditions leading to rapid chloroplast degradation and eventual cell death. The cellular machinery involved in such degradation, however, remains unknown. Recently, it was demonstrated that whole damaged chloroplasts can be transported to the central vacuole via a process requiring autophagosomes and core components of the autophagy machinery. The relationship between this process, referred to as chlorophagy, and the degradation of 1 O 2 -stressed chloroplasts and cells has remained unexplored. Results To further understand 1 O 2 -induced cellular degradation and determine what role autophagy may play, the expression of autophagy-related genes was monitored in 1 O 2 -stressed fc2 seedlings and found to be induced. Although autophagosomes were present in fc2 cells, they did not associate with chloroplasts during 1 O 2 stress. Mutations affecting the core autophagy machinery ( atg5 , atg7 , and atg10 ) were unable to suppress 1 O 2 -induced cell death or chloroplast protrusion into the central vacuole, suggesting autophagosome formation is dispensable for such 1 O 2 –mediated cellular degradation. However, both atg5 and atg7 led to specific defects in chloroplast ultrastructure and photosynthetic efficiencies, suggesting core autophagy machinery is involved in protecting chloroplasts from photo-oxidative damage. Finally, genes predicted to be involved in microautophagy were shown to be induced in stressed fc2 seedlings, indicating a possible role for an alternate form of autophagy in the dismantling of 1 O 2 -damaged chloroplasts. Conclusions Our results support the hypothesis that 1 O 2 -dependent cell death is independent from autophagosome formation, canonical autophagy, and chlorophagy. Furthermore, autophagosome-independent microautophagy may be involved in degrading 1 O 2 -damaged chloroplasts. At the same time, canonical autophagy may still play a role in protecting chloroplasts from 1 O 2 -induced photo-oxidative stress. Together, this suggests chloroplast function and degradation is a complex process utilizing multiple autophagy and degradation machineries, possibly depending on the type of stress or damage incurred.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2025

Dataset for Leveraging CryoEM and AI-Driven Morphological Feature Analysis for Insights on Bacterial Structures

This repository hosts an AI-assisted image segmentation and analysis pipeline for Pantoea sp. YR343 cryo-electron microscopy (cryoEM) datasets. The workflow automates membrane thickness measurements, flagella detection, and field-of-view (FOV) screening from low-dose, high-resolution cryoEM micrographs eliminating the need for slow manual annotation. By integrating deep-learning based segmentation (YOLOv11) with quantitative post-processing, this toolkit provides a scalable and reproducible way to study bacterial morphology under hydrated, near-native conditions. The GitHub repository for AI-based tools for cryoEM bacteria ultrastructures can be found here: https://github.com/Sireesiru/Cryo-EM-Ultrastructures/tree/main

60 APPLIED LIFE SCIENCES↗
DOE OSTI2022

Wood combustion nanoparticles emitted by conventional and advanced technology cordwood boilers, and their interactions in vitro with human lung epithelial monolayers

Biomass-burning boilers and stoves are widely used in many parts of the world, producing combustion emissions linked with health risks. Here, combustion emission nanoparticles (NPs) were collected from four representative wood burning boilers using oak cordwood at specific times in the burn cycle. The morphology and composition of the NPs was characterized using transmission electron microscopy and energy dispersive X-ray analysis. To determine the degree of NP cytotoxicity with human lung tissue, the combustion NPs were introduced to incubated lung bronchial epithelial monolayers (NCI-H292) in vitro at doses of 0.1×10 -6 and 3.0×10 -6 kg/L for 2 and 4 h. Histochemical analysis showed that cell death increased by a factor of 3.5 for both doses after 4 h when compared to the control. Ultrapure NPs prepared by wet chemical methods were also introduced to the epithelial lung cells for similar doses and exposure times and the cultures exhibited significantly reduced mortality. Electron microscopy was used to study the mechanism of cell mortality for the synthesized and combustion-based NPs by examining how the NP byproducts interacted with individual cell organelles. It was found that cell survival was strongly correlated with the absence of contaminants (salts, heavy metals, poly aromatic hydrocarbons) associated with the NPs entering the cells. Synthesized NPs consisting of pure carbon were relatively well tolerated and could be excreted without damaging the cell ultrastructure. Thus, careful removal of extraneous contaminants by controlling the burn cycle with a catalyst is essential to minimize the health and environmental effects of wood biofuel combustion. In better words, optimized advanced technology wood-burning boilers and stoves can provide a CO 2 -neutral energy source and significantly contribute to a future where fossil fuels have a reduced role.

32 ENERGY CONSERVATION, CONSUMPTION, AND UTILIZATI↗
DOE OSTI2023

Imaging Intact Filamentous Fungi from Spore to Hyphal Tip on the Nanoscale

Previously, the Pacific Northwest National Laboratory was limited by a 3-order of magnitude gap in resolution for direct 2-D and 3-D imaging of chemical, biological, energy and materials science systems. Our imaging instrumentation could directly visualize 3-D ultrastructure without labeling at resolutions less than 10-nanometers or greater than 10-micrometers. To address this gap, we procured and commissioned a Sigray NanoFast Bio-Lambda laboratory-based x-ray nanotomography system. This equipment provides the capability to image through tens of micrometers of organic materials at down to 35-nanometer resolution to bridge the nanoscale to the mesoscale for biological systems, organic polymers, environmental and particulate samples.

47 OTHER INSTRUMENTATION↗
DOE OSTI2025

The molecular architecture distinctions between compression, opposite and normal wood of Pinus radiata

In gymnosperms compression wood is a specialised type of structural cell wall formed in response to biomechanical stresses. The differences in terms of gross structure, ultrastructure and chemistry are well-known. However, the differences between compression wood, normal wood, and opposite wood regarding the arrangements and interactions of the various polymers and water within their cell walls still needs to be established. The analysis of 13 C-labelled Pinus radiata by solid-state NMR spectroscopy and other complementary techniques revealed several new aspects of compression and opposite wood molecular architecture. Compared to normal wood, compression wood has a lower water content, its overall nanoporosity is reduced, and the water and matrix polymers have a lower molecular mobility. Galactan, which is a specific marker of compression wood, is broadly distributed within the cell wall, disordered, and not aligned with cellulose, and is found to be in close proximity to xylan. Dehydroabietic acid (a resin acid) is immobilised and close to the H-lignin only in compression wood. Although the overall molecular mobility of normal wood and opposite wood are similar, opposite wood has different arabinose conformations, a large increase in the amount of chain ends, contains significantly more galactan and has additional unassigned mobile components highlighting the different molecular arrangement of cell wall polymers in opposite and normal wood.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2023

Disruption of Z-Disc Function Promotes Mechanical Dysfunction in Human Myocardium: Evidence for a Dual Myofilament Modulatory Role by Alpha-Actinin 2

The ACTN2 gene encodes α-actinin 2, located in the Z-disc of the sarcomeres in striated muscle. In this study, we sought to investigate the effects of an ACTN2 missense variant of unknown significance (p.A868T) on cardiac muscle structure and function. Left ventricular free wall samples were obtained at the time of cardiac transplantation from a heart failure patient with the ACTN2 A868T heterozygous variant. This variant is in the EF 3–4 domain known to interact with titin and α-actinin. At the ultrastructural level, ACTN2 A868T cardiac samples presented small structural changes in cardiomyocytes when compared to healthy donor samples. However, contractile mechanics of permeabilized ACTN2 A868T variant cardiac tissue displayed higher myofilament Ca 2+ sensitivity of isometric force, reduced sinusoidal stiffness, and faster rates of tension redevelopment at all Ca 2+ levels. Small-angle X-ray diffraction indicated increased separation between thick and thin filaments, possibly contributing to changes in muscle kinetics. Molecular dynamics simulations indicated that while the mutation does not significantly impact the structure of α-actinin on its own, it likely alters the conformation associated with titin binding. Our results can be explained by two Z-disc mediated communication pathways: one pathway that involves α-actinin’s interaction with actin, affecting thin filament regulation, and the other pathway that involves α-actinin’s interaction with titin, affecting thick filament activation. This work establishes the role of α-actinin 2 in modulating cross-bridge kinetics and force development in the human myocardium as well as how it can be involved in the development of cardiac disease.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2022

Montage electron tomography of vitrified specimens

Cryo-electron tomography provides detailed views of macromolecules in situ. However, imaging a large field of view to provide more cellular context requires reducing magnification during data collection, which in turn restricts the resolution. To circumvent this trade-off between field of view and resolution, we have developed a montage data collection scheme that uniformly distributes the dose throughout the specimen. In this approach, sets of slightly overlapping circular tiles are collected at high magnification and stitched to form a composite projection image at each tilt angle. These montage tilt-series are then reconstructed into massive tomograms with a small pixel size but a large field of view. For proof-of-principle, we applied this method to the thin edge of HeLa cells. Thon rings to better than 10 Å were detected in the montaged tilt-series, and diverse cellular features were observed in the resulting tomograms. These results indicate that the additional dose required by this technique is not prohibitive to performing structural analysis to intermediate resolution across a large field of view. We anticipate that montage tomography will prove particularly useful for lamellae, increase the likelihood of imaging rare cellular events, and facilitate visual proteomics.

46 INSTRUMENTATION RELATED TO NUCLEAR SCIENCE AND ↗