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Search indexed NASA NTRS and DOE OSTI research on propulsion, heat transfer, battery materials and energy systems. Follow report and document links to the original sources.

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At least 1,531 records · Page 85
All sourcesNASA NTRSDOE OSTI
DOE OSTI2018

Autophagy induced by type III secretion system toxins enhances clearance of Pseudomonas aeruginosa from human corneal epithelial cells

Highlights: • Ocular P. aeruginosa isolates induce autophagy in human corneal epithelial cells. • T3SS mutants were defective in inducing autophagy and becn1 expression. • T3SS (−)ve strains were less sensitive to external autophagy modulators. • Pro-autophagic role of T3SS regulates intracellular survival of P. aeruginosa. Corneal ulcers caused by Pseudomonas aeruginosa may lead to severe visual disability due to impaired bacterial clearance from corneal tissues. Our purpose was to study the role of autophagy in the intracellular clearance of P. aeruginosa from human corneal epithelial cells (HCET) and its regulation by the bacterial type III secretion system (T3SS) toxins. Nine different corneal ulcer isolates of P. aeruginosa, PAO1 and T3SS mutants of PAO1 were used to infect HCET cells. Induction of autophagy (Immunofluorescence and Western blot) and pro-inflammatory gene expression (real time PCR) by P. aeruginosa and the role of autophagy in intracellular bacterial clearance were studied in the context of T3SS genotypes. The clinical isolates and PAO1 induced autophagy irrespective of the T3SS genotype, whereas the T3SS mutants were relatively defective in inducing autophagy and becn1 gene expression. External induction of autophagy significantly reduced the intracellular load of P. aeruginosa strains that were associated with worst clinical outcomes. The T3SS negative isolate and PAO1ΔexoST were less sensitive to pharmacological modulation of autophagy and had relatively higher replication potential, suggesting a possible mechanism of bacterial survival in the absence of T3SS toxins. Overall, our results highlight a selective role for autophagy in bacterial clearance from corneal epithelial cells and emphasize the pro-autophagic role of bacterial toxins in the context of corneal ulcers.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

GALNT3 inhibits NF-κB signaling during influenza A virus infection

Highlights: • A direct role of GANLT3 in regulating host responses during IAV infection. • First report that GALNT3 inhibits NF-κB signaling by preventing the translocation of p-P65 into nucleus. • Reveal the direct involvement of GALNT3 during viral infections. Protein glycosylation, attaching glycans covalently onto amino acid side chains of protein by various glycosyltransferase, is the most common post-translational modification. The UDP-GalNAc transferase 3 (GANLT3), encoded by Galnt3, transfers N-acetyl-d-galactosamine to hydroxyl groups of the side chains of Ser/Thr residues, initiating mucin type O-glycosylation of proteins. Most researches as yet focus on the involvement and abnormal expression of GALNT3 in various tumors. In this study, we found that GALNT3 was significantly decreased in the lungs after influenza A virus (IAV) infection in mice. Overexpression of GALNT3 in cell lines markedly inhibited IAV replication. Further experiments demonstrated that GALNT3 inhibited NF-κB signaling by preventing the translocation of phosphorylated P65 into nucleus. Therefore, our results reveal an important role of GALNT3 in regulating host responses during IAV infection, indicating the broad functions of the GALNT family, and the direct involvement of GALNTs during viral infections.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

Heat shock protein 70 and heat shock protein 90 synergistically increase hepatitis B viral capsid assembly

Highlights: • Heat shock protein 70 (Hsp70) interacts with Cp149 dimer. • Hsp70 synergistically increases formation of HBV capsid with Hsp90. • Inhibition of Hsp70 reduces HBV biogenesis through suppression of HBV capsid assembly. Hepatitis B virus (HBV) infection can cause chronic liver diseases, cirrhosis, and hepatocellular carcinoma (HCC). Heat shock proteins (Hsps) are important factors in the formation of the HBV capsid and in genome replication during the viral life cycle. Hsp90 is known to promote capsid assembly. However, the functional roles of Hsp70 in HBV capsid assembly with Hsp90 have not been studied so far. Using microscale thermophoresis analyses and in vitro nucleocapsid formation assays, we found that Hsp70 bound to a HBV core protein dimer and facilitated HBV capsid assembly. Inhibition of Hsp70 by methylene blue (MB) led to a decrease in capsid assembly. Moreover, Hsp70 inhibition reduced intracellular capsid formation and HBV virus particle number in HepG2.2.15 cells. Furthermore, we examined synergism between Hsp70 and Hsp90 on HBV capsid formation in vitro. Our results clarify the role of Hsp70 in HBV capsid formation via an interaction with core dimers and in synergistically promoting capsid assembly with Hsp90.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

Daunorubicin, a topoisomerase II poison, suppresses viral production of hepatitis B virus by inducing cGAS-dependent innate immune response

Hepatitis B virus (HBV) causes hepatic diseases such as chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma. These diseases are closely associated with persistent HBV infection. To prevent the progression of hepatic diseases, it is thus important to suppress persistent HBV infection. Daunorubicin (DNR), a topoisomerase II (Top II) poison, is a clinically used anticancer agent with a wide spectrum of activity against malignancies. DNR was recently reported to cause DNA damage-dependent interferon (IFN)-β induction through exogenous cyclic GMP-AMP synthetase (cGAS) and subsequently to suppress Ebola virus replication. In the present study, we demonstrated that DNR caused the inhibition of cell proliferation, but not cell death, through the DNA damage response in immortalized human hepatocyte NKNT-3/NTCP cells. Interestingly, DNR triggered the endogenous cGAS-dependent innate immune response and subsequently suppressed viral production of HBV in NKNT-3/NTCP cells. Top II poisons may be anti-HBV drug candidates.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

Both the N- and C- terminal regions of the Chlamydial inclusion protein D (IncD) are required for interaction with the pleckstrin homology domain of the ceramide transport protein CERT

Highlights: • Both the N- and C-termini of IncD are required for the CERT-IncD interaction. • IncD residues essential for the binding to CERT are conserved among Chlamydiaces. • IncD forms multiple oligomers composed of a dimeric unit. Chlamydia trachomatis is an obligate intracellular bacterium that replicates within a membranous compartment, the inclusion, in host cells. Its intracellular life cycle requires host sphingolipids, which are in part acquired through the ER-Golgi localized ceramide transport protein (CERT). The Chlamydia-encoded inclusion membrane protein IncD is composed of two closely linked long hydrophobic domains with their N- and C-termini exposed to the host cytosol. IncD binds directly to the pleckstrin homology (PH) domain of CERT, likely redirecting ceramide to the inclusion. The precise regions of IncD required for this interaction have not been delineated. Using co-transfection studies together with phylogenetic studies, we demonstrate that both the IncD N- and C-terminal regions are required for binding to the CERT PH domain and define key interaction residues. Native gel electrophoresis analysis demonstrates that the transmembrane region of IncD forms SDS-resistant but dithiothreitol-sensitive homodimers, which in turn can assemble to form higher order oligomers through additional N- and C-terminal domain contacts. IncD oligomerization may facilitate high affinity binding to CERT, allowing C. trachomatis to efficiently redirect host ceramide to the inclusion.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

Effects of molecular crowding on a bimolecular group I ribozyme and its derivative that self-assembles to form ribozyme oligomers

Highlights: • PEG rescued mutations in the bimolecular group I ribozyme more effectively than those in the oligomeric form. In the RNA world, enrichment of self-replicating RNAs would have been beneficial to their survival, amplification, and evolution. Self-assembly of RNAs may be a strategy by which they enrich themselves. We examined the effects of molecular crowding on the activity of a bimolecular group I ribozyme and its derivative that self-assembles to form ribozyme oligomers. In a comparative activity assay using PEG as a molecular crowder, PEG rescued mutations in the parent bimolecular ribozyme more effectively than those in the oligomeric form.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2014

The effect of retinal pigment epithelial cell patch size on growth factor expression

The spatial organization of retinal pigment epithelial (RPE) cells grown in culture was controlled using micropatterning techniques in order to examine the effect of patch size on cell health and differentiation. Understanding this effect is a critical step in the development of multiplexed high throughput fluidic assays and provides a model for replicating disease states associated with the deterioration of retinal tissue during age-related macular degeneration (AMD). Microcontact printing of fibronectin on polystyrene and glass substrates was used to promote cell attachment, forming RPE patches of controlled size and shape. These colonies mimic the effect of atrophy and loss-of-function that occurs in the retina during degenerative diseases such as AMD. After 72 hours of cell growth, levels of vascular endothelial growth factor (VEGF), an important biomarker of AMD, were measured. Cells were counted and morphological indicators of cell viability and tight junction formation were assessed via fluorescence microscopy. As a result, up to a twofold increase of VEGF expression per cell was measured as colony size decreased, suggesting that the local microenvironment of, and connections between, RPE cells influences growth factor expression leading to the initiation and progression of diseases such as AMD.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2021

Dissecting the Shared Genetic Architecture of Suicide Attempt, Psychiatric Disorders, and Known Risk Factors

Suicide is a leading cause of death worldwide, and non-fatal suicide attempts, which occur far more frequently, are a major source of disability and social and economic burden. Both have substantial genetic etiology, which is partially shared and partially distinct from that of related psychiatric disorders. Methods: We conducted a genome-wide association study (GWAS) of 29,782 suicide attempt (SA) cases and 519,961 controls in the International Suicide Genetics Consortium. The GWAS of SA was conditioned on psychiatric disorders using GWAS summary statistics via mtCOJO, to remove genetic effects on SA mediated by psychiatric disorders. We investigated the shared and divergent genetic architectures of SA, psychiatric disorders and other known risk factors. Results: Two loci reached genome-wide significance for SA: the major histocompatibility complex and an intergenic locus on chromosome 7, which remained associated with SA after conditioning on psychiatric disorders and replicated in an independent cohort from the Million Veteran Program. This locus has been implicated in risk-taking, smoking, and insomnia. SA showed strong genetic correlation with psychiatric disorders, particularly major depression, and also with smoking, pain, risk-taking, sleep disturbances, lower educational attainment, reproductive traits, lower socioeconomic status and poorer general health. After conditioning on psychiatric disorders, the genetic correlations between SA and psychiatric disorders decreased, whereas those with non-psychiatric traits remained largely unchanged. Conclusions: Our results identify a risk locus that contributes more strongly to SA than other phenotypes and suggest a shared underlying biology between SA and known risk factors that is not mediated by psychiatric disorders.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2025

Opportunities in multiscale modeling of mosquito-borne flaviviruses

Mosquito-borne flaviviruses, such as Zika, dengue, West Nile, and yellow fever virus, represent a growing public health concern due to their widespread distribution and the severe diseases they cause. These viruses are difficult to control as climate change and urbanization help mosquitoes expand into new areas, increasing the risk of outbreaks. Mathematical models play a key role in understanding their spread, providing insights at every level—from how the virus multiplies inside cells to how it circulates through entire populations. This review examines various approaches used in modeling arboviruses, including microscale models that focus on cellular and molecular dynamics, mesoscale models that address within-host processes, and macroscale models that capture population-level transmission. We briefly summarize the methodology used for models at each scale, which primarily consists of sets of differential equations with parameters that represent physical rates of change for different subprocesses. We particularly highlight how temperature affects virus transmission, which is key to understanding the impact of climate change. We also show how multiscale models can connect viral replication, immune response, and the spread of infection at a larger scale. This is essential for developing better vaccines and treatments, evaluating disease control measures, predicting the impact of climate change, and improving public health responses to outbreaks.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2021

Assessment of a tomography-informed polyhedral discrete element modelling approach for complex-shaped granular woody biomass in stress consolidation

The design of handling equipment for granular biomass primarily requires experiments. Discrete element models (DEM) can provide designers with detailed insight into the behaviour of granular materials. However, granular biomass comprising complex-shaped particles is difficult to model with DEM. A tomography-informed DEM approach and an exhaustive assessment of the ability of the approach to predict the bulk behaviour of milled pines using experimental data is presented. Nano-CT scan was conducted to obtain 3D particle surface geometries as the basis for particle shape approximation by a polyhedral model and a sphero-polyhedral model. These models were applied in the simulation of a compressibility test. Our parametric study showed that particle Young's modulus and restitution coefficient are the two main properties influencing the simulated bulk behaviour of the DEM particles and that the level of approximating DEM particle shape for real particles is critical for accurately replicating the bulk behaviour of milled pines. The polyhedral model demonstrated better suitability than its sphero-polyhedral counterpart for modelling pine particles. The polyhedral model calibrated in a compressibility test was then applied in the simulations of a friction test without additional parameter tuning. Interlocking was dominant in the shear of bulk pine particles. Remarkably, the polyhedral model predicted the frictional behaviour of the pine particles when compared to the experimental results. The limitations of the model, as well as possible ways for enhancement, are discussed. This work provided novel insights into the suitability of complex-shaped DEM models for granular woody biomass.

Biomass flow↗
DOE OSTI2020

A dynamic thermal algal growth model for pilot-scale open-channel raceways

Here this study describes the makeup of and results from a simulation consisting of a lumped thermal model integrated with a dynamic algae growth model to simulate the microalgae productivity of an open-channel raceway cultivation system. The thermal model considers the dynamic effects of weather, light absorption, convective heat transfer, radiation heat transfer, conductive heat transfer, thermal capacitance, and water control strategies. The dynamic algae growth model solves a set of ordinary differential equations consisting of growth functions dependent on incident radiation, temperature, nutrient availability, basal metabolism, and losses due to dark- and photo-respiration. Relative errors in the predicted ash-free dry weight of Nannochloropsis oceanica are 12.5%, -6.1%, and 4.4% for three separate replicates of cultivation cycles (~4.2 m 2 ) performed at AzCATI during the ATP 3 Unified Field Studies in Fall, Spring, and Summer. This research demonstrates that thermal modeling is an essential contributor to the validation of microalgae growth models.

09 BIOMASS FUELS↗
DOE OSTI2019

Proteomic studies of bone and skeletal health outcomes

Proteins are an essential part of essentially all biological processes, and there is enormous variation in protein forms and concentrations that is not reflected in DNA or RNA. Recently there have been rapid advances in the ability to measure protein sequence, modification and concentration, particularly with methods based in mass spectrometry. Global measures of proteins in tissues or in the circulation provide a broad assessment of the proteome that can be extremely useful for discovery, and targeted proteomic measures can yield specific and sensitive assessments of specific peptides and proteins. While most proteomic measures are directed at the detection of consensus peptide sequences, mass spectrometry based proteomic methods also allow a detailed examination of the peptide sequence differences that result from genetic variants and that may have important effects on protein function. In evaluating proteomic data, a number of analytical considerations are important, including an understanding of missing data, the challenge of multiple testing and replication, and the use of rapidly evolving methods in systems biology. While proteomics has not yet had a major impact in skeletal research, interesting recent research has used these approaches in the study of bone cell biology and the discovery of biomarkers of skeletal disorders. Proteomics can be expected to have an increasing influence in the study of bone biology and pathophysiology

Proteomic, Bone↗
DOE OSTI2023

Effect of constitutive law on the erythrocyte membrane response to large strains

Three constitutive laws, that is the Skalak, neo-Hookean and Yeoh laws, commonly employed for describing the erythrocyte membrane mechanics are theoretically analyzed and numerically investigated to assess their accuracy for capturing erythrocyte deformation characteristics and morphology. In this work, particular emphasis is given to the nonlinear deformation regime, where it is known that the discrepancies between constitutive laws are most prominent. Hence, the experiments of optical tweezers and micropipette aspiration are considered here, for which relationships between the individual shear elastic moduli of the constitutive laws can also be established through analysis of the tension-deformation relationship. All constitutive laws were found to adequately predict the axial and transverse deformations of a red blood cell subjected to stretching with optical tweezers for a constant shear elastic modulus value. As opposed to Skalak law, the neo-Hookean and Yeoh laws replicated the erythrocyte membrane folding, that has been experimentally observed, with the trade-off of sustaining significant area variations. For the micropipette aspiration, the suction pressure-aspiration length relationship could be excellently predicted for a fixed shear elastic modulus value only when Yeoh law was considered. Importantly, the neo-Hookean and Yeoh laws reproduced the membrane wrinkling at suction pressures close to those experimentally measured. None of the constitutive laws suffered from membrane area compressibility in the micropipette aspiration case.

97 MATHEMATICS AND COMPUTING↗
DOE OSTI2023

The role of oak species in long-term soil P loss in a humid river bottomland

There is a gap in our understanding of if and how bottomland forest type will affect long-term nutrient cycling and loss. This study aims to determine how different forests affect soil hydrologic variability and whole-soil P loss in a humid-subtropical setting. Here, we used replicate-sampling and measured soil physical, chemical, and mineralogical properties at 12 sites in two forest ecosystems, post oak (Quercus stellata) and cherry bark oak (Quercus pagoda) in Clarks River National Wildlife Refuge in Western Kentucky. We hypothesize that wetting–drying events in redox soils of forested bottomlands can cause positive feedback in whole-soil P loss. Trees with greater P demand (e.g., post oak) take up more water creating more frequent and pronounced episodes in swelling and shrinking of expandable clays. Repeated swelling and shrinking of clays occlude the surface of Fe-Mn oxides from further adsorption of P in acidic soil. This can lead to greater loss or plant uptake of available P. Our results show (i) a significant difference in mean whole-soil P loss between the oak species with more loss in soils underlying the post oak forest, and (ii) a difference in the total P found in the sap- and heartwood of the two oak species. Soil analysis reveals that the clay mineralogy of the post and cherry bark oak sites are similar, and thus, may only play a minor role in governing the whole-soil P loss difference. However, the leaf data analysis suggests that the post oak site could be P and nitrogen-limited, while the cherry bark is only nitrogen limited. Our study shows that differences in the oak forest ecosystem may affect the long-term balance in water and nutrient uptake and may alter the redistribution of nutrients in the canopy and the underlying soils.

58 GEOSCIENCES↗
DOE OSTI2021

Circulating SARS-CoV-2 spike N439K variants maintain fitness while evading antibody-mediated immunity

SARS-CoV-2 can mutate and evade immunity, with consequences for efficacy of emerging vaccines and antibody therapeutics. Here, we demonstrate that the immunodominant SARS-CoV-2 spike (S) receptor binding motif (RBM) is a highly variable region of S and provide epidemiological, clinical, and molecular characterization of a prevalent, sentinel RBM mutation, N439K. We demonstrate N439K S protein has enhanced binding affinity to the hACE2 receptor, and N439K viruses have similar in vitro replication fitness and cause infections with similar clinical outcomes as compared to wild type. We show the N439K mutation confers resistance against several neutralizing monoclonal antibodies, including one authorized for emergency use by the US Food and Drug Administration (FDA), and reduces the activity of some polyclonal sera from persons recovered from infection. Immune evasion mutations that maintain virulence and fitness such as N439K can emerge within SARS-CoV-2 S, highlighting the need for ongoing molecular surveillance to guide development and usage of vaccines and therapeutics.

60 APPLIED LIFE SCIENCES↗