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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 955 records · Page 53
All sourcesNASA NTRSDOE OSTI
DOE OSTI2025

Metabolomic and transcriptomic remodeling of bone marrow myeloid cells in response to maternal obesity

Maternal obesity puts the offspring at high risk of developing obesity and cardiometabolic diseases in adulthood. Here, we utilized a mouse model of maternal high-fat diet (HFD)-induced obesity that recapitulates metabolic perturbations seen in humans. We show increased adiposity in the offspring of HFD-fed mothers (Off-HFD) when compared with the offspring of regular diet-fed mothers (Off-RD). We have previously reported significant immune perturbations in the bone marrow of newly weaned Off-HFD. Here, we hypothesized that lipid metabolism is altered in the bone marrow of Off-HFD versus Off-RD. To test this hypothesis, we investigated the lipidomic profile of bone marrow cells collected from 3-week-old Off-RD and Off-HFD. Diacylglycerols (DAGs), triacylglycerols (TAGs), sphingolipids, and phospholipids were remarkably different between the groups, independent of fetal sex. Levels of cholesteryl esters were significantly decreased in Off-HFD, suggesting reduced delivery of cholesterol. These were accompanied by age-dependent progression of mitochondrial dysfunction in bone marrow cells. We subsequently isolated CD11b+ myeloid cells from 3-wk-old mice and conducted metabolomic, lipidomic, and transcriptomic analyses. The lipidomic profiles of myeloid cells were similar to those of bone marrow cells and included increases in DAGs and decreased TAGs. Transcriptomics revealed altered expression of genes related to immune pathways, including macrophage alternative activation, B-cell receptors, and transforming growth factor-β signaling. All told, this study revealed lipidomic, metabolomic, and gene expression abnormalities in bone marrow cells broadly, and in bone marrow myeloid cells particularly, in the newly weaned offspring of mothers with obesity, which might at least partially explain the progression of metabolic and cardiovascular diseases in their adulthood.

RNA sequencing↗
DOE OSTI2015

Differential Effects Of Octanoate And Heptanoate On Myocardial Metabolism During Extracorporeal Membrane Oxygenation In An Infant Swine Model

Background: Nutritional energy support during extracorporeal membrane oxygenation (ECMO) should promote successful myocardial adaptation and eventual weaning from the ECMO circuit. Fatty acids (FAs) are a major myocardial energy source, and medium-chain FAs (MCFAs) are easily taken up by cell and mitochondria without membrane transporters. Oddnumbered MCFAs supply carbons to the citric acid cycle (CAC) via anaplerotic propionyl-CoA as well as acetyl-CoA, the predominant betaoxidation product for even-numbered MCFA. Theoretically, this anaplerotic pathway enhances carbon entry into the CAC, and provides superior energy state and preservation of protein synthesis. We tested this hypothesis in an immature swine model undergoing ECMO. Methods: Fifteen male Yorkshire pigs (26-45 days old) with 8-hour ECMO were received either normal saline, heptanoate (odd-numbered MCFA) or octanoate (even-numbered MCFA) at 2.3 μmol/kg body wt/min as MCFAs systemically during ECMO (n = 5 per group). The 13-Carbon (13C)-labeled substrates ([2-13C]lactate, [5,6,7-13C3]heptanoate and [U-13C6]leucine) were systemically infused as metabolic markers for the final 60 minutes before left ventricular tissue extraction. Extracted tissues were analyzed for the 13C-labeled and absolute concentrations of metabolites by nuclear magnetic resonance and gas chromatography-mass spectrometry. Results: Octanoate produced markedly higher myocardial citrate concentration, and led to a higher [ATP]/[ADP] ratio compared with other http://mc.manuscriptcentral.com/jpen Journal of Parenteral and Enteral Nutrition For Peer Review groups. Unexpectedly, octanoate increased the flux of propionyl-CoA relative to acetyl-CoA into the CAC as well as heptanoate. MCFAs promoted increases in leucine oxidation, but were not associated with a difference in fractional protein synthesis rate. Conclusion: Octanoate provides energetic advantages to the heart over heptanoate, while preserving protein synthesis.

amino acids↗
DOE OSTI2013

Myocardial Oxidative Metabolism and Protein Synthesis during Mechanical Circulatory Support by Extracorporeal Membrane Oxygenation

Extracorporeal membrane oxygenation (ECMO) provides mechanical circulatory support essential for survival in infants and children with acute cardiac decompensation. However, ECMO also causes metabolic disturbances, which contribute to total body wasting and protein loss. Cardiac stunning can also occur which prevents ECMO weaning, and contributes to high mortality. The heart may specifically undergo metabolic impairments, which influence functional recovery. We tested the hypothesis that ECMO alters oxidative. We focused on the amino acid leucine, and integration with myocardial protein synthesis. We used a translational immature swine model in which we assessed in heart (i) the fractional contribution of leucine (FcLeucine) and pyruvate (FCpyruvate) to mitochondrial acetyl-CoA formation by nuclear magnetic resonance and (ii) global protein fractional synthesis (FSR) by gas chromatography-mass spectrometry. Immature mixed breed Yorkshire male piglets (n = 22) were divided into four groups based on loading status (8 hours of normal circulation or ECMO) and intracoronary infusion [13C6,15N]-L-leucine (3.7 mM) alone or with [2-13C]-pyruvate (7.4 mM). ECMO decreased pulse pressure and correspondingly lowered myocardial oxygen consumption (~ 40%, n = 5), indicating decreased overall mitochondrial oxidative metabolism. However, FcLeucine was maintained and myocardial protein FSR was marginally increased. Pyruvate addition decreased tissue leucine enrichment, FcLeucine, and Fc for endogenous substrates as well as protein FSR. Conclusion: The heart under ECMO shows reduced oxidative metabolism of substrates, including amino acids, while maintaining (i) metabolic flexibility indicated by ability to respond to pyruvate, and (ii) a normal or increased capacity for global protein synthesis, suggesting an improved protein balance.

Environmental Molecular Sciences Laboratory↗
DOE OSTI2012

TRIIODOTHYRONINE INCREASES MYOCARDIAL FUNCTION AND PYRUVATE ENTRY INTO THE CITRIC ACID CYCLE AFTER REPERFUSION IN A MODEL OF INFANT CARDIOPULMONARY BYPASS

We utilized a translational model of infant CPB to test the hypothesis that T3 modulates pyruvate entry into the citric acid cycle (CAC) thereby providing the energy support for improved cardiac function after ischemia-reperfusion. Methods and Results: Neonatal piglets received intracoronary [2-13Carbon(13C)]-pyruvate for 40 minutes (8 mM) during control aerobic conditions (Cont) or immediately after reperfusion (IR) from global hypothermic ischemia. A third group (IR-Tr) received T3 (1.2 ug/kg) during reperfusion. We assessed absolute CAC intermediate levels (aCAC) and flux parameters into the CAC through oxidative pyruvate decarboxylation (PDC ) and anaplerotic carboxylation (PC; ) using 13C-labeled pyruvate and isotopomer analysis by gas and liquid chromatography-mass spectrometry and 13C NMR. Neither IR nor IR-Tr modified aCAC. However, compared to IR, T3 (group IR-Tr) increased cardiac power and oxygen consumption after CPB while elevating both PDC and PC (~ four-fold). T3 inhibited IR induced reductions in CAC intermediate molar percent enrichment (MPE) and oxaloacetate(citrate)/malate MPE ratio; an index of aspartate entry into the CAC. Conclusions: T3 markedly enhances PC and PDC thereby providing substrate for elevated cardiac function and work after reperfusion. The increases in pyruvate flux occur with preservation of the CAC intermediate pool. Additionally, T3 inhibition of reductions in CAC intermediate MPEs indicates that T3 reduces the reliance on amino acids (AA) for anaplerosis after reperfusion. Thus, AA should be more available for other functions such as protein synthesis.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2024

germs-lab/PAPER_miscanthus_soil_response

Nutrient inputs influence the sustainability of bioenergy crop production through contemporary (shortly after addition) and legacy effects (persisting over years) on microbial nitrogen (N) and carbon cycling, which contribute to greenhouse gas emissions. However, the relative importance of contemporary and legacy effects and how that could vary by crop functional types is poorly understood. Considering its rhizomatous roots and perennial growth, we hypothesized that Miscanthus × giganteus (M×g) would be more sensitive to legacy N fertilization and the historical context of its environment than an annual crop like maize. To test this hypothesis, we examined the effects of legacy and contemporary N inputs on nitrous oxide (N2O) and carbon dioxide (CO2) emissions, as well as key N cycling genes in soils where M×g and maize were grown. A 150-day soil incubation experiment was conducted using soils from a long-term M×g and maize fertility experiment with three historic N fertilization rates (0, 112, and 336 kg N ha−1 year−1) and a contemporary amendment (60 mg N kg−1) with negative control (0 mg N kg−1). We observed significant increases in cumulative N2O emissions in Mxg soils relative to maize soils, particularly at higher legacy fertilization rates, while contemporary N had no significant effect. Bacterial amoA gene abundance, which plays a significant role in nitrification in nutrient-rich soils, also increased with higher legacy fertilization rates in M×g soils but was unaffected by the contemporary N. In maize soils, legacy and contemporary N did not significantly affect N2O emissions, but cumulative CO2 emissions and amoA gene abundance significantly increased. The abundances of norB genes were not significantly influenced by either legacy fertilization or contemporary N amendments in either soil. Our findings demonstrate the greater importance of fertilization history over contemporary N in mediating soil N2O emissions, particularly for perennial bioenergy crops.

Lee, Jaejin↗
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 OSTI2018

Metabolic Response of the Immature Right Ventricle to Acute Pressure Overloading

Background Surgical palliation or repair of complex congenital heart disease in early infancy can produce right ventricular (RV) pressure overload, often leading to acute hemodynamic decompensation. The mechanisms causing this acute RV dysfunction remain unclear. We tested the hypothesis that the immature right ventricle lacks the ability to modify substrate metabolism in order to meet increased energy demands induced by acute pressure overloading. Methods and Results Twenty-two infant male mixed breed Yorkshire piglets were randomized to a sham operation (Control) or pulmonary artery banding yielding >2-fold elevation over baseline RV systolic pressure. We used carbon 13 ( 13 C)-labeled substrates and proton nuclear magnetic resonance to assess RV energy metabolism. [Phosphocreatine]/[ATP] was significantly lower after pulmonary artery banding. [Phosphocreatine]/[ATP] inversely correlated with energy demand indexed by maximal sustained RV systolic pressure/left ventricular systolic pressure. Fractional contributions of fatty acids to citric acid cycle were significantly lower in the pulmonary artery banding group than in the Control group (medium-chain fatty acids; 14.5±1.6 versus 8.2±1.0%, long-chain fatty acids; 9.3±1.5 versus 5.1±1.1%). 13 C-flux analysis showed that flux via pyruvate decarboxylation did not increase during RV pressure overloading. Conclusions Acute RV pressure overload yielded a decrease in [phosphocreatine]/[ATP] ratio, implying that ATP production did not balance the increasing ATP requirement. Relative fatty acids oxidation decreased without a reciprocal increase in pyruvate decarboxylation. The data imply that RV inability to adjust substrate oxidation contributes to energy imbalance, and potentially to contractile failure. The data suggest that interventions directed at increasing RV pyruvate decarboxylation flux could ameliorate contractile dysfunction associated with acute pressure overloading.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2022

Observed Covariations in Boundary Layer and Cumulus Cloud Layer Processes

In this paper we examine variations in boundary-layer processes spanning the shallow to deep cumulus transition. This is accomplished by differentiating boundary layer properties on the basis of convective outcomes, ranging from shallow to deep, as observed at the Atmospheric Radiation Measurement (ARM) Southern Great Plains (SGP) site in Oklahoma, USA. Doppler lidar, radar, and radiosonde data are combined to determine statistical differences in boundary layer and cloud layer properties using a large sample (236) of days with a range of convective outcomes: shallow, congestus, and deep convection. In these analyses, the radar characterizes diurnal cloud depth, the lidar quantifies updraft and downdraft properties in the subcloud layer, and daily radiosonde data provides the convective inhibition (CIN). Combined, these data are used to test the hypothesis that deep convection occurs when the strength of the boundary layer turbulence (i.e., TKE) exceeds the strength of the energy barrier (i.e., CIN) at the top of the CBL. Results show that days with deep convective clouds have significantly lower vertical velocity variance and weaker updrafts within the subcloud layer. However, CIN values are also found to be significantly lower on deep convective days, allowing for these weaker updrafts to penetrate the energy barrier and reach the level of free convection (LFC). In contrast, shallow convective outcomes occur when the updrafts are strong in an absolute sense, but are weak when compared to the strength of the energy barrier. These findings support the use of the CIN/TKE framework in parameterizing convection in coarse resolution models.

54 ENVIRONMENTAL SCIENCES↗
DOE OSTI2021

Spontaneous Cyclogenesis without Radiative and Surface-Flux Feedbacks

Tropical cyclones (TCs) are among the most intense and feared storms in the world. What physical processes lead to cyclogenesis remains the most mysterious aspect of TC physics. Here, we study spontaneous TC genesis in rotating radiative–convective equilibrium using cloud-resolving simulations over an f plane with constant sea surface temperature. Previous studies proposed that spontaneous TC genesis requires either radiative or surface-flux feedbacks. To test this hypothesis, we perform mechanism-denial experiments, in which we switch off both feedback processes in numerical simulations. We find that TCs can self-emerge even without radiative and surface-flux feedbacks. Although these feedbacks accelerate the genesis and impact the size of the TCs, TCs in the experiments without them can reach similar intensities as those in the control experiment. We show that TC genesis is associated with an increase in the available potential energy (APE) and that convective heating dominates the APE production. Overall, our result suggests that spontaneous TC genesis may result from a cooperative interaction between convection and circulation and that radiative and surface-flux feedbacks accelerate the process. Furthermore, we find that increasing the planetary rotation favors spontaneous TC genesis.

54 ENVIRONMENTAL SCIENCES↗
DOE OSTI2016

Selective cerebral perfusion prevents abnormalities in glutamate cycling and neuronal apoptosis in a model of infant deep hypothermic circulatory arrest and reperfusion

Rationale: Deep hypothermic circulatory arrest (DHCA) is often required for the repair of complex congenital cardiac defects in infants. However, DHCA induces neuroapoptosis associated with later development of neurocognitive abnormalities. Selective cerebral perfusion (SCP) theoretically provides superior neural protection possibly through modifications in cerebral substrate oxidation and closely integrated glutamate cycling. Objectives: We tested the hypothesis that SCP modulates glucose entry into the citric acid cycle, and ameliorates abnormalities in glutamate flux which occur in association neuroapoptosis during DHCA. Methods and Results: Eighteen male Yorkshire piglets (age 34-44 days) were assigned randomly to 2 groups of 7 (DHCA or DHCA with SCP for 60 minutes at 18 °C) and 4 control pigs without cardiopulmonary bypass support. After the completion of rewarming from DHCA, 13-Carbon-labeled (13C) glucose as a metabolic tracer was infused. We used gas chromatography-mass spectrometry (GCMS) and nuclear magnetic resonance for metabolic analysis in the frontal cortex. Following 2.5 hours of cerebral reperfusion, we observed similar cerebral ATP levels, absolute levels of lactate and citric acid cycle intermediates, and 13C-enrichment. However, DHCA induced significant abnormalities in glutamate cycling resulting in reduced glutamate/glutamine and elevated γ-aminobutyric acid (GABA)/glutamate along with neuroapoptosis (TUNEL), which were all prevented by SCP. Conclusions: DHCA alone induces abnormalities in cycling of the major neurotransmitters in association with neuroapoptosis, but does not alter cerebral glucose utilization during reperfusion. The data suggest that SCP prevents these modifications in glutamate/glutamine/GABA cycling and protects the cerebral cortex from neuroapoptosis.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2023

NREM sleep as a novel protective cognitive reserve factor in the face of Alzheimer's disease pathology

Alzheimer’s disease (AD) pathology impairs cognitive function. Yet some individuals with high amounts of AD pathology suffer marked memory impairment, while others with the same degree of pathology burden show little impairment. Why is this? One proposed explanation is cognitive reserve i.e., factors that confer resilience against, or compensation for the effects of AD pathology. Deep NREM slow wave sleep (SWS) is recognized to enhance functions of learning and memory in healthy older adults. However, that the quality of NREM SWS (NREM slow wave activity, SWA) represents a novel cognitive reserve factor in older adults with AD pathology, thereby providing compensation against memory dysfunction otherwise caused by high AD pathology burden, remains unknown. Here, we tested this hypothesis in cognitively normal older adults (N = 62) by combining 11 C-PiB (Pittsburgh compound B) positron emission tomography (PET) scanning for the quantification of β-amyloid (Aβ) with sleep electroencephalography (EEG) recordings to quantify NREM SWA and a hippocampal-dependent face-name learning task. We demonstrated that NREM SWA significantly moderates the effect of Aβ status on memory function. Specifically, NREM SWA selectively supported superior memory function in individuals suffering high Aβ burden, i.e., those most in need of cognitive reserve (B = 2.694, p = 0.019). In contrast, those without significant Aβ pathological burden, and thus without the same need for cognitive reserve, did not similarly benefit from the presence of NREM SWA (B = -0.115, p = 0.876). This interaction between NREM SWA and Aβ status predicting memory function was significant after correcting for age, sex, Body Mass Index, gray matter atrophy, and previously identified cognitive reserve factors, such as education and physical activity (p = 0.042). These findings indicate that NREM SWA is a novel cognitive reserve factor providing resilience against the memory impairment otherwise caused by high AD pathology burden. Furthermore, this cognitive reserve function of NREM SWA remained significant when accounting both for covariates, and factors previously linked to resilience, suggesting that sleep might be an independent cognitive reserve resource. Beyond such mechanistic insights are potential therapeutic implications. Unlike many other cognitive reserve factors (e.g., years of education, prior job complexity), sleep is a modifiable factor. As such, it represents an intervention possibility that may aid the preservation of cognitive function in the face of AD pathology, both present moment and longitudinally.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

Association of chronic fatigue syndrome with premature telomere attrition

Background: Chronic fatigue syndrome (CFS), also known as myalgic encephalomyelitis (ME), is a severely debilitating condition of unknown etiology. The symptoms and risk factors of ME/CFS share features of accelerated aging implicated in several diseases. Using telomere length as a marker, this study was performed to test the hypothesis that ME/CFS is associated with accelerated aging. Methods: Participant (n = 639) data came from the follow-up time point of the Georgia CFS surveillance study. Using the 1994 CFS Research Case Definition with questionnaire-based subscale thresholds for fatigue, function, and symptoms, participants were classified into four illness groups: CFS if all criteria were met (n = 64), CFS-X if CFS with exclusionary conditions (n = 77), ISF (insufficient symptoms/fatigue) if only some criteria were met regardless of exclusionary conditions (n = 302), and NF (non-fatigued) if no criteria and no exclusionary conditions (n = 196). Relative telomere length (T/S ratio) was measured using DNA from whole blood and real-time PCR. General linear models were used to estimate the association of illness groups or T/S ratio with demographics, biological measures and covariates with significance set at p < 0.05. Results: The mean T/S ratio differed significantly by illness group (p = 0.0017); the T/S ratios in CFS (0.90 ± 0.03) and ISF (0.94 ± 0.02) were each significantly lower than in NF (1.06 ± 0.04). Differences in T/S ratio by illness groups remained significant after adjustment for covariates of age, sex, body mass index, waist–hip ratio, post-exertional malaise and education attainment. Telomere length was shorter by 635, 254 and 424 base pairs in CFS, CFS-X and ISF, respectively, compared to NF. This shorter telomere length translates to roughly 10.1–20.5, 4.0–8.2 and 6.6–13.7 years of additional aging in CFS, CFS-X and ISF compared to NF respectively. Further, stratified analyses based on age and sex demonstrated that the association of ME/CFS with short telomeres is largely moderated by female subjects < 45 years old. Conclusions: This study found a significant association of ME/CFS with premature telomere attrition that is largely moderated by female subjects < 45 years old. Our results indicate that ME/CFS could be included in the list of conditions associated with accelerated aging. Further work is needed to evaluate the functional significance of accelerated aging in ME/CFS.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

Increasing the economic value of lignocellulosic stillage through medium-chain fatty acid production

Background Lignocellulosic biomass is viewed as an abundant renewable source of liquid fuels and chemicals that are currently derived from petroleum. When lignocellulosic biomass is used for ethanol production, the resulting liquid residue (stillage) contains large amounts of organic material that could be further transformed into recoverable bioproducts, hence enhancing the economics of the biorefinery. Results Here we test the hypothesis that a bacterial community could transform the organics in stillage into valuable bioproducts. We demonstrate the ability of this microbiome to convert stillage organics into medium-chain fatty acids (MCFAs), identify the predominant community members, and perform a technoeconomic analysis of recovering MCFAs as co-products of ethanol production. Steady-state operation of a stillage-fed bioreactor showed that 18% of the organic matter in stillage was converted to MCFAs. Xylose and complex carbohydrates were the primary substrates transformed. During the MCFA production period, the five major genera represented more than 95% of the community, including Lactobacillus, Roseburia, Atopobium, Olsenella, and Pseudoramibacter . To assess the potential benefits of producing MCFAs from stillage, we modeled the economics of ethanol and MCFA co-production, at MCFA productivities observed during reactor operation. Conclusions The analysis predicts that production of MCFAs, ethanol, and electricity could reduce the minimum ethanol selling price from 2.15 dollars 1.76 dollars gal -1 ($2.68 gal -1 gasoline equivalents) when compared to a lignocellulosic biorefinery that produces only ethanol and electricity.

09 BIOMASS FUELS↗
DOE OSTI2017

A cognitive electrophysiological signature differentiates amnestic mild cognitive impairment from normal aging

Background: Noninvasive and effective biomarkers for early detection of amnestic mild cognitive impairment (aMCI) before measurable changes in behavioral performance remain scarce. Cognitive event-related potentials (ERPs) measure synchronized synaptic neural activity associated with a cognitive event. Loss of synapses is a hallmark of the neuropathology of early Alzheimer’s disease (AD). In the present study, we tested the hypothesis that ERP responses during working memory retrieval discriminate aMCI from cognitively normal controls (NC) matched in age and education. Methods: Eighteen NC, 17 subjects with aMCI, and 13 subjects with AD performed a delayed match-to-sample task specially designed not only to be easy enough for impaired participants to complete but also to generate comparable performance between subjects with NC and those with aMCI. Scalp electroencephalography, memory accuracy, and reaction times were measured. Results: Whereas memory performance separated the AD group from the others, the performance of NC and subjects with aMCI was similar. In contrast, left frontal cognitive ERP patterns differentiated subjects with aMCI from NC. Enhanced P3 responses at left frontal sites were associated with nonmatching relative to matching stimuli during working memory tasks in patients with aMCI and AD, but not in NC. The accuracy of discriminating aMCI from NC was 85% by using left frontal match/nonmatch effect combined with nonmatch reaction time. Conclusions: The left frontal cognitive ERP indicator holds promise as a sensitive, simple, affordable, and noninvasive biomarker for detection of early cognitive impairment.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2021

Meanders as a scaling motif for understanding of floodplain soil microbiome and biogeochemical potential at the watershed scale

Abstract Background Biogeochemical exports from watersheds are modulated by the activity of microorganisms that function over micron scales. Here, we tested the hypothesis that meander-bound regions share a core microbiome and exhibit patterns of metabolic potential that broadly predict biogeochemical processes in floodplain soils along a river corridor. Results We intensively sampled the microbiomes of floodplain soils located in the upper, middle, and lower reaches of the East River, Colorado. Despite the very high microbial diversity and complexity of the soils, we reconstructed 248 quality draft genomes representative of subspecies. Approximately one third of these bacterial subspecies was detected across all three locations at similar abundance levels, and ~ 15% of species were detected in two consecutive years. Within the meander-bound floodplains, we did not detect systematic patterns of gene abundance based on sampling position relative to the river. However, across meanders, we identified a core floodplain microbiome that is enriched in capacities for aerobic respiration, aerobic CO oxidation, and thiosulfate oxidation with the formation of elemental sulfur. Given this, we conducted a transcriptomic analysis of the middle floodplain. In contrast to predictions made based on the prominence of gene inventories, the most highly transcribed genes were relatively rare amoCAB and nxrAB (for nitrification) genes, followed by genes involved in methanol and formate oxidation, and nitrogen and CO 2 fixation. Within all three meanders, low soil organic carbon correlated with high activity of genes involved in methanol, formate, sulfide, hydrogen, and ammonia oxidation, nitrite oxidoreduction, and nitrate and nitrite reduction. Overall, the results emphasize the importance of sulfur, one-carbon and nitrogen compound metabolism in soils of the riparian corridor. Conclusions The disparity between the scale of a microbial cell and the scale of a watershed currently limits the development of genomically informed predictive models describing watershed biogeochemical function. Meander-bound floodplains appear to serve as scaling motifs that predict aggregate capacities for biogeochemical transformations, providing a foundation for incorporating riparian soil microbiomes in watershed models. Widely represented genetic capacities did not predict in situ activity at one time point, but rather they define a reservoir of biogeochemical potential available as conditions change.

54 ENVIRONMENTAL SCIENCES↗
DOE OSTI2013

IL-12Rβ2 is critical for survival of primary Francisella tularensis LVS infection

Abstract IL-12Rβ2 is critical in parenteral and mucosal host resistance to primary Francisella tularensis LVS infection, and controls liver damage. Using a panel of vaccines that provided different degrees of protection, we previously identified the IL-12 receptor subunit β2 as a mediator, whose relative expression correlated with strength of protection against secondary lethal challenge of vaccinated mice with an intracellular bacterium, the LVS of Francisella tularensis. The present study therefore tested the hypothesis that IL-12Rβ2 is an important mediator in resistance to LVS by directly examining its role during infections. IL-12Rβ2 KO mice were highly susceptible to LVS primary infection, administered i.d. or i.n. The LD50 of LVS infection of KO mice were 2 logs lower than those of WT mice, regardless of route. Five days after infection with LVS, bacterial organ burdens were significantly higher in IL-12Rβ2 KO mice. IL-12Rβ2 KO mice infected with lethal doses of LVS had more severe liver pathology, including significant increases in the liver enzymes ALT and AST. Despite decreased levels of IFN-γ, LVS-vaccinated IL-12Rβ2 KO mice survived large lethal LVS secondary challenge. Consistent with in vivo protection, in vitro intramacrophage LVS growth was well-controlled in cocultures containing WT or IL-12Rβ2 KO LVS-immune splenocytes. Thus, survival of secondary LVS challenge was not strictly dependent on IL-12Rβ2. However, IL-12Rβ2 is important in parenteral and mucosal host resistance to primary LVS infection and in the ability of WT mice to clear LVS infection and serves to restrict liver damage.

Melillo, Amanda A.↗
DOE OSTI2024

Odor exposure during imprinting periods increases odorant-specific sensitivity and receptor gene expression in coho salmon ( Oncorhynchus kisutch )

ABSTRACT Pacific salmon are well known for their homing migrations; juvenile salmon learn odors associated with their natal streams prior to seaward migration, and then use these retained odor memories to guide them back from oceanic feeding grounds to their river of origin to spawn several years later. This memory formation, termed olfactory imprinting, involves (at least in part) sensitization of the peripheral olfactory epithelium to specific odorants. We hypothesized that this change in peripheral sensitivity is due to exposure-dependent increases in the expression of odorant receptor (OR) proteins that are activated by specific odorants experienced during imprinting. To test this hypothesis, we exposed juvenile coho salmon, Oncorhynchus kisutch, to the basic amino acid odorant l-arginine during the parr–smolt transformation (PST), when imprinting occurs, and assessed sensitivity of the olfactory epithelium to this and other odorants. We then identified the coho salmon ortholog of a basic amino acid odorant receptor (BAAR) and determined the mRNA expression levels of this receptor and other transcripts representing different classes of OR families. Exposure to l-arginine during the PST resulted in increased sensitivity to that odorant and a specific increase in BAAR mRNA expression in the olfactory epithelium relative to other ORs. These results suggest that specific increases in ORs activated during imprinting may be an important component of home stream memory formation and this phenomenon may ultimately be useful as a marker of successful imprinting to assess management strategies and hatchery practices that may influence straying in salmon.

Dittman, Andrew H. (ORCID:000000016482359X)↗