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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 829 records · Page 46
All sourcesNASA NTRSDOE OSTI
DOE OSTI2018

Short- and long-term effects of high-fat diet feeding and voluntary exercise on hepatic lipid metabolism in mice

Highlights: • Voluntary exercise for 1 week (short-term exercise) significantly reduced fat accumulation in the liver. • Short-term exercise induced a downregulation of lipogenic proteins and an upregulation of lipolytic proteins in liver. • Long-term voluntary exercise downregulated the expression of hepatic lipogenesis-associated proteins. Exercise is an effective tool for improving high-fat diet induced fat accumulation in the liver. However, the process of fat accumulation in the liver and the efficacy of early intervention with exercise remain unclear. The aim of this study was to investigate the short- and long-term effects of high-fat diet feeding and voluntary exercise on hepatic lipid metabolism in mice. Male C57BL/6J mice aged 6 weeks were randomly divided into two groups, the control group and high-fat diet feeding group, and fed a normal or high-fat diet for 12 weeks. After 6 weeks, mice in the high-fat diet feeding group were further divided into no exercise group and voluntary exercise training group, with mice in the exercise group provided a running wheel for 6 weeks. Body weight, food intake, and wheel rotation counts were measured every second day for 12 weeks. We found that voluntary exercise for 1 week (short-term exercise) significantly reduced fat accumulation in the liver by downregulating the expression of hepatic lipogenesis-associated proteins and upregulating the expression of hepatic lipolysis-associated proteins, as determined through western blotting and histology. Further, voluntary exercise for 6 weeks (long-term exercise) downregulated the expression of hepatic lipogenesis-associated proteins. These results suggest that hepatic lipogenesis and/or hepatic lipolysis mediate the beneficial effects of voluntary exercise on hepatic fat accumulation.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2014

A National-Scale Comparison of Resource and Nutrient Demands for Algae-Based Biofuel Production by Lipid Extraction and Hydrothermal Liquefaction

Algae’s high productivity provides potential resource advantages over other fuel crops. However, demand for land, water, and nutrients must be minimized to avoid impacts on food production. We apply our national-scale, open-pond, growth and resource models to assess several biomass to fuel technological pathways based on Chlorella. We compare resource demands between hydrothermal liquefaction (HTL) and lipid extraction (LE) to meet 1.89E+10 and 7.95E+10 L yr-1 biofuel targets. We estimate nutrient demands where post-fuel biomass is consumed as co-products and recycling by anaerobic digestion (AD) or catalytic hydrothermal gasification (CHG). Sites are selected through prioritization based on fuel value relative to a set of site-specific resource costs. The highest priority sites are located along the Gulf of Mexico coast, but potential sites exist nationwide. We find that HTL reduces land and freshwater consumption by up to 46% and saline groundwater by around 70%. Without recycling, nitrogen (N) and phosphorous (P) demand is reduced 33%, but is large relative to current U.S. agricultural consumption. The most nutrient-efficient pathways are LE+CHG for N and HTL+CHG for P (by 42%). Resource gains for HTL+CHG are offset by a 344% increase in N consumption relative to LE+CHG (with potential for further recycling). Nutrient recycling is essential to effective use of alternative nutrient sources. Modeling of utilization availability and costs remains, but we find that for HTL+CHG at the 7.95E+10 L yr-1 production target, municipal sources can offset 17% of N and 40% of P demand and animal manures can generally meet demands.

algae biofuel, sustainability, flue gas, nitrogen,↗
DOE OSTI2024

Engineering and evolution of Yarrowia lipolytica for producing lipids from lignocellulosic hydrolysates

Yarrowia lipolytica, an oleaginous yeast, shows promise for industrial fermentation due to its robust acetyl-CoA flux and well-developed genetic engineering tools. However, its lack of an active xylose metabolism restricts the conversion of cellulosic sugars to valuable products. To address this, metabolic engineering, and adaptive laboratory evolution (ALE) were applied to the Y. lipolytica PO1f strain, resulting in an efficient xylose-assimilating strain (XEV). Whole-genome sequencing (WGS) of the XEV followed by reverse engineering revealed that the amplification of the heterologous oxidoreductase pathway and a mutation in the GTPase-activating protein gene (YALI0B12100g) might be the primary reasons for improved xylose assimilation in the XEV strain. When a sorghum hydrolysate was used, the XEV strain showed superior xylose consumption and lipid production compared to its parental strain (X123). This study advances our understanding of xylose metabolism in Y. lipolytica and proposes effective metabolic engineering strategies for optimizing lignocellulosic hydrolysates.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2011

Crystallizing Transmembrane Peptides in Lipidic Mesophases

Structure determination of membrane proteins by crystallographic means has been facilitated by crystallization in lipidic mesophases. It has been suggested, however, that this so-called in meso method, as originally implemented, would not apply to small protein targets having {le}4 transmembrane crossings. In our study, the hypothesis that the inherent flexibility of the mesophase would enable crystallogenesis of small proteins was tested using a transmembrane pentadecapeptide, linear gramicidin, which produced structure-grade crystals. This result suggests that the in meso method should be considered as a viable means for high-resolution structure determination of integral membrane peptides, many of which are predicted to be coded for in the human genome.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2015

Synthetic biology for microbial production of lipid-based biofuels

The risks of maintaining current CO 2 emission trends have led to interest in producing biofuels using engineered microbes. Microbial biofuels reduce emissions because CO 2 produced by fuel combustion is offset by CO2 captured by growing biomass, which is later used as feedstock for biofuel fermentation. Hydrocarbons found in petroleum fuels share striking similarity with biological lipids. Here in this paper we review synthetic metabolic pathways based on fatty acid and isoprenoid metabolism to produce alkanes and other molecules suitable as biofuels. Lastly, we further discuss engineering strategies to optimize engineered biosynthetic routes, as well as the potential of synthetic biology for sustainable manufacturing.

09 BIOMASS FUELS↗
DOE OSTI2018

Thermal actuation in $\mathrm{TRPV1}$: Role of embedded lipids and intracellular domains

The transient response potential cation channel TRPV1 responds to high temperature, but many of the mechanisms driving its thermal actuation remain unclear. Its recently resolved structure has enabled a number of molecular dynamics (MD) studies focused on illuminating these mechanisms. Here we add to these efforts by performing the first all-atom MD simulations of its most recently resolved structure at different temperatures. While the complete, thermally induced transition of TRPV1 from its closed to open configuration remains elusive, our analysis of the hydrogen bonding networks, thermodynamics, hydration, and principal components of motion provide a wealth of information on the mechanisms which initiate or influence the thermal opening in TRPV1. In particular, we (i) support the previously proposed mechanism driving thermal actuation in the extracellular pore of TRPV1, (ii) present new hypotheses regarding the thermal actuation in the C-terminal and adjacent linker domains, and (iii) support and build upon the existing hypothesis regarding the role of the vanilloid binding pocket and lipids embedded therein.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2015

Honokiol activates the LKB1–AMPK signaling pathway and attenuates the lipid accumulation in hepatocytes

Honokiol is a bioactive neolignan compound isolated from the species of Magnolia. This study was designed to elucidate the cellular mechanism by which honokiol alleviates the development of non-alcoholic steatosis. HepG2 cells were treated with honokiol for 1 h, and then exposed to 1 mM free fatty acid (FFA) for 24 h to simulate non-alcoholic steatosis in vitro. C57BL/6 mice were fed with a high-fat diet for 28 days, and honokiol (10 mg/kg/day) was daily treated. Honokiol concentration-dependently attenuated intracellular fat overloading and triglyceride (TG) accumulation in FFA-exposed HepG2 cells. These effects were blocked by pretreatment with an AMP-activated protein kinase (AMPK) inhibitor. Honokiol significantly inhibited sterol regulatory element-binding protein-1c (SREBP-1c) maturation and the induction of lipogenic proteins, stearoyl-CoA desaturase-1 (SCD-1) and fatty acid synthase (FAS) in FFA-exposed HepG2 cells, but these effects were blocked by pretreatment of an AMPK inhibitor. Honokiol induced AMPK phosphorylation and subsequent acetyl-CoA carboxylase (ACC) phosphorylation, which were inhibited by genetic deletion of liver kinase B1 (LKB1). Honokiol stimulated LKB1 phosphorylation, and genetic deletion of LKB1 blocked the effect of honokiol on SREBP-1c maturation and the induction of SCD-1 and FAS proteins in FFA-exposed HepG2 cells. Honokiol attenuated the increases in hepatic TG and lipogenic protein levels and fat accumulation in the mice fed with high-fat diet, while significantly induced LKB1 and AMPK phosphorylation. Taken together, our findings suggest that honokiol has an anti-lipogenic effect in hepatocytes, and this effect may be mediated by the LKB1–AMPK signaling pathway, which induces ACC phosphorylation and inhibits SREBP-1c maturation in hepatocytes. - Highlights: • Honokiol attenuates lipid accumulation induced by free fatty acid in hepatocyte. • Honokiol inhibits the increase in lipogenic enzyme levels induced by free fatty acid. • Honokiol induces the phosphorylation of AMPK and ACC and inhibits SREBP-1c maturation. • LKB1–AMPK signaling pathway mediates anti-lipogenic effect of honokiol in hepatocyte. • Honokiol activates LKB1 and AMPK and inhibits nonalcoholic steatosis in HFD-fed mice.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2015

Diacyltransferase Activity and Chain Length Specificity of Mycobacterium tuberculosis PapA5 in the Synthesis of Alkyl β-Diol Lipids

Although classified as Gram-positive bacteria, Corynebacterineae possess an asymmetric outer membrane that imparts structural and thereby physiological similarity to more distantly related Gram-negative bacteria. Like lipopolysaccharide in Gram-negative bacteria, lipids in the outer membrane of Corynebacterineae have been associated with the virulence of pathogenic species such as Mycobacterium tuberculosis (Mtb). For example, Mtb strains that lack long, branched-chain alkyl esters known as dimycocerosates (DIMs) are significantly attenuated in model infections. The resultant interest in the biosynthetic pathway of these unusual virulence factors has led to the elucidation of many of the steps leading to the final esterification of the alkyl beta-diol, phthiocerol, with branched-chain fatty acids know as mycocerosates. PapA5 is an acyltransferase implicated in these final reactions. We here show that PapA5 is indeed the terminal enzyme in DIM biosynthesis by demonstrating its dual esterification activity and chain-length preference using synthetic alkyl beta-diol substrate analogues. Applying these analogues to a series of PapA5 mutants, we also revise a model for the substrate binding within PapA5. Finally, we demonstrate that the Mtb Ser/Thr kinase PknB modifies PapA5 on three Thr residues, including two (T196, T198) located on an unresolved loop. These results clarify the DIM biosynthetic pathway and suggest possible mechanisms by which DIM biosynthesis may be regulated by the post-translational modification of PapA5.

Environmental Molecular Sciences Laboratory↗
DOE OSTI2016

Understanding the Interaction of Pluronics L61 and L64 with a DOPC Lipid Bilayer: An Atomistic Molecular Dynamics Study

In this paper, we investigate the interactions of Pluronics L61 and L64 with a dioleylphosphatidylcholine (DOPC) lipid bilayer by atomistic molecular dynamics simulations using the all-atom OPLS force field. Our results show that the initial configuration of the polymer with respect to the bilayer determines its final conformation within the bilayer. When the polymer is initially placed at the lipid/water interface, we observe partial insertion of the polymer in a U-shaped conformation. On the other hand, when the polymer is centered at the bilayer, it stabilizes to a transmembrane state, which facilitates water transport across the bilayer. We show that membrane thickness decreases while its fluidity increases in the presence of Pluronics. When the polymer concentration inside the bilayer is high, pore formation is initiated with L64. Finally, our results show good agreement with existing experimental data and reveal that the hydrophilic/lipophilic balance of the polymer plays a critical role in the interaction mechanisms as well as in the dynamics of Pluronics with and within the bilayer.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗
DOE OSTI2017

Calcium and zinc differentially affect the structure of lipid membranes

Interactions of calcium (Ca 2+ ) and zinc (Zn 2+ ) cations with biomimetic membranes made of dipalmitoylphosphatidylcholine (DPPC) were studied by small angle neutron diffraction (SAND). Experiments show that the structure of these lipid bilayers is differentially affected by the two divalent cations. Initially, both Ca 2+ and Zn 2+ cause DPPC bilayers to thicken, while further increases in Ca 2+ concentration result in the bilayer thinning, eventually reverting to having the same thickness as pure DPPC. The binding of Zn 2+ , on the other hand, causes the bilayers to swell to a maximum thickness, and the addition of more Zn 2+ does not result in a further thickening of the membrane. Agreement between our results obtained using oriented planar membranes and those from vesicular samples implies that the effect of cations on bilayer thickness is the result of electrostatic interactions, rather than geometrical constraints due to bilayer curvature. This notion is further reinforced by MD simulations. Lastly, the radial distribution functions reveal a strong interaction between Ca 2+ and the phosphate oxygens, while Zn 2+ shows a much weaker binding specificity.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗
DOE OSTI2021

Inhibition of Amyloid β-Induced Lipid Membrane Permeation and Amyloid β Aggregation by K162

Alzheimer's disease (AD) is characterized by progressive neurodegeneration associated with amyloid β (Aβ) peptide aggregation. The aggregation of Aβ monomers (AβMs) leads to the formation of Aβ oligomers (AβOs), the neurotoxic Aβ form, capable of permeating the cell membrane. Here, we investigated the effect of a fluorene-based active drug candidate, named K162, on both Aβ aggregation and AβO toxicity toward the bilayer lipid membrane (BLM). Electrochemical impedance spectroscopy (EIS), atomic force microscopy (AFM), and molecular dynamics (MD) were employed to show that K162 inhibits AβOs-induced BLM permeation, thus preserving BLM integrity. In the presence of K162, only shallow defects on the BLM surface were formed. Apparently, K162 modifies Aβ aggregation by bypassing the formation of toxic AβOs, and only nontoxic AβMs, dimers (AβDs), and fibrils (AβFs) are produced. Unlike other Aβ toxicity inhibitors, K162 preserves neurologically beneficial AβMs. This unique K162 inhibition mechanism provides an alternative AD therapeutic strategy that could be explored in the future.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗
DOE OSTI2015

Metagenomic and lipid analyses reveal a diel cycle in a hypersaline microbial ecosystem

Marine microbial communities experience daily fluctuations in light and temperature that can have important ramifications for carbon and nutrient cycling. Elucidation of such short time scale community-wide dynamics is hindered by system complexity. Hypersaline aquatic environments have lower species richness than marine environments and can be well-defined spatially, hence they provide a model system for diel cycle analysis. For this study, we conducted a 3-day time series experiment in a well-defined pool in hypersaline Lake Tyrrell, Australia. Microbial communities were tracked by combining cultivation-independent lipidomic, metagenomic and microscopy methods. The ratio of total bacterial to archaeal core lipids in the planktonic community increased by up to 58% during daylight hours and decreased by up to 32% overnight. However, total organism abundances remained relatively consistent over 3 days. Metagenomic analysis of the planktonic community composition, resolved at the genome level, showed dominance by Haloquadratum species and six uncultured members of the Halobacteriaceae . The post 0.8 μm filtrate contained six different nanohaloarchaeal types, three of which have not been identified previously, and cryo-transmission electron microscopy imaging confirmed the presence of small cells. Notably, these nano-sized archaea showed a strong diel cycle, with a pronounced increase in relative abundance over the night periods. We detected no eukaryotic algae or other photosynthetic primary producers, suggesting that carbon resources may derive from patchily distributed microbial mats at the sediment-water interface or from surrounding land. Results show the operation of a strong community-level diel cycle, probably driven by interconnected temperature, light abundance, dissolved oxygen concentration and nutrient flux effects.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2016

Lipidic cubic phase injector is a viable crystal delivery system for time-resolved serial crystallography

Serial femtosecond crystallography (SFX) using X-ray free-electron laser sources is an emerging method with considerable potential for time-resolved pump-probe experiments. Here we present a lipidic cubic phase SFX structure of the light-driven proton pump bacteriorhodopsin (bR) to 2.3 Å resolution and a method to investigate protein dynamics with modest sample requirement. Time-resolved SFX (TR-SFX) with a pump-probe delay of 1 ms yields difference Fourier maps compatible with the dark to M state transition of bR. Importantly, the method is very sample efficient and reduces sample consumption to about 1 mg per collected time point. Accumulation of M intermediate within the crystal lattice is confirmed by time-resolved visible absorption spectroscopy. Furthermore, this study provides an important step towards characterizing the complete photocycle dynamics of retinal proteins and demonstrates the feasibility of a sample efficient viscous medium jet for TR-SFX.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2016

Heterogeneous silicon mesostructures for lipid-supported bioelectric interfaces

Silicon-based materials have widespread application as biophysical tools and biomedical devices. Here we introduce a biocompatible and degradable mesostructured form of silicon with multi-scale structural and chemical heterogeneities. The material was synthesized using mesoporous silica as a template through a chemical vapour deposition process. It has an amorphous atomic structure, an ordered nanowire-based framework and random submicrometre voids, and shows an average Young’s modulus that is 2–3 orders of magnitude smaller than that of single-crystalline silicon. In addition, we used the heterogeneous silicon mesostructures to design a lipid-bilayer-supported bioelectric interface that is remotely controlled and temporally transient, and that permits non-genetic and subcellular optical modulation of the electrophysiology dynamics in single dorsal root ganglia neurons. Our findings suggest that the biomimetic expansion of silicon into heterogeneous and deformable forms can open up opportunities in extracellular biomaterial or bioelectric systems.

Jiang, Yuanwen↗
DOE OSTI2018

Crystal structure of lipid A disaccharide synthase LpxB from Escherichia coli

Most Gram-negative bacteria are surrounded by a glycolipid called lipopolysaccharide (LPS), which forms a barrier to hydrophobic toxins and, in pathogenic bacteria, is a virulence factor. During LPS biosynthesis, a membrane-associated glycosyltransferase (LpxB) forms a tetra-acylated disaccharide that is further acylated to form the membrane anchor moiety of LPS. Here we solve the structure of a soluble and catalytically competent LpxB by X-ray crystallography. The structure reveals that LpxB has a glycosyltransferase-B family fold but with a highly intertwined, C-terminally swapped dimer comprising four domains. We identify key catalytic residues with a product, UDP, bound in the active site, as well as clusters of hydrophobic residues that likely mediate productive membrane association or capture of lipidic substrates. These studies provide the basis for rational design of antibiotics targeting a crucial step in LPS biosynthesis.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2026

Bacteria covalently incorporate polyfluoroalkyl carboxylates into membrane lipids

Per- and polyfluoroalkyl substances (PFASs), also known as forever chemicals, are global contaminants, but understanding of microbiota–PFAS interactions is limited. Here we show that bacteria covalently incorporate n:3 fluorotelomer carboxylates (FTCAs) into phosphatidylethanolamine and phosphatidylglycerol, two prominent components of bacterial lipid bilayers. Lipidomics of the soil bacterium Pseudomonas sp. strain 273 grown in the presence of 7:3 FTCA or 8:3 FTCA estimated that 7–12% of the bacterium’s glycerophospholipid pool contains the respective polyfluoroacyl chains. This covalent incorporation was observed in five other axenic bacterial cultures tested, including other Pseudomonas species, Escherichia coli and Enterococcus faecalis, albeit with lower incorporation percentages. Incorporation occurred over a broad concentration range, and n:3 FTCAs with varying chain length were covalently incorporated into membranes. Biotransformation of polyfluoroalkyl substances (also known as precursors) results in n:3 FTCA intermediates, which bacteria can covalently incorporate into their glycerophospholipid pools. We conclude that bacteria can form fluoromembranes when exposed to precursors and are a potential PFAS sink.

Xie, Yongchao [University of Tennessee, Knoxville ↗
DOE OSTI2024

Lung and liver editing by lipid nanoparticle delivery of a stable CRISPR–Cas9 ribonucleoprotein

Lipid nanoparticle (LNP) delivery of clustered regularly interspaced short palindromic repeat (CRISPR) ribonucleoproteins (RNPs) could enable high-efficiency, low-toxicity and scalable in vivo genome editing if efficacious RNP–LNP complexes can be reliably produced. Here we engineer a thermostable Cas9 from Geobacillus stearothermophilus (GeoCas9) to generate iGeoCas9 variants capable of >100× more genome editing of cells and organs compared with the native GeoCas9 enzyme. Furthermore, iGeoCas9 RNP–LNP complexes edit a variety of cell types and induce homology-directed repair in cells receiving codelivered single-stranded DNA templates. Using tissue-selective LNP formulations, we observe genome-editing levels of 16-37% in the liver and lungs of reporter mice that receive single intravenous injections of iGeoCas9 RNP–LNPs. In addition, iGeoCas9 RNPs complexed to biodegradable LNPs edit the disease-causing SFTPC gene in lung tissue with 19% average efficiency, representing a major improvement over genome-editing levels observed previously using viral or nonviral delivery strategies. These results show that thermostable Cas9 RNP–LNP complexes can expand the therapeutic potential of genome editing.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2023

Long-term super-resolution inner mitochondrial membrane imaging with a lipid probe

The inner mitochondrial membrane (IMM) generates power to drive cell function, and its dynamics control mitochondrial health and cellular homeostasis. Here, we describe the cell-permeant, lipid-like small molecule MAO-N 3 and use it to assemble high-density environmentally sensitive (HIDE) probes that selectively label and image the IMM in live cells and multiple cell states. MAO-N 3 pairs with strain-promoted azide–alkyne click chemistry-reactive fluorophores to support HIDE imaging using confocal, structured illumination, single-molecule localization and stimulated emission depletion microscopy, all with significantly improved resistance to photobleaching. These probes generate images with excellent spatial and temporal resolution, require no genetic manipulations, are non-toxic in model cell lines and primary cardiomyocytes (even under conditions that amplify the effects of mitochondrial toxins) and can visualize mitochondrial dynamics for 12.5 h. This probe will enable comprehensive studies of IMM dynamics with high temporal and spatial resolution.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗