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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 217 records · Page 12
All sourcesNASA NTRSDOE OSTI
DOE OSTI2023

Comparison of the Antiviral Activity of Remdesivir, Chloroquine, and Interferon-β as Single or Dual Agents Against the Human Beta-Coronavirus OC43

The human beta-coronavirus strain, OC43, provides a useful model for testing the antiviral activity of various agents. We compared the activity of several antiviral drugs against OC43, including remdesivir, chloroquine, interferon (IFN)-β, IFN-λ1, and IFN-λ4, in two distinct cell types: human colorectal carcinoma cell line (HCT-8 cells) and normal human bronchial epithelial (NHBE) cells. We also tested whether these agents mediate additive, synergistic, or antagonistic activity against OC43 infection when used in combination. When used as single agents, remdesivir exhibited stronger antiviral activity than chloroquine, and IFN-β exhibited stronger activity than IFN-λ1 or IFN-λ4 against OC43 in both HCT-8 and NHBE cells. Anakinra (IL-1 inhibitor) and tocilizumab (IL-6 inhibitor) did not mediate any antiviral activity. The combination of IFN-β plus chloroquine or remdesivir resulted in higher synergy scores and higher expression of IFN-stimulated genes than did IFN-β alone. In contrast, the combination of remdesivir plus chloroquine resulted in an antagonistic interaction in NHBE cells. Our findings indicate that the combined use of IFN-β plus remdesivir or chloroquine induces maximal antiviral activity against human coronavirus strain OC43 in primary human respiratory epithelial cells. Furthermore, our experimental OC43 virus infection model provides an excellent method for evaluating the biological activity of antiviral drugs.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2022

Mushroom body input connections form independently of sensory activity in Drosophila melanogaster

Associative brain centers, such as the insect mushroom body, need to represent sensory information in an efficient manner. In Drosophila melanogaster, the Kenyon cells of the mushroom body integrate inputs from a random set of olfactory projection neurons, but some projection neurons—namely those activated by a few ethologically meaningful odors—connect to Kenyon cells more frequently than others. This biased and random connectivity pattern is conceivably advantageous, as it enables the mushroom body to represent a large number of odors as unique activity patterns while prioritizing the representation of a few specific odors. How this connectivity pattern is established remains largely unknown. Here, we test whether the mechanisms patterning the connections between Kenyon cells and projection neurons depend on sensory activity or whether they are hardwired. We mapped a large number of mushroom body input connections in partially anosmic flies—flies lacking the obligate odorant co-receptor Orco—and in wild-type flies. Statistical analyses of these datasets reveal that the random and biased connectivity pattern observed between Kenyon cells and projection neurons forms normally in the absence of most olfactory sensory activity. Finally, this finding supports the idea that even comparatively subtle, population-level patterns of neuronal connectivity can be encoded by fixed genetic programs and are likely to be the result of evolved prioritization of ecologically and ethologically salient stimuli.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2025

Data for "Viral-mediated Delivery of Morphogenic Regulators Enables Leaf Transformation in Sorghum bicolor (L.)"

Recent advancements in monocot transformation, using leaf tissue as explant material, have expanded the number of grass species capable of transgenesis. However, the complexity of vectors and reliance on inducible excision of essential morphogenic regulators have so far limited widespread application. Plant RNA viruses, such as Foxtail Mosaic Virus (FoMV), present a unique opportunity to express morphogenic regulator genes, such as Babyboom ( Bbm ), Wuschel2 ( Wus2 ), Wuschel-like homeobox protein 2a ( Wox2a ) and the GROWTH-REGULATING FACTOR 4 (GRF4) GRF-INTERACTING FACTOR 1 (GIF1) fusion protein transiently in leaf explant tissues. Furthermore, altruistic delivery of conventional and viral vectors could provide opportunities to simplify vectors used for leaf transformation—facilitating vector optimization and reducing reliance on morphogenic regulator gene integration. In this study, both viral and conventional T-DNA vectors were tested for their ability to promote the formation of embryonic calli, a critical step in leaf transformation protocols, using Sorghum bicolor leaf explants. Although conventional leaf transformation vectors yielded viable embryonic calli (43.2 ± 2.9%: GRF4-GIF1, 50.2 ± 3%: Bbm/Wus2), altruistic conventional vectors employing the GRF4-GIF1 morphogenic regulator resulted in improved efficiencies (61.3 ± 4.7%). Altruistic delivery was further enhanced with the use of viral vectors employing both GRF4-GIF1 and Bbm/Wus2 regulators, resulting in 75.1 ± 2.3% and 79.2 ± 2.5% embryonic calli formation, respectively. Embryonic calli generated from both conventional and viral vectors produced shoots expressing fluorescent reporters, which were confirmed using molecular analysis. This work provides an important proof-of-concept for the use of both altruistic vectors and viral-expressed morphogenic regulators for improving plant transformation.

gene editing↗
DOE OSTI2024

Formation and retrieval of cell assemblies in a biologically realistic spiking neural network model of area CA3 in the mouse hippocampus

The hippocampal formation is critical for episodic memory, with area Cornu Ammonis 3 (CA3) a necessary substrate for auto-associative pattern completion. Recent theoretical and experimental evidence suggests that the formation and retrieval of cell assemblies enable these functions. Yet, how cell assemblies are formed and retrieved in a full-scale spiking neural network (SNN) of CA3 that incorporates the observed diversity of neurons and connections within this circuit is not well understood. Here, we demonstrate that a data-driven SNN model quantitatively reflecting the neuron type-specific population sizes, intrinsic electrophysiology, connectivity statistics, synaptic signaling, and long-term plasticity of the mouse CA3 is capable of robust auto-association and pattern completion via cell assemblies. Our results show that a broad range of assembly sizes could successfully and systematically retrieve patterns from heavily incomplete or corrupted cues after a limited number of presentations. Furthermore, performance was robust with respect to partial overlap of assemblies through shared cells, substantially enhancing memory capacity. These novel findings provide computational evidence that the specific biological properties of the CA3 circuit produce an effective neural substrate for associative learning in the mammalian brain.

hetero-association↗
DOE OSTI2024

Familial Alzheimer mutations stabilize synaptotoxic γ-secretase-substrate complexes

Mutations that cause familial Alzheimer’s disease (FAD) are found in amyloid precursor protein (APP) and presenilin, the catalytic component of γ-secretase, that together produce amyloid β-peptide (Aβ). Nevertheless, whether Aβ is the primary disease driver remains controversial. We report here that FAD mutations disrupt initial proteolytic events in the multistep processing of APP substrate C99 by γ-secretase. Cryoelectron microscopy reveals that a substrate mimetic traps γ-secretase during the transition state, and this structure aligns with activated enzyme-substrate complex captured by molecular dynamics simulations. In silico simulations and in cellulo fluorescence microscopy support stabilization of enzyme-substrate complexes by FAD mutations. Neuronal expression of C99 and/or presenilin-1 in Caenorhabditis elegans leads to synaptic loss only with FAD-mutant transgenes. Designed mutations that stabilize the enzyme-substrate complex and block Aβ production likewise led to synaptic loss. Collectively, these findings implicate the stalled process—not the products—of γ-secretase cleavage of substrates in FAD pathogenesis.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2021

Buffer concentration dramatically affects the stability of S-nitrosothiols in aqueous solutions

S-nitrosothiols (RSNOs) are an important group of nitric oxide (NO)-donating compounds with low toxicity and wide biomedical applications. In this paper, we, for the first time, demonstrate that the concentration of buffer remarkably affects the stability of RSNOs including naturally occurring S-nitrosoglutathione (GSNO) and synthetic S-nitroso-N-acetylpenicillamine (SNAP). For a solution with a high concentration of GSNO (e.g., 50 mM) and an initial near-neutral pH, the optimal buffer concentration is close to the GSNO concentration under our experimental conditions. A lower buffer concentration does not have adequate buffer capacity to resist the pH drop caused by GSNO decomposition. The decreased solution pH further accelerates GSNO decomposition because GSNO is most stable at near-neutral pH according to our density functional theory (DFT) calculations. A higher-than-optimal buffer concentration also reduces the GSNO stability because buffer ingredients including phosphate, Tris base, and HEPES consume NO/N 2 O 3 . In contrast to GSNO, the highest SNAP stability is obtained when the starting solution at a neutral pH does not contain buffer species, and the stability decreases as the buffer concentration increases. Furthermore, this is because SNAP is more stable at mildly acidic pH and the SNAP decomposition-induced pH drop stabilizes the donor. When the RSNO concentration is low (e.g., 1 mM), the buffer concentration also matters because any excess buffer accelerates the donor decomposition. Since the effect of buffer concentration was previously overlooked and suboptimal buffer concentrations were often used, this paper will aid in the formulation of RSNO solutions to obtain the maximum stability for prolonged storage and sustained NO release.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2023

Plants use molecular mechanisms mediated by biomolecular condensates to integrate environmental cues with development

This review highlights recent literature on biomolecular condensates in plant development and discusses challenges for fully dissecting their functional roles. Plant developmental biology has been inundated with descriptive examples of biomolecular condensate formation, but it is only recently that mechanistic understanding has been forthcoming. Here, we discuss recent examples of potential roles biomolecular condensates play at different stages of the plant life cycle. We group these examples based on putative molecular functions, including sequestering interacting components, enhancing dwell time, and interacting with cytoplasmic biophysical properties in response to environmental change. We explore how these mechanisms could modulate plant development in response to environmental inputs and discuss challenges and opportunities for further research into deciphering molecular mechanisms to better understand the diverse roles that biomolecular condensates exert on life.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2022

Burning questions for a warming and changing world: 15 unknowns in plant abiotic stress

Abstract We present unresolved questions in plant abiotic stress biology as posed by 15 research groups with expertise spanning eco-physiology to cell and molecular biology. Common themes of these questions include the need to better understand how plants detect water availability, temperature, salinity, and rising carbon dioxide (CO2) levels; how environmental signals interface with endogenous signaling and development (e.g. circadian clock and flowering time); and how this integrated signaling controls downstream responses (e.g. stomatal regulation, proline metabolism, and growth versus defense balance). The plasma membrane comes up frequently as a site of key signaling and transport events (e.g. mechanosensing and lipid-derived signaling, aquaporins). Adaptation to water extremes and rising CO2 affects hydraulic architecture and transpiration, as well as root and shoot growth and morphology, in ways not fully understood. Environmental adaptation involves tradeoffs that limit ecological distribution and crop resilience in the face of changing and increasingly unpredictable environments. Exploration of plant diversity within and among species can help us know which of these tradeoffs represent fundamental limits and which ones can be circumvented by bringing new trait combinations together. Better defining what constitutes beneficial stress resistance in different contexts and making connections between genes and phenotypes, and between laboratory and field observations, are overarching challenges.

Biochemistry & Molecular Biology↗
DOE OSTI2024

Rapid and efficient in planta genome editing in sorghum using foxtail mosaic virus‐mediated sgRNA delivery

SUMMARY The requirement of in vitro tissue culture for the delivery of gene editing reagents limits the application of gene editing to commercially relevant varieties of many crop species. To overcome this bottleneck, plant RNA viruses have been deployed as versatile tools for in planta delivery of recombinant RNA. Viral delivery of single‐guide RNAs (sgRNAs) to transgenic plants that stably express CRISPR‐associated (Cas) endonuclease has been successfully used for targeted mutagenesis in several dicotyledonous and few monocotyledonous plants. Progress with this approach in monocotyledonous plants is limited so far by the availability of effective viral vectors. We engineered a set of foxtail mosaic virus (FoMV) and barley stripe mosaic virus (BSMV) vectors to deliver the fluorescent protein AmCyan to track viral infection and movement in Sorghum bicolor . We further used these viruses to deliver and express sgRNAs to Cas9 and Green Fluorescent Protein (GFP) expressing transgenic sorghum lines, targeting Phytoene desaturase ( PDS ), Magnesium‐chelatase subunit I ( MgCh ), 4‐hydroxy‐3‐methylbut‐2‐enyl diphosphate reductase , orthologs of maize Lemon white1 ( Lw1 ) or GFP . The recombinant BSMV did neither infect sorghum nor deliver or express AmCyan and sgRNAs. In contrast, the recombinant FoMV systemically spread throughout sorghum plants and induced somatic mutations with frequencies reaching up to 60%. This mutagenesis led to visible phenotypic changes, demonstrating the potential of FoMV for in planta gene editing and functional genomics studies in sorghum.

54 ENVIRONMENTAL SCIENCES↗
DOE OSTI2024

Data for Rapid and Efficient in planta Genome Editing in Sorghum Using Foxtail Mosaic Virus-mediated sgRNA Delivery

The requirement of in vitro tissue culture for the delivery of gene editing reagents limits the application of gene editing to commercially relevant varieties of many crop species. To overcome this bottleneck, plant RNA viruses have been deployed as versatile tools for in planta delivery of recombinant RNA. Viral delivery of single-guide RNAs (sgRNAs) to transgenic plants that stably express CRISPR-associated (Cas) endonuclease has been successfully used for targeted mutagenesis in several dicotyledonous and few monocotyledonous plants. Progress with this approach in monocotyledonous plants is limited so far by the availability of effective viral vectors. We engineered a set of foxtail mosaic virus (FoMV) and barley stripe mosaic virus (BSMV) vectors to deliver the fluorescent protein AmCyan to track viral infection and movement in Sorghum bicolor . We further used these viruses to deliver and express sgRNAs to Cas9 and Green Fluorescent Protein (GFP) expressing transgenic sorghum lines, targeting Phytoene desaturase (PDS), Magnesium-chelatase subunit I (MgCh), 4-hydroxy-3-methylbut-2-enyl diphosphate reductase, orthologs of maize Lemon white1 (Lw1) or GFP. The recombinant BSMV did neither infect sorghum nor deliver or express AmCyan and sgRNAs. In contrast, the recombinant FoMV systemically spread throughout sorghum plants and induced somatic mutations with frequencies reaching up to 60%. This mutagenesis led to visible phenotypic changes, demonstrating the potential of FoMV for in planta gene editing and functional genomics studies in sorghum.

Feedstock Production↗
DOE OSTI2026

Data for "Genetics of flooding tolerance in an F2 Miscanthus sacchariflorus ssp. lutarioriparius × M. sinensis population"

This dataset contains all data and supplementary materials from "Genetics of flooding tolerance in an F2 Miscanthus sacchariflorus ssp. lutarioriparius × M. sinensis population". 1. The dataset S1 table contains the raw phenotypic data collected during the experiment. 2. The dataset S2 table contains the LSmean values for the 24 traits studied. 3. The dataset S3 table contains the TASSEL GBSv2 map, marker information, and genotype data used for mapping. 4. The dataset S4 table contains information on candidate genes found in each of the QTL intervals. 5. The dataset S5 table contains the GO annotations and KEGG enrichment analyses for those candidate genes. 6. The dataset S6 table contains information on the sequences used to classify AP2 ERF transcription factors. 7. The dataset S7 table contains information on AP2 ERF orthologs between Miscanthus and rice based on synteny. 8. Supplementary file 1 contains the ANOVA results using the raw phenotypic data collected from protocol "A". 9. Supplementary file 2 contains the ANOVA results using the raw phenotypic data collected from protocol "B". 10. Supplementary file 3 contains notes on the comparison of SNP calling methods. 11. Supplementary file 4 is a script for analyzing candidate genes found in QTL intervals.

Miscanthus, flood, partial submergence, complete s↗
DOE OSTI2024

Phytosulfokine downregulates defense‐related WRKY transcription factors and attenuates pathogen‐associated molecular pattern‐triggered immunity

SUMMARY Phytosulfokine (PSK) is a plant growth‐promoting peptide hormone that is perceived by its cell surface receptors PSKR1 and PSKR2 in Arabidopsis. Plants lacking the PSK receptors show phenotypes consistent with PSK signaling repressing some plant defenses. To gain further insight into the PSK signaling mechanism, comprehensive transcriptional profiling of Arabidopsis treated with PSK was performed, and the effects of PSK treatment on plant defense readouts were monitored. Our study indicates that PSK's major effect is to downregulate defense‐related genes; it has a more modest effect on the induction of growth‐related genes. WRKY transcription factors (TFs) emerged as key regulators of PSK‐responsive genes, sharing commonality with a pathogen‐associated molecular pattern (PAMP) responses, flagellin 22 (flg22), but exhibiting opposite regulatory directions. These PSK‐induced transcriptional changes were accompanied by biochemical and physiological changes that reduced PAMP responses, notably mitogen‐activated protein kinase (MPK) phosphorylation (previously implicated in WRKY activation) and the cell wall modification of callose deposition. Comparison with previous studies using other growth stimuli (the sulfated plant peptide containing sulfated tyrosine [PSY] and Pseudomonas simiae strain WCS417) also reveals WRKY TFs' overrepresentations in these pathways, suggesting a possible shared mechanism involving WRKY TFs for plant growth–defense trade‐off.

Liu, Dian [Biochemistry and Molecular Biophysics T↗