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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 37 records · Page 2
All sourcesNASA NTRSDOE OSTI
NASA NTRS1999

A Quantitative Study of Oxygen as a Metabolic Regulator

An acute reduction in oxygen (O2) delivery to a tissue is generally associated with a decrease in phosphocreatine, increases in ADP, NADH/NAD, and inorganic phosphate, increased rates of glycolysis and lactate production, and reduced rates of pyruvate and fatty acid oxidation. However, given the complexity of the human bioenergetic system and its components, it is difficult to determine quantitatively how cellular metabolic processes interact to maintain ATP homeostasis during stress (e.g., hypoxia, ischemia, and exercise). Of special interest is the determination of mechanisms relating tissue oxygenation to observed metabolic responses at the tissue, organ, and whole body levels and the quantification of how changes in tissue O2 availability affect the pathways of ATP synthesis and the metabolites that control these pathways. In this study, we extend a previously developed mathematical model of human bioenergetics to provide a physicochemical framework that permits quantitative understanding of O2 as a metabolic regulator. Specifically, the enhancement permits studying the effects of variations in tissue oxygenation and in parameters controlling the rate of cellular respiration on glycolysis, lactate production, and pyruvate oxidation. The whole body is described as a bioenergetic system consisting of metabolically distinct tissue/organ subsystems that exchange materials with the blood. In order to study the dynamic response of each subsystem to stimuli, we solve the ordinary differential equations describing the temporal evolution of metabolite levels, given the initial concentrations. The solver used in the present study is the packaged code LSODE, as implemented in the NASA Lewis kinetics and sensitivity analysis code, LSENS. A major advantage of LSENS is the efficient procedures supporting systematic sensitivity analysis, which provides the basic methods for studying parameter sensitivities (i.e., changes in model behavior due to parameter variation). Sensitivity analysis establishes relationships between model predictions and problem parameters (i.e., initial concentrations, rate coefficients, etc). It helps determine the effects of uncertainties or changes in these input parameters on the predictions, which ultimately are compared with experimental observations in order to validate the model. Sensitivity analysis can identify parameters that must be determined accurately because of their large effect on the model predictions and parameters that need not be known with great precision because they have little or no effect on the solution. This capability may prove to be important in optimizing the design of experiments, thereby reducing the use of animals. This approach can be applied to study the metabolic effects of reduced oxygen delivery to cardiac muscle due to local myocardial ischemia and the effects of acute hypoxia on brain metabolism. Other important applications of sensitivity analysis include identification of quantitatively relevant pathways and biochemical species within an overall mechanism, when examining the effects of a genetic anomaly or pathological state on energetic system components and whole system behavior.

Radhakrishnan, Krishnan↗
NASA NTRS2015

Benefits of Microalgae for Human Space Exploration

Algae have long been known to offer a number of benefits to support long duration human space exploration. Algae contain proteins, essential amino acids, vitamins, and lipids needed for human consumption, and can be produced using waste streams, while consuming carbon dioxide, and producing oxygen. In comparison with higher plants, algae have higher growth rates, fewer environmental requirements, produce far less "waste" tissue, and are resistant to digestion and/or biodegradation. As an additional benefit, algae produce many components (fatty acids, H2, etc.) which are useful as biofuels. On Earth, micro-algae survive in many harsh environments including low humidity, extremes in temperature, pH, and as well as high salinity and solar radiation. Algae have been shown to survive inmicro-gravity, and can adapt to high and low light intensity while retaining their ability to perform nitrogen fixation and photosynthesis. Studies have demonstrated that some algae are resistant to the space radiation environment, including solar ultraviolet radiation. It remains to be experimentally demonstrated, however, that an algal-based system could fulfil the requirements for a space-based Bioregenerative Life Support System (BLSS) under comparable spaceflight power, mass, and environmental constraints. Two specific challenges facing algae cultivation in space are that (i) conventional growth platforms require large masses of water, which in turn require a large amount of propulsion fuel, and (ii) most nutrient delivery mechanisms (predominantly bubbling) are dependent on gravity. To address these challenges, we have constructed a low water biofilm based bioreactor whose operation is enabled by capillary forces. Preliminary characterization of this Surface Adhering BioReactor (SABR) suggests that it can serve as a platform for cultivating algae in space which requires about 10 times less mass than conventional reactors without sacrificing growth rate. Further work is necessary to compare the performance of microalgae-based systems, including SABR, with systems based on higher plants, as well as conventional physicochemical-based systems. Ongoing and future work in our laboratory is therefore directed determining the feasibility of using algae as a component of a BLSS in space.

Algae↗
DOE OSTI2021

Fatty acid derived alkyl ether fuels for compression ignition

A fuel for an internal combustion engine includes a fatty alkyl ether having a formula corresponding to formula (II): wherein x is 1-8, and y is 0 to 3; and the alkyl is an alkyl group having a number of carbon atoms that is less than the number of carbon atoms in the alkyl chain on the opposite side of the oxygen atom. The fatty alky ether can be used as a neat fuel or blend with biodiesel, diesel, ethanol or other fuels. The fatty alkyl ethers are improved in cetane number and cold flow properties over a biodiesel with fatty acid methyl acid methyl ester compounds. This is particularly valuable for compression ignition engines. A method of combustion in several types of engines is also disclosed.

Monroe, Eric↗
DOE OSTI2022

Genome‐wide CRISPR‐Cas9 screen reveals a persistent null‐hyphal phenotype that maintains high carotenoid production in Yarrowia lipolytica

Abstract Yarrowia lipolytica is a metabolic engineering host of growing industrial interest due to its ability to metabolize hydrocarbons, fatty acids, glycerol, and other renewable carbon sources. This dimorphic yeast undergoes a stress‐induced transition to a multicellular hyphal state, which can negatively impact biosynthetic activity, reduce oxygen and nutrient mass transfer in cell cultures, and increase culture viscosity. Identifying mutations that prevent the formation of hyphae would help alleviate the bioprocess challenges that they create. To this end, we conducted a genome‐wide CRISPR screen to identify genetic knockouts that prevent the transition to hyphal morphology. The screen identified five mutants with a null‐hyphal phenotype— ΔRAS2 , ΔRHO5 , ΔSFL1 , ΔSNF2 , and ΔPAXIP1 . Of these hits, only ΔRAS2 suppressed hyphal formation in an engineered lycopene production strain over a multiday culture. The RAS2 knockout was also the only genetic disruption characterized that did not affect lycopene production, producing more than 5 mg L −1 OD −1 from a heterologous pathway with enhanced carbon flux through the mevalonate pathway. These data suggest that a ΔRAS2 mutant of Y. lipolytica could prove useful in engineering a metabolic engineering host of the production of carotenoids and other biochemicals.

59 BASIC BIOLOGICAL SCIENCES↗
NASA NTRS1996

Nutritional Products from Space Research

Six scientists from Martin Marietta who did research for NASA on algae as food supply, oxygen source and a recycling agent for long duration space travel founded Martek Biosciences Corporation. Martek's main product is Formulaid for infants, an algae-based, vegetable-like oil containing two essential polyunsaturated fatty acids known as DHA (docosahexaenoic acid) and ARA (arachidonic acid). The acids are found in human milk but not in most infant formulas, and they are believed to be associated with mental and visual development. Formulaid is on the market in two European countries and licensed to the Mead Johnson Division of Bristol-Myers Squibb, American Home Products and others.

Source record↗
NASA NTRS1987

Hyperbaric hyperoxia reversibly inhibits erythrocyte phospholipid fatty acid turnover

The effect of hyperbaric hyperoxia on the acylation of membrane phospholipid was studied by measuring the rates of activation of exogenous tritiated oleic acid to acyl thioester and of transesterification of the thioester into membrane phospholipids in intact human erythrocytes obtained 1 h after an exposure of the subjects to a hyperbaric oxygen atmosphere (3.5 h, 100 pct O2, 3 ATA). Exposure to pure oxygen was found to inhibit both the acylation and transesterification reactions by more than 30 percent, with partial recovery detected 24 h later. On the other hand, no rate changes were observed when isolated membranes from the same batches of cells were used in similar experiments. It is suggested that the decrease in the incorporation of tritiated oleic acid after hyperbaric hyperoxia may reflect an early event in the pathogenesis of oxygen-induced cellular injury and that it may be a useful index for the assessment of the tolerance of tissues to hyperoxia.

Dise, Craig A.↗
DOE OSTI2024

Rubisco supplies pyruvate for the 2- C -methyl-D-erythritol-4-phosphate pathway

RIBULOSE-1,5-BISPHOSPHATE CARBOXYLASE/OXYGENASE (Rubisco) produces pyruvate in the chloroplast through β-elimination of the aci-carbanion intermediate. Here we show that this side reaction supplies pyruvate for isoprenoid, fatty acid and branched-chain amino acid biosynthesis in photosynthetically active tissue. 13 C labelling studies of intact Arabidopsis plants demonstrate that the total carbon commitment to pyruvate is too large for phosphoenolpyruvate to serve as a precursor. Low oxygen stimulates Rubisco carboxylase activity and increases pyruvate production and flux through the 2-C-methyl-d-erythritol-4-phosphate (MEP) pathway, which supplies the precursors for plastidic isoprenoid biosynthesis. Metabolome analysis of mutants defective in phosphoenolpyruvate or pyruvate import and biochemical characterization of isolated chloroplasts further support Rubisco as the main source of pyruvate in chloroplasts. Seedlings incorporated exogenous, 13 C-labelled pyruvate into MEP pathway intermediates, while adult plants did not, underscoring the developmental transition in pyruvate sourcing. Rubisco β-elimination leading to pyruvate constituted 0.7% of the product profile in in vitro assays, which translates to 2% of the total carbon leaving the Calvin–Benson–Bassham cycle. These insights solve the “pyruvate paradox”, improve the fit of metabolic models for central metabolism and connect the MEP pathway directly to carbon assimilation.

Plant physiology↗
NASA NTRS1991

The effects of oxygen on the evolution of microbial membranes

One prokaryote, Methylococcus capsulatus, synthesizes both hopanoids and sterols and, thus, provides a unique opportunity to study the evolution of membrane function. When M. capsulatus was grown at different temperatures, lipid analysis of the whole cells showed that both sterol and unsaturated fatty acid levels decreased at higher growth temperatures; sterol concentrations were 0.116 micro mole/micro mole phospholipid at 30 C and 0.025 micro mole/mirco mole phospholipid at 45 C, while the saturated to unsaturated fatty acid ratio increased from 0.397 to 1.475. Hopane polyol levels were constant over this range; however, methylation of the A-ring decreased markedly in cells grown at 30 C. These results imply that sterol and hopane molecules are required for enhancement of some specific membrane function, potentially by modulating membrane fluidity.

Jahnke, L. L.↗
DOE OSTI2023

Improving Volatile Fatty Acid Productivity of Anaerobic Digestion

Typical anaerobic digestion (AD) focusses on complete conversion of waste to biogas (primarily carbon dioxide and methane). However, the intermediate metabolites of the AD process, which includes short- and long-chain volatile fatty acids (VFAs), that could serve as the precursors for useful industrial applications are typically ignored. The goal of this project is to eliminate production of biogas while enhancing the production of the intermediate VFAs. Using a mixed microbial consortium (from rumen sources and waste-water sludge), we have determined the optimal carbon loading (chemical oxygen demand, "COD") and optimal pH, that results in high VFA concentrations from food waste. The best VFA yields were obtained using 15 g COD/L and a pH of 9.0 for this substrate. pH 9 produced over 200% higher VFA titers than the controlled conditions (i.e., ph 7.0) after 35 d of digestion, in comparison to pH 5 that showed - 88% higher titers than the control digestion. As expected, the cumulative biogas production was highest in the pH 7.0 condition, in comparison to pH 5.0 or pH 9.0. We further observed that removal of VFAs using solid-liquid separation technique reduce the inhibitory effects of VFAs, thereby leading to overall improvement in conversion efficiency. 16s rRNA analysis is being carried out to explain and identify the biocatalysts that enable VFA production in these AD cultures. Additional efforts to improve VFA yields via increasing the total solid content, temperature optimizations, VFA removal via electrodialysis, and improving hydrolysis via microaeration will be presented.

anaerobic digestion↗
DOE OSTI2021

Microbial communities for valorizing biomass using the carboxylate platform to produce volatile fatty acids: A review

The carboxylate platform employs a diverse microbial consortium of anaerobes in which the methanogens are inhibited. Nearly all biomass components are digested to a mixture of C1-C8 monocarboxylic acids and their corresponding salts. The methane-arrested anaerobic digestion proceeds readily without needing to sterilize biomass or equipment. It accepts a wide range of feedstocks (e.g., agricultural residues, municipal solid waste, sewage sludge, animal manure, food waste, algae, and energy crops), and produces high product yields. This review highlights several important aspects of the platform, including its thermodynamic underpinnings, influences of inoculum source and operating conditions on product formation, and downstream chemical processes that convert the carboxylates to hydrocarbon fuels and oxygenated chemicals. Furthermore, this review further establishes the carboxylate platform as a viable and economical route to industrial biomass utilization.

59 BASIC BIOLOGICAL SCIENCES↗
NASA NTRS1972

Cadmium poisoning of oxygen reduction on platinum electrode in potassium hydroxide

Experiment with a rotating disk and ring apparatus showed no poisoning by cadmium in 8.5 M KOH, alone or with Cl(-) or CO3(=). Poisoning does not occur either in 0.1 M KOH supernatant at CdO, but a partially reversible poisoning results from .0001 M CdCl2 and traces of fatty acid are present. Evidence indicates that the catastrophic poisoning affects the four-electron O2 reduction more than it does the one-electron H3O(+) discharge.

Miller, R. O.↗
NASA NTRS1972

Rare-gas effects on metabolism and inert gas narcosis

The detailed examination is reported of the theory that narcosis results from expansion of the cell membrane under high partial pressures. The research is partially based on the hypothesis that, like oxygen toxicity, the mechanism of metabolic effects of rare gases may be similar at both low and high pressures and are simply more observable at high pressures. Using adult female goats, the parameters measured include oxygen consumption, CO2 production, respiration rate, heart rate, rectal and skin temperatures and the analysis of electroencephalograms and evoked response. Additionally, the specific activity is measured of plasma glucose subsequent to injection of glucose-UL-C-14, intravenous infusion, specific activity of expired CO2, unesterified fatty acid levels and whole blood lactate-to-pyruvate ratios. Also studied were the effects of acetylsalicylic acid, vitamin E and cationic detergents (which alleviate narcosis) upon metabolic changes induced by high pressure narcosis.

Source record↗
NASA NTRS2005

Nutrition for Space Exploration

Nutrition has proven to be critical throughout the history of human exploration, on both land and water. The importance of nutrition during long-duration space exploration is no different. Maintaining optimal nutritional status is critical for all bodily systems, especially in light of the fact that that many are also affected by space flight itself. Major systems of concern are bone, muscle, the cardiovascular system, the immune system, protection against radiation damage, and others. The task ahead includes defining the nutritional requirements for space travelers, ensuring adequacy of the food system, and assessing crew nutritional status before, during, and after flight. Accomplishing these tasks will provide significant contributions to ensuring crew health on long-duration missions. In addition, development and testing of nutritional countermeasures to effects of space flight is required, and assessment of the impact of other countermeasures (such as exercise and pharmaceuticals) on nutrition is also critical for maintaining overall crew health. Vitamin D stores of crew members are routinely low after long-duration space flight. This occurs even when crew members take vitamin D supplements, suggesting that vitamin D metabolism may be altered during space flight. Vitamin D is essential for efficient absorption of calcium, and has numerous other benefits for other tissues with vitamin D receptors. Protein is a macronutrient that requires additional study to define the optimal intake for space travelers. Administration of protein to bed rest subjects can effectively mitigate muscle loss associated with disuse, but too much or too little protein can also have negative effects on bone. In another bed rest study, we found that the ratio of protein to potassium was correlated with the level of bone resorption: the higher the ratio, the more bone resorption. These relationships warrant further study to optimize the beneficial effect of protein on both bone and muscle during space flight. Omega3 fatty acids are currently being studied as a means of protecting against radiation-induced cancer. They have also recently been implicated as having a role in mitigating the physical wasting, or cachexia, caused by cancer. The mechanism of muscle loss associated with this type of cachexia is similar to the mechanism of muscle loss during disuse or space flight. Omega3 fatty acids have already been shown to have protective effects on bone and cardiovascular function. Omega3 fatty acids could be an ideal countermeasure for space flight because they have protective effects on multiple systems. A definition of optimal nutrient intake requirements for long-duration space travel should also include antioxidants. Astronauts are exposed to numerous sources of oxidative stress, including radiation, elevated oxygen exposure during extravehicular activity, and physical and psychological stress. Elevated levels of oxidative damage are related to increased risk for cataracts, cardiovascular disease, and cancer. Many groundbased studies show the protective effects of antioxidants against oxidative damage induced by radiation or oxygen. Balancing the diet with foods that have high levels of antioxidants would be another ideal countermeasure because it should have minimal side effects on crew health. Antioxidant supplements, however, are often used without having data on their effectiveness or side effects. High doses of supplements have been associated with bone and cardiovascular problems, but research on antioxidant effects during space flight has not been conducted. Much work must be done before we can send crews on exploration missions. Nutrition is often assumed to be the simple provision of food items that will be stable throughout the mission. As outlined briefly above, the situation is much more complex than food provision. As explorers throughout history have found, failure to truly understand the role of nutrition can be catastrophic. When huns are in environments unlike any they have seen before, this is more true than ever.

Smith, Scott M.↗
NASA NTRS2000

Metabolic Adaptation to Muscle Ischemia

Although all tissues in the body can adapt to varying physiological/pathological conditions, muscle is the most adaptable. To understand the significance of cellular events and their role in controlling metabolic adaptations in complex physiological systems, it is necessary to link cellular and system levels by means of mechanistic computational models. The main objective of this work is to improve understanding of the regulation of energy metabolism during skeletal/cardiac muscle ischemia by combining in vivo experiments and quantitative models of metabolism. Our main focus is to investigate factors affecting lactate metabolism (e.g., NADH/NAD) and the inter-regulation between carbohydrate and fatty acid metabolism during a reduction in regional blood flow. A mechanistic mathematical model of energy metabolism has been developed to link cellular metabolic processes and their control mechanisms to tissue (skeletal muscle) and organ (heart) physiological responses. We applied this model to simulate the relationship between tissue oxygenation, redox state, and lactate metabolism in skeletal muscle. The model was validated using human data from published occlusion studies. Currently, we are investigating the difference in the responses to sudden vs. gradual onset ischemia in swine by combining in vivo experimental studies with computational models of myocardial energy metabolism during normal and ischemic conditions.

Cabrera, Marco E.↗
DOE OSTI2022

Aureochromes maintain polyunsaturated fatty acid content in Nannochloropsis oceanica

Abstract Nannochloropsis oceanica, like other stramenopile microalgae, is rich in long-chain polyunsaturated fatty acids (LC-PUFAs) such as eicosapentaenoic acid (EPA). We observed that fatty acid desaturases (FADs) involved in LC-PUFA biosynthesis were among the strongest blue light-induced genes in N. oceanica CCMP1779. Blue light was also necessary for maintaining LC-PUFA levels in CCMP1779 cells, and growth under red light led to a reduction in EPA content. Aureochromes are stramenopile-specific proteins that contain a light–oxygen–voltage (LOV)-sensing domain that associates with a flavin mononucleotide and is able to sense blue light. These proteins also contain a basic leucine zipper DNA-binding motif and can act as blue light-regulated transcription factors by associating with an E-box like motif, which we found enriched in the promoters of blue light-induced genes. We demonstrated that, in vitro, two CCMP1779 aureochromes were able to absorb blue light. Moreover, the loss or reduction of the expression of any of the three aureochrome genes led to a decrease in the blue light-specific induction of several FADs in CCMP1779. EPA content was also significantly reduced in NoAUREO2 and NoAUREO4 mutants. Taken together, our results indicate that aureochromes mediate blue light-dependent regulation of LC-PUFA content in N. oceanica CCMP1779 cells.

Plant Sciences↗
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 OSTI2022

Genome and proteome analyses show the gaseous alkane degrader Desulfosarcina sp. strain BuS5 as an extreme metabolic specialist

The metabolic potential of the sulfate-reducing bacterium Desulfosarcina sp. strain BuS5, currently the only pure culture able to oxidize the volatile alkanes propane and butane without oxygen, was investigated via genomics, proteomics and physiology assays. Complete genome sequencing revealed that strain BuS5 encodes a single alkyl-succinate synthase, an enzyme which apparently initiates oxidation of both propane and butane. The formed alkyl-succinates are oxidized to CO 2 via beta oxidation and the oxidative Wood–Ljungdahl pathways as shown by proteogenomics analyses. Strain BuS5 conserves energy via the canonical sulfate reduction pathway and electron bifurcation. An ability to utilize long-chain fatty acids, mannose and oligopeptides, suggested by automated annotation pipelines, was not supported by physiology assays and in-depth analyses of the corresponding genetic systems. Consistently, comparative genomics revealed a streamlined BuS5 genome with a remarkable paucity of catabolic modules. These results establish strain BuS5 as an exceptional metabolic specialist, able to grow only with propane and butane, for which we propose the name Desulfosarcina aeriophaga BuS5. This highly restrictive lifestyle, most likely the result of habitat-driven evolutionary gene loss, may provide D. aeriophaga BuS5 a competitive edge in sediments impacted by natural gas seeps.

59 BASIC BIOLOGICAL SCIENCES↗