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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 19 records
All sourcesNASA NTRSDOE OSTI
DOE OSTI2024

Transcriptomic and metabolomic changes in postharvest sugarbeet roots reveal widespread metabolic changes in storage and identify genes potentially responsible for respiratory sucrose loss

Endogenous metabolism is primarily responsible for losses in sucrose content and processing quality in postharvest sugarbeet roots. The genes responsible for this metabolism and the transcriptional changes that regulate it, however, are largely unknown. To identify genes and metabolic pathways that participate in postharvest sugarbeet root metabolism and the transcriptional changes that contribute to their regulation, transcriptomic and metabolomic profiles were generated for sugarbeet roots at harvest and after 12, 40 and 120 d storage at 5 and 12°C and gene expression and metabolite concentration changes related to storage duration or temperature were identified. During storage, 8656 genes, or 34% of all expressed genes, and 225 metabolites, equivalent to 59% of detected metabolites, were altered in expression or concentration, indicating extensive transcriptional and metabolic changes in stored roots. These genes and metabolites contributed to a wide range of cellular and molecular functions, with carbohydrate metabolism being the function to which the greatest number of genes and metabolites classified. Because respiration has a central role in postharvest metabolism and is largely responsible for sucrose loss in sugarbeet roots, genes and metabolites involved in and correlated to respiration were identified. Seventy-five genes participating in respiration were differentially expressed during storage, including two bidirectional sugar transporter SWEET17 genes that highly correlated with respiration rate. Weighted gene co-expression network analysis identified 1896 additional genes that positively correlated with respiration rate and predicted a pyruvate kinase gene to be a central regulator or biomarker for respiration rate. Overall, these results reveal the extensive and diverse physiological and metabolic changes that occur in stored sugarbeet roots and identify genes with potential roles as regulators or biomarkers for respiratory sucrose loss.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2023

Atp7b-dependent choroid plexus dysfunction causes transient copper deficit and metabolic changes in the developing mouse brain

Copper (Cu) has a multifaceted role in brain development, function, and metabolism. Two homologous Cu transporters, Atp7a (Menkes disease protein) and Atp7b (Wilson disease protein), maintain Cu homeostasis in the tissue. Atp7a mediates Cu entry into the brain and activates Cu-dependent enzymes, whereas the role of Atp7b is less clear. We show that during postnatal development Atp7b is necessary for normal morphology and function of choroid plexus (ChPl). Inactivation of Atp7b causes reorganization of ChPl’ cytoskeleton and cell-cell contacts, loss of Slc31a1 from the apical membrane, and a decrease in the length and number of microvilli and cilia. In ChPl lacking Atp7b, Atp7a is upregulated but remains intracellular, which limits Cu transport into the brain and results in significant Cu deficit, which is reversed only in older animals. Cu deficiency is associated with down-regulation of Atp7a in locus coeruleus and catecholamine imbalance, despite normal expression of dopamine-β-hydroxylase. In addition, there are notable changes in the brain lipidome, which can be attributed to inhibition of diacylglyceride-to-phosphatidylethanolamine conversion. These results identify the new role for Atp7b in developing brain and identify metabolic changes that could be exacerbated by Cu chelation therapy.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2024

Lignin engineering in poplar via heterologous expression of dehydroshikimate dehydratase induces distinct transcriptional and metabolic changes in the shikimate and phenylpropanoid pathways

Understanding how crops respond to such genetic modifications at the transcriptional and metabolic levels is needed to facilitate further improvement and field deployment. In this work, we gathered some fundamental knowledge on lignin-modified QsuB poplar grown in a greenhouse using RNA-seq and metabolomics.

Aromatics↗
DOE OSTI2021

Radiation exposure induces cross-species temporal metabolic changes that are mitigated in mice by amifostine

Exposure to acute, damaging radiation may occur through a variety of events from cancer therapy and industrial accidents to terrorist attacks and military actions. Our understanding of how to protect individuals and mitigate the effects of radiation injury or Acute Radiation Syndrome (ARS) is still limited. There are only a few Food and Drug Administration-approved therapies for ARS; whereas, amifostine is limited to treating low dose (0.7–6 Gy) radiation poisoning arising from cancer radiotherapy. An early intervention is critical to treat ARS, which necessitates identifying diagnostic biomarkers to quickly characterize radiation exposure. Towards this end, a multiplatform metabolomics study was performed to comprehensively characterize the temporal changes in metabolite levels from mice and non-human primate serum samples following γ-irradiation. The metabolomic signature of amifostine was also evaluated in mice as a model for radioprotection. The NMR and mass spectrometry metabolomics analysis identified 23 dysregulated pathways resulting from the radiation exposure. These metabolomic alterations exhibited distinct trajectories within glucose metabolism, phospholipid biosynthesis, and nucleotide metabolism. A return to baseline levels with amifostine treatment occurred for these pathways within a week of radiation exposure. Together, our data suggests a unique physiological change that is independent of radiation dose or species. Furthermore, a metabolic signature of radioprotection was observed through the use of amifostine prophylaxis of ARS.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2024

Expression of dehydroshikimate dehydratase in poplar induces transcriptional and metabolic changes in the phenylpropanoid pathway

Abstract Modification of lignin in feedstocks via genetic engineering aims to reduce biomass recalcitrance to facilitate efficient conversion processes. These improvements can be achieved by expressing exogenous enzymes that interfere with native biosynthetic pathways responsible for the production of the lignin precursors. In planta expression of a bacterial 3-dehydroshikimate dehydratase in poplar trees reduced lignin content and altered the monomer composition, which enabled higher yields of sugars after cell wall polysaccharide hydrolysis. Understanding how plants respond to such genetic modifications at the transcriptional and metabolic levels is needed to facilitate further improvement and field deployment. In this work, we acquired fundamental knowledge on lignin-modified poplar expressing 3-dehydroshikimate dehydratase using RNA-seq and metabolomics. The data clearly demonstrate that changes in gene expression and metabolite abundance can occur in a strict spatiotemporal fashion, revealing tissue-specific responses in the xylem, phloem, or periderm. In the poplar line that exhibited the strongest reduction in lignin, we found that 3% of the transcripts had altered expression levels and ~19% of the detected metabolites had differential abundance in the xylem from older stems. The changes affected predominantly the shikimate and phenylpropanoid pathways as well as secondary cell wall metabolism, and resulted in significant accumulation of hydroxybenzoates derived from protocatechuate and salicylate.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2023

Divergent Metabolic Changes in Rhizomes of Lowland and Upland Switchgrass (Panicum virgatum) from Early Season through Dormancy Onset

High-biomass-yielding southerly adapted switchgrasses (Panicum virgatum L.) frequently suffer from unpredictable winter hardiness at more northerly sites arising from damage to rhizomes that prevent effective spring regrowth. Previously, changes occurring over the growing season in rhizomes sampled from a cold-adapted tetraploid upland cultivar, Summer, demonstrated a role for abscisic acid (ABA), starch accumulation, and transcriptional reprogramming as drivers of dormancy onset and potential keys to rhizome health during winter dormancy. Here, rhizome metabolism of a high-yielding southerly adapted tetraploid switchgrass cultivar, Kanlow—which is a significant source of genetics for yield improvement—was studied over a growing season at a northern site. Metabolite levels and transcript abundances were combined to develop physiological profiles accompanying greening through the onset of dormancy in Kanlow rhizomes. Next, comparisons of the data to rhizome metabolism occurring in the adapted upland cultivar Summer were performed. These data revealed both similarities as well as numerous differences in rhizome metabolism that were indicative of physiological adaptations unique to each cultivar. Similarities included elevated ABA levels and accumulation of starch in rhizomes during dormancy onset. Notable differences were observed in the accumulation of specific metabolites, the expression of genes encoding transcription factors, and several enzymes linked to primary metabolism.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2022

Pathophysiological Integration of Metabolic Reprogramming in Breast Cancer

Metabolic changes that facilitate tumor growth are one of the hallmarks of cancer. The triggers of these metabolic changes are located in the tumor parenchymal cells, where oncogenic mutations induce an imperative need to proliferate and cause tumor initiation and progression. Cancer cells undergo significant metabolic reorganization during disease progression that is tailored to their energy demands and fluctuating environmental conditions. Oxidative stress plays an essential role as a trigger under such conditions. These metabolic changes are the consequence of the interaction between tumor cells and stromal myofibroblasts. The metabolic changes in tumor cells include protein anabolism and the synthesis of cell membranes and nucleic acids, which all facilitate cell proliferation. They are linked to catabolism and autophagy in stromal myofibroblasts, causing the release of nutrients for the cells of the tumor parenchyma. Metabolic changes lead to an interstitium deficient in nutrients, such as glucose and amino acids, and acidification by lactic acid. Together with hypoxia, they produce functional changes in other cells of the tumor stroma, such as many immune subpopulations and endothelial cells, which lead to tumor growth. Thus, immune cells favor tissue growth through changes in immunosuppression. This review considers some of the metabolic changes described in breast cancer.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2025

Hepatocellular Metabolic Profile: Understanding Post-Thawing Metabolic Shift in Primary Hepatocytes In Vitro

Primary human hepatocytes (PHHs) are widely used as in vitro models for liver function and drug metabolism studies, yet their metabolic stability post-thawing remains an open question. To better characterize early metabolic changes, we conducted a time-course experiment using liquid chromatography-tandem mass spectrometry (LC-MS/MS) to analyze metabolic shifts in PHHs cultured in suspension. Unexposed and exposed (acetaminophen-treated) samples were evaluated, and TITAN analysis was applied to determine the time point of maximal metabolic change at both individual metabolite and global metabolic profile levels. Our results indicate that the majority of metabolic shifts occur within the first five hours post-thawing. In the early culture time points, substantial metabolic overlap was observed between unexposed and exposed cells, suggesting a conserved biological response likely related to cellular recovery. However, at later time points, metabolite profiles diverged, with acetaminophen treatment-specific metabolic changes emerging, potentially reflecting differences in homeostatic restoration versus hepatotoxic responses. Our study highlights the importance of considering early post-thawing metabolic dynamics in experimental design and offers insights for optimizing hepatocyte culture protocols to better replicate in vivo physiological conditions.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2024

Continuous cropping of potato changed the metabolic pathway of root exudates to drive rhizosphere microflora

For potato production, continuous cropping (CC) could lead to autotoxicity buildup and microflora imbalance in the field soil, which may result in failure of crops and reduction in yield. In this study, non-targeted metabolomics (via liquid chromatography with tandem mass spectrometry (LC–MS/MS)) combined with metagenomic profiling (via high-throughput amplicon sequencing) were used to evaluate correlations between metabolomics of potato root exudates and communities of bacteria and fungi around potato plants to illustrate the impacts of CC. Potato plants were grown in soil collected from fields with various CC years (0, 1, 4, and 7 years). Metabolomic analysis showed that the contents and types of potential autotoxins in potato root exudates increased significantly in CC4 and CC7 plants (i.e., grown in soils with 4 and 7 years of CC). The differentially expressed metabolites were mainly produced via alpha-linolenic acid metabolism in plant groups CC0 and CC1 (i.e., no CC or 1 year CC). The metabolomics of the groups CC4 and CC7 became dominated by styrene degradation, biosynthesis of siderophore group non-ribosomal peptides, phenylpropanoid biosynthesis, and biosynthesis of various plant secondary metabolites. Continuous cropping beyond 4 years significantly changed the bacterial and fungal communities in the soil around the potato crops, with significant reduction of beneficial bacteria and accumulation of harmful fungi. Correlations between DEMs and microflora biomarkers were established with strong significances. These results suggested that continuous cropping of potato crops changed their metabolism as reflected in the plant root exudates and drove rhizosphere microflora to directions less favorable to plant growth, and it needs to be well managed to assure potato yield.

Xing, Yanhong↗
DOE OSTI2024

Impact of sunitinib resistance on clear cell renal cell carcinoma therapeutic sensitivity in vitro

Sunitinib resistance creates a major clinical challenge for the treatment of advanced clear cell renal cell carcinoma (ccRCC) and functional and metabolic changes linked to sunitinib resistance are not fully understood. We sought to characterize the molecular and metabolic changes induced by the development of sunitinib resistance in ccRCC by developing and characterizing two human ccRCC cell lines resistant to sunitinib. Consistent with the literature, sunitinib-resistant ccRCC cell lines presented an aberrant overexpression of Axl and PD-L1, as well as a metabolic rewiring characterized by enhanced OXPHOS and glutamine metabolism. Therapeutic challenges of sunitinib-resistant ccRCC cell lines in vitro using small molecule inhibitors targeting Axl, AMPK and p38, as well as using PD-L1 blocking therapeutic antibodies, showed limited CTL-mediated cytotoxicity in a co-culture model. However, the AMPK activator metformin appears to sensitize the effect of PD-L1 blocking therapeutic antibodies and to enhance CTLs’ cytotoxic effects on ccRCC cells. These effects were not broadly observed with the Axl and the p38 inhibitors. Taken together, these data suggest that targeting certain pathways aberrantly activated by sunitinib resistance such as the AMPK/PDL1 axis might sensitize ccRCC to immunotherapies as a second-line therapeutic approach.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2026

Endophyte‐induced systemic spatial reprogramming of metabolism in Populus trichocarpa roots under drought

Beneficial, facultative endophytes help plants thrive in challenging environments by altering their host's metabolism, but how these cellular scale metabolic changes propagate to the systems biology scale is unknown. In this work, we employed a high-resolution chemical imaging approach to map metabolic changes at the Populus trichocarpa root-zone and cell-type levels combined with machine learning (ML) models to identify root metabolites and exudates that have predictive power over treatment class. We found that a nine-strain consortium of beneficial endophytes differentially altered the metabolome of droughted root tissues in a manner specific to cell type and root zone, with endophyte abundance showing a clear correlation to individual metabolites. Our study demonstrates that integrating spatial metabolomics with ML can reveal localized metabolic patterns linked to root–microbe interactions and generate novel hypotheses about underlying biological mechanisms.

Drought↗
DOE OSTI2022

Evolutionary Origins of Metabolic Reprogramming in Cancer

Metabolic changes that facilitate tumor growth are one of the hallmarks of cancer. These changes are not specific to tumors but also take place during the physiological growth of tissues. Indeed, the cellular and tissue mechanisms present in the tumor have their physiological counterpart in the repair of tissue lesions and wound healing. These molecular mechanisms have been acquired during metazoan evolution, first to eliminate the infection of the tissue injury, then to enter an effective regenerative phase. Cancer itself could be considered a phenomenon of antagonistic pleiotropy of the genes involved in effective tissue repair. Cancer and tissue repair are complex traits that share many intermediate phenotypes at the molecular, cellular, and tissue levels, and all of these are integrated within a Systems Biology structure. Complex traits are influenced by a multitude of common genes, each with a weak effect. This polygenic component of complex traits is mainly unknown and so makes up part of the missing heritability. Here, we try to integrate these different perspectives from the point of view of the metabolic changes observed in cancer.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2021

Non-destructive quantification of anaerobic gut fungi and methanogens in co-culture reveals increased fungal growth rate and changes in metabolic flux relative to mono-culture

Abstract Background Quantification of individual species in microbial co-cultures and consortia is critical to understanding and designing communities with prescribed functions. However, it is difficult to physically separate species or measure species-specific attributes in most multi-species systems. Anaerobic gut fungi (AGF) (Neocallimastigomycetes) are native to the rumen of large herbivores, where they exist as minority members among a wealth of prokaryotes. AGF have significant biotechnological potential owing to their diverse repertoire of potent lignocellulose-degrading carbohydrate-active enzymes (CAZymes), which indirectly bolsters activity of other rumen microbes through metabolic exchange. While decades of literature suggest that polysaccharide degradation and AGF growth are accelerated in co-culture with prokaryotes, particularly methanogens, methods have not been available to measure concentrations of individual species in co-culture. New methods to disentangle the contributions of AGF and rumen prokaryotes are sorely needed to calculate AGF growth rates and metabolic fluxes to prove this hypothesis and understand its causality for predictable co-culture design. Results We present a simple, microplate-based method to measure AGF and methanogen concentrations in co-culture based on fluorescence and absorbance spectroscopies. Using samples of < 2% of the co-culture volume, we demonstrate significant increases in AGF growth rate and xylan and glucose degradation rates in co-culture with methanogens relative to mono-culture. Further, we calculate significant differences in AGF metabolic fluxes in co-culture relative to mono-culture, namely increased flux through the energy-generating hydrogenosome organelle. While calculated fluxes highlight uncertainties in AGF primary metabolism that preclude definitive explanations for this shift, our method will enable steady-state fluxomic experiments to probe AGF metabolism in greater detail. Conclusions The method we present to measure AGF and methanogen concentrations enables direct growth measurements and calculation of metabolic fluxes in co-culture. These metrics are critical to develop a quantitative understanding of interwoven rumen metabolism, as well as the impact of co-culture on polysaccharide degradation and metabolite production. The framework presented here can inspire new methods to probe systems beyond AGF and methanogens. Simple modifications to the method will likely extend its utility to co-cultures with more than two organisms or those grown on solid substrates to facilitate the design and deployment of microbial communities for bioproduction and beyond.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2024

Green microalga Chromochloris zofingiensis conserves substrate uptake pattern but changes their metabolic uses across trophic transition

The terrestrial green alga Chromochloris zofingiensis is an emerging model species with potential applications including production of triacylglycerol or astaxanthin. How C. zofingiensis interacts with the diverse substrates during trophic transitions is unknown. To characterize its substrate utilization and secretion dynamics, we cultivated the alga in a soil-based defined medium in transition between conditions with and without glucose supplementation. Then, we examined its exometabolite and endometabolite profiles. This analysis revealed that regardless of trophic modes, C. zofingiensis preferentially uptakes exogenous lysine, arginine, and purines, while secreting orotic acid. Here, we obtained metabolomic evidences that C. zofingiensis may use arginine for putrescine synthesis when in transition to heterotrophy, and for the TCA cycle during transition to photoautotrophy. We also report that glucose and fructose most effectively inhibited photosynthesis among thirteen different sugars. The utilized or secreted metabolites identified in this study provide important information to improve C. zofingiensis cultivation, and to expand its potential industrial and pharmaceutical applications.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2025

Developmentally-specific physiological and metabolic responses support drought resilience in switchgrass and constrains biofuel yield

Switchgrass (Panicum virgatum) is a promising bioenergy crop due in part to its resilience to drought stress. However, the significance of drought timing remains poorly understood, both from a plant biology perspective and its impact on downstream biofuel production. This study determines the developmental stage-specific physiological and metabolic responses of switchgrass to drought stress and its implications for biofuel production using a custom-built programmable irrigation system. Vegetative, flowering, and senescence-stage drought significantly reduced carbon dioxide assimilation, and stomatal conductance without affecting biomass yield. Metabolic profiling revealed significant accumulation of glucose, fructose, quinic acid, shikimate and GABA during vegetative-stage drought, while flowering and senescence stages exhibited limited metabolic changes. Similarly, specialized metabolites also displayed distinct developmental patterns, with vegetative-stage drought driving the most pronounced metabolic alterations. Thermochemically-treated and hydrolyzed switchgrass biomass from vegetative-stage drought showed elevated lignocellulose-derived compounds and saponins with the latter most positively correlating with fermentation lag times. Conversely, senescence-stage drought enhanced ethanol yields while lowering saponin levels in the hydrolysates. While vegetative-stage drought enhanced physiological resilience, it compromises downstream biofuel production by introducing fermentation inhibitors, particularly saponins.

biofuel↗
DOE OSTI2020

Microbial inputs at the litter layer translate climate into altered organic matter properties

Plant litter chemistry is altered during decomposition but it remains unknown if these alterations, and thus the composition of residual litter, will change in response to climate. Selective microbial mineralization of litter components and the accumulation of microbial necromass can drive litter compositional change, but the extent to which these mechanisms respond to climate remains poorly understood. We addressed this knowledge gap by studying needle litter decomposition along a boreal forest climate transect. Specifically, we investigated how the composition and/or metabolism of the decomposer community varies with climate, and if that variation is associated with distinct modifications of litter chemistry during decomposition. We analyzed the composition of microbial phospholipid fatty acids (PLFA) in the litter layer and measured natural abundance δ 13 CPLFA values as an integrated measure of microbial metabolisms. Changes in litter chemistry and δ 13 C values were measured in litterbag experiments conducted at each transect site. A warmer climate was associated with higher litter nitrogen concentrations as well as altered microbial community structure (lower fungi:bacteria ratios) and microbial metabolism (higher δ 13 CPLFA). Litter in warmer transect regions accumulated less aliphatic-C (lipids, waxes) and retained more O-alkyl-C (carbohydrates), consistent with enhanced 13 C-enrichment in residual litter, than in colder regions. These results suggest that chemical changes during litter decomposition will change with climate, driven primarily by indirect climate effects (e.g. greater nitrogen availability and decreased fungi:bacteria ratios) rather than direct temperature effects. A positive correlation between microbial biomass δ 13 C values and 13 C-enrichment during decomposition suggests that change in litter chemistry is driven more by distinct microbial necromass inputs than differences in the selective removal of litter components. Our study highlights the role that microbial inputs during early litter decomposition can play in shaping surface litter contribution to soil organic matter as it responds to climate warming effects such as greater nitrogen availability.

13C↗
DOE OSTI2019

In-Situ Metabolomic Analysis of Setaria viridis Roots Colonized by Beneficial Endophytic Bacteria

Over the past decades, crop yields have risen in parallel with increasing use of fossil-fuel derived nitrogen (N) fertilizers, but with concomitant negative impacts on climate and water resources. There is a need for more sustainable agricultural practices, and biological nitrogen fixation (BNF) could be part of the solution. A variety of nitrogen-fixing, epiphytic and endophytic plant growth promoting bacteria (PGPB) are known to stimulate plant growth. However, compared to the rhizobium-legume symbiosis, little mechanistic information is available as to how PGPB affect plant metabolism. Therefore, we investigated the metabolic changes in roots of the model grass species Setaria viridis upon endophytic colonization by Herbaspirillum seropedicae SmR1 (fix + ) or a fix - mutant strain (SmR54), compared to uninoculated roots. Endophytic colonization of the root is highly localized and, hence, analysis of whole root segments dilutes the metabolic signature of those few cells impacted by the bacteria. Therefore, we utilized in situ laser ablation electrospray ionization mass spectrometry (LAESI-MS) to sample only those root segments at or adjacent to the sites of bacterial colonization. We report netabolites involved in purine, zeatin, and riboflavin pathways were significantly more abundant in inoculated plants while metabolites indicative of nitrogen, starch, and sucrose metabolism were reduced in roots inoculated with the fix - strain or uninoculated, presumably due to N limitation. Interestingly, compounds, involved in indole-alkaloid biosynthesis were more abundant in the roots colonized by the fix - strain, perhaps reflecting a plant defense response.

59 BASIC BIOLOGICAL SCIENCES↗