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  1. Vitamin B12-impaired metabolism produces apoptosis and Parkinson phenotype in rats expressing the transcobalamin-oleosin chimera in substantia nigra.

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    Carlos Enrique Orozco-Barrios

    Full Text Available BACKGROUND: Vitamin B12 is indispensable for proper brain functioning and cytosolic synthesis of S-adenosylmethionine. Whether its deficiency produces effects on viability and apoptosis of neurons remains unknown. There is a particular interest in investigating these effects in Parkinson disease where Levodopa treatment is known to increase the consumption of S-adenosylmethionine. To cause deprivation of vitamin B12, we have recently developed a cell model that produces decreased synthesis of S-adenosylmethionine by anchoring transcobalamin (TCII to the reticulum through its fusion with Oleosin (OLEO. METHODOLOGY: Gene constructs including transcobalamin-oleosin (TCII-OLEO and control constructs, green fluorescent protein-transcobalamin-oleosin (GFP-TCII-OLEO, oleosin-transcobalamin (OLEO-TCII, TCII and OLEO were used for expression in N1E-115 cells (mouse neuroblastoma and in substantia nigra of adult rats, using a targeted transfection with a Neurotensin polyplex system. We studied the viability and the apoptosis in the transfected cells and targeted tissue. The turning behavior was evaluated in the rats transfected with the different plasmids. PRINCIPAL FINDINGS: The transfection of N1E-115 cells by the TCII-OLEO-expressing plasmid significantly affected cell viability and increased immunoreactivity of cleaved Caspase-3. No change in propidium iodide uptake (used as a necrosis marker was observed. The transfected rats lost neurons immunoreactive to tyrosine hydroxylase. The expression of TCII-OLEO was observed in cells immunoreactive to tyrosine hydroxylase of the substantia nigra, with a superimposed expression of cleaved Caspase-3. These cellular and tissular effects were not observed with the control plasmids. Rats transfected with TCII-OLEO expressing plasmid presented with a significantly higher number of turns, compared with those transfected with the other plasmids. CONCLUSIONS/SIGNIFICANCE: In conclusion, the TCII-OLEO transfection

  2. Metabolic evolution of Escherichia coli strains that produce organic acids

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    Grabar, Tammy; Gong, Wei; Yocum, R Rogers

    2014-10-28

    This invention relates to the metabolic evolution of a microbial organism previously optimized for producing an organic acid in commercially significant quantities under fermentative conditions using a hexose sugar as sole source of carbon in a minimal mineral medium. As a result of this metabolic evolution, the microbial organism acquires the ability to use pentose sugars derived from cellulosic materials for its growth while retaining the original growth kinetics, the rate of organic acid production and the ability to use hexose sugars as a source of carbon. This invention also discloses the genetic change in the microorganism that confers the ability to use both the hexose and pentose sugars simultaneously in the production of commercially significant quantities of organic acids.

  3. Circulating Metabolic Profile of High Producing Holstein Dairy Cows

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    Aliasghar CHALMEH

    2015-07-01

    Full Text Available Assessing the metabolic profile based on the concept that the laboratory measurement of certain circulating components is a tool to evaluate metabolic status of dairy cows. Veterinarian also can evaluate the energy input-output relationships by assessing the metabolic profile to prevent and control of negative energy balance, metabolic disorders and nutritional insufficiencies. In the present study, 25 multiparous Holstein dairy cows were divided to 5 equal groups containing early, mid and late lactation, and far-off and close-up dry. Blood samples were collected from all cows through jugular venipuncture and sera were evaluated for glucose, insulin, β-hydroxybutyric acid (BHBA, non-esterified fatty acid (NEFA, cholesterol, triglyceride (TG, high, low and very low density lipoproteins (HDL, LDL and VLDL. Insulin levels in mid lactation and close-up dry cows were significantly higher than other groups (P<0.05 and the lowest insulin concentration was detected in far-off dry group. Serum concentrations of NEFA and BHBA in early and mid-lactation and close-up dry cows were significantly higher than late lactation and far-off dry animals (P<0.05. Baseline levels of cholesterol in mid and late lactation were significantly higher than other groups. The level of LDL in mid lactation cows was higher than others significantly, and its value in far-off dry cows was significantly lower than other group (P<0.05. It may be concluded that the detected changes among different groups induce commonly by negative energy balance, lactogenesis and fetal growth in each state. The presented metabolic profile can be considered as a tool to assess the energy balance in dairy cows at different physiologic states. It can be used to evaluate the metabolic situations of herd and manage the metabolic and production disorders.

  4. Metabolic engineering toward 1-butanol derivatives in solvent producing clostridia

    NARCIS (Netherlands)

    Siemerink, M.A.J.

    2010-01-01

    Chapter 1 of this thesis gives an overview about the history of the acetone, butanol and ethanol (ABE) fermentation. The responsible solventogenic clostridia with their central metabolism are briefly discussed. Despite the fact that scientific research on the key organisms of the ABE process has

  5. Artificial sweeteners produce the counterintuitive effect of inducing metabolic derangements.

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    Swithers, Susan E

    2013-09-01

    The negative impact of consuming sugar-sweetened beverages on weight and other health outcomes has been increasingly recognized; therefore, many people have turned to high-intensity sweeteners like aspartame, sucralose, and saccharin as a way to reduce the risk of these consequences. However, accumulating evidence suggests that frequent consumers of these sugar substitutes may also be at increased risk of excessive weight gain, metabolic syndrome, type 2 diabetes, and cardiovascular disease. This paper discusses these findings and considers the hypothesis that consuming sweet-tasting but noncaloric or reduced-calorie food and beverages interferes with learned responses that normally contribute to glucose and energy homeostasis. Because of this interference, frequent consumption of high-intensity sweeteners may have the counterintuitive effect of inducing metabolic derangements. Copyright © 2013 Elsevier Ltd. All rights reserved.

  6. Quantitative Tools for Dissection of Hydrogen-Producing Metabolic Networks-Final Report

    Energy Technology Data Exchange (ETDEWEB)

    Rabinowitz, Joshua D.; Dismukes, G.Charles.; Rabitz, Herschel A.; Amador-Noguez, Daniel

    2012-10-19

    During this project we have pioneered the development of integrated experimental-computational technologies for the quantitative dissection of metabolism in hydrogen and biofuel producing microorganisms (i.e. C. acetobutylicum and various cyanobacteria species). The application of these new methodologies resulted in many significant advances in the understanding of the metabolic networks and metabolism of these organisms, and has provided new strategies to enhance their hydrogen or biofuel producing capabilities. As an example, using mass spectrometry, isotope tracers, and quantitative flux-modeling we mapped the metabolic network structure in C. acetobutylicum. This resulted in a comprehensive and quantitative understanding of central carbon metabolism that could not have been obtained using genomic data alone. We discovered that biofuel production in this bacterium, which only occurs during stationary phase, requires a global remodeling of central metabolism (involving large changes in metabolite concentrations and fluxes) that has the effect of redirecting resources (carbon and reducing power) from biomass production into solvent production. This new holistic, quantitative understanding of metabolism is now being used as the basis for metabolic engineering strategies to improve solvent production in this bacterium. In another example, making use of newly developed technologies for monitoring hydrogen and NAD(P)H levels in vivo, we dissected the metabolic pathways for photobiological hydrogen production by cyanobacteria Cyanothece sp. This investigation led to the identification of multiple targets for improving hydrogen production. Importantly, the quantitative tools and approaches that we have developed are broadly applicable and we are now using them to investigate other important biofuel producers, such as cellulolytic bacteria.

  7. Glucose metabolism in the antibiotic producing actinomycete Nonomuraea sp ATCC 39727

    DEFF Research Database (Denmark)

    Gunnarsson, Nina; Bruheim, Per; Nielsen, Jens

    2004-01-01

    The actinomycete Nonomuraea sp. ATCC 39727, producer of the glycopeptide A40926 that is used as precursor for the novel antibiotic dalbavancin, has an unusual carbon metabolism. Glucose is primarily metabolized via the Entner-Doudoroff (ED) pathway, although the energetically more favorable Embden...... - Meyerhof - Parnas (EMP) pathway is present in this organism. Moreover, Nonomuraea utilizes a PPi-dependent phosphofructokinase, an enzyme that has been connected with anaerobic metabolism in eukaryotes and higher plants, but recently has been recognized in several actinomycetes. In order to study its...

  8. Change in energy metabolism of in vitro produced embryos: an alternative to make them more cryoresistant?

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    Luzia Renata Oliveira Dias

    2017-08-01

    Full Text Available For the development of in vitro produced (IVP as well as in vivo produced bovine embryos, it is extremely important that their energy metabolism works properly because the embryo must be able to metabolize energy substrates that are necessary for producing energy. Lipids play an important role in early embryonic development, acting as source of energy for oocytes and embryos. However, it is known that oocytes and embryos, mainly IVP, accumulate large amounts of lipids in the cytoplasm. Although they are extremely important in embryonic development, lipids have been associated with the reduced survival of bovine embryos following cryopreservation. There is evidence that at least four different categories of lipids affect embryo survival after cryopreservation, including triglycerides (TAG, free fatty acids, cholesterol and phospholipids. Thus, many studies are being conducted to improve the resistance of IVP embryos to the cryopreservation process by reducing the concentration or removing the source of serum from the medium or by reducing oocyte/embryo lipids using mechanical or chemical means. Regarding the use of delipidating agents that reduce the uptake and synthesis of fatty acids (FA by cells, substances such as phenazine ethosulfate (PES, forskolin, L-carnitine and isomers of conjugated linoleic acid (CLA have been utilized. This review aims to address important issues related to embryonic energy metabolism, the importance of lipid metabolism and its relation to the cryopreservation of IVP bovine embryos by summarizing the latest research in this field.

  9. Metabolic responses to pyruvate kinase deletion in lysine producing Corynebacterium glutamicum

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    Wittmann Christoph

    2008-03-01

    Full Text Available Abstract Background Pyruvate kinase is an important element in flux control of the intermediate metabolism. It catalyzes the irreversible conversion of phosphoenolpyruvate into pyruvate and is under allosteric control. In Corynebacterium glutamicum, this enzyme was regarded as promising target for improved production of lysine, one of the major amino acids in animal nutrition. In pyruvate kinase deficient strains the required equimolar ratio of the two lysine precursors oxaloacetate and pyruvate can be achieved through concerted action of the phosphotransferase system (PTS and phosphoenolpyruvate carboxylase (PEPC, whereby a reduced amount of carbon may be lost as CO2 due to reduced flux into the tricarboxylic acid (TCA cycle. In previous studies, deletion of pyruvate kinase in lysine-producing C. glutamicum, however, did not yield a clear picture and the exact metabolic consequences are not fully understood. Results In this work, deletion of the pyk gene, encoding pyruvate kinase, was carried out in the lysine-producing strain C. glutamicum lysCfbr, expressing a feedback resistant aspartokinase, to investigate the cellular response to deletion of this central glycolytic enzyme. Pyk deletion was achieved by allelic replacement, verified by PCR analysis and the lack of in vitro enzyme activity. The deletion mutant showed an overall growth behavior (specific growth rate, glucose uptake rate, biomass yield which was very similar to that of the parent strain, but differed in slightly reduced lysine formation, increased formation of the overflow metabolites dihydroxyacetone and glycerol and in metabolic fluxes around the pyruvate node. The latter involved a flux shift from pyruvate carboxylase (PC to PEPC, by which the cell maintained anaplerotic supply of the TCA cycle. This created a metabolic by-pass from PEP to pyruvate via malic enzyme demonstrating its contribution to metabolic flexibility of C. glutamicum on glucose. Conclusion The metabolic

  10. Chemical and Metabolic Aspects of Antimetabolite Toxins Produced by Pseudomonas syringae Pathovars

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    Eva Arrebola

    2011-08-01

    Full Text Available Pseudomonas syringae is a phytopathogenic bacterium present in a wide variety of host plants where it causes diseases with economic impact. The symptoms produced by Pseudomonas syringae include chlorosis and necrosis of plant tissues, which are caused, in part, by antimetabolite toxins. This category of toxins, which includes tabtoxin, phaseolotoxin and mangotoxin, is produced by different pathovars of Pseudomonas syringae. These toxins are small peptidic molecules that target enzymes of amino acids’ biosynthetic pathways, inhibiting their activity and interfering in the general nitrogen metabolism. A general overview of the toxins’ chemistry, biosynthesis, activity, virulence and potential applications will be reviewed in this work.

  11. Effect of produced water on feeding and metabolism of Atlantic cod (Gadus morhua)

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    Volkoff, H.; Parrish, C.; Hamoutene, D.; Mabrouk, G.; Samuelson, S.; Mansour, A.; Lee, K.

    2007-01-01

    This paper addressed concerns regarding potentially detrimental cumulative effects of waste products from oil industry activities on marine organisms around production sites. The metabolic capacities, feeding and digestive physiology of fish have been shown to change with environmental parameters, which could impact the growth and health status of fish populations. In this study, the effects of produced water (PW) on feeding and metabolism of Atlantic cod was investigated by exposing fish to 0.100 ppm (x 10,000 PW dilution) or 200 ppm (x 500 dilution) of PW for 76 days. Throughout the experiment, food intake and mean weight were monitored. In addition, serum lipids, metabolites and gene expression of a brain appetite regulating factor were measured at the end of the experiment. No significant differences were observed in weight gain or food intake between the 3 groups of fish. Serum metabolites and neuropeptide Y expression remained unchanged between groups. The study is ongoing to complete comparative measurements of whole blood fatty acid profiles in plasma. The preliminary results indicate that feeding and metabolism in cod is not affected by produced water

  12. Evolutionary optimization of metabolic pathways. Theoretical reconstruction of the stoichiometry of ATP and NADH producing systems.

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    Ebenhöh, O; Heinrich, R

    2001-01-01

    The structural design of ATP and NADH producing systems, such as glycolysis and the citric acid cycle (TCA), is analysed using optimization principles. It is assumed that these pathways combined with oxidative phosphorylation have reached, during their evolution, a high efficiency with respect to ATP production rates. On the basis of kinetic and thermodynamic principles, conclusions are derived concerning the optimal stoichiometry of such pathways. Extending previous investigations, both the concentrations of adenine nucleotides as well as nicotinamide adenine dinucleotides are considered variable quantities. This implies the consideration of the interaction of an ATP and NADH producing system, an ATP consuming system, a system coupling NADH consumption with ATP production and a system consuming NADH decoupled from ATP production. It is examined in what respect real metabolic pathways can be considered optimal by studying a large number of alternative pathways. The kinetics of the individual reactions are described by linear or bilinear functions of reactant concentrations. In this manner, the steady-state ATP production rate can be calculated for any possible ATP and NADH producing pathway. It is shown that most of the possible pathways result in a very low ATP production rate and that the very efficient pathways share common structural properties. Optimization with respect to the ATP production rate is performed by an evolutionary algorithm. The following results of our analysis are in close correspondence to the real design of glycolysis and the TCA cycle. (1) In all efficient pathways the ATP consuming reactions are located near the beginning. (2) In all efficient pathways NADH producing reactions as well as ATP producing reactions are located near the end. (3) The number of NADH molecules produced by the consumption of one energy-rich molecule (glucose) amounts to four in all efficient pathways. A distance measure and a measure for the internal ordering of

  13. Proteomic evidences for rex regulation of metabolism in toxin-producing Bacillus cereus ATCC 14579.

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    Sabrina Laouami

    Full Text Available The facultative anaerobe, Bacillus cereus, causes diarrheal diseases in humans. Its ability to deal with oxygen availability is recognized to be critical for pathogenesis. The B. cereus genome comprises a gene encoding a protein with high similarities to the redox regulator, Rex, which is a central regulator of anaerobic metabolism in Bacillus subtilis and other Gram-positive bacteria. Here, we showed that B. cereus rex is monocistronic and down-regulated in the absence of oxygen. The protein encoded by rex is an authentic Rex transcriptional factor since its DNA binding activity depends on the NADH/NAD+ ratio. Rex deletion compromised the ability of B. cereus to cope with external oxidative stress under anaerobiosis while increasing B. cereus resistance against such stress under aerobiosis. The deletion of rex affects anaerobic fermentative and aerobic respiratory metabolism of B. cereus by decreasing and increasing, respectively, the carbon flux through the NADH-recycling lactate pathway. We compared both the cellular proteome and exoproteome of the wild-type and Δrex cells using a high throughput shotgun label-free quantitation approach and identified proteins that are under control of Rex-mediated regulation. Proteomics data have been deposited to the ProteomeXchange with identifier PXD000886. The data suggest that Rex regulates both the cross-talk between metabolic pathways that produce NADH and NADPH and toxinogenesis, especially in oxic conditions.

  14. Proteomic evidences for rex regulation of metabolism in toxin-producing Bacillus cereus ATCC 14579.

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    Laouami, Sabrina; Clair, Géremy; Armengaud, Jean; Duport, Catherine

    2014-01-01

    The facultative anaerobe, Bacillus cereus, causes diarrheal diseases in humans. Its ability to deal with oxygen availability is recognized to be critical for pathogenesis. The B. cereus genome comprises a gene encoding a protein with high similarities to the redox regulator, Rex, which is a central regulator of anaerobic metabolism in Bacillus subtilis and other Gram-positive bacteria. Here, we showed that B. cereus rex is monocistronic and down-regulated in the absence of oxygen. The protein encoded by rex is an authentic Rex transcriptional factor since its DNA binding activity depends on the NADH/NAD+ ratio. Rex deletion compromised the ability of B. cereus to cope with external oxidative stress under anaerobiosis while increasing B. cereus resistance against such stress under aerobiosis. The deletion of rex affects anaerobic fermentative and aerobic respiratory metabolism of B. cereus by decreasing and increasing, respectively, the carbon flux through the NADH-recycling lactate pathway. We compared both the cellular proteome and exoproteome of the wild-type and Δrex cells using a high throughput shotgun label-free quantitation approach and identified proteins that are under control of Rex-mediated regulation. Proteomics data have been deposited to the ProteomeXchange with identifier PXD000886. The data suggest that Rex regulates both the cross-talk between metabolic pathways that produce NADH and NADPH and toxinogenesis, especially in oxic conditions.

  15. Consumption of honey, sucrose, and high fructose corn syrup produce similar metabolic effects in glucose tolerant and glucose intolerant individuals

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    Background: Current public health recommendations call for reduction of added sugars; however, controversy exits over whether all nutritive sweeteners produce similar metabolic effects. Objective: To compare effects of chronic consumption of three nutritive sweeteners (honey, sucrose and high fructo...

  16. Metabolic engineering of a haploid strain derived from a triploid industrial yeast for producing cellulosic ethanol.

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    Kim, Soo Rin; Skerker, Jeffrey M; Kong, In Iok; Kim, Heejin; Maurer, Matthew J; Zhang, Guo-Chang; Peng, Dairong; Wei, Na; Arkin, Adam P; Jin, Yong-Su

    2017-03-01

    Many desired phenotypes for producing cellulosic biofuels are often observed in industrial Saccharomyces cerevisiae strains. However, many industrial yeast strains are polyploid and have low spore viability, making it difficult to use these strains for metabolic engineering applications. We selected the polyploid industrial strain S. cerevisiae ATCC 4124 exhibiting rapid glucose fermentation capability, high ethanol productivity, strong heat and inhibitor tolerance in order to construct an optimal yeast strain for producing cellulosic ethanol. Here, we focused on developing a general approach and high-throughput screening method to isolate stable haploid segregants derived from a polyploid parent, such as triploid ATCC 4124 with a poor spore viability. Specifically, we deleted the HO genes, performed random sporulation, and screened the resulting segregants based on growth rate, mating type, and ploidy. Only one stable haploid derivative (4124-S60) was isolated, while 14 other segregants with a stable mating type were aneuploid. The 4124-S60 strain inherited only a subset of desirable traits present in the parent strain, same as other aneuploids, suggesting that glucose fermentation and specific ethanol productivity are likely to be genetically complex traits and/or they might depend on ploidy. Nonetheless, the 4124-60 strain did inherit the ability to tolerate fermentation inhibitors. When additional genetic perturbations known to improve xylose fermentation were introduced into the 4124-60 strain, the resulting engineered strain (IIK1) was able to ferment a Miscanthus hydrolysate better than a previously engineered laboratory strain (SR8), built by making the same genetic changes. However, the IIK1 strain showed higher glycerol and xylitol yields than the SR8 strain. In order to decrease glycerol and xylitol production, an NADH-dependent acetate reduction pathway was introduced into the IIK1 strain. By consuming 2.4g/L of acetate, the resulting strain (IIK1A

  17. Wax esters of different compositions produced via engineering of leaf chloroplast metabolism in Nicotiana benthamiana.

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    Aslan, Selcuk; Sun, Chuanxin; Leonova, Svetlana; Dutta, Paresh; Dörmann, Peter; Domergue, Frédéric; Stymne, Sten; Hofvander, Per

    2014-09-01

    In a future bio-based economy, renewable sources for lipid compounds at attractive cost are needed for applications where today petrochemical derivatives are dominating. Wax esters and fatty alcohols provide diverse industrial uses, such as in lubricant and surfactant production. In this study, chloroplast metabolism was engineered to divert intermediates from de novo fatty acid biosynthesis to wax ester synthesis. To accomplish this, chloroplast targeted fatty acyl reductases (FAR) and wax ester synthases (WS) were transiently expressed in Nicotiana benthamiana leaves. Wax esters of different qualities and quantities were produced providing insights to the properties and interaction of the individual enzymes used. In particular, a phytyl ester synthase was found to be a premium candidate for medium chain wax ester synthesis. Catalytic activities of FAR and WS were also expressed as a fusion protein and determined functionally equivalent to the expression of individual enzymes for wax ester synthesis in chloroplasts. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

  18. Insights into metabolic osmoadaptation of the ectoines-producer bacterium Chromohalobacter salexigens through a high-quality genome scale metabolic model.

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    Piubeli, Francine; Salvador, Manuel; Argandoña, Montserrat; Nieto, Joaquín J; Bernal, Vicente; Pastor, Jose M; Cánovas, Manuel; Vargas, Carmen

    2018-01-09

    The halophilic bacterium Chromohalobacter salexigens is a natural producer of ectoines, compatible solutes with current and potential biotechnological applications. As production of ectoines is an osmoregulated process that draws away TCA intermediates, bacterial metabolism needs to be adapted to cope with salinity changes. To explore and use C. salexigens as cell factory for ectoine(s) production, a comprehensive knowledge at the systems level of its metabolism is essential. For this purpose, the construction of a robust and high-quality genome-based metabolic model of C. salexigens was approached. We generated and validated a high quality genome-based C. salexigens metabolic model (iFP764). This comprised an exhaustive reconstruction process based on experimental information, analysis of genome sequence, manual re-annotation of metabolic genes, and in-depth refinement. The model included three compartments (periplasmic, cytoplasmic and external medium), and two salinity-specific biomass compositions, partially based on experimental results from C. salexigens. Using previous metabolic data as constraints, the metabolic model allowed us to simulate and analyse the metabolic osmoadaptation of C. salexigens under conditions for low and high production of ectoines. The iFP764 model was able to reproduce the major metabolic features of C. salexigens. Flux Balance Analysis (FBA) and Monte Carlo Random sampling analysis showed salinity-specific essential metabolic genes and different distribution of fluxes and variation in the patterns of correlation of reaction sets belonging to central C and N metabolism, in response to salinity. Some of them were related to bioenergetics or production of reducing equivalents, and probably related to demand for ectoines. Ectoines metabolic reactions were distributed according to its correlation in four modules. Interestingly, the four modules were independent both at low and high salinity conditions, as they did not correlate to each

  19. Metabolic Engineering of Yeast to Produce Fatty Acid-derived Biofuels: Bottlenecks and Solutions

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    Jiayuan eSheng

    2015-06-01

    Full Text Available Fatty acid-derived biofuels can be a better solution than bioethanol to replace petroleum fuel, since they have similar energy content and combustion properties as current transportation fuels. The environmentally friendly microbial fermentation process has been used to synthesize advanced biofuels from renewable feedstock. Due to their robustness as well as the high tolerance to fermentation inhibitors and phage contamination, yeast strains such as Saccharomyces cerevisiae and Yarrowia lipolytica have attracted tremendous attention in recent studies regarding the production of fatty acid-derived biofuels, including fatty acids, fatty acid ethyl esters, fatty alcohols, and fatty alkanes. However, the native yeast strains cannot produce fatty acids and fatty acid-derived biofuels in large quantities. To this end, we have summarized recent publications in this review on metabolic engineering of yeast strains to improve the production of fatty acid-derived biofuels, identified the bottlenecks that limit the productivity of biofuels, and categorized the appropriate approaches to overcome these obstacles.

  20. Metabolic flexibility of d-ribose producer strain of Bacillus pumilus under environmental perturbations

    DEFF Research Database (Denmark)

    Srivastava, Rajesh K.; Maiti, Soumen K.; Das, Debasish

    2012-01-01

    The metabolic reaction rate vector is a bridge that links gene and protein expression alterations to the phenotypic endpoint. We present a simple approach for the estimation of flux distribution at key branch points in the metabolic network by using substrate uptake, metabolite secretion rate, an...

  1. Integrated analysis of gene expression and metabolic fluxes in PHA-producing Pseudomonas putida grown on glycerol.

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    Beckers, Veronique; Poblete-Castro, Ignacio; Tomasch, Jürgen; Wittmann, Christoph

    2016-05-03

    Given its high surplus and low cost, glycerol has emerged as interesting carbon substrate for the synthesis of value-added chemicals. The soil bacterium Pseudomonas putida KT2440 can use glycerol to synthesize medium-chain-length poly(3-hydroxyalkanoates) (mcl-PHA), a class of biopolymers of industrial interest. Here, glycerol metabolism in P. putida KT2440 was studied on the level of gene expression (transcriptome) and metabolic fluxes (fluxome), using precisely adjusted chemostat cultures, growth kinetics and stoichiometry, to gain a systematic understanding of the underlying metabolic and regulatory network. Glycerol-grown P. putida KT2440 has a maintenance energy requirement [0.039 (mmolglycerol (gCDW h)(-1))] that is about sixteen times lower than that of other bacteria, such as Escherichia coli, which provides a great advantage to use this substrate commercially. The shift from carbon (glycerol) to nitrogen (ammonium) limitation drives the modulation of specific genes involved in glycerol metabolism, transport electron chain, sensors to assess the energy level of the cell, and PHA synthesis, as well as changes in flux distribution to increase the precursor availability for PHA synthesis (Entner-Doudoroff pathway and pyruvate metabolism) and to reduce respiration (glyoxylate shunt). Under PHA-producing conditions (N-limitation), a higher PHA yield was achieved at low dilution rate (29.7 wt% of CDW) as compared to a high rate (12.8 wt% of CDW). By-product formation (succinate, malate) was specifically modulated under these regimes. On top of experimental data, elementary flux mode analysis revealed the metabolic potential of P. putida KT2440 to synthesize PHA and identified metabolic engineering targets towards improved production performance on glycerol. This study revealed the complex interplay of gene expression levels and metabolic fluxes under PHA- and non-PHA producing conditions using the attractive raw material glycerol as carbon substrate. This

  2. A hybrid approach identifies metabolic signatures of high-producers for chinese hamster ovary clone selection and process optimization.

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    Popp, Oliver; Müller, Dirk; Didzus, Katharina; Paul, Wolfgang; Lipsmeier, Florian; Kirchner, Florian; Niklas, Jens; Mauch, Klaus; Beaucamp, Nicola

    2016-09-01

    In-depth characterization of high-producer cell lines and bioprocesses is vital to ensure robust and consistent production of recombinant therapeutic proteins in high quantity and quality for clinical applications. This requires applying appropriate methods during bioprocess development to enable meaningful characterization of CHO clones and processes. Here, we present a novel hybrid approach for supporting comprehensive characterization of metabolic clone performance. The approach combines metabolite profiling with multivariate data analysis and fluxomics to enable a data-driven mechanistic analysis of key metabolic traits associated with desired cell phenotypes. We applied the methodology to quantify and compare metabolic performance in a set of 10 recombinant CHO-K1 producer clones and a host cell line. The comprehensive characterization enabled us to derive an extended set of clone performance criteria that not only captured growth and product formation, but also incorporated information on intracellular clone physiology and on metabolic changes during the process. These criteria served to establish a quantitative clone ranking and allowed us to identify metabolic differences between high-producing CHO-K1 clones yielding comparably high product titers. Through multivariate data analysis of the combined metabolite and flux data we uncovered common metabolic traits characteristic of high-producer clones in the screening setup. This included high intracellular rates of glutamine synthesis, low cysteine uptake, reduced excretion of aspartate and glutamate, and low intracellular degradation rates of branched-chain amino acids and of histidine. Finally, the above approach was integrated into a workflow that enables standardized high-content selection of CHO producer clones in a high-throughput fashion. In conclusion, the combination of quantitative metabolite profiling, multivariate data analysis, and mechanistic network model simulations can identify metabolic

  3. Effects of an equol-producing bacterium isolated from human faeces on isoflavone and lignan metabolism in mice.

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    Tamura, Motoi; Hori, Sachiko; Nakagawa, Hiroyuki; Yamauchi, Satoshi; Sugahara, Takuya

    2016-07-01

    Equol is a metabolite of daidzein that is produced by intestinal microbiota. The oestrogenic activity of equol is stronger than daidzein. Equol-producing bacteria are believed to play an important role in the gut. The rod-shaped and Gram-positive anaerobic equol-producing intestinal bacterium Slackia TM-30 was isolated from healthy human faeces and its effects on urinary phyto-oestrogen, plasma and faecal lipids were assessed in adult mice. The urinary amounts of equol in urine were significantly higher in mice receiving the equol-producing bacterium TM-30 (BAC) group than in the control (CO) group (P mice. The equol-producing bacterium TM-30 likely influences the metabolism of phyto-oestrogen via changes in the gastrointestinal environment. © 2015 Society of Chemical Industry. © 2015 Society of Chemical Industry.

  4. Differences of hormones involved in adipose metabolism and lactation between high and low producing Holstein cows during heat stress

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    Mingzi Qu

    2015-12-01

    Full Text Available The experiment was conducted to evaluate hormonal involvement in the adipose metabolism and lactation between high and low producing dairy cows in a hot environment. Forty Holstein healthy cows with a similar parity were used and assigned into high producing group (average production 41.44 ± 2.25 kg/d and low producing group (average production 29.92 ± 1.02 kg/d with 20 cows in each group. Blood samples were collected from caudal vein to determine the difference of hormones related to adipose metabolism and lactation. The highest, lowest, and average temperature humidity index (THI, recorded as 84.02, 79.35 and 81.89, respectively, indicated that cows were at the state of high heat stress. No significant differences between high and low producing groups were observed in the levels of nonestesterified fatty acid (NEFA, β-hydroxybutyrate (β-OHB, total cholesterol (TCHO, and insulin (INS (P > 0.05. However, the very low density lipoprotein (VLDL, apolipoprotein B100 (apoB-100, high-density lipoprotein (HDL-C and estrogen (E2 concentrations in high producing group were significantly higher than those of low producing group (P  0.05, whereas high producing group had a rise in the insulin-like growth factor-1 (IGF-1 level compared with low producing group (P < 0.05. These results indicated that, during summer, high and low producing dairy cows have similar levels of lipid catabolism, but high producing dairy cows have advantages in outputting hepatic triglyceride (TG.

  5. Beneficial effects on host energy metabolism of short-chain fatty acids and vitamins produced by commensal and probiotic bacteria.

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    LeBlanc, Jean Guy; Chain, Florian; Martín, Rebeca; Bermúdez-Humarán, Luis G; Courau, Stéphanie; Langella, Philippe

    2017-05-08

    The aim of this review is to summarize the effect in host energy metabolism of the production of B group vitamins and short chain fatty acids (SCFA) by commensal, food-grade and probiotic bacteria, which are also actors of the mammalian nutrition. The mechanisms of how these microbial end products, produced by these bacterial strains, act on energy metabolism will be discussed. We will show that these vitamins and SCFA producing bacteria could be used as tools to recover energy intakes by either optimizing ATP production from foods or by the fermentation of certain fibers in the gastrointestinal tract (GIT). Original data are also presented in this work where SCFA (acetate, butyrate and propionate) and B group vitamins (riboflavin, folate and thiamine) production was determined for selected probiotic bacteria.

  6. Metabolic Engineering of the Moss Physcomitrella patens as a Green Cell Factory to Produce Terpenoids

    DEFF Research Database (Denmark)

    Zhan, Xin

    also achieved with the yields of 1.3 and 0.035 mg/g dry weight respectively, after several metabolic engineering strategies were tried, including HMGR overexpression, CPS/KS gene disruption and plastidic localization of the terpene synthases. In order to synthesize more valuable perfumery ingredient (Z...

  7. Metabolic flux rearrangement in the amino acid metabolism reduces ammonia stress in the α1-antitrypsin producing human AGE1.HN cell line.

    Science.gov (United States)

    Priesnitz, Christian; Niklas, Jens; Rose, Thomas; Sandig, Volker; Heinzle, Elmar

    2012-03-01

    This study focused on metabolic changes in the neuronal human cell line AGE1.HN upon increased ammonia stress. Batch cultivations of α(1)-antitrypsin (A1AT) producing AGE1.HN cells were carried out in media with initial ammonia concentrations ranging from 0mM to 5mM. Growth, A1AT production, metabolite dynamics and finally metabolic fluxes calculated by metabolite balancing were compared. Growth and A1AT production decreased with increasing ammonia concentration. The maximum A1AT concentration decreased from 0.63g/l to 0.51g/l. Central energy metabolism remained relatively unaffected exhibiting only slightly increased glycolytic flux at high initial ammonia concentration in the medium. However, the amino acid metabolism was significantly changed. Fluxes through transaminases involved in amino acid degradation were reduced concurrently with a reduced uptake of amino acids. On the other hand fluxes through transaminases working in the direction of amino acid synthesis, i.e., alanine and phosphoserine, were increased leading to increased storage of excess nitrogen in extracellular alanine and serine. Glutamate dehydrogenase flux was reversed increasingly fixing free ammonia with increasing ammonia concentration. Urea production additionally observed was associated with arginine uptake by the cells and did not increase at high ammonia stress. It was therefore not used as nitrogen sink to remove excess ammonia. The results indicate that the AGE1.HN cell line can adapt to ammonia concentrations usually present during the cultivation process to a large extent by changing metabolism but with slightly reduced A1AT production and growth. Copyright © 2012 Elsevier Inc. All rights reserved.

  8. Rhabdomyosarcoma cells show an energy producing anabolic metabolic phenotype compared with primary myocytes

    Directory of Open Access Journals (Sweden)

    Higashi Richard M

    2008-10-01

    Full Text Available Abstract Background The functional status of a cell is expressed in its metabolic activity. We have applied stable isotope tracing methods to determine the differences in metabolic pathways in proliferating Rhabdomysarcoma cells (Rh30 and human primary myocytes in culture. Uniformly 13C-labeled glucose was used as a source molecule to follow the incorporation of 13C into more than 40 marker metabolites using NMR and GC-MS. These include metabolites that report on the activity of glycolysis, Krebs' cycle, pentose phosphate pathway and pyrimidine biosynthesis. Results The Rh30 cells proliferated faster than the myocytes. Major differences in flux through glycolysis were evident from incorporation of label into secreted lactate, which accounts for a substantial fraction of the glucose carbon utilized by the cells. Krebs' cycle activity as determined by 13C isotopomer distributions in glutamate, aspartate, malate and pyrimidine rings was considerably higher in the cancer cells than in the primary myocytes. Large differences were also evident in de novo biosynthesis of riboses in the free nucleotide pools, as well as entry of glucose carbon into the pyrimidine rings in the free nucleotide pool. Specific labeling patterns in these metabolites show the increased importance of anaplerotic reactions in the cancer cells to maintain the high demand for anabolic and energy metabolism compared with the slower growing primary myocytes. Serum-stimulated Rh30 cells showed higher degrees of labeling than serum starved cells, but they retained their characteristic anabolic metabolism profile. The myocytes showed evidence of de novo synthesis of glycogen, which was absent in the Rh30 cells. Conclusion The specific 13C isotopomer patterns showed that the major difference between the transformed and the primary cells is the shift from energy and maintenance metabolism in the myocytes toward increased energy and anabolic metabolism for proliferation in the Rh30 cells

  9. Effects of algal-produced neurotoxins on metabolic activity in telencephalon, optic tectum and cerebellum of Atlantic salmon (Salmo salar)

    International Nuclear Information System (INIS)

    Bakke, Marit Jorgensen; Horsberg, Tor Einar

    2007-01-01

    Neurotoxins from algal blooms have been reported to cause mortality in a variety of species, including sea birds, sea mammals and fish. Farmed fish cannot escape harmful algal blooms and their potential toxins, thus they are more vulnerable for exposure than wild stocks. Sublethal doses of the toxins are likely to affect fish behaviour and may impair cognitive abilities. In the present study, changes in the metabolic activity in different parts of the Atlantic salmon (Salmo salar) brain involved in central integration and cognition were investigated after exposure to sublethal doses of three algal-produced neurotoxins; saxitoxin (STX), brevetoxin (BTX) and domoic acid (DA). Fish were randomly selected to four groups for i.p. injection of saline (control) or one of the neurotoxins STX (10 μg STX/kg bw), BTX (68 μg BTX/kg bw) or DA (6 mg DA/kg bw). In addition, 14 C-2-deoxyglucose was i.m. injected to measure brain metabolic activity by autoradiography. The three regions investigated were telencephalon (Tel), optic tectum (OT) and cerebellum (Ce). There were no differences in the metabolic activity after STX and BTX exposure compared to the control in these regions. However, a clear increase was observed after DA exposure. When the subregions with the highest metabolic rate were pseudocoloured in the three brain regions, the three toxins caused distinct differences in the respective patterns of metabolic activation. Fish exposed to STX displayed similar patterns as the control fish, whereas fish exposed to BTX and DA showed highest metabolic activity in subregions different from the control group. All three neurotoxins affected subregions that are believed to be involved in cognitive abilities in fish

  10. Redox state and energy metabolism during liver regeneration: alterations produced by acute ethanol administration.

    Science.gov (United States)

    Gutiérrez-Salinas, J; Miranda-Garduño, L; Trejo-Izquierdo, E; Díaz-Muñoz, M; Vidrio, S; Morales-González, J A; Hernández-Muñoz, R

    1999-12-01

    Ethanol metabolism can induce modifications in liver metabolic pathways that are tightly regulated through the availability of cellular energy and through the redox state. Since partial hepatectomy (PH)-induced liver proliferation requires an oversupply of energy for enhanced syntheses of DNA and proteins, the present study was aimed at evaluating the effect of acute ethanol administration on the PH-induced changes in cellular redox and energy potentials. Ethanol (5 g/kg body weight) was administered to control rats and to two-thirds hepatectomized rats. Quantitation of the liver content of lactate, pyruvate, beta-hydroxybutyrate, acetoacetate, and adenine nucleotides led us to estimate the cytosolic and mitochondrial redox potentials and energy parameters. Specific activities in the liver of alcohol-metabolizing enzymes also were measured in these animals. Liver regeneration had no effect on cellular energy availability, but induced a more reduced cytosolic redox state accompanied by an oxidized mitochondrial redox state during the first 48 hr of treatment; the redox state normalized thereafter. Administration of ethanol did not modify energy parameters in PH rats, but this hepatotoxin readily blocked the PH-induced changes in the cellular redox state. In addition, proliferating liver promoted decreases in the activity of alcohol dehydrogenase (ADH) and of cytochrome P4502E1 (CYP2E1); ethanol treatment prevented the PH-induced diminution of ADH activity. In summary, our data suggest that ethanol could minimize the PH-promoted metabolic adjustments mediated by redox reactions, probably leading to an ineffective preparatory event that culminates in compensatory liver growth after PH in the rat.

  11. PPAR? population shift produces disease-related changes in molecular networks associated with metabolic syndrome

    OpenAIRE

    Jurkowski, W; Roomp, K; Crespo, I; Schneider, J G; del Sol, A

    2011-01-01

    Peroxisome proliferator-activated receptor gamma (PPARγ) is a key regulator of adipocyte differentiation and has an important role in metabolic syndrome. Phosphorylation of the receptor's ligand-binding domain at serine 273 has been shown to change the expression of a large number of genes implicated in obesity. The difference in gene expression seen when comparing wild-type phosphorylated with mutant non-phosphorylated PPARγ may have important consequences for the cellular molecular network,...

  12. Metabolic regulation and behavior: how hunger produces arousal - an insect study.

    Science.gov (United States)

    Wicher, Dieter

    2007-12-01

    The metabolic state affects the level of general activity of an organism. Satiety is related to relaxation while hunger is coupled to elevated activity which supports the chance to balance the energy deficiency. The unrestricted food availability in modern industrial nations along with no required locomotor activity are risk factors to develop disorders such as obesity. One of the strategies to find new targets for future treatment of metabolic disorders in men is to gain detailed knowledge of molecular and cellular mechanisms involved in the regulation of metabolic homeostasis in less complex, i.e. invertebrate systems. This review reports recent molecular studies in insects about how hunger signals may be linked to global activation. Adipokinetic peptide hormones (AKHs) are the insect counterpart to the mammalian glucagon. They are released upon lack of energy and mobilize internal fuel reserves. In addition, AKHs stimulate the locomotor activity which involves their activity within the central nervous system. In the cockroach Periplaneta americana various neurons express the AKH receptor. Some of these, the dorsal unpaired median (DUM) neurons belonging to a general arousal system, release the biogenic amine octopamine, the insect counterpart to mammalian adrenergic hormones. The two Periplaneta AKHs activate Gs proteins, and AKH I also potently activates Gq proteins. AKH I and - less effectively - AKH II accelerate spiking of DUM neurons via an increase of a pacemaking Ca2+ current. Systemically injected AKH I stimulates locomotion in contrast to AKH II. This behavioral difference corresponds to the different effectiveness of the AKHs on the level of G-proteins.

  13. Novel technologies combined with traditional metabolic engineering strategies facilitate the construction of shikimate-producing Escherichia coli.

    Science.gov (United States)

    Gu, Pengfei; Fan, Xiangyu; Liang, Quanfeng; Qi, Qingsheng; Li, Qiang

    2017-09-29

    Shikimate is an important intermediate in the aromatic amino acid pathway, which can be used as a promising building block for the synthesis of biological compounds, such as neuraminidase inhibitor Oseltamivir (Tamiflu ® ). Compared with traditional methods, microbial production of shikimate has the advantages of environmental friendliness, low cost, feed stock renewability, and product selectivity and diversity, thus receiving more and more attentions. The development of metabolic engineering allows for high-efficiency production of shikimate of Escherichia coli by improving the intracellular level of precursors, blocking downstream pathway, releasing negative regulation factors, and overexpressing rate-limiting enzymes. In addition, novel technologies derived from systems and synthetic biology have opened a new avenue towards construction of shikimate-producing strains. This review summarized successful and applicable strategies derived from traditional metabolic engineering and novel technologies for increasing accumulation of shikimate in E. coli.

  14. Sneaker Male Squid Produce Long-lived Spermatozoa by Modulating Their Energy Metabolism *

    Science.gov (United States)

    Hirohashi, Noritaka; Tamura-Nakano, Miwa; Nakaya, Fumio; Iida, Tomohiro; Iwata, Yoko

    2016-01-01

    Spermatozoa released by males should remain viable until fertilization. Hence, sperm longevity is governed by intrinsic and environmental factors in accordance with the male mating strategy. However, whether intraspecific variation of insemination modes can impact sperm longevity remains to be elucidated. In the squid Heterololigo bleekeri, male dimorphism (consort and sneaker) is linked to two discontinuous insemination modes that differ in place and time. Notably, only sneaker male spermatozoa inseminated long before egg spawning can be stored in the seminal receptacle. We found that sneaker spermatozoa exhibited greater persistence in fertilization competence and flagellar motility than consort ones because of a larger amount of flagellar glycogen. Sneaker spermatozoa also showed higher capacities in glucose uptake and lactate efflux. Lactic acidosis was considered to stabilize CO2-triggered self-clustering of sneaker spermatozoa, thus establishing hypoxia-induced metabolic changes and sperm survival. These results, together with comparative omics analyses, suggest that postcopulatory reproductive contexts define sperm longevity by modulating the inherent energy levels and metabolic pathways. PMID:27385589

  15. Sneaker Male Squid Produce Long-lived Spermatozoa by Modulating Their Energy Metabolism.

    Science.gov (United States)

    Hirohashi, Noritaka; Tamura-Nakano, Miwa; Nakaya, Fumio; Iida, Tomohiro; Iwata, Yoko

    2016-09-09

    Spermatozoa released by males should remain viable until fertilization. Hence, sperm longevity is governed by intrinsic and environmental factors in accordance with the male mating strategy. However, whether intraspecific variation of insemination modes can impact sperm longevity remains to be elucidated. In the squid Heterololigo bleekeri, male dimorphism (consort and sneaker) is linked to two discontinuous insemination modes that differ in place and time. Notably, only sneaker male spermatozoa inseminated long before egg spawning can be stored in the seminal receptacle. We found that sneaker spermatozoa exhibited greater persistence in fertilization competence and flagellar motility than consort ones because of a larger amount of flagellar glycogen. Sneaker spermatozoa also showed higher capacities in glucose uptake and lactate efflux. Lactic acidosis was considered to stabilize CO2-triggered self-clustering of sneaker spermatozoa, thus establishing hypoxia-induced metabolic changes and sperm survival. These results, together with comparative omics analyses, suggest that postcopulatory reproductive contexts define sperm longevity by modulating the inherent energy levels and metabolic pathways. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  16. Metabolic engineering of F. oxysporum to improve its ethanol-producing capability

    Directory of Open Access Journals (Sweden)

    George E Anasontzis

    2016-05-01

    Full Text Available Fusarium oxysporum is one of the few filamentous fungi capable of fermenting ethanol directly from plant cell wall biomass. It has the enzymatic toolbox necessary to break down biomass to its monosaccharides and, under anaerobic and microaerobic conditions, ferments them to ethanol. Although these traits could enable its use in consolidated processes and thus bypass some of the bottlenecks encountered in ethanol production from lignocellulosic material when Saccharomyces cerevisiae is used—namely its inability to degrade lignocellulose and to consume pentoses—two major disadvantages of F. oxysporum compared to the yeast—its low growth rate and low ethanol productivity—hinder the further development of this process.We had previously identified phosphoglucomutase and transaldolase, two major enzymes of glucose catabolism and the pentose phosphate pathway, as possible bottlenecks in the metabolism of the fungus and we had reported the effect of their constitutive production on the growth characteristics of the fungus. In this study, we investigated the effect of their constitutive production on ethanol productivity under anaerobic conditions. We report an increase in ethanol yield and a concomitant decrease in acetic acid production. Metabolomics analysis revealed that the genetic modifications applied did not simply accelerate the metabolic rate of the microorganism; they also affected the relative concentrations of the various metabolites suggesting an increased channeling towards the chorismate pathway, an activation of the γ-aminobutyric acid shunt, and an excess in NADPH regeneration.

  17. Production of exopolysaccharides by Lactobacillus and Bifidobacterium strains of human origin, and metabolic activity of the producing bacteria in milk.

    Science.gov (United States)

    Salazar, N; Prieto, A; Leal, J A; Mayo, B; Bada-Gancedo, J C; de los Reyes-Gavilán, C G; Ruas-Madiedo, P

    2009-09-01

    This work reports on the physicochemical characterization of 21 exopolysaccharides (EPS) produced by Lactobacillus and Bifidobacterium strains isolated from human intestinal microbiota, as well as the growth and metabolic activity of the EPS-producing strains in milk. The strains belong to the species Lactobacillus casei, Lactobacillus rhamnosus, Lactobacillus plantarum, Lactobacillus vaginalis, Bifidobacterium animalis, Bifidobacterium longum, and Bifidobacterium pseudocatenulatum. The molar mass distribution of EPS fractions showed 2 peaks of different sizes, which is a feature shared with some EPS from bacteria of food origin. In general, we detected an association between the EPS size distribution and the EPS-producing species, although because of the low numbers of human bacterial EPS tested, we could not conclusively establish a correlation. The main monosaccharide components of the EPS under study were glucose, galactose, and rhamnose, which are the same as those found in food polymers; however, the rhamnose and glucose ratios was generally higher than the galactose ratio in our human bacterial EPS. All EPS-producing strains were able to grow and acidify milk; most lactobacilli produced lactic acid as the main metabolite. The lactic acid-to-acetic acid ratio in bifidobacteria was 0.7, close to the theoretical ratio, indicating that the EPS-producing strains did not produce an excessive amount of acetic acid, which could adversely affect the sensory properties of fermented milks. With respect to their viscosity-intensifying ability, L. plantarum H2 and L. rhamnosus E41 and E43R were able to increase the viscosity of stirred, fermented milks to a similar extent as the EPS-producing Streptococcus thermophilus strain used as a positive control. Therefore, these human EPS-producing bacteria could be used as adjuncts in mixed cultures for the formulation of functional foods if probiotic characteristics could be demonstrated. This is the first article reporting the

  18. Producing Acetic Acid of Acetobacter pasteurianus by Fermentation Characteristics and Metabolic Flux Analysis.

    Science.gov (United States)

    Wu, Xuefeng; Yao, Hongli; Liu, Qing; Zheng, Zhi; Cao, Lili; Mu, Dongdong; Wang, Hualin; Jiang, Shaotong; Li, Xingjiang

    2018-03-19

    The acetic acid bacterium Acetobacter pasteurianus plays an important role in acetic acid fermentation, which involves oxidation of ethanol to acetic acid through the ethanol respiratory chain under specific conditions. In order to obtain more suitable bacteria for the acetic acid industry, A. pasteurianus JST-S screened in this laboratory was compared with A. pasteurianus CICC 20001, a current industrial strain in China, to determine optimal fermentation parameters under different environmental stresses. The maximum total acid content of A. pasteurianus JST-S was 57.14 ± 1.09 g/L, whereas that of A. pasteurianus CICC 20001 reached 48.24 ± 1.15 g/L in a 15-L stir stank. Metabolic flux analysis was also performed to compare the reaction byproducts. Our findings revealed the potential value of the strain in improvement of industrial vinegar fermentation.

  19. Metabolic stress responses in Drosophila are modulated by brain neurosecretory cells that produce multiple neuropeptides.

    Directory of Open Access Journals (Sweden)

    Lily Kahsai

    Full Text Available In Drosophila, neurosecretory cells that release peptide hormones play a prominent role in the regulation of development, growth, metabolism, and reproduction. Several types of peptidergic neurosecretory cells have been identified in the brain of Drosophila with release sites in the corpora cardiaca and anterior aorta. We show here that in adult flies the products of three neuropeptide precursors are colocalized in five pairs of large protocerebral neurosecretory cells in two clusters (designated ipc-1 and ipc-2a: Drosophila tachykinin (DTK, short neuropeptide F (sNPF and ion transport peptide (ITP. These peptides were detected by immunocytochemistry in combination with GFP expression driven by the enhancer trap Gal4 lines c929 and Kurs-6, both of which are expressed in ipc-1 and 2a cells. This mix of colocalized peptides with seemingly unrelated functions is intriguing and prompted us to initiate analysis of the function of the ten neurosecretory cells. We investigated the role of peptide signaling from large ipc-1 and 2a cells in stress responses by monitoring the effect of starvation and desiccation in flies with levels of DTK or sNPF diminished by RNA interference. Using the Gal4-UAS system we targeted the peptide knockdown specifically to ipc-1 and 2a cells with the c929 and Kurs-6 drivers. Flies with reduced DTK or sNPF levels in these cells displayed decreased survival time at desiccation and starvation, as well as increased water loss at desiccation. Our data suggest that homeostasis during metabolic stress requires intact peptide signaling by ipc-1 and 2a neurosecretory cells.

  20. Metabolic engineering of Escherichia coli for producing adipic acid through the reverse adipate-degradation pathway.

    Science.gov (United States)

    Zhao, Mei; Huang, Dixuan; Zhang, Xiaojuan; Koffas, Mattheos A G; Zhou, Jingwen; Deng, Yu

    2018-04-03

    Adipic acid is an important dicarboxylic acid mainly used for the production of nylon 6-6 fibers and resins. Previous studies focused on the biological production of adipic acid directly from different substrates, resulting in low yields and titers. In this study, a five-step reverse adipate-degradation pathway (RADP) identified in Thermobifida fusca has been reconstructed in Escherichia coli BL21 (DE3). The resulting strain (Mad136) produced 0.3gL -1 adipic acid with a 11.1% theoretical yield in shaken flasks, and we confirmed that the step catalyzed by 5-carboxy-2-pentenoyl-CoA reductase (Tfu_1647) as the rate-limiting step of the RADP. Overexpression of Tfu_1647 by pTrc99A carried by strain Mad146 produced with a 49.5% theoretical yield in shaken flasks. We further eliminated pathways for major metabolites competing for carbon flux by CRISPR/Cas9 and deleted the succinate-CoA ligase gene to promote accumulation of succinyl-CoA, which is the precursor for adipic acid synthesis. The final engineered strain Mad123146, which could achieve 93.1% of the theoretical yield in the shaken flask, was able to produce 68.0gL -1 adipic acid by fed-batch fermentation. To the best of our knowledge, these results constitute the highest adipic acid titer reported in E. coli. Copyright © 2018. Published by Elsevier Inc.

  1. PPARγ population shift produces disease-related changes in molecular networks associated with metabolic syndrome.

    Science.gov (United States)

    Jurkowski, W; Roomp, K; Crespo, I; Schneider, J G; Del Sol, A

    2011-08-11

    Peroxisome proliferator-activated receptor gamma (PPARγ) is a key regulator of adipocyte differentiation and has an important role in metabolic syndrome. Phosphorylation of the receptor's ligand-binding domain at serine 273 has been shown to change the expression of a large number of genes implicated in obesity. The difference in gene expression seen when comparing wild-type phosphorylated with mutant non-phosphorylated PPARγ may have important consequences for the cellular molecular network, the state of which can be shifted from the healthy to a stable diseased state. We found that a group of differentially expressed genes are involved in bi-stable switches and form a core network, the state of which changes with disease progression. These findings support the idea that bi-stable switches may be a mechanism for locking the core gene network into a diseased state and for efficiently propagating perturbations to more distant regions of the network. A structural analysis of the PPARγ-RXRα dimer complex supports the hypothesis of a major structural change between the two states, and this may represent an important mechanism leading to the differential expression observed in the core network.

  2. Metabolic profiles in five high-producing Swedish dairy herds with a history of abomasal displacement and ketosis

    Directory of Open Access Journals (Sweden)

    Stengärde Lena

    2008-08-01

    Full Text Available Abstract Background Body condition score and blood profiles have been used to monitor management and herd health in dairy cows. The aim of this study was to examine BCS and extended metabolic profiles, reflecting both energy metabolism and liver status around calving in high-producing herds with a high incidence of abomasal displacement and ketosis and to evaluate if such profiles can be used at herd level to pinpoint specific herd problems. Methods Body condition score and metabolic profiles around calving in five high-producing herds with high incidences of abomasal displacement and ketosis were assessed using linear mixed models (94 cows, 326 examinations. Cows were examined and blood sampled every three weeks from four weeks ante partum (ap to nine weeks postpartum (pp. Blood parameters studied were glucose, fructosamine, non-esterified fatty acids (NEFA, insulin, β-hydroxybutyrate, aspartate aminotransferase, glutamate dehydrogenase, haptoglobin and cholesterol. Results All herds had overconditioned dry cows that lost body condition substantially the first 4–6 weeks pp. Two herds had elevated levels of NEFA ap and three herds had elevated levels pp. One herd had low levels of insulin ap and low levels of cholesterol pp. Haptoglobin was detected pp in all herds and its usefulness is discussed. Conclusion NEFA was the parameter that most closely reflected the body condition losses while these losses were not seen in glucose and fructosamine levels. Insulin and cholesterol were potentially useful in herd profiles but need further investigation. Increased glutamate dehydrogenase suggested liver cell damage in all herds.

  3. Metabolic profiles in five high-producing Swedish dairy herds with a history of abomasal displacement and ketosis

    Science.gov (United States)

    Stengärde, Lena; Tråvén, Madeleine; Emanuelson, Ulf; Holtenius, Kjell; Hultgren, Jan; Niskanen, Rauni

    2008-01-01

    Background Body condition score and blood profiles have been used to monitor management and herd health in dairy cows. The aim of this study was to examine BCS and extended metabolic profiles, reflecting both energy metabolism and liver status around calving in high-producing herds with a high incidence of abomasal displacement and ketosis and to evaluate if such profiles can be used at herd level to pinpoint specific herd problems. Methods Body condition score and metabolic profiles around calving in five high-producing herds with high incidences of abomasal displacement and ketosis were assessed using linear mixed models (94 cows, 326 examinations). Cows were examined and blood sampled every three weeks from four weeks ante partum (ap) to nine weeks postpartum (pp). Blood parameters studied were glucose, fructosamine, non-esterified fatty acids (NEFA), insulin, β-hydroxybutyrate, aspartate aminotransferase, glutamate dehydrogenase, haptoglobin and cholesterol. Results All herds had overconditioned dry cows that lost body condition substantially the first 4–6 weeks pp. Two herds had elevated levels of NEFA ap and three herds had elevated levels pp. One herd had low levels of insulin ap and low levels of cholesterol pp. Haptoglobin was detected pp in all herds and its usefulness is discussed. Conclusion NEFA was the parameter that most closely reflected the body condition losses while these losses were not seen in glucose and fructosamine levels. Insulin and cholesterol were potentially useful in herd profiles but need further investigation. Increased glutamate dehydrogenase suggested liver cell damage in all herds. PMID:18687108

  4. Metabolic Engineering of Escherichia coli for Producing Astaxanthin as the Predominant Carotenoid

    Directory of Open Access Journals (Sweden)

    Qian Lu

    2017-09-01

    Full Text Available Astaxanthin is a carotenoid of significant commercial value due to its superior antioxidant potential and wide applications in the aquaculture, food, cosmetic and pharmaceutical industries. A higher ratio of astaxanthin to the total carotenoids is required for efficient astaxanthin production. β-Carotene ketolase and hydroxylase play important roles in astaxanthin production. We first compared the conversion efficiency to astaxanthin in several β-carotene ketolases from Brevundimonas sp. SD212, Sphingomonas sp. DC18, Paracoccus sp. PC1, P. sp. N81106 and Chlamydomonas reinhardtii with the recombinant Escherichia coli cells that synthesize zeaxanthin due to the presence of the Pantoea ananatis crtEBIYZ. The B. sp. SD212 crtW and P. ananatis crtZ genes are the best combination for astaxanthin production. After balancing the activities of β-carotene ketolase and hydroxylase, an E. coli ASTA-1 that carries neither a plasmid nor an antibiotic marker was constructed to produce astaxanthin as the predominant carotenoid (96.6% with a specific content of 7.4 ± 0.3 mg/g DCW without an addition of inducer.

  5. Genealogy profiling through strain improvement by using metabolic network analysis: metabolic flux genealogy of several generations of lysine-producing corynebacteria.

    Science.gov (United States)

    Wittmann, Christoph; Heinzle, Elmar

    2002-12-01

    A comprehensive approach of metabolite balancing, (13)C tracer studies, gas chromatography-mass spectrometry, matrix-assisted laser desorption ionization-time of flight mass spectrometry, and isotopomer modeling was applied for comparative metabolic network analysis of a genealogy of five successive generations of lysine-producing Corynebacterium glutamicum. The five strains examined (C. glutamicum ATCC 13032, 13287, 21253, 21526, and 21543) were previously obtained by random mutagenesis and selection. Throughout the genealogy, the lysine yield in batch cultures increased markedly from 1.2 to 24.9% relative to the glucose uptake flux. Strain optimization was accompanied by significant changes in intracellular flux distributions. The relative pentose phosphate pathway (PPP) flux successively increased, clearly corresponding to the product yield. Moreover, the anaplerotic net flux increased almost twofold as a consequence of concerted regulation of C(3) carboxylation and C(4) decarboxylation fluxes to cover the increased demand for lysine formation; thus, the overall increase was a consequence of concerted regulation of C(3) carboxylation and C(4) decarboxylation fluxes. The relative flux through isocitrate dehydrogenase dropped from 82.7% in the wild type to 59.9% in the lysine-producing mutants. In contrast to the NADPH demand, which increased from 109 to 172% due to the increasing lysine yield, the overall NADPH supply remained constant between 185 and 196%, resulting in a decrease in the apparent NADPH excess through strain optimization. Extrapolated to industrial lysine producers, the NADPH supply might become a limiting factor. The relative contributions of PPP and the tricarboxylic acid cycle to NADPH generation changed markedly, indicating that C. glutamicum is able to maintain a constant supply of NADPH under completely different flux conditions. Statistical analysis by a Monte Carlo approach revealed high precision for the estimated fluxes, underlining the

  6. Metabolism

    Science.gov (United States)

    ... functions: Anabolism (uh-NAB-uh-liz-um), or constructive metabolism, is all about building and storing. It ... in infants and young children. Hypothyroidism slows body processes and causes fatigue (tiredness), slow heart rate, excessive ...

  7. Metabolism

    Science.gov (United States)

    ... a particular food provides to the body. A chocolate bar has more calories than an apple, so ... acid phenylalanine, needed for normal growth and protein production). Inborn errors of metabolism can sometimes lead to ...

  8. Physiologic and metabolic characterization of a new marine isolate (BM39 of Pantoea sp. producing high levels of exopolysaccharide

    Directory of Open Access Journals (Sweden)

    Silvi Silvia

    2013-01-01

    Full Text Available Abstract Background Marine environments are the widest fonts of biodiversity representing a resource of both unexploited or unknown microorganisms and new substances having potential applications. Among microbial products, exopolysaccharides (EPS have many physiological functions and practical applications. Since EPS production by many bacteria is too scarce for practical use and only few species are known for their high levels of production, the search of new high EPS producers is of paramount importance. Many marine bacteria, that produce EPS to cope with strong environmental stress, could be potentially exploited at the industrial level. Results A novel bacterium, strain BM39, previously isolated from sediments collected in the Tyrrhenian Sea, was selected for its production of very high levels of EPS. BM39 was affiliated to Pantoea sp. (Enterobacteriaceae by 16S rRNA gene sequencing and biochemical tests. According to the phylogenetic tree, this strain, being quite far from the closest known Pantoea species (96% identity with P. agglomerans and P. ananatis could belong to a new species. EPS production was fast (maximum of ca. 21 g/L in 24 h on glucose medium and mainly obtained during the exponential growth. Preliminary characterization, carried out by thin layer and gel filtration chromatography, showed that the EPS, being a glucose homopolymer with MW of ca. 830 kDa, appeared to be different from those of other bacteria of same genus. The bacterium showed a typical slightly halophilic behavior growing optimally at NaCl 40 ‰ (growing range 0-100 ‰. Flow cytometry studies indicated that good cell survival was maintained for 24 h at 120 ‰. Survival decreased dramatically with the increase of salinity being only 1 h at 280 ‰. The biochemical characterization, carried out with the Biolog system, showed that MB39 had a rather limited metabolic capacity. Its ability, rather lower than that of P. agglomerans, was almost only confined to

  9. Physiologic and metabolic characterization of a new marine isolate (BM39) of Pantoea sp. producing high levels of exopolysaccharide

    Science.gov (United States)

    2013-01-01

    Background Marine environments are the widest fonts of biodiversity representing a resource of both unexploited or unknown microorganisms and new substances having potential applications. Among microbial products, exopolysaccharides (EPS) have many physiological functions and practical applications. Since EPS production by many bacteria is too scarce for practical use and only few species are known for their high levels of production, the search of new high EPS producers is of paramount importance. Many marine bacteria, that produce EPS to cope with strong environmental stress, could be potentially exploited at the industrial level. Results A novel bacterium, strain BM39, previously isolated from sediments collected in the Tyrrhenian Sea, was selected for its production of very high levels of EPS. BM39 was affiliated to Pantoea sp. (Enterobacteriaceae) by 16S rRNA gene sequencing and biochemical tests. According to the phylogenetic tree, this strain, being quite far from the closest known Pantoea species (96% identity with P. agglomerans and P. ananatis) could belong to a new species. EPS production was fast (maximum of ca. 21 g/L in 24 h on glucose medium) and mainly obtained during the exponential growth. Preliminary characterization, carried out by thin layer and gel filtration chromatography, showed that the EPS, being a glucose homopolymer with MW of ca. 830 kDa, appeared to be different from those of other bacteria of same genus. The bacterium showed a typical slightly halophilic behavior growing optimally at NaCl 40 ‰ (growing range 0-100 ‰). Flow cytometry studies indicated that good cell survival was maintained for 24 h at 120 ‰. Survival decreased dramatically with the increase of salinity being only 1 h at 280 ‰. The biochemical characterization, carried out with the Biolog system, showed that MB39 had a rather limited metabolic capacity. Its ability, rather lower than that of P. agglomerans, was almost only confined to the metabolization of

  10. Carbon-flux distribution within Streptomyces coelicolor metabolism: a comparison between the actinorhodin-producing strain M145 and its non-producing derivative M1146.

    Directory of Open Access Journals (Sweden)

    Fabien Coze

    Full Text Available Metabolic Flux Analysis is now viewed as essential to elucidate the metabolic pattern of cells and to design appropriate genetic engineering strategies to improve strain performance and production processes. Here, we investigated carbon flux distribution in two Streptomyces coelicolor A3 (2 strains: the wild type M145 and its derivative mutant M1146, in which gene clusters encoding the four main antibiotic biosynthetic pathways were deleted. Metabolic Flux Analysis and (13C-labeling allowed us to reconstruct a flux map under steady-state conditions for both strains. The mutant strain M1146 showed a higher growth rate, a higher flux through the pentose phosphate pathway and a higher flux through the anaplerotic phosphoenolpyruvate carboxylase. In that strain, glucose uptake and the flux through the Krebs cycle were lower than in M145. The enhanced flux through the pentose phosphate pathway in M1146 is thought to generate NADPH enough to face higher needs for biomass biosynthesis and other processes. In both strains, the production of NADPH was higher than NADPH needs, suggesting a key role for nicotinamide nucleotide transhydrogenase for redox homeostasis. ATP production is also likely to exceed metabolic ATP needs, indicating that ATP consumption for maintenance is substantial.Our results further suggest a possible competition between actinorhodin and triacylglycerol biosynthetic pathways for their common precursor, acetyl-CoA. These findings may be instrumental in developing new strategies exploiting S. coelicolor as a platform for the production of bio-based products of industrial interest.

  11. Design of aqueous two-phase systems for purification of hyaluronic acid produced by metabolically engineered Lactococcus lactis.

    Science.gov (United States)

    Rajendran, Vivek; Puvendran, Kirubhakaran; Guru, Bharath Raja; Jayaraman, Guhan

    2016-02-01

    Hyaluronic acid has a wide range of biomedical applications and its commercial value is highly dependent on its purity and molecular weight. This study highlights the utility of aqueous two-phase separation as a primary recovery step for hyaluronic acid and for removal of major protein impurities from fermentation broths. Metabolically engineered cultures of a lactate dehydrogenase mutant strain of Lactococcus lactis (L. lactis NZ9020) were used to produce high-molecular-weight hyaluronic acid. The cell-free fermentation broth was partially purified using a polyethylene glycol/potassium phosphate system, resulting in nearly 100% recovery of hyaluronic acid in the salt-rich bottom phase in all the aqueous two-phase separation experiments. These experiments were optimized for maximum removal of protein impurities in the polyethylene glycol rich top phase. The removal of protein impurities resulted in substantial reduction of membrane fouling in the subsequent diafiltration process, carried out with a 300 kDa polyether sulfone membrane. This step resulted in considerable purification of hyaluronic acid, without any loss in recovery and molecular weight. Diafiltration was followed by an adsorption step to remove minor impurities and achieve nearly 100% purity. The final hyaluronic acid product was characterized by Fourier-transform IR and NMR spectroscopy, confirming its purity. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  12. Metabolic flux analysis of a phenol producing mutant of Pseudomonas putida S12: Verification and complementation of hypotheses derived from transcriptomics

    NARCIS (Netherlands)

    Wierckx, N.; Ruijssenaars, H.J.; Winde, J.H.de; Schmid, A.; Blank, L.M.

    2009-01-01

    The physiological effects of genetic and transcriptional changes observed in a phenol producing mutant of the solvent-tolerant Pseudomonas putida S12 were assessed with metabolic flux analysis. The upregulation of a malate/lactate dehydrogenase encoding gene could be connected to a flux increase

  13. Effects of Prepartum Monensin Feeding on Energy Metabolism and Reproductive Performance of Postpartum High-Producing Holstein Dairy Cows

    Directory of Open Access Journals (Sweden)

    Mahmood Changizi Mohammadi, Abbas Rowshan Ghasrodashti1, Amin Tamadon2,3 and Mohammad Amin Behzadi4*

    2012-01-01

    Full Text Available This study was designed to determine the effects of monensin in preparturient diet on postpartum milk production, energy metabolism, and reproductive performance of Holstein dairy cows. Forty Holstein dairy cows on close-up period were randomly divided into monensin treated (300 mg/day in close-up ration, top dress and control groups. Body condition score (BCS was estimated three weeks before and three weeks after calving. Milk production and milk fat percentage were recorded in both groups within 3 weeks postpartum. Blood samples were collected from five randomly selected cows of each group three weeks after calving. Serum concentrations of insulin like growth factor-I (IGF-I, insulin, glucose, and beta-hydroxybutyrate (BHBA were measured. Calving to the first observed estrus interval and calving to conception interval were compared between two groups. The results of the experiment showed that loss of BCS (P=0.3, increase of milk production (P=0.9, and milk fat percentage (P>0.05 were not significantly different between two groups during the period of study. In addition, mean serum glucose concentration (P=0.001 and serum insulin concentration (P=0.01 in monensin group were significantly higher than control cows in the first week postpartum. Moreover, serum BHBA concentration did not significantly change in monensin group. Serum IGF-I concentration in monensin group was significantly higher than control group in three weeks postpartum (P<0.01. The present study indicated that monensin treatment decreased calving to the first observed estrus interval (P=0.05 and calving to conception interval (P=0.002. In conclusion, supplementing the close-up ration can increase postpartum serum IGF-I concentration and prevent the increase of serum BHBA concentration. These may result in enhancement reproductive performance of high-producing dairy cows.

  14. Presence and metabolism of endogenous androgenic-anabolic steroid hormones in meat-producing animals: a review.

    Science.gov (United States)

    Scarth, J; Akre, C; van Ginkel, L; Le Bizec, B; De Brabander, H; Korth, W; Points, J; Teale, P; Kay, J

    2009-05-01

    The presence and metabolism of endogenous steroid hormones in meat-producing animals has been the subject of much research over the past 40 years. While significant data are available, no comprehensive review has yet been performed. Species considered in this review are bovine, porcine, ovine, equine, caprine and cervine, while steroid hormones include the androgenic-anabolic steroids testosterone, nandrolone and boldenone, as well as their precursors and metabolites. Information on endogenous steroid hormone concentrations is primarily useful in two ways: (1) in relation to pathological versus 'normal' physiology and (2) in relation to the detection of the illegal abuse of these hormones in residue surveillance programmes. Since the major focus of this review is on the detection of steroids abuse in animal production, the information gathered to date is used to guide future research. A major deficiency in much of the existing published literature is the lack of standardization and formal validation of experimental approach. Key articles are cited that highlight the huge variation in reported steroid concentrations that can result when samples are analysed by different laboratories under different conditions. These deficiencies are in most cases so fundamental that it is difficult to make reliable comparisons between data sets and hence it is currently impossible to recommend definitive detection strategies. Standardization of the experimental approach would need to involve common experimental protocols and collaboratively validated analytical methods. In particular, standardization would need to cover everything from the demographic of the animal population studied, the method of sample collection and storage (especially the need to sample live versus slaughter sampling since the two methods of surveillance have very different requirements, particularly temporally), sample preparation technique (including mode of extraction, hydrolysis and derivatization), the end

  15. Probing the redox metabolism in the strictly anaerobic, extremely thermophilic, hydrogen-producing Caldicellulosiruptor saccharolyticus using amperometry

    DEFF Research Database (Denmark)

    Kostesha, Natalie; Willquist, Karin; Emnéus, Jenny

    2011-01-01

    Changes in the redox metabolism in the anaerobic, extremely thermophilic, hydrogen-forming bacterium Caldicellulosiruptor saccharolyticus were probed for the first time in vivo using mediated amperometry with ferricyanide as a thermotolerant external mediator. Clear differences in the intracellul...

  16. The Investment in Scent: Time-Resolved Metabolic Processes in Developing Volatile-Producing Nigella sativa L. Seeds

    Science.gov (United States)

    Toubiana, David; Botnick, Ilan; Szymanski, Jedrzej; Khozin-Goldberg, Inna; Nikoloski, Zoran; Lewinsohn, Efraim; Fait, Aaron

    2013-01-01

    The interplay of processes in central and specialized metabolisms during seed development of Nigella sativa L. was studied by using a high-throughput metabolomics technology and network-based analysis. Two major metabolic shifts were identified during seed development: the first was characterized by the accumulation of storage lipids (estimated as total fatty acids) and N-compounds, and the second by the biosynthesis of volatile organic compounds (VOCs) and a 30% average decrease in total fatty acids. Network-based analysis identified coordinated metabolic processes during development and demonstrated the presence of five network communities. Enrichment analysis indicated that different compound classes, such as sugars, amino acids, and fatty acids, are largely separated and over-represented in certain communities. One community displayed several terpenoids and the central metabolites, shikimate derived amino acids, raffinose, xylitol and glycerol–3-phosphate. The latter are related to precursors of the mevalonate-independent pathway for VOC production in the plastid; also plastidial fatty acid 18∶3n-3 abundant in “green” seeds grouped with several major terpenes. The findings highlight the interplay between the components of central metabolism and the VOCs. The developmental regulation of Nigella seed metabolism during seed maturation suggests a substantial re-allocation of carbon from the breakdown of fatty acids and from N-compounds, probably towards the biosynthesis of VOCs. PMID:24019893

  17. The investment in scent: time-resolved metabolic processes in developing volatile-producing Nigella sativa L. seeds.

    Directory of Open Access Journals (Sweden)

    Wentao Xue

    Full Text Available The interplay of processes in central and specialized metabolisms during seed development of Nigella sativa L. was studied by using a high-throughput metabolomics technology and network-based analysis. Two major metabolic shifts were identified during seed development: the first was characterized by the accumulation of storage lipids (estimated as total fatty acids and N-compounds, and the second by the biosynthesis of volatile organic compounds (VOCs and a 30% average decrease in total fatty acids. Network-based analysis identified coordinated metabolic processes during development and demonstrated the presence of five network communities. Enrichment analysis indicated that different compound classes, such as sugars, amino acids, and fatty acids, are largely separated and over-represented in certain communities. One community displayed several terpenoids and the central metabolites, shikimate derived amino acids, raffinose, xylitol and glycerol-3-phosphate. The latter are related to precursors of the mevalonate-independent pathway for VOC production in the plastid; also plastidial fatty acid 18∶3n-3 abundant in "green" seeds grouped with several major terpenes. The findings highlight the interplay between the components of central metabolism and the VOCs. The developmental regulation of Nigella seed metabolism during seed maturation suggests a substantial re-allocation of carbon from the breakdown of fatty acids and from N-compounds, probably towards the biosynthesis of VOCs.

  18. 10-oxo-12(Z)-octadecenoic acid, a linoleic acid metabolite produced by gut lactic acid bacteria, enhances energy metabolism by activation of TRPV1.

    Science.gov (United States)

    Kim, Minji; Furuzono, Tomoya; Yamakuni, Kanae; Li, Yongjia; Kim, Young-Il; Takahashi, Haruya; Ohue-Kitano, Ryuji; Jheng, Huei-Fen; Takahashi, Nobuyuki; Kano, Yuriko; Yu, Rina; Kishino, Shigenobu; Ogawa, Jun; Uchida, Kunitoshi; Yamazaki, Jun; Tominaga, Makoto; Kawada, Teruo; Goto, Tsuyoshi

    2017-11-01

    Gut microbiota can regulate the host energy metabolism; however, the underlying mechanisms that could involve gut microbiota-derived compounds remain to be understood. Therefore, in this study, we investigated the effects of KetoA [10-oxo-12( Z )-octadecenoic acid]-a linoleic acid metabolite produced by gut lactic acid bacteria-on whole-body energy metabolism and found that dietary intake of KetoA could enhance energy expenditure in mice, thereby protecting mice from diet-induced obesity. By using Ca 2+ imaging and whole-cell patch-clamp methods, KetoA was noted to potently activate transient receptor potential vanilloid 1 (TRPV1) and enhance noradrenalin turnover in adipose tissues. In addition, KetoA up-regulated genes that are related to brown adipocyte functions, including uncoupling protein 1 (UCP1) in white adipose tissue (WAT), which was later diminished in the presence of a β-adrenoreceptor blocker. By using obese and diabetic model KK-Ay mice, we further show that KetoA intake ameliorated obesity-associated metabolic disorders. In the absence of any observed KetoA-induced antiobesity effect or UCP1 up-regulation in TRPV1-deficient mice, we prove that the antiobesity effect of KetoA was caused by TRPV1 activation-mediated browning in WAT. KetoA produced in the gut could therefore be involved in the regulation of host energy metabolism.-Kim, M., Furuzono, T., Yamakuni, K., Li, Y., Kim, Y.-I., Takahashi, H., Ohue-Kitano, R., Jheng, H.-F., Takahashi, N., Kano, Y., Yu, R., Kishino, S., Ogawa, J., Uchida, K., Yamazaki, J., Tominaga, M., Kawada, T., Goto, T. 10-oxo-12( Z )-octadecenoic acid, a linoleic acid metabolite produced by gut lactic acid bacteria, enhances energy metabolism by activation of TRPV1. © FASEB.

  19. In Silico Analysis of the Small Molecule Content of Outer Membrane Vesicles Produced by Bacteroides thetaiotaomicron Indicates an Extensive Metabolic Link between Microbe and Host

    Directory of Open Access Journals (Sweden)

    William A. Bryant

    2017-12-01

    Full Text Available The interactions between the gut microbiota and its host are of central importance to the health of the host. Outer membrane vesicles (OMVs are produced ubiquitously by Gram-negative bacteria including the gut commensal Bacteroides thetaiotaomicron. These vesicles can interact with the host in various ways but until now their complement of small molecules has not been investigated in this context. Using an untargeted high-coverage metabolomic approach we have measured the small molecule content of these vesicles in contrasting in vitro conditions to establish what role these metabolites could perform when packed into these vesicles. B. thetaiotaomicron packs OMVs with a highly conserved core set of small molecules which are strikingly enriched with mouse-digestible metabolites and with metabolites previously shown to be associated with colonization of the murine GIT. By use of an expanded genome-scale metabolic model of B. thetaiotaomicron and a potential host (the mouse we have established many possible metabolic pathways between the two organisms that were previously unknown, and have found several putative novel metabolic functions for mouse that are supported by gene annotations, but that do not currently appear in existing mouse metabolic networks. The lipidome of these OMVs bears no relation to the mouse lipidome, so the purpose of this particular composition of lipids remains unclear. We conclude from this analysis that through intimate symbiotic evolution OMVs produced by B. thetaiotaomicron are likely to have been adopted as a conduit for small molecules bound for the mammalian host in vivo.

  20. Multi-omic profiling of EPO producing Chinese hamster ovary cell panel reveals metabolic adaptation to heterologous protein production

    DEFF Research Database (Denmark)

    Ley, Daniel; Kazemi Seresht, Ali; Engmark, Mikael

    Heterologous protein production in CHO cells imposes a burden on the host cell metabolism and impact cellular physiology on a global scale. In this work, a multi-omics approach was applied to characterize the physiological impact of erythropoietin production, and discover production bottlenecks, ...

  1. Multi-omic profiling of EPO-producing Chinese hamster ovary cell panel reveals metabolic adaptation to heterologous protein production

    DEFF Research Database (Denmark)

    Ley, Daniel; Kazemi Seresht, Ali; Engmark, Mikael

    2015-01-01

    Chinese hamster ovary (CHO) cells are the preferred production host for many therapeutic proteins. The production of heterologous proteins in CHO cells imposes a burden on the host cell metabolism and impact cellular physiology on a global scale. In this work, a multi-omics approach was applied...

  2. MOST-visualization: software for producing automated textbook-style maps of genome-scale metabolic networks.

    Science.gov (United States)

    Kelley, James J; Maor, Shay; Kim, Min Kyung; Lane, Anatoliy; Lun, Desmond S

    2017-08-15

    Visualization of metabolites, reactions and pathways in genome-scale metabolic networks (GEMs) can assist in understanding cellular metabolism. Three attributes are desirable in software used for visualizing GEMs: (i) automation, since GEMs can be quite large; (ii) production of understandable maps that provide ease in identification of pathways, reactions and metabolites; and (iii) visualization of the entire network to show how pathways are interconnected. No software currently exists for visualizing GEMs that satisfies all three characteristics, but MOST-Visualization, an extension of the software package MOST (Metabolic Optimization and Simulation Tool), satisfies (i), and by using a pre-drawn overview map of metabolism based on the Roche map satisfies (ii) and comes close to satisfying (iii). MOST is distributed for free on the GNU General Public License. The software and full documentation are available at http://most.ccib.rutgers.edu/. dslun@rutgers.edu. Supplementary data are available at Bioinformatics online. © The Author (2017). Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com

  3. Ileal transposition surgery produces ileal length-dependent changes in food intake, body weight, gut hormones and glucose metabolism in rats.

    Science.gov (United States)

    Ramzy, A R; Nausheen, S; Chelikani, P K

    2014-03-01

    Enhanced stimulation of the lower gut is hypothesized to play a key role in the weight loss and resolution of diabetes following bariatric surgeries. Ileal transposition (IT) permits study of the effects of direct lower gut stimulation on body weight, glucose homeostasis and other metabolic adaptations without the confounds of gastric restriction or foregut exclusion. However, the underlying mechanisms and the length of the ileum sufficient to produce metabolic benefits following IT surgery remain largely unknown. To determine the effects of transposing varying lengths of the ileum to upper jejunum on food intake, body weight, glucose tolerance and lower gut hormones, and the expression of key markers of glucose and lipid metabolism in skeletal muscle and adipose tissue in rats. Adult male Sprague-Dawley rats (n=9/group) were subjected to IT surgery with translocation of 5, 10 or 20 cm of the ileal segment to proximal jejunum or sham manipulations. Daily food intake and body weight were recorded, and an intraperitoneal glucose tolerance test was performed. Blood samples were assayed for hormones and tissue samples for mRNA (RT-qPCR) and/or protein abundance (immunoblotting) of regulatory metabolic markers. We demonstrate that IT surgery exerts ileal length-dependent effects on multiple parameters including: (1) decreased food intake and weight gain, (2) improved glucose tolerance, (3) increased tissue expression and plasma concentrations of glucagon-like peptide-1 (GLP-1) and peptide YY (PYY), and decreased leptin concentrations and (4) upregulation of key markers of glucose metabolism (glucose transporter-4 (GLUT-4), insulin receptor substrate 1 (IRS-1), adenosine monophosphate-activated protein kinase (AMPK), hexokinase (HK) and phosphofructokinase (PFK)) together with a downregulation of lipogenic markers (fatty acid synthase (FAS)) in muscle and adipose tissue. Together, our data demonstrate that the reduction in food intake and weight gain, increase in lower

  4. Metabolic Engineering of Plants to Produce Precursors (Phloroglucinol and 1,2,4-butanetriol) of Energetic Materials

    Science.gov (United States)

    2015-01-02

    crop , we have developed an efficient regeneration system for this plant. 15. SUBJECT TERMS Metabolic engineering. Energetic materials. Plants...34. These proof-of-concept experiments were carried out in Arabidopsis. To introduce these pathways into Miscanthus, a non-food crop , we have developed an...To see if there is differential accumulation of phloroglucinol and phlorin in roots and shoots, we grew plants hydroponically for 3 weeks, shoots and

  5. Construction of expression vectors for metabolic engineering of the vanillin-producing actinomycete Amycolatopsis sp. ATCC 39116.

    Science.gov (United States)

    Fleige, Christian; Steinbüchel, Alexander

    2014-01-01

    Amycolatopsis sp. ATCC 39116 is able to synthesize the important flavoring agent vanillin from cheap natural substrates. The bacterium is therefore of great interest for the industry and used for the fermentative production of vanillin. In order to improve the production of natural vanillin with Amycolatopsis sp. ATCC 39116, the strain has been genetically engineered to optimize the metabolic flux towards the desired product. Extensive metabolic engineering was hitherto hampered, due to the lack of genetic tools like functional promoters and expression vectors. In this study, we report the establishment of a plasmid-based gene expression system for Amycolatopsis sp. ATCC 39116 that allows a further manipulation of the genotype. Four new Escherichia coli-Amycolatopsis shuttle vectors harboring different promoter elements were constructed, and the functionality of these regulatory elements was proven by the expression of the reporter gene gusA, encoding a β-glucuronidase. Glucuronidase activity was detected in all plasmid-harboring strains, and remarkable differences in the expression strength of the reporter gene depending on the used promoter were observed. The new expression vectors will promote the further genetic engineering of Amycolatopsis sp. ATCC 39116 to get insight into the metabolic network and to improve the strain for a more efficient industrial use.

  6. Effect of urinary tract infection on the urinary metabolic characteristic as a risk factor in producing urolithiasis

    Directory of Open Access Journals (Sweden)

    Alireza Eskandarifar

    2016-05-01

    Full Text Available Urinary metabolic disorders are one of the most common causes of stone formation in children. The purpose of this study was to evaluate the effect of urinary tract infections in the urinary metabolic characteristics as a risk factor in the incidence of urolithiasis. This case-control study was conducted in 222 children with urolithiasis in the range of 6 months to 16 years old in Sanandaj, Kurdistan, Iran during 2012-14. Patients were divided into two groups based on those with urinary tract infection and without urinary tract infection. Then, urine samples were collected from both groups, and levels of calcium, oxalate, citrate, uric acid, creatinine, and cysteine were measured. The collected information was analyzed using software SPSS (version 16. The ratio Average levels of calcium, magnesium, oxalate, cysteine, uric acid to creatinine in urine showed no significant difference between two groups based on statistical analysis. However, the amount of citrate to creatinine in children with urinary tract infection and urolithiasis was clearly less P=0.01. The results of this study show that the urinary tract infection cannot change the urinary metabolic characteristics, but it can be considered as a risk factor in kidney stone formation due to the reduced amount of citrate in the urine.

  7. Metabolic flux analysis of a phenol producing mutant of Pseudomonas putida S12: verification and complementation of hypotheses derived from transcriptomics.

    Science.gov (United States)

    Wierckx, Nick; Ruijssenaars, Harald J; de Winde, Johannes H; Schmid, Andreas; Blank, Lars M

    2009-08-20

    The physiological effects of genetic and transcriptional changes observed in a phenol producing mutant of the solvent-tolerant Pseudomonas putida S12 were assessed with metabolic flux analysis. The upregulation of a malate/lactate dehydrogenase encoding gene could be connected to a flux increase from malate to oxaloacetate. A mutation in the pykA gene decreased in vitro pyruvate kinase activity, which is consistent with a lower flux from phosphoenolpyruvate to pyruvate. Changes in the oprB-1, gntP and gnuK genes, encoding a glucose-selective porin, gluconokinase and a gluconate transporter respectively, altered the substrate uptake profile. Metabolic flux analysis furthermore revealed cellular events not predicted by the transcriptome analysis. Gluconeogenic formation of glucose-6-phosphate from triose-3-phosphate was abolished, in favour of increased phosphoenolpyruvate production. An increased pentose phosphate pathway flux resulted in higher erythrose-4-phosphate production. Thus, the availability of these two central phenol precursors was improved. Furthermore, metabolic fluxes were redistributed such that the overall TCA cycle flux was unaffected and energy production increased. Engineering P. putida S12 for phenol production has yielded a strain that channels carbon fluxes to previously unfavourable routes to reconcile the drain on metabolites required for phenol production, while maintaining basal flux levels through central carbon metabolism.

  8. Amino Acid Sensor Kinase Gcn2 Is Required for Conidiation, Secondary Metabolism, and Cell Wall Integrity in the Taxol-Producer Pestalotiopsis microspora

    Directory of Open Access Journals (Sweden)

    Dan Wang

    2017-09-01

    Full Text Available The canonical Gcn2/Cpc1 kinase in fungi coordinates the expression of target genes in response to amino acid starvation. To investigate its possible role in secondary metabolism, we characterized a gcn2 homolog in the taxol-producing fungus Pestalotiopsis microspora. Deletion of the gene led to severe physiological defects under amino acid starvation, suggesting a conserved function of gcn2 in amino acid sensing. The mutant strain Δgcn2 displayed retardation in vegetative growth. It generated dramatically fewer conidia, suggesting a connection between amino acid metabolism and conidiation in this fungus. Importantly, disruption of the gene altered the production of secondary metabolites by HPLC profiling. For instance, under amino acid starvation, the deletion strain Δgcn2 barely produced secondary metabolites including the known natural product pestalotiollide B. Even more, we showed that gcn2 played critical roles in the tolerance to several stress conditions. Δgcn2 exhibited a hypersensitivity to Calcofluor white and Congo red, implying a role of Gcn2 in maintaining the integrity of the cell wall. This study suggests that Gcn2 kinase is an important global regulator in the growth and development of filamentous fungi and will provide knowledge for the manipulation of secondary metabolism in P. microspora.

  9. Expression pattern of glucose metabolism genes in relation to development rate of buffalo (Bubalus bubalis) oocytes and in vitro-produced embryos.

    Science.gov (United States)

    Kumar, Parveen; Rajput, Sandeep; Verma, Arpana; De, Sachinandan; Datta, Tirtha Kumar

    2013-11-01

    The expression pattern of glucose metabolism genes (hexokinase, phosphofructokinase, glucose-6-phosphate dehydrogenase [G6PDH], lactate dehydrogenase [LDH], and pyruvate dehydrogenase [PDH]) were studied in buffalo in vitro-matured oocytes and in vitro-produced embryos cultured under different glucose concentrations (0 mM, 1.5 mM, 5.6 mM, and 10 mM) during in vitro maturation of oocytes and culture of IVF produced embryos. The expression of the genes varied significantly over the cleavage stages under different glucose concentrations. Developmental rate of embryos was highest under a constant glucose level (5.6 mM) throughout during maturation of oocytes and embryo culture. Expression pattern of glucose metabolism genes under optimum glucose level (5.6 mM) indicated that glycolysis is the major pathway of glucose metabolism during oocyte maturation and early embryonic stages (pre-maternal to zygotic transition [MZT]) and shifts to oxidative phosphorylation during post-MZT stages in buffalo embryos. Higher glucose level (10 mM) caused abrupt changes in gene expression and resulted in shifting toward anaerobic metabolism of glucose during post-MZT stages. This resulted in decreased development rate of embryos during post-MZT stages. High expression of LDH and PDH in the control groups (0 mM glucose) indicated that in absence of glucose, embryos try to use available pyruvate and lactate sources, but succumb to handle the post-MZT energy requirement, resulting to poor development rate. Expression pattern of G6PDH during oocyte maturation as well early embryonic development was found predictive of quality and development competence of oocytes/ embryos. Copyright © 2013 Elsevier Inc. All rights reserved.

  10. Effect of Temperature on Precipitation Rate of Calcium Carbonate Produced through Microbial Metabolic Process of Bio Materials

    Directory of Open Access Journals (Sweden)

    Prima Yane Putri

    2016-09-01

    Full Text Available Concrete is the most widely used construction material in civil engineering. But plain concrete is a brittle material and has little resistance to cracking. The cracking in concrete promotes deterioration such as the corrosion of reinforcing rebar, therefore, repair in filling the crack is often carried out. Recently, repair methods using bio-based materials associated with microbial metabolic processes leading to precipitation of calcium carbonate have been intensively studied. In this study, influencing factors on the precipitation rate depending on the constituents of bio-based material comprising yeast, glucose and calcium acetate mixed in tris buffer solution was examined for improving the rate of initial reactions. In addition, effect of temperature change on the amount of calcium carbonate precipitation was also investigated. The precipitates were identified by X-ray diffraction. It was shown that the increase of temperature lead to a change on calcium carbonate precipitation and caused the pH decrease under 7.0.

  11. Soybeans grown in the Chernobyl area produce fertile seeds that have increased heavy metal resistance and modified carbon metabolism.

    Science.gov (United States)

    Klubicová, Katarína; Danchenko, Maksym; Skultety, Ludovit; Berezhna, Valentyna V; Uvackova, Lubica; Rashydov, Namik M; Hajduch, Martin

    2012-01-01

    Plants grow and reproduce in the radioactive Chernobyl area, however there has been no comprehensive characterization of these activities. Herein we report that life in this radioactive environment has led to alteration of the developing soybean seed proteome in a specific way that resulted in the production of fertile seeds with low levels of oil and β-conglycinin seed storage proteins. Soybean seeds were harvested at four, five, and six weeks after flowering, and at maturity from plants grown in either non-radioactive or radioactive plots in the Chernobyl area. The abundance of 211 proteins was determined. The results confirmed previous data indicating that alterations in the proteome include adaptation to heavy metal stress and mobilization of seed storage proteins. The results also suggest that there have been adjustments to carbon metabolism in the cytoplasm and plastids, increased activity of the tricarboxylic acid cycle, and decreased condensation of malonyl-acyl carrier protein during fatty acid biosynthesis.

  12. The Sexual Advantage of Looking, Smelling, and Tasting Good: The Metabolic Network that Produces Signals for Pollinators.

    Science.gov (United States)

    Borghi, Monica; Fernie, Alisdair R; Schiestl, Florian P; Bouwmeester, Harro J

    2017-04-01

    A striking feature of the angiosperms that use animals as pollen carriers to sexually reproduce is the great diversity of their flowers with regard to morphology and traits such as color, odor, and nectar. These traits are underpinned by the synthesis of secondary metabolites such as pigments and volatiles, as well as carbohydrates and amino acids, which are used by plants to lure and reward animal pollinators. We review here the knowledge of the metabolic network that supports the biosynthesis of these compounds and the behavioral responses that these molecules elicit in the animal pollinators. Such knowledge provides us with a deeper insight into the ecology and evolution of plant-pollinator interactions, and should help us to better manage these ecologically essential interactions in agricultural ecosystems. Copyright © 2016 Elsevier Ltd. All rights reserved.

  13. Soybeans Grown in the Chernobyl Area Produce Fertile Seeds that Have Increased Heavy Metal Resistance and Modified Carbon Metabolism

    Science.gov (United States)

    Klubicová, Katarína; Danchenko, Maksym; Skultety, Ludovit; Berezhna, Valentyna V.; Uvackova, Lubica; Rashydov, Namik M.; Hajduch, Martin

    2012-01-01

    Plants grow and reproduce in the radioactive Chernobyl area, however there has been no comprehensive characterization of these activities. Herein we report that life in this radioactive environment has led to alteration of the developing soybean seed proteome in a specific way that resulted in the production of fertile seeds with low levels of oil and β-conglycinin seed storage proteins. Soybean seeds were harvested at four, five, and six weeks after flowering, and at maturity from plants grown in either non-radioactive or radioactive plots in the Chernobyl area. The abundance of 211 proteins was determined. The results confirmed previous data indicating that alterations in the proteome include adaptation to heavy metal stress and mobilization of seed storage proteins. The results also suggest that there have been adjustments to carbon metabolism in the cytoplasm and plastids, increased activity of the tricarboxylic acid cycle, and decreased condensation of malonyl-acyl carrier protein during fatty acid biosynthesis. PMID:23110204

  14. Soybeans grown in the Chernobyl area produce fertile seeds that have increased heavy metal resistance and modified carbon metabolism.

    Directory of Open Access Journals (Sweden)

    Katarína Klubicová

    Full Text Available Plants grow and reproduce in the radioactive Chernobyl area, however there has been no comprehensive characterization of these activities. Herein we report that life in this radioactive environment has led to alteration of the developing soybean seed proteome in a specific way that resulted in the production of fertile seeds with low levels of oil and β-conglycinin seed storage proteins. Soybean seeds were harvested at four, five, and six weeks after flowering, and at maturity from plants grown in either non-radioactive or radioactive plots in the Chernobyl area. The abundance of 211 proteins was determined. The results confirmed previous data indicating that alterations in the proteome include adaptation to heavy metal stress and mobilization of seed storage proteins. The results also suggest that there have been adjustments to carbon metabolism in the cytoplasm and plastids, increased activity of the tricarboxylic acid cycle, and decreased condensation of malonyl-acyl carrier protein during fatty acid biosynthesis.

  15. Metabolic engineering of Klebsiella oxytoca M5a1 to produce optically pure D-lactate in mineral salts medium.

    Science.gov (United States)

    Sangproo, Maytawadee; Polyiam, Pattharasedthi; Jantama, Sirima Suvarnakuta; Kanchanatawee, Sunthorn; Jantama, Kaemwich

    2012-09-01

    Klebsiella oxytoca strains were constructed to produce optical pure d-lactate by pH-controlled batch fermentation in mineral salts medium. The alcohol dehydrogenase gene, adhE, and the phospho-transacetylase/acetate kinase A genes, pta-ackA, were deleted from the wild type. KMS002 (ΔadhE) and KMS004 (ΔadhE Δpta-ackA) exhibited d-lactate production as a primary pathway for the regeneration of NAD(+). Both strains produced 11-13 g/L of d-lactate in medium containing 2% (w/v) glucose with yields of 0.64-0.71 g/g glucose used. In sugarcane molasses, KMS002 and KMS004 produced 22-24 g/L of d-lactate with yields of 0.80-0.87 g/g total sugars utilized. Both strains also utilized maltodextrin derived from cassava starch and produced d-lactate at a concentration of 33-34 g/L with yields of 0.91-0.92 g/g maltodextrin utilized. These d-lactate yields are higher than those reported for engineered E. coli strains. Copyright © 2012 Elsevier Ltd. All rights reserved.

  16. Metabolism of DMSP, DMS and DMSO by the cultivable bacterial community associated with the DMSP-producing dinoflagellate Scrippsiella trochoidea

    Digital Repository Service at National Institute of Oceanography (India)

    Hatton, A.D.; Shenoy, D.M.; Hart, M.C.; Mogg, A.; Green, D.H.

    dm-3) with or without glucose (5 mmol dm-3). Vials were sealed with PTFE-lined crimp tops. Control vials were set up to check for chemical degradation of substrates (without bacteria) and for any production of biogenic sulfur compounds produced..., Cooper WJ (eds) Biogenic sulfur in the environment. American Chemical Society, Washington, pp 167–181 Kiene RP, Linn LJ (2000a) Distribution and turnover of dissolved DMSP and its relationship with bacterial production and dimethylsulfide in the Gulf...

  17. Assessment of metabolic flux distribution in the thermophilic hydrogen producer Caloramator celer as affected by external pH and hydrogen partial pressure.

    Science.gov (United States)

    Ciranna, Alessandro; Pawar, Sudhanshu S; Santala, Ville; Karp, Matti; van Niel, Ed W J

    2014-03-28

    Caloramator celer is a strict anaerobic, alkalitolerant, thermophilic bacterium capable of converting glucose to hydrogen (H2), carbon dioxide, acetate, ethanol and formate by a mixed acid fermentation. Depending on the growth conditions C. celer can produce H2 at high yields. For a biotechnological exploitation of this bacterium for H2 production it is crucial to understand the factors that regulate carbon and electron fluxes and therefore the final distribution of metabolites to channel the metabolic flux towards the desired product. Combining experimental results from batch fermentations with genome analysis, reconstruction of central carbon metabolism and metabolic flux analysis (MFA), this study shed light on glucose catabolism of the thermophilic alkalitolerant bacterium C. celer. Two innate factors pertaining to culture conditions have been identified to significantly affect the metabolic flux distribution: culture pH and partial pressures of H2 (PH2). Overall, at alkaline to neutral pH the rate of biomass synthesis was maximized, whereas at acidic pH the lower growth rate and the less efficient biomass formation are accompanied with more efficient energy recovery from the substrate indicating high cell maintenance possibly to sustain intracellular pH homeostasis. Higher H2 yields were associated with fermentation at acidic pH as a consequence of the lower synthesis of other reduced by-products such as formate and ethanol. In contrast, PH2 did not affect the growth of C. celer on glucose. At high PH2 the cellular redox state was balanced by rerouting the flow of carbon and electrons to ethanol and formate production allowing unaltered glycolytic flux and growth rate, but resulting in a decreased H2 synthesis. C. celer possesses a flexible fermentative metabolism that allows redistribution of fluxes at key metabolic nodes to simultaneously control redox state and efficiently harvest energy from substrate even under unfavorable conditions (i.e. low pH and high

  18. Prolonged rote learning produces delayed memory facilitation and metabolic changes in the hippocampus of the ageing human brain

    Directory of Open Access Journals (Sweden)

    Prendergast Julie

    2009-11-01

    Full Text Available Abstract Background Repeated rehearsal is one method by which verbal material may be transferred from short- to long-term memory. We hypothesised that extended engagement of memory structures through prolonged rehearsal would result in enhanced efficacy of recall and also of brain structures implicated in new learning. Twenty-four normal participants aged 55-70 (mean = 60.1 engaged in six weeks of rote learning, during which they learned 500 words per week every week (prose, poetry etc.. An extensive battery of memory tests was administered on three occasions, each six weeks apart. In addition, proton magnetic resonance spectroscopy (1H-MRS was used to measure metabolite levels in seven voxels of interest (VOIs (including hippocampus before and after learning. Results Results indicate a facilitation of new learning that was evident six weeks after rote learning ceased. This facilitation occurred for verbal/episodic material only, and was mirrored by a metabolic change in left posterior hippocampus, specifically an increase in NAA/(Cr+Cho ratio. Conclusion Results suggest that repeated activation of memory structures facilitates anamnesis and may promote neuronal plasticity in the ageing brain, and that compliance is a key factor in such facilitation as the effect was confined to those who engaged fully with the training.

  19. Prolonged rote learning produces delayed memory facilitation and metabolic changes in the hippocampus of the ageing human brain.

    LENUS (Irish Health Repository)

    Roche, Richard Ap

    2009-01-01

    BACKGROUND: Repeated rehearsal is one method by which verbal material may be transferred from short- to long-term memory. We hypothesised that extended engagement of memory structures through prolonged rehearsal would result in enhanced efficacy of recall and also of brain structures implicated in new learning. Twenty-four normal participants aged 55-70 (mean = 60.1) engaged in six weeks of rote learning, during which they learned 500 words per week every week (prose, poetry etc.). An extensive battery of memory tests was administered on three occasions, each six weeks apart. In addition, proton magnetic resonance spectroscopy (1H-MRS) was used to measure metabolite levels in seven voxels of interest (VOIs) (including hippocampus) before and after learning. RESULTS: Results indicate a facilitation of new learning that was evident six weeks after rote learning ceased. This facilitation occurred for verbal\\/episodic material only, and was mirrored by a metabolic change in left posterior hippocampus, specifically an increase in NAA\\/(Cr+Cho) ratio. CONCLUSION: Results suggest that repeated activation of memory structures facilitates anamnesis and may promote neuronal plasticity in the ageing brain, and that compliance is a key factor in such facilitation as the effect was confined to those who engaged fully with the training.

  20. Prebiotic potential of L-sorbose and xylitol in promoting the growth and metabolic activity of specific butyrate-producing bacteria in human fecal culture.

    Science.gov (United States)

    Sato, Tadashi; Kusuhara, Shiro; Yokoi, Wakae; Ito, Masahiko; Miyazaki, Kouji

    2017-01-01

    Dietary low-digestible carbohydrates (LDCs) affect gut microbial metabolism, including the production of short-chain fatty acids. The ability of various LDCs to promote butyrate production was evaluated in in vitro human fecal cultures. Fecal suspensions from five healthy males were anaerobically incubated with various LDCs. L-Sorbose and xylitol markedly promoted butyrate formation in cultures. Bacterial 16S rRNA gene-based denaturing gradient gel electrophoresis analyses of these fecal cultures revealed a marked increase in the abundance of bacteria closely related to the species Anaerostipes hadrus or A. caccae or both, during enhanced butyrate formation from L-sorbose or xylitol. By using an agar plate culture, two strains of A. hadrus that produced butyrate from each substrate were isolated from the feces of two donors. Furthermore, of 12 species of representative colonic butyrate producers, only A. hadrus and A. caccae demonstrated augmented butyrate production from L-sorbose or xylitol. These findings suggest that L-sorbose and xylitol cause prebiotic stimulation of the growth and metabolic activity of Anaerostipes spp. in the human colon. © FEMS 2016. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  1. Selenium treatment differentially affects sulfur metabolism in high and low glucosinolate producing cultivars of broccoli (Brassica oleracea L.).

    Science.gov (United States)

    McKenzie, Marian J; Chen, Ronan K Y; Leung, Susanna; Joshi, Srishti; Rippon, Paula E; Joyce, Nigel I; McManus, Michael T

    2017-12-01

    The effect of selenium (Se) application on the sulfur (S)-rich glucosinolate (GSL)-containing plant, broccoli (Brassica oleracea L. var. italica) was examined with a view to producing germplasm with increased Se and GSL content for human health, and to understanding the influence of Se on the regulation of GSL production. Two cultivars differing in GSL content were compared. Increased Se application resulted in an increase in Se uptake in planta, but no significant change in total S or total GSL content in either cultivar. Also no significant change was observed in the activity of ATP sulfurylase (ATPS, EC 2.7.7.4) or O-acetylserine(thiol) lyase (OASTL, EC 2.5.1.47) with increased Se application. However, in the first investigation of APS kinase (APSK, EC 2.7.1.25) expression in response to Se fertilisation, an increase in transcript abundance of one variant of APS kinase 1 (BoAPSK1A) was observed in both cultivars, and an increase in BoAPSK2 transcript abundance was observed in the low GSL producing cultivar. A mechanism by which increased APSK transcription may provide a means of controlling the content of S-containing compounds, including GSLs, following Se uptake is proposed. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  2. Metabolic engineering of the moss Physcomitrella patens to produce the sesquiterpenoids patchoulol and α/β-santalene

    Directory of Open Access Journals (Sweden)

    Xin eZhan

    2014-11-01

    Full Text Available The moss Physcomitrella patens, has been genetically engineered to produce patchoulol and β-santalene, two valuable sesquiterpenoid ingredients in the fragrance industry. The highest yield of patchoulol achieved was 1.34 mg/g dry weight. This was achieved by non-targeted transformation of the patchoulol synthase and either a yeast or P. patens HMGR gene under the control of a 35S promoter. Santalene synthase targeted to the plastids yielded 0.039 mg/g dry weight of α/β santalene; cytosolic santalene synthase and 35S controlled HMGR afforded 0.022 mg/g dry weight. It has been observed that the final yield of the fragrance molecules is dependent on the expression of the synthase. This is the first report of heterologous production of sesquiterpenes in moss and it opens up a promising source for light-driven production of valuable fragrance ingredients.

  3. Metabolic engineering of Escherichia coli to produce 2'-fucosyllactose via salvage pathway of guanosine 5'-diphosphate (GDP)-l-fucose.

    Science.gov (United States)

    Chin, Young-Wook; Seo, Nari; Kim, Jae-Han; Seo, Jin-Ho

    2016-11-01

    2'-Fucosyllactose (2-FL) is one of the key oligosaccharides in human milk. In the present study, the salvage guanosine 5'-diphosphate (GDP)-l-fucose biosynthetic pathway from fucose was employed in engineered Escherichia coli BL21star(DE3) for efficient production of 2-FL. Introduction of the fkp gene coding for fucokinase/GDP-l-fucose pyrophosphorylase (Fkp) from Bacteroides fragilis and the fucT2 gene encoding α-1,2-fucosyltransferase from Helicobacter pylori allows the engineered E. coli to produce 2-FL from fucose, lactose and glycerol. To enhance the lactose flux to 2-FL production, the attenuated, and deleted mutants of β-galactosidase were employed. Moreover, the 2-FL yield and productivity were further improved by deletion of the fucI-fucK gene cluster coding for fucose isomerase (FucI) and fuculose kinase (FucK). Finally, fed-batch fermentation of engineered E. coli BL21star(DE3) deleting lacZ and fucI-fucK, and expressing fkp and fucT2 resulted in 23.1 g/L of extracellular concentration of 2-FL and 0.39 g/L/h productivity. Biotechnol. Bioeng. 2016;113: 2443-2452. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  4. Inulin-type fructan degradation capacity of Clostridium cluster IV and XIVa butyrate-producing colon bacteria and their associated metabolic outcomes.

    Science.gov (United States)

    Moens, F; De Vuyst, L

    2017-05-30

    Four selected butyrate-producing colon bacterial strains belonging to Clostridium cluster IV (Butyricicoccus pullicaecorum DSM 23266 T and Faecalibacterium prausnitzii DSM 17677 T ) and XIVa (Eubacterium hallii DSM 17630 and Eubacterium rectale CIP 105953 T ) were studied as to their capacity to degrade inulin-type fructans and concomitant metabolite production. Cultivation of these strains was performed in bottles and fermentors containing a modified medium for colon bacteria, including acetate, supplemented with either fructose, oligofructose, or inulin as the sole energy source. Inulin-type fructan degradation was not a general characteristic among these strains. B. pullicaecorum DSM 23266 T and E. hallii DSM 17630 could only ferment fructose and did not degrade oligofructose or inulin. E. rectale CIP 105953 T and F. prausnitzii DSM 17677 T fermented fructose and could degrade both oligofructose and inulin. All chain length fractions of oligofructose were degraded simultaneously (both strains) and both long and short chain length fractions of inulin were degraded either simultaneously (E. rectale CIP 105953 T ) or consecutively (F. prausnitzii DSM 17677 T ), indicating an extracellular polymer degradation mechanism. B. pullicaecorum DSM 23266 T and E. hallii DSM 17630 produced high concentrations of butyrate, CO 2 , and H 2 from fructose. E. rectale CIP 105953 T produced lactate, butyrate, CO 2 , and H 2 , from fructose, oligofructose, and inulin, whereas F. prausnitzii DSM 17677 T produced butyrate, formate, CO 2 , and traces of lactate from fructose, oligofructose, and inulin. Based on carbon recovery and theoretical metabolite production calculations, an adapted stoichiometrically balanced metabolic pathway for butyrate, formate, lactate, CO 2 , and H 2 production by members of both Clostridium cluster IV and XIVa butyrate-producing bacteria was constructed.

  5. Taxonomic characterization and metabolic analysis of the Halomonas sp. KM-1, a highly bioplastic poly(3-hydroxybutyrate)-producing bacterium.

    Science.gov (United States)

    Kawata, Yoshikazu; Shi, Lian-Hua; Kawasaki, Kazunori; Shigeri, Yasushi

    2012-04-01

    In a brief previous report, the gram-negative moderately halophilic bacterium, Halomonas sp. KM-1, that was isolated in our laboratory was shown to produce the bioplastic, poly(3-hydroxybutyrate) (PHB), using biodiesel waste glycerol (Kawata and Aiba, Biosci. Biotechnol. Biochem., 74, 175-177, 2010). Here, we further characterized this KM-1 strain and compared it to other Halomonas strains. Strain KM-1 was subjected to a polyphasic taxonomic study. Strain KM-1 was rod-shaped and formed colonies on a plate that were cream-beige in color, smooth, opaque, and circular with entire edges. KM-1 grew under environmental conditions of 0.1%-10% (w/v) NaCl, pH 6.5-10.5 and at temperatures between 10°C and 45°C. The G+C content of strain KM-1 was 63.9 mol%. Of the 16 Halomonas strains examined in this study, the strain KM-1 exhibited the highest production of PHB (63.6%, w/v) in SOT medium supplemented with 10% glycerol, 10.0 g/L sodium nitrate and 2.0 g/L dipotassium hydrogen phosphate. The intracellular structures within which PHB accumulated had the appearance of intracellular granules with a diameter of approximately 0.5 μm, as assessed by electron microscopy. The intra- and extra-cellular metabolites of strain KM-1 were analyzed by capillary electrophoresis mass spectrometry. In spite of the high amount of PHB stored intra-cellularly, as possible precursors for PHB only a small quantity of 3-hydroxybutyric acid and acetyl CoA, and no quantity of 3-hydroxybutyl CoA, acetoacetyl CoA and acetoacetate were detected either intra- or extra-cellularly, suggesting highly efficient conversion of these precursors to PHB. Copyright © 2011 The Society for Biotechnology, Japan. All rights reserved.

  6. Metabolic engineering of a glycerol-oxidative pathway in Lactobacillus panis PM1 for utilization of bioethanol thin stillage: potential to produce platform chemicals from glycerol.

    Science.gov (United States)

    Kang, Tae Sun; Korber, Darren R; Tanaka, Takuji

    2014-12-01

    Lactobacillus panis PM1 has the ability to produce 1,3-propanediol (1,3-PDO) from thin stillage (TS), which is the major waste material after bioethanol production, and is therefore of significance. However, the fact that L. panis PM1 cannot use glycerol as a sole carbon source presents a considerable problem in terms of utilization of this strain in a wide range of industrial applications. Accordingly, L. panis PM1 was genetically engineered to directly utilize TS as a fermentable substrate for the production of valuable platform chemicals without the need for exogenous nutrient supplementation (e.g., sugars and nitrogen sources). An artificial glycerol-oxidative pathway, comprised of glycerol facilitator, glycerol kinase, glycerol 3-phosphate dehydrogenase, triosephosphate isomerase, and NADPH-dependent aldehyde reductase genes of Escherichia coli, was introduced into L. panis PM1 in order to directly utilize glycerol for the production of energy for growth and value-added chemicals. A pH 6.5 culture converted glycerol to mainly lactic acid (85.43 mM), whereas a significant amount of 1,3-propanediol (59.96 mM) was formed at pH 7.5. Regardless of the pH, ethanol (82.16 to 83.22 mM) was produced from TS fermentations, confirming that the artificial pathway metabolized glycerol for energy production and converted it into lactic acid or 1,3-PDO and ethanol in a pH-dependent manner. This study demonstrates the cost-effective conversion of TS to value-added chemicals by the engineered PM1 strain cultured under industrial conditions. Thus, application of this strain or these research findings can contribute to reduced costs of bioethanol production. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

  7. Effects of clonal variation on growth, metabolism, and productivity in response to trophic factor stimulation: a study of Chinese hamster ovary cells producing a recombinant monoclonal antibody.

    Science.gov (United States)

    Dahodwala, Hussain; Nowey, Mark; Mitina, Tatyana; Sharfstein, Susan T

    2012-01-01

    The growth, metabolism, and productivity of five Chinese hamster ovary (CHO) clones were explored in response to stimulation with insulin (5 mg/L) and LONG(®)R(3)IGF-I (20 μg/L or 100 μg/L). All five clones were derived from the same parental CHO cell line (DG44) and produced the same recombinant monoclonal antibody, with varying specific productivities. There was no uniform response among the clones to stimulation with the different trophic factors. One of the high productivity clones (clone D) exhibited significantly better growth in response to LONG(®)R(3)IGF-I; whereas the other clones showed equivalent or slightly better growth in the presence of insulin. Three out of the five clones had higher specific productivities in the presence of insulin (although not statistically significant); one was invariant, and the final clone exhibited slightly higher specific productivity in the presence of LONG(®)R(3)IGF-I. Total product titers exhibited moderate variation between culture conditions, again with neither trophic factor being clearly superior. Overall product titers were affected by variations in both integrated viable cell density and specific productivity. Nutrient uptake and metabolite generation patterns varied strongly between clones and much less with culture conditions. These results point to the need for careful clonal analysis when selecting clones, particularly for platform processes where media and culture conditions are predetermined.

  8. Consumption of Honey, Sucrose, and High-Fructose Corn Syrup Produces Similar Metabolic Effects in Glucose-Tolerant and -Intolerant Individuals.

    Science.gov (United States)

    Raatz, Susan K; Johnson, LuAnn K; Picklo, Matthew J

    2015-10-01

    Public health recommendations call for a reduction in added sugars; however, controversy exists over whether all nutritive sweeteners produce similar metabolic effects. The objective was to compare the effects of the chronic consumption of 3 nutritive sweeteners [honey, sucrose, and high-fructose corn syrup containing 55% fructose (HFCS55)] on circulating glucose, insulin, lipids, and inflammatory markers; body weight; and blood pressure in individuals with normal glucose tolerance (GT) and those with impaired glucose tolerance (IGT). In a crossover design, participants consumed daily, in random order, 50 g carbohydrate from assigned sweeteners for 2 wk with a 2- to 4-wk washout period between treatments. Participants included 28 GT and 27 IGT volunteers with a mean age of 38.9 ± 3.6 y and 52.1 ± 2.7 y, respectively, and a body mass index (in kg/m(2)) of 26 ± 0.8 and 31.5 ± 1.0, respectively. Body weight, blood pressure (BP), serum inflammatory markers, lipids, fasting glucose and insulin, and oral-glucose-tolerance tests (OGTTs) were completed pre- and post-treatment. The OGTT incremental areas under the curve (iAUCs) for glucose and insulin were determined and homeostasis model assessment of insulin resistance (HOMA-IR) scores were calculated. Body weight and serum glucose, insulin, inflammatory markers, and total and LDL-cholesterol concentrations were significantly higher in the IGT group than in the GT group at baseline. Glucose, insulin, HOMA-IR, and the OGTT iAUC for glucose or insulin did not differ by treatment, but all responses were significantly higher in the IGT group compared with the GT group. Body weight was unchanged by treatment. Systolic BP was unchanged, whereas diastolic BP was significantly lower in response to sugar intake across all treatments. An increase in high-sensitivity C-reactive protein (hsCRP) was observed in the IGT group in response to all sugars. No treatment effect was observed for interleukin 6. HDL cholesterol did not

  9. Postpartum resumption of cyclic ovarian function, first estrus and re-conception and their relation to energy metabolism in high-producing dairy cows

    Directory of Open Access Journals (Sweden)

    Huszenicza Gyula

    2004-01-01

    Full Text Available In the last few decades a continuous increase was observed in average milk production of dairy cows all over the world. Simultaneously, however, a dramatic decrease was seen in reproductive performance. This tendency is attributed to the increased incidence of bacterial complications in uterine involution, as well as to the high occurrence of ovarian malfunctions in the postpartum period. The aim of this paper is to review the physiology and pathology of the latter, really complex phenomenon. The nutritional basis of this process, that the requirements of high-producing dairy cows shift abruptly after parturition as the daily milk yield rapidly increases and the ensuing negative energy balance (NEB will extend 10-12 weeks. In the context of the high genetic merit dairy cow, the pp NEB is the difference between the dietary intake of utilizable energy and the expenditure of energy for body mass maintenance and milk synthesis. In principle, it is a physiological phenomenon, which may, however, result in more or less severe disorders in both the metabolism and reproduction and so it may lead to great economic losses in modern dairy practice [112]. In the first 3-4 weeks after calving the NEB is highly correlated with both milk yield and the interval to first ovulation. Because the number of ovulatory estrous cycles preceding the insemination (AI has been shown to influence the conception rate, the length of the pp interval to first ovulation provides an important parameter for assessing the effect of NEB on reproductive performance Š19, 20¹.

  10. Research Advances: Calorie Restriction and Increased Longevity Linked to Metabolic Changes; Isotope Ratios Reveal Trickery in the Produce Aisle; An Ancient Inca Tax and Metallurgy in Peru

    Science.gov (United States)

    King, Angela G.

    2007-01-01

    The different lifelong patterns related to different levels of energy metabolism and the activities of the microbes in various animals are described. The analysis shows that many important beneficial changes occur due to the activities of symbiotic bacteria living in the intestinal tract.

  11. Metabolic alterations produced by 3-nitropropionic acid in rat striata and cultured astrocytes: quantitative in vitro 1H nuclear magnetic resonance spectroscopy and biochemical characterization

    International Nuclear Information System (INIS)

    Chang, C.; Wan, Y.L.; Goh, C.C.; Tsai, M.J.

    1997-01-01

    Quantitative high resolution in vitro 1 H nuclear magnetic resonance spectroscopy was employed to study the metabolic effects of 3-nitropropionic acid associated with aging from perchloric acid extracts of rat striata. Systemic injection of 3-nitropropionic acid in rats at a dose of 10 mg/kg/day for seven consecutive days significantly impaired energy metabolism in rats one, four and eight months of age, as evidenced by a marked elevation of succinate and lactate levels. However, a significant decrease in N-acetyl-l-aspartate level, a neuronal marker, was observed in four- and eight-month-old rats but not in one-month-old rats. This would indicate that rats at four to eight months are more susceptible to 3-nitropropionic acid than those at one month. A significant decrease in GABA level was observed in four-month-old 3-nitropropionic acid-treated rats, which is consistent with the literature that GABAergic neurons are particularly vulnerable to 3-nitropropionic acid treatment. In addition, glutamine and glutamate levels were markedly decreased at four and eight months in 3-nitropropionic acid-treated rats. Since glutamine is synthesized predominantly in glia, the observation above suggests that 3-nitropropionic acid intoxication may involve perturbation of energy metabolism, glial injury and consequent neuronal damage. Astrocytes which are essential in the metabolism of glutamate and glutamine were used to further assess 3-nitropropionic acid-induced toxicity. Glial proliferation, mitochondrial metabolism and glutamine synthetase activity were all reduced by 3-nitropropionic acid treatment with a concomitant increase, in a dose-dependent manner, of lactate levels, suggesting that 3-nitropropionic acid is also detrimental to astrocytes in vivo and thus may affect metabolic interaction between neurons and glia.These results not only imply that 3-nitropropionic acid blocks energy metabolism prior to exerting neurotoxic damage but also demonstrate that the degree of

  12. Biomass composition, lipid characterization, and metabolic profile analysis of the fed-batch fermentation process of two different docosahexanoic acid producing Schizochytrium sp. strains.

    Science.gov (United States)

    Qu, Liang; Ren, Lu-Jing; Li, Juan; Sun, Guan-Nan; Sun, Li-Na; Ji, Xiao-Jun; Nie, Zhi-Kui; Huang, He

    2013-12-01

    Growth and fermentation characteristics, biomass composition, lipid characterization and metabolic profiling analysis of two different Schizochytrium sp. strains, the original strain and the industrial adaptive strain, were investigated in the fed-batch fermentation process. The final cell biomass, total lipids content, docosahexanoic acid (DHA) content and DHA productivity of the adaptive strain were much higher than those of the original strain. The metabolic distinctions which extensively existed between these two strains were revealed by the score plot of principal component analysis. In addition, potential biomarkers responsible for discriminating different strains were identified as myo-inositol, histidine, alanine, asparagine, cysteine, and oxalic acid. These findings provided new insights into the industrial strain screening and further improvement of DHA production by Schizochytrium sp.

  13. Fructose Alters Intermediary Metabolism of Glucose in Human Adipocytes and Diverts Glucose to Serine Oxidation in the One–Carbon Cycle Energy Producing Pathway

    Directory of Open Access Journals (Sweden)

    Vijayalakshmi Varma

    2015-06-01

    Full Text Available Increased consumption of sugar and fructose as sweeteners has resulted in the utilization of fructose as an alternative metabolic fuel that may compete with glucose and alter its metabolism. To explore this, human Simpson-Golabi-Behmel Syndrome (SGBS preadipocytes were differentiated to adipocytes in the presence of 0, 1, 2.5, 5 or 10 mM of fructose added to a medium containing 5 mM of glucose representing the normal blood glucose concentration. Targeted tracer [1,2-13C2]-d-glucose fate association approach was employed to examine the influence of fructose on the intermediary metabolism of glucose. Increasing concentrations of fructose robustly increased the oxidation of [1,2-13C2]-d-glucose to 13CO2 (p < 0.000001. However, glucose-derived 13CO2 negatively correlated with 13C labeled glutamate, 13C palmitate, and M+1 labeled lactate. These are strong markers of limited tricarboxylic acid (TCA cycle, fatty acid synthesis, pentose cycle fluxes, substrate turnover and NAD+/NADP+ or ATP production from glucose via complete oxidation, indicating diminished mitochondrial energy metabolism. Contrarily, a positive correlation was observed between glucose-derived 13CO2 formed and 13C oleate and doses of fructose which indicate the elongation and desaturation of palmitate to oleate for storage. Collectively, these results suggest that fructose preferentially drives glucose through serine oxidation glycine cleavage (SOGC pathway one-carbon cycle for NAD+/NADP+ production that is utilized in fructose-induced lipogenesis and storage in adipocytes.

  14. Results of preliminary clinical trials of the positron emission mammography system PEM-I: a dedicated breast imaging system producing glucose metabolic images using FDG.

    Science.gov (United States)

    Murthy, K; Aznar, M; Thompson, C J; Loutfi, A; Lisbona, R; Gagnon, J H

    2000-11-01

    Early detection of breast cancer is crucial for efficient and effective treatment. We have developed an instrument for positron emission mammography (PEM) called PEM-I that performs high-resolution metabolic imaging of breast cancer. Images of glucose metabolism are obtained after injection of 75 MBq FDG. The PEM detectors are integrated into a conventional mammography system, allowing acquisition of the emission images immediately after the mammogram, without subject repositioning, and accurate coregistration of images from the 2 modalities. In this article, we present the results of the first clinical pilot study with the instrument. Sixteen subjects (age range, 34-76 y) were studied. All subjects were nondiabetic, nonpregnant, and without a history of cancer. They had recently been found to have suggestive mammography findings or a palpable breast mass and underwent lumpectomy or mastectomy within 2 wk of the study. Results from the PEM study were compared with those from mammography and pathology. A PEM test was classified positive (indicating the presence of cancer) if significant focal uptake was seen in the image or if the counting rate in the breast with suggestive findings was significantly higher than in the contralateral breast. Of the 16 subjects studied, 14 were evaluable. Ten cancerous tumors and 4 benign tumors were confirmed by pathologic examination after complete removal of the tumor. PEM correctly detected the presence of disease in 8 of 10 subjects. Findings were false-negative in 2 instances and false-positive in none, giving the instrument 80% sensitivity, 100% specificity, and 86% accuracy. Our preliminary results suggest that PEM can offer a noninvasive method for the diagnosis of breast cancer. Metabolic images from PEM contain unique information not available from conventional morphologic imaging techniques and aid in expeditiously establishing the diagnosis of cancer. In all subjects, the PEM images were of diagnostic quality, with an

  15. Effect of metabolic products of Aspergillus oryzae on the formation of aroma components by sake yeast. : On the aroma produced by yeast (XI)

    OpenAIRE

    小泉, 武夫; 鈴木, 昌治; 佐藤, 直樹; 角田, 潔和; 野白, 喜久雄; T., KOIZUMI; M., SUZUKI; N., SATOH; K., KAKUTA; K., NOJIRO; 東京農業大学醸造学科; 東京農業大学醸造学科; 東京農業大学醸造学科; 東京農業大学醸造学科; 東京農業大学醸造学科

    1981-01-01

    We have investigated the effect of metabolic products of A.oryzae on the formation of aroma components by sake yeast. Addition of extract of rice-koji or culture broth of A. oryzae to Hayduck medium increased the aroma formation of sake yeast. Mevalonic acid, a specific product of A. oryzae, stimulated the aroma formation of sake yeast. Products of A. oryzae had a greater stimulative effect on aroma formation in alcoholic fermentation by sake yeast than those of A. awamori. Aroma formation in...

  16. The metabolic response of P. putida KT2442 producing high levels of polyhydroxyalkanoate under single- and multiple-nutrient-limited growth: Highlights from a multi-level omics approach

    Directory of Open Access Journals (Sweden)

    Poblete-Castro Ignacio

    2012-03-01

    Full Text Available Abstract Background Pseudomonas putida KT2442 is a natural producer of polyhydroxyalkanoates (PHAs, which can substitute petroleum-based non-renewable plastics and form the basis for the production of tailor-made biopolymers. However, despite the substantial body of work on PHA production by P. putida strains, it is not yet clear how the bacterium re-arranges its whole metabolism when it senses the limitation of nitrogen and the excess of fatty acids as carbon source, to result in a large accumulation of PHAs within the cell. In the present study we investigated the metabolic response of KT2442 using a systems biology approach to highlight the differences between single- and multiple-nutrient-limited growth in chemostat cultures. Results We found that 26, 62, and 81% of the cell dry weight consist of PHA under conditions of carbon, dual, and nitrogen limitation, respectively. Under nitrogen limitation a specific PHA production rate of 0.43 (g·(g·h-1 was obtained. The residual biomass was not constant for dual- and strict nitrogen-limiting growth, showing a different feature in comparison to other P. putida strains. Dual limitation resulted in patterns of gene expression, protein level, and metabolite concentrations that substantially differ from those observed under exclusive carbon or nitrogen limitation. The most pronounced differences were found in the energy metabolism, fatty acid metabolism, as well as stress proteins and enzymes belonging to the transport system. Conclusion This is the first study where the interrelationship between nutrient limitations and PHA synthesis has been investigated under well-controlled conditions using a system level approach. The knowledge generated will be of great assistance for the development of bioprocesses and further metabolic engineering work in this versatile organism to both enhance and diversify the industrial production of PHAs.

  17. Metabolic Engineering

    Indian Academy of Sciences (India)

    IAS Admin

    Metabolic engineering is a process for modulating the me- tabolism of the organisms so as to produce the required amounts of the desired metabolite through genetic manipula- tions. Considering its advantages over the other chemical synthesis routes, this area of biotechnology is likely to revolu- tionize the way in which ...

  18. Metabolic engineering of oilseed crops to produce high levels of novel acetyl glyceride oils with reduced viscosity, freezing point and calorific value.

    Science.gov (United States)

    Liu, Jinjie; Rice, Adam; McGlew, Kathleen; Shaw, Vincent; Park, Hyunwoo; Clemente, Tom; Pollard, Mike; Ohlrogge, John; Durrett, Timothy P

    2015-08-01

    Seed oils have proved recalcitrant to modification for the production of industrially useful lipids. Here, we demonstrate the successful metabolic engineering and subsequent field production of an oilseed crop with the highest accumulation of unusual oil achieved so far in transgenic plants. Previously, expression of the Euonymus alatus diacylglycerol acetyltransferase (EaDAcT) gene in wild-type Arabidopsis seeds resulted in the accumulation of 45 mol% of unusual 3-acetyl-1,2-diacyl-sn-glycerols (acetyl-TAGs) in the seed oil (Durrett et al., 2010 PNAS 107:9464). Expression of EaDAcT in dgat1 mutants compromised in their ability to synthesize regular triacylglycerols increased acetyl-TAGs to 65 mol%. Camelina and soybean transformed with the EaDAcT gene accumulate acetyl-triacylglycerols (acetyl-TAGs) at up to 70 mol% of seed oil. A similar strategy of coexpression of EaDAcT together with RNAi suppression of DGAT1 increased acetyl-TAG levels to up to 85 mol% in field-grown transgenic Camelina. Additionally, total moles of triacylglycerol (TAG) per seed increased 20%. Analysis of the acetyl-TAG fraction revealed a twofold reduction in very long chain fatty acids (VLCFA), consistent with their displacement from the sn-3 position by acetate. Seed germination remained high, and seedlings were able to metabolize the stored acetyl-TAGs as rapidly as regular triacylglycerols. Viscosity, freezing point and caloric content of the Camelina acetyl-TAG oils were reduced, enabling use of this oil in several nonfood and food applications. © 2015 Society for Experimental Biology, Association of Applied Biologists and John Wiley & Sons Ltd.

  19. Bi-articular Knee-Ankle-Foot Exoskeleton Produces Higher Metabolic Cost Reduction than Weight-Matched Mono-articular Exoskeleton

    Science.gov (United States)

    Malcolm, Philippe; Galle, Samuel; Derave, Wim; De Clercq, Dirk

    2018-01-01

    The bi-articular m. gastrocnemius and the mono-articular m. soleus have different and complementary functions during walking. Several groups are starting to use these biological functions as inspiration to design prostheses with bi-articular actuation components to replace the function of the m. gastrocnemius. Simulation studies indicate that a bi-articular configuration and spring that mimic the m. gastrocnemius could be beneficial for orthoses or exoskeletons. Our aim was to test the effect of a bi-articular and spring configuration that mimics the m. gastrocnemius and compare this to a no-spring and mono-articular configuration. We tested nine participants during walking with knee-ankle-foot exoskeletons with dorsally mounted pneumatic muscle actuators. In the bi-articular plus spring condition the pneumatic muscles were attached to the thigh segment with an elastic cord. In the bi-articular no-spring condition the pneumatic muscles were also attached to the thigh segment but with a non-elastic cord. In the mono-articular condition the pneumatic muscles were attached to the shank segment. We found the highest reduction in metabolic cost of 13% compared to walking with the exoskeleton powered-off in the bi-articular plus spring condition. Possible explanations for this could be that the exoskeleton delivered the highest total positive work in this condition at the ankle and the knee and provided more assistance during the isometric phase of the biological plantarflexors. As expected we found that the bi-articular conditions reduced m. gastrocnemius EMG more than the mono-articular condition but this difference was not significant. We did not find that the mono-articular condition reduces the m. soleus EMG more than the bi-articular conditions. Knowledge of specific effects of different exoskeleton configurations on metabolic cost and muscle activation could be useful for providing customized assistance for specific gait impairments. PMID:29551959

  20. Bi-articular Knee-Ankle-Foot Exoskeleton Produces Higher Metabolic Cost Reduction than Weight-Matched Mono-articular Exoskeleton

    Directory of Open Access Journals (Sweden)

    Philippe Malcolm

    2018-03-01

    Full Text Available The bi-articular m. gastrocnemius and the mono-articular m. soleus have different and complementary functions during walking. Several groups are starting to use these biological functions as inspiration to design prostheses with bi-articular actuation components to replace the function of the m. gastrocnemius. Simulation studies indicate that a bi-articular configuration and spring that mimic the m. gastrocnemius could be beneficial for orthoses or exoskeletons. Our aim was to test the effect of a bi-articular and spring configuration that mimics the m. gastrocnemius and compare this to a no-spring and mono-articular configuration. We tested nine participants during walking with knee-ankle-foot exoskeletons with dorsally mounted pneumatic muscle actuators. In the bi-articular plus spring condition the pneumatic muscles were attached to the thigh segment with an elastic cord. In the bi-articular no-spring condition the pneumatic muscles were also attached to the thigh segment but with a non-elastic cord. In the mono-articular condition the pneumatic muscles were attached to the shank segment. We found the highest reduction in metabolic cost of 13% compared to walking with the exoskeleton powered-off in the bi-articular plus spring condition. Possible explanations for this could be that the exoskeleton delivered the highest total positive work in this condition at the ankle and the knee and provided more assistance during the isometric phase of the biological plantarflexors. As expected we found that the bi-articular conditions reduced m. gastrocnemius EMG more than the mono-articular condition but this difference was not significant. We did not find that the mono-articular condition reduces the m. soleus EMG more than the bi-articular conditions. Knowledge of specific effects of different exoskeleton configurations on metabolic cost and muscle activation could be useful for providing customized assistance for specific gait impairments.

  1. Bi-articular Knee-Ankle-Foot Exoskeleton Produces Higher Metabolic Cost Reduction than Weight-Matched Mono-articular Exoskeleton.

    Science.gov (United States)

    Malcolm, Philippe; Galle, Samuel; Derave, Wim; De Clercq, Dirk

    2018-01-01

    The bi-articular m. gastrocnemius and the mono-articular m. soleus have different and complementary functions during walking. Several groups are starting to use these biological functions as inspiration to design prostheses with bi-articular actuation components to replace the function of the m. gastrocnemius. Simulation studies indicate that a bi-articular configuration and spring that mimic the m. gastrocnemius could be beneficial for orthoses or exoskeletons. Our aim was to test the effect of a bi-articular and spring configuration that mimics the m. gastrocnemius and compare this to a no-spring and mono-articular configuration. We tested nine participants during walking with knee-ankle-foot exoskeletons with dorsally mounted pneumatic muscle actuators. In the bi-articular plus spring condition the pneumatic muscles were attached to the thigh segment with an elastic cord. In the bi-articular no-spring condition the pneumatic muscles were also attached to the thigh segment but with a non-elastic cord. In the mono-articular condition the pneumatic muscles were attached to the shank segment. We found the highest reduction in metabolic cost of 13% compared to walking with the exoskeleton powered-off in the bi-articular plus spring condition . Possible explanations for this could be that the exoskeleton delivered the highest total positive work in this condition at the ankle and the knee and provided more assistance during the isometric phase of the biological plantarflexors. As expected we found that the bi-articular conditions reduced m. gastrocnemius EMG more than the mono-articular condition but this difference was not significant. We did not find that the mono-articular condition reduces the m. soleus EMG more than the bi-articular conditions . Knowledge of specific effects of different exoskeleton configurations on metabolic cost and muscle activation could be useful for providing customized assistance for specific gait impairments.

  2. Combining Genomics and Metabolomics for the Discovery of Regulatory Genes and Their Use in Metabolic Engineering to Produce ‘Healthy Foods’

    NARCIS (Netherlands)

    Martin, C.; Luo, J.; Lebouteiller, B.; Mock, H.P.; Matros, A.; Peterek, S.; Schijlen, E.G.W.M.; Hall, R.D.; Shintu, L.; Colquhoun, I.; Weisshaar, B.; Butelli, E.

    2012-01-01

    Plants often accumulate their natural products to relatively low levels, so there is a lot of interest in breeding or engineering plants that produce higher levels. It has been shown that the most effective way to increase the accumulation of secondary metabolites is to increase the activity of

  3. Biomarkers involved in energy metabolism and oxidative stress response in the liver of Goodea gracilis Hubbs and Turner, 1939 exposed to the microcystin-producing Microcystis aeruginosa LB85 strain.

    Science.gov (United States)

    Olivares Rubio, Hugo F; Martínez-Torres, M Lysset; Nájera-Martínez, Minerva; Dzul-Caamal, Ricardo; Domínguez-López, María Lilia; García-Latorre, Ethel; Vega-López, Armando

    2015-09-01

    Goodea gracilis is an endemic fish that only habitats in some water bodies of Central Mexico that are contaminated with cyanobacteria-producing microcystins (MC); however, a lack of information on this topic prevails. With the aim to generate the first approximation about the physiological changes elicited by cyanobacterium that produce MC congeners in this fish species, specimens born in the laboratory was exposed for 96 h to cell densities of 572.5, 1145, 2290, 4580, and 9160 × 10(6) cells of Microcystis aeruginosa strain LB85/L, and a set of novel endpoint related to hepatic gluconeogenesis (ADH/LDH) and pro-oxidant forces O2., H2 O2 ) in addition to biomarkers of oxidative damage and antioxidant response was evaluated in the liver. Results suggest that high inhibition of protein serine/threonine phosphatase (PP) may trigger many metabolic processes, such as those related to hepatic gluconeogenesis (ADH/LDH) and pro-oxidant O2⋅, H2 O2 , TBARS, ROOH, RC=O) as well as antioxidant (SOD, CAT, GPx) response to oxidative stress. Particularly, we observed that inhibition of LDH and PP, and H2 O2 increase and TBARS production were the key damages induced by high densities of M. aeruginosa. However, changes between aerobic and anaerobic metabolism related with ROS metabolism and ADH/LDH balance are apparently an acclimation of this fish species to exposure to cyanobacteria or their MCs. Fish species living in environments potentially contaminated with cyanobacteria or their MCs possess mechanisms of acclimation that allow them to offset the damage induced, even in the case of fish that have never been exposed to MCs. © 2014 Wiley Periodicals, Inc.

  4. Comparison of enriched palmitic acid and calcium salts of palm fatty acids distillate fat supplements on milk production and metabolic profiles of high-producing dairy cows.

    Science.gov (United States)

    Rico, D E; Ying, Y; Harvatine, K J

    2014-09-01

    A variable response to fat supplementation has been reported in dairy cows, which may be due to cow production level, environmental conditions, or diet characteristics. In the present experiment, the effect of a high palmitic acid supplement was investigated relative to a conventional Ca salts of palm fatty acids (Ca-FA) supplement in 16 high-producing Holstein cows (46.6±12.4kg of milk/d) arranged in a crossover design with 14-d periods. The experiment was conducted in a non-heat-stress season with 29.5% neutral detergent fiber diets. Treatments were (1) high palmitic acid (PA) supplement fed as free FA [1.9% of dry matter (DM); 84.8% C16:0] and (2) Ca-FA supplement (2.3% of DM; 47.7% C16:0, 35.9% C18:1, and 8.4% C18:2). The PA supplement tended to increase DM intake, and increased the yields of milk and energy-corrected milk. Additionally, PA increased the yields of milk fat, protein, and lactose, whereas milk concentrations of these components were not affected. The yields of milk de novo and 16-C FA were increased by PA compared with Ca-FA (7 and 20%, respectively), whereas the yield of preformed FA was higher in Ca-FA. A reduction in milk fat concentration of de novo and 16-C FA and a marginal elevation in trans-10 C18:1 in Ca-FA is indicative of altered ruminal biohydrogenation and increased risk of milk fat depression. No effect of treatment on plasma insulin was observed. A treatment by time interaction was detected for plasma nonesterified fatty acids (NEFA), which tended to be higher in Ca-FA than in PA before feeding. Overall, the palmitic acid supplement improved production performance in high-producing cows while posing a lower risk for milk fat depression compared with a supplement higher in unsaturated FA. Copyright © 2014 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

  5. Engineering of Secondary Metabolism.

    Science.gov (United States)

    O'Connor, Sarah E

    2015-01-01

    Secondary (specialized) metabolites, produced by bacteria, fungi, plants, and other organisms, exhibit enormous structural variation, and consequently display a wide range of biological activities. Secondary metabolism improves and modulates the phenotype of the host producer. Furthermore, these biological activities have resulted in the use of secondary metabolites in a variety of industrial and pharmaceutical applications. Metabolic engineering presents a powerful strategy to improve access to these valuable molecules. A critical overview of engineering approaches in secondary metabolism is presented, both in heterologous and native hosts. The recognition of the increasing role of compartmentalization in metabolic engineering is highlighted. Engineering approaches to modify the structure of key secondary metabolite classes are also critically evaluated.

  6. Engineering Cellular Metabolism

    DEFF Research Database (Denmark)

    Nielsen, Jens; Keasling, Jay

    2016-01-01

    Metabolic engineering is the science of rewiring the metabolism of cells to enhance production of native metabolites or to endow cells with the ability to produce new products. The potential applications of such efforts are wide ranging, including the generation of fuels, chemicals, foods, feeds...... of metabolic engineering and will discuss how new technologies can enable metabolic engineering to be scaled up to the industrial level, either by cutting off the lines of control for endogenous metabolism or by infiltrating the system with disruptive, heterologous pathways that overcome cellular regulation....

  7. Disruption of rcsB by a duplicated sequence in a curli-producing Escherichia coli O157:H7 results in differential gene expression in relation to biofilm formation, stress responses and metabolism.

    Science.gov (United States)

    Sharma, V K; Bayles, D O; Alt, D P; Looft, T; Brunelle, B W; Stasko, J A

    2017-03-08

    Escherichia coli O157:H7 (O157) strain 86-24, linked to a 1986 disease outbreak, displays curli- and biofilm-negative phenotypes that are correlated with the lack of Congo red (CR) binding and formation of white colonies (CR - ) on a CR-containing medium. However, on a CR medium this strain produces red isolates (CR + ) capable of producing curli fimbriae and biofilms. To identify genes controlling differential expression of curli fimbriae and biofilm formation, the RNA-Seq profile of a CR + isolate was compared to the CR - parental isolate. Of the 242 genes expressed differentially in the CR + isolate, 201 genes encoded proteins of known functions while the remaining 41 encoded hypothetical proteins. Among the genes with known functions, 149 were down- and 52 were up-regulated. Some of the upregulated genes were linked to biofilm formation through biosynthesis of curli fimbriae and flagella. The genes encoding transcriptional regulators, such as CsgD, QseB, YkgK, YdeH, Bdm, CspD, BssR and FlhDC, which modulate biofilm formation, were significantly altered in their expression. Several genes of the envelope stress (cpxP), heat shock (rpoH, htpX, degP), oxidative stress (ahpC, katE), nutrient limitation stress (phoB-phoR and pst) response pathways, and amino acid metabolism were downregulated in the CR + isolate. Many genes mediating acid resistance and colanic acid biosynthesis, which influence biofilm formation directly or indirectly, were also down-regulated. Comparative genomics of CR + and CR - isolates revealed the presence of a short duplicated sequence in the rcsB gene of the CR + isolate. The alignment of the amino acid sequences of RcsB of the two isolates showed truncation of RcsB in the CR + isolate at the insertion site of the duplicated sequence. Complementation of CR + isolate with rcsB of the CR - parent restored parental phenotypes to the CR + isolate. The results of this study indicate that RcsB is a global regulator affecting bacterial survival in

  8. Mathematical modelling of metabolism

    DEFF Research Database (Denmark)

    Gombert, Andreas Karoly; Nielsen, Jens

    2000-01-01

    Mathematical models of the cellular metabolism have a special interest within biotechnology. Many different kinds of commercially important products are derived from the cell factory, and metabolic engineering can be applied to improve existing production processes, as well as to make new processes...... available. Both stoichiometric and kinetic models have been used to investigate the metabolism, which has resulted in defining the optimal fermentation conditions, as well as in directing the genetic changes to be introduced in order to obtain a good producer strain or cell line. With the increasing...... availability of genomic information and powerful analytical techniques, mathematical models also serve as a tool for understanding the cellular metabolism and physiology....

  9. Metabolic Panel

    Science.gov (United States)

    A metabolic panel is a group of tests that measures different chemicals in the blood. These tests are usually done on ... and liver. There are two types: basic metabolic panel (BMP) and comprehensive metabolic panel (CMP). The BMP ...

  10. Consumption of Walnuts in Combination with Other Whole Foods Produces Physiologic, Metabolic, and Gene Expression Changes in Obese C57BL/6J High-Fat-Fed Male Mice.

    Science.gov (United States)

    Luo, Ting; Miranda-Garcia, Omar; Adamson, Allysa; Hamilton-Reeves, Jill; Sullivan, Debra K; Kinchen, Jason M; Shay, Neil F

    2016-09-01

    Although a reductionist approach has sought to understand the roles of individual nutrients and biochemicals in foods, it has become apparent that there can be differences when studying food components in isolation or within the natural matrix of a whole food. The objective of this study was to determine the ability of whole-food intake to modulate the development of obesity and other metabolic dysfunction in mice fed a high-fat (HF), Western-style obesogenic diet. To test the hypothesis that an n-3 (ω-3) polyunsaturated fatty acid-rich food could synergize with other, largely polyphenol-rich foods by producing greater reductions in metabolic disease conditions, the intake of English walnuts was evaluated in combination with 9 other whole foods. Eight-week-old male C57Bl/6J mice were fed low-fat (LF; 10% fat) and HF control diets, along with an HF diet with 8.6% (wt:wt) added walnuts for 9 wk. The HF control diet contained 46% fat with added sucrose (10.9%, wt:wt) and cholesterol (1%, wt:wt); the added sucrose and cholesterol were not present in the LF diet. Other groups were provided the walnut diet with a second whole food-raspberries, apples, cranberries, tart cherries, broccoli sprouts, olive oil, soy protein, or green tea. All of the energy-containing whole foods were added at an energy level equivalent to 1.5 servings/d. Body weights, food intake, and glucose tolerance were determined. Postmortem, serum lipids and inflammatory markers, hepatic fat, gene expression, and the relative concentrations of 594 biochemicals were measured. The addition of walnuts with either raspberries, apples, or green tea reduced glucose area under the curve compared with the HF diet alone (-93%, -64%, and -54%, respectively, P sprouts or green tea (-49% and -61%, respectively, P < 0.05) had reduced hepatic fat concentrations. There were differences in global gene expression patterns related to whole-food content, with many examples of differences in LF- and HF-fed mice, HF- and

  11. Iron metabolism in man.

    Science.gov (United States)

    von Drygalski, Annette; Adamson, John W

    2013-09-01

    Iron metabolism in man is a highly regulated process designed to provide iron for erythropoiesis, mitochondrial energy production, electron transport, and cell proliferation. The mechanisms of iron handling also protect cells from the deleterious effects of free iron, which can produce oxidative damage of membranes, proteins, and lipids. Over the past decade, several important molecules involved in iron homeostasis have been discovered, and their function has expanded our understanding of iron trafficking under normal and pathological conditions. Physiologic iron metabolism is strongly influenced by inflammation, which clinically leads to anemia. Although hepcidin, a small circulating peptide produced by the liver, has been found to be the key regulator of iron trafficking, molecular pathways of iron sensing that control iron metabolism and hepcidin production are still incompletely understood. With this review, we provide an overview of the current understanding of iron metabolism, the recently discovered regulators of iron trafficking, and a focus on the effects of inflammation on the process.

  12. VRML metabolic network visualizer.

    Science.gov (United States)

    Rojdestvenski, Igor

    2003-03-01

    A successful date collection visualization should satisfy a set of many requirements: unification of diverse data formats, support for serendipity research, support of hierarchical structures, algorithmizability, vast information density, Internet-readiness, and other. Recently, virtual reality has made significant progress in engineering, architectural design, entertainment and communication. We experiment with the possibility of using the immersive abstract three-dimensional visualizations of the metabolic networks. We present the trial Metabolic Network Visualizer software, which produces graphical representation of a metabolic network as a VRML world from a formal description written in a simple SGML-type scripting language.

  13. Metabolic Syndrome

    Science.gov (United States)

    Metabolic syndrome is a group of conditions that put you at risk for heart disease and diabetes. These conditions ... agree on the definition or cause of metabolic syndrome. The cause might be insulin resistance. Insulin is ...

  14. Drug Metabolism

    Indian Academy of Sciences (India)

    IAS Admin

    Chemistry of Drug Metabolism. Drug metabolism is a chemical process, where enzymes play a crucial role in the conversion of one chemical species to another. The major family of enzymes associated with these metabolic reactions is the cytochrome P450 family. The structural features and functional activity of these ...

  15. Nucleotide Metabolism

    DEFF Research Database (Denmark)

    Martinussen, Jan; Willemoës, M.; Kilstrup, Mogens

    2011-01-01

    Metabolic pathways are connected through their utilization of nucleotides as supplier of energy, allosteric effectors, and their role in activation of intermediates. Therefore, any attempt to exploit a given living organism in a biotechnological process will have an impact on nucleotide metabolism...

  16. Metabolism of phencyclidine

    International Nuclear Information System (INIS)

    Hoag, M.K.P.

    1987-01-01

    Phencyclidine (PCP) is a drug of abuse which may produce, in some users, a persistent schizophreniform psychosis. The possibility that long term effects of PCP are mediated by metabolic activation of the parent compound to reactive species is consistent with the demonstration of metabolism-dependent covalent binding of radiolabeled PCP in vivo and in vitro to macromolecules in rodent lung, liver, and kidney. Formation of the electrophilic iminium ion metabolite of PCP is believed to be critical for covalent binding since binding was inhibited by cyanide ion at concentrations which did not inhibit metabolism of PCP but did trap the iminium ion to form the corresponding alpha-aminonitrile. The present studies were designed to characterize further the biological fate of PCP by identifying possible macromolecular targets of the reactive metabolite(s)

  17. MYC, Metabolism, and Cancer

    Science.gov (United States)

    Stine, Zachary E.; Walton, Zandra E.; Altman, Brian J.; Hsieh, Annie L.; Dang, Chi V.

    2015-01-01

    Summary The MYC oncogene encodes a transcription factor, MYC, whose broad effects make its precise oncogenic role enigmatically elusive. The evidence to date suggests that MYC triggers selective gene expression amplification to promote cell growth and proliferation. Through its targets, MYC coordinates nutrient acquisition to produce ATP and key cellular building blocks that increase cell mass and trigger DNA replication and cell division. In cancer, genetic and epigenetic derangements silence checkpoints and unleash MYC’s cell growth- and proliferation-promoting metabolic activities. Unbridled growth in response to deregulated MYC expression creates dependence on MYC-driven metabolic pathways, such that reliance on specific metabolic enzymes provides novel targets for cancer therapy. PMID:26382145

  18. Drug Metabolism

    Indian Academy of Sciences (India)

    Home; Journals; Resonance – Journal of Science Education; Volume 19; Issue 3. Drug Metabolism: A Fascinating Link Between Chemistry and Biology. Nikhil Taxak Prasad V Bharatam. General Article Volume 19 Issue 3 March 2014 pp 259-282 ...

  19. Drug Metabolism

    Indian Academy of Sciences (India)

    IAS Admin

    Drug metabolism may be defined as the biochemical modifica- tion of one chemical form to another, occurring usually through ..... Endogenous. Enzyme. Drugs. Cofactor. Glucuronidation. UDP glucoronic. UDP-. Chloramphenicol, acid glucuronosyltransferase morphine, paracetamol, salicylic acid, fenoprofen, desipramine,.

  20. Metabolic Myopathies.

    Science.gov (United States)

    Tarnopolsky, Mark A

    2016-12-01

    Metabolic myopathies are genetic disorders that impair intermediary metabolism in skeletal muscle. Impairments in glycolysis/glycogenolysis (glycogen-storage disease), fatty acid transport and oxidation (fatty acid oxidation defects), and the mitochondrial respiratory chain (mitochondrial myopathies) represent the majority of known defects. The purpose of this review is to develop a diagnostic and treatment algorithm for the metabolic myopathies. The metabolic myopathies can present in the neonatal and infant period as part of more systemic involvement with hypotonia, hypoglycemia, and encephalopathy; however, most cases present in childhood or in adulthood with exercise intolerance (often with rhabdomyolysis) and weakness. The glycogen-storage diseases present during brief bouts of high-intensity exercise, whereas fatty acid oxidation defects and mitochondrial myopathies present during a long-duration/low-intensity endurance-type activity or during fasting or another metabolically stressful event (eg, surgery, fever). The clinical examination is often normal between acute events, and evaluation involves exercise testing, blood testing (creatine kinase, acylcarnitine profile, lactate, amino acids), urine organic acids (ketones, dicarboxylic acids, 3-methylglutaconic acid), muscle biopsy (histology, ultrastructure, enzyme testing), MRI/spectroscopy, and targeted or untargeted genetic testing. Accurate and early identification of metabolic myopathies can lead to therapeutic interventions with lifestyle and nutritional modification, cofactor treatment, and rapid treatment of rhabdomyolysis.

  1. Animal metabolism

    International Nuclear Information System (INIS)

    Walburg, H.E.

    1977-01-01

    Studies on placental transport included the following: clearance of tritiated water as a baseline measurement for transport of materials across perfused placentas; transport of organic and inorganic mercury across the perfused placenta of the guinea pig in late gestation; and transport of cadmium across the perfused placenta of the guinea pig in late gestation. Studies on cadmium absorption and metabolism included the following: intestinal absorption and retention of cadmium in neonatal rats; uptake and distribution of an oral dose of cadmium in postweanling male and female, iron-deficient and normal rats; postnatal viability and growth in rat pups after oral cadmium administration during gestation; and the effect of calcium and phosphorus on the absorption and toxicity of cadmium. Studies on gastrointestinal absorption and mineral metabolism included: uptake and distribution of orally administered plutonium complex compounds in male mice; gastrointestinal absorption of 144 Ce in the newborn mouse, rat, and pig; and gastrointestinal absorption of 95 Nb by rats of different ages. Studies on iodine metabolism included the following: influence of thyroid status and thiocyanate on iodine metabolism in the bovine; effects of simulated fallout radiation on iodine metabolism in dairy cattle; and effects of feeding iodine binding agents on iodine metabolism in the calf

  2. What is Metabolic Syndrome?

    Science.gov (United States)

    ... Research Home / Metabolic Syndrome Metabolic Syndrome What Is Metabolic syndrome is the name for a group of risk ... three metabolic risk factors to be diagnosed with metabolic syndrome. A large waistline. This also is called abdominal ...

  3. [Metabolic myopathies].

    Science.gov (United States)

    Papazian, Óscar; Rivas-Chacón, Rafael

    2013-09-06

    To review the metabolic myopathies manifested only by crisis of myalgias, cramps and rigidity of the muscles with decreased voluntary contractions and normal inter crisis neurologic examination in children and adolescents. These metabolic myopathies are autosomic recessive inherited enzymatic deficiencies of the carbohydrates and lipids metabolisms. The end result is a reduction of intra muscle adenosine triphosphate, mainly through mitochondrial oxidative phosphorylation, with decrease of available energy for muscle contraction. The one secondary to carbohydrates intra muscle metabolism disorders are triggered by high intensity brief (fatty acids metabolism disorders are triggered by low intensity prolonged (> 10 min) exercises. The conditions in the first group in order of decreasing frequency are the deficiencies of myophosforilase (GSD V), muscle phosphofructokinase (GSD VII), phosphoglycerate mutase 1 (GSD X) and beta enolase (GSD XIII). The conditions in the second group in order of decreasing frequency are the deficiencies of carnitine palmitoyl transferase II and very long chain acyl CoA dehydrogenase. The differential characteristics of patients in each group and within each group will allow to make the initial presumptive clinical diagnosis in the majority and then to order only the necessary tests to achieve the final diagnosis. Treatment during the crisis includes hydration, glucose and alkalinization of urine if myoglobin in blood and urine are elevated. Prevention includes avoiding exercise which may induce the crisis and fasting. The prognosis is good with the exception of rare cases of acute renal failure due to hipermyoglobinemia because of severe rabdomyolisis.

  4. Primary Metabolic Pathways and Metabolic Flux Analysis

    DEFF Research Database (Denmark)

    Villadsen, John

    2015-01-01

    his chapter introduces the metabolic flux analysis (MFA) or stoichiometry-based MFA, and describes the quantitative basis for MFA. It discusses the catabolic pathways in which free energy is produced to drive the cell-building anabolic pathways. An overview of these primary pathways provides...... the reader who is primarily trained in the engineering sciences with atleast a preliminary introduction to biochemistry and also shows how carbon is drained off the catabolic pathways to provide precursors for cell mass building and sometimes for important industrial products. The primary pathways...... to be examined in the following are: glycolysis, primarily by the EMP pathway, but other glycolytic pathways is also mentioned; fermentative pathways in which the redox generated in the glycolytic reactions are consumed; reactions in the tricarboxylic acid (TCA) cycle, which produce biomass precursors and redox...

  5. Metabolic Engineering

    Indian Academy of Sciences (India)

    IAS Admin

    and in vitro to be able to alter properties of the encoded enzyme, and (6) assemble an array of genes for their expression inside the host cell. Although bacteria and yeast are the pioneering hosts for metabolic engineering, other organisms such as fungi, animal as well as plant cells are also used nowadays for similar experi ...

  6. Metabolic syndrome

    Science.gov (United States)

    ... gov/pubmed/26718656 . Ruderman NB, Shulman GI. Metabolic syndrome. In: Jameson JL, De Groot LJ, de Kretser DM, et al, eds. Endocrinology: Adult and Pediatric . 7th ed. Philadelphia, PA: Elsevier Saunders; 2016:chap 43. Review ... NIH MedlinePlus Magazine Read more Health ...

  7. Metabolic Disorders

    Science.gov (United States)

    Metabolism is the process your body uses to get or make energy from the food you eat. Food is made up of proteins, carbohydrates, and fats. Chemicals in your digestive system break the food parts down into sugars and acids, your body's ...

  8. Metabolic Reprogramming in Glioma

    Directory of Open Access Journals (Sweden)

    Elizabeth A. Stoll

    2017-04-01

    Full Text Available Many cancers have long been thought to primarily metabolize glucose for energy production—a phenomenon known as the Warburg Effect, after the classic studies of Otto Warburg in the early twentieth century. Yet cancer cells also utilize other substrates, such as amino acids and fatty acids, to produce raw materials for cellular maintenance and energetic currency to accomplish cellular tasks. The contribution of these substrates is increasingly appreciated in the context of glioma, the most common form of malignant brain tumor. Multiple catabolic pathways are used for energy production within glioma cells, and are linked in many ways to anabolic pathways supporting cellular function. For example: glycolysis both supports energy production and provides carbon skeletons for the synthesis of nucleic acids; meanwhile fatty acids are used both as energetic substrates and as raw materials for lipid membranes. Furthermore, bio-energetic pathways are connected to pro-oncogenic signaling within glioma cells. For example: AMPK signaling links catabolism with cell cycle progression; mTOR signaling contributes to metabolic flexibility and cancer cell survival; the electron transport chain produces ATP and reactive oxygen species (ROS which act as signaling molecules; Hypoxia Inducible Factors (HIFs mediate interactions with cells and vasculature within the tumor environment. Mutations in the tumor suppressor p53, and the tricarboxylic acid cycle enzymes Isocitrate Dehydrogenase 1 and 2 have been implicated in oncogenic signaling as well as establishing metabolic phenotypes in genetically-defined subsets of malignant glioma. These pathways critically contribute to tumor biology. The aim of this review is two-fold. Firstly, we present the current state of knowledge regarding the metabolic strategies employed by malignant glioma cells, including aerobic glycolysis; the pentose phosphate pathway; one-carbon metabolism; the tricarboxylic acid cycle, which is

  9. Metabolic Reprogramming in Glioma.

    Science.gov (United States)

    Strickland, Marie; Stoll, Elizabeth A

    2017-01-01

    Many cancers have long been thought to primarily metabolize glucose for energy production-a phenomenon known as the Warburg Effect, after the classic studies of Otto Warburg in the early twentieth century. Yet cancer cells also utilize other substrates, such as amino acids and fatty acids, to produce raw materials for cellular maintenance and energetic currency to accomplish cellular tasks. The contribution of these substrates is increasingly appreciated in the context of glioma, the most common form of malignant brain tumor. Multiple catabolic pathways are used for energy production within glioma cells, and are linked in many ways to anabolic pathways supporting cellular function. For example: glycolysis both supports energy production and provides carbon skeletons for the synthesis of nucleic acids; meanwhile fatty acids are used both as energetic substrates and as raw materials for lipid membranes. Furthermore, bio-energetic pathways are connected to pro-oncogenic signaling within glioma cells. For example: AMPK signaling links catabolism with cell cycle progression; mTOR signaling contributes to metabolic flexibility and cancer cell survival; the electron transport chain produces ATP and reactive oxygen species (ROS) which act as signaling molecules; Hypoxia Inducible Factors (HIFs) mediate interactions with cells and vasculature within the tumor environment. Mutations in the tumor suppressor p53, and the tricarboxylic acid cycle enzymes Isocitrate Dehydrogenase 1 and 2 have been implicated in oncogenic signaling as well as establishing metabolic phenotypes in genetically-defined subsets of malignant glioma. These pathways critically contribute to tumor biology. The aim of this review is two-fold. Firstly, we present the current state of knowledge regarding the metabolic strategies employed by malignant glioma cells, including aerobic glycolysis; the pentose phosphate pathway; one-carbon metabolism; the tricarboxylic acid cycle, which is central to amino acid

  10. Metabolic alkalosis.

    Science.gov (United States)

    Khanna, A; Kurtzman, N A

    2006-01-01

    Metabolic alkalosis is a primary pathophysiologic event characterized by the gain of bicarbonate or the loss of nonvolatile acid from extracellular fluid. The kidney preserves normal acid-base balance by two mechanisms: bicarbonate reclamation mainly in the proximal tubule and bicarbonate generation predominantly in the distal nephron. Bicarbonate reclamation is mediated mainly by a Na-H antiporter and to a smaller extent by the H-ATPase. The principal factors affecting HCO 3 reabsorption include effective arterial blood volume, glomerular filtration rate, chloride, and potassium. Bicarbonate regeneration is primarily affected by distal Na delivery and reabsorption, aldosterone, arterial pH, and arterial pCO2. To generate metabolic alkalosis, either a gain of base or a loss of acid, must occur. The loss of acid may be via the GI tract or by the kidney. Excess base may be gained by oral or parenteral HCO 3 administration or by lactate, acetate, or citrate administration. Factors that help maintain metabolic alkalosis include decreased glomerular filtration rate (GFR), volume contraction, hypokalemia, hypochloremia, and aldosterone excess. Clinical states associated with metabolic alkalosis are vomiting, mineralocorticoid excess, the adrenogenital syndrome, licorice ingestion, diuretic administration, and Bartter's and Gitelma's Syndromes. The effects of metabolic alkalosis on the body are varied and include effects on the central nervous system, myocardium, skeletal muscle, and the liver. Treatment of this disorder is simple, once the pathophysiology of the cause is delineated. Therapy consists of reversing the contributory factors promoting alkalosis and in severe cases, administration of carbonic anhydrase inhibitors, acid infusion, and low bicarbonate dialysis.

  11. MYC, Metabolism, and Cancer.

    Science.gov (United States)

    Stine, Zachary E; Walton, Zandra E; Altman, Brian J; Hsieh, Annie L; Dang, Chi V

    2015-10-01

    The MYC oncogene encodes a transcription factor, MYC, whose broad effects make its precise oncogenic role enigmatically elusive. The evidence to date suggests that MYC triggers selective gene expression amplification to promote cell growth and proliferation. Through its targets, MYC coordinates nutrient acquisition to produce ATP and key cellular building blocks that increase cell mass and trigger DNA replication and cell division. In cancer, genetic and epigenetic derangements silence checkpoints and unleash MYC's cell growth- and proliferation-promoting metabolic activities. Unbridled growth in response to deregulated MYC expression creates dependence on MYC-driven metabolic pathways, such that reliance on specific metabolic enzymes provides novel targets for cancer therapy. MYC's expression and activity are tightly regulated in normal cells by multiple mechanisms, including a dependence upon growth factor stimulation and replete nutrient status. In cancer, genetic deregulation of MYC expression and loss of checkpoint components, such as TP53, permit MYC to drive malignant transformation. However, because of the reliance of MYC-driven cancers on specific metabolic pathways, synthetic lethal interactions between MYC overexpression and specific enzyme inhibitors provide novel cancer therapeutic opportunities. ©2015 American Association for Cancer Research.

  12. Biological Art of Producing Useful Chemicals

    Indian Academy of Sciences (India)

    Home; Journals; Resonance – Journal of Science Education; Volume 21; Issue 3. Metabolic Engineering: Biological Art of Producing Useful Chemicals. Ram Kulkarni. General Article Volume 21 Issue 3 March 2016 pp 233-237. Fulltext. Click here to view fulltext PDF. Permanent link:

  13. Systems Metabolic Engineering of Escherichia coli.

    Science.gov (United States)

    Choi, Kyeong Rok; Shin, Jae Ho; Cho, Jae Sung; Yang, Dongsoo; Lee, Sang Yup

    2016-05-01

    Systems metabolic engineering, which recently emerged as metabolic engineering integrated with systems biology, synthetic biology, and evolutionary engineering, allows engineering of microorganisms on a systemic level for the production of valuable chemicals far beyond its native capabilities. Here, we review the strategies for systems metabolic engineering and particularly its applications in Escherichia coli. First, we cover the various tools developed for genetic manipulation in E. coli to increase the production titers of desired chemicals. Next, we detail the strategies for systems metabolic engineering in E. coli, covering the engineering of the native metabolism, the expansion of metabolism with synthetic pathways, and the process engineering aspects undertaken to achieve higher production titers of desired chemicals. Finally, we examine a couple of notable products as case studies produced in E. coli strains developed by systems metabolic engineering. The large portfolio of chemical products successfully produced by engineered E. coli listed here demonstrates the sheer capacity of what can be envisioned and achieved with respect to microbial production of chemicals. Systems metabolic engineering is no longer in its infancy; it is now widely employed and is also positioned to further embrace next-generation interdisciplinary principles and innovation for its upgrade. Systems metabolic engineering will play increasingly important roles in developing industrial strains including E. coli that are capable of efficiently producing natural and nonnatural chemicals and materials from renewable nonfood biomass.

  14. Radiometric detection of bacterial metabolism

    International Nuclear Information System (INIS)

    Camargo, E.E.; Wagner Junior, H.N.

    1979-01-01

    The measurement of 14 CO 2 produced by the bacterial oxidation of labelled compounds is discussed as a means of evaluating the bacterial metabolism. The following items are discussed:automated radiometric detection, types of graphs, clinical applications of the radiometric system and influential factors. Complementary studies on bacterial assimilation of substances are presented. (M.A.) [pt

  15. Biological defense system against xenobiotics in meat-producing animals

    OpenAIRE

    Abdelrahem Abdallah Darwish, Wageh Sobhy

    2010-01-01

    Meat-producing animals are frequently exposed during their lifetime to a lot of xenobiotics which affect on their biological systems, growth, disease response and lead to changes on the carcass quality. These changes may have some public health impact if people consumed such contaminated meat or meat products. Meat-producing animals have developed enzyme systems which help them to metabolize such xenobiotics. Studying of the profile of the different enzymes used in xenobiotics metabolism may ...

  16. Dynamics of pyruvate metabolism in Lactococcus lactis

    DEFF Research Database (Denmark)

    Melchiorsen, Claus Rix; Jensen, Niels B.S.; Christensen, Bjarke

    2001-01-01

    The pyruvate metabolism in the lactic acid bacterium Lactococcus lactis was studied in anaerobic cultures under transient conditions. During growth of L. lactis in continuous culture at high dilution rate, homolactic product formation was observed, i.e., lactate was produced as the major end...... product. At a lower dilution rate, the pyruvate metabolism shifted towards mixed acid-product formation where formate, acetate, and ethanol were produced in addition to lactate. The regulation of the shift in pyruvate metabolism was investigated by monitoring the dynamic behavior of L. lactis...

  17. Brookhaven Linac Isotope Producer

    Data.gov (United States)

    Federal Laboratory Consortium — The Brookhaven Linac Isoptope Producer (BLIP)—positioned at the forefront of research into radioisotopes used in cancer treatment and diagnosis—produces commercially...

  18. Engineering microbes to produce biofuels.

    Science.gov (United States)

    Wackett, Lawrence P

    2011-06-01

    The current biofuels landscape is chaotic. It is controlled by the rules imposed by economic forces and driven by the necessity of finding new sources of energy, particularly motor fuels. The need is bringing forth great creativity in uncovering new candidate fuel molecules that can be made via metabolic engineering. These next generation fuels include long-chain alcohols, terpenoid hydrocarbons, and diesel-length alkanes. Renewable fuels contain carbon derived from carbon dioxide. The carbon dioxide is derived directly by a photosynthetic fuel-producing organism(s) or via intermediary biomass polymers that were previously derived from carbon dioxide. To use the latter economically, biomass depolymerization processes must improve and this is a very active area of research. There are competitive approaches with some groups using enzyme based methods and others using chemical catalysts. With the former, feedstock and end-product toxicity loom as major problems. Advances chiefly rest on the ability to manipulate biological systems. Computational and modular construction approaches are key. For example, novel metabolic networks have been constructed to make long-chain alcohols and hydrocarbons that have superior fuel properties over ethanol. A particularly exciting approach is to implement a direct utilization of solar energy to make a usable fuel. A number of approaches use the components of current biological systems, but re-engineer them for more direct, efficient production of fuels. Copyright © 2010 Elsevier Ltd. All rights reserved.

  19. Producing Against Poverty

    NARCIS (Netherlands)

    Ypeij, Annelou

    2000-01-01

    Producing against Poverty is an anthropological research on micro-entrepreneurs in Lima, Peru. It analyses the way micro-producers accumulate capital. The anthropological approach of the book starts with an analysis of the daily lives of the micro-producers. Its gender approach makes a comparison

  20. Metabolism of xenobiotics of human environments.

    Science.gov (United States)

    Croom, Edward

    2012-01-01

    Xenobiotics have been defined as chemicals to which an organism is exposed that are extrinsic to the normal metabolism of that organism. Without metabolism, many xenobiotics would reach toxic concentrations. Most metabolic activity inside the cell requires energy, cofactors, and enzymes in order to occur. Xenobiotic-metabolizing enzymes can be divided into phase I, phase II, and transporter enzymes. Lipophilic xenobiotics are often first metabolized by phase I enzymes, which function to make xenobiotics more polar and provide sites for conjugation reactions. Phase II enzymes are conjugating enzymes and can directly interact with xenobiotics but more commonly interact with metabolites produced by phase I enzymes. Through both passive and active transport, these more polar metabolites are eliminated. Most xenobiotics are cleared through multiple enzymes and pathways. The relationship between chemical concentrations, enzyme affinity and quantity, and cofactor availability often determine which metabolic reactions dominate in a given individual. Copyright © 2012 Elsevier Inc. All rights reserved.

  1. Carbohydrate Metabolism Disorders

    Science.gov (United States)

    ... you eat. Food is made up of proteins, carbohydrates, and fats. Chemicals in your digestive system (enzymes) ... metabolic disorder, something goes wrong with this process. Carbohydrate metabolism disorders are a group of metabolic disorders. ...

  2. Precision metabolic engineering: The design of responsive, selective, and controllable metabolic systems.

    Science.gov (United States)

    McNerney, Monica P; Watstein, Daniel M; Styczynski, Mark P

    2015-09-01

    Metabolic engineering is generally focused on static optimization of cells to maximize production of a desired product, though recently dynamic metabolic engineering has explored how metabolic programs can be varied over time to improve titer. However, these are not the only types of applications where metabolic engineering could make a significant impact. Here, we discuss a new conceptual framework, termed "precision metabolic engineering," involving the design and engineering of systems that make different products in response to different signals. Rather than focusing on maximizing titer, these types of applications typically have three hallmarks: sensing signals that determine the desired metabolic target, completely directing metabolic flux in response to those signals, and producing sharp responses at specific signal thresholds. In this review, we will first discuss and provide examples of precision metabolic engineering. We will then discuss each of these hallmarks and identify which existing metabolic engineering methods can be applied to accomplish those tasks, as well as some of their shortcomings. Ultimately, precise control of metabolic systems has the potential to enable a host of new metabolic engineering and synthetic biology applications for any problem where flexibility of response to an external signal could be useful. Copyright © 2015 International Metabolic Engineering Society. Published by Elsevier Inc. All rights reserved.

  3. Biofuel metabolic engineering with biosensors

    Science.gov (United States)

    Morgan, Stacy-Anne; Nadler, Dana C.; Yokoo, Rayka; Savage, David F.

    2016-01-01

    Metabolic engineering offers the potential to renewably produce important classes of chemicals, particularly biofuels, at an industrial scale. DNA synthesis and editing techniques can generate large pathway libraries, yet identifying the best variants is slow and cumbersome. Traditionally, analytical methods like chromatography and mass spectrometry have been used to evaluate pathway variants, but such techniques cannot be performed with high throughput. Biosensors - genetically encoded components that actuate a cellular output in response to a change in metabolite concentration - are therefore a promising tool for rapid and high-throughput evaluation of candidate pathway variants. Applying biosensors can also dynamically tune pathways in response to metabolic changes, improving balance and productivity. Here, we describe the major classes of biosensors and briefly highlight recent progress in applying them to biofuel-related metabolic pathway engineering. PMID:27768949

  4. Profiling metabolic networks to study cancer metabolism.

    Science.gov (United States)

    Hiller, Karsten; Metallo, Christian M

    2013-02-01

    Cancer is a disease of unregulated cell growth and survival, and tumors reprogram biochemical pathways to aid these processes. New capabilities in the computational and bioanalytical characterization of metabolism have now emerged, facilitating the identification of unique metabolic dependencies that arise in specific cancers. By understanding the metabolic phenotype of cancers as a function of their oncogenic profiles, metabolic engineering may be applied to design synthetically lethal therapies for some tumors. This process begins with accurate measurement of metabolic fluxes. Here we review advanced methods of quantifying pathway activity and highlight specific examples where these approaches have uncovered potential opportunities for therapeutic intervention. Copyright © 2012 Elsevier Ltd. All rights reserved.

  5. Metabolism Disrupting Chemicals and Metabolic Disorders

    Science.gov (United States)

    Heindel, Jerrold J.; Blumberg, Bruce; Cave, Mathew; Machtinger, Ronit; Mantovani, Alberto; Mendez, Michelle A.; Nadal, Angel; Palanza, Paola; Panzica, Giancarlo; Sargis, Robert; Vandenberg, Laura N.; Saal, Frederick vom

    2016-01-01

    The recent epidemics of metabolic diseases, obesity, type 2 diabetes(T2D), liver lipid disorders and metabolic syndrome have largely been attributed to genetic background and changes in diet, exercise and aging. However, there is now considerable evidence that other environmental factors may contribute to the rapid increase in the incidence of these metabolic diseases. This review will examine changes to the incidence of obesity, T2D and non-alcoholic fatty liver disease (NAFLD), the contribution of genetics to these disorders and describe the role of the endocrine system in these metabolic disorders. It will then specifically focus on the role of endocrine disrupting chemicals (EDCs) in the etiology of obesity, T2D and NAFLD while finally integrating the information on EDCs on multiple metabolic disorders that could lead to metabolic syndrome. We will specifically examine evidence linking EDC exposures during critical periods of development with metabolic diseases that manifest later in life and across generations. PMID:27760374

  6. Biologically produced sulfur

    NARCIS (Netherlands)

    Kleinjan, W.E.; Keizer, de A.; Janssen, A.J.H.

    2003-01-01

    Sulfur compound oxidizing bacteria produce sulfur as an intermediate in the oxidation of hydrogen sulfide to sulfate. Sulfur produced by these microorganisms can be stored in sulfur globules, located either inside or outside the cell. Excreted sulfur globules are colloidal particles which are

  7. Consumers and Producers

    NARCIS (Netherlands)

    E. Maira (Elisa)

    2018-01-01

    markdownabstractIn the last few decades, advances in information and communication technology have dramatically changed the way consumers and producers interact in the marketplace. The Internet and social media have torn down the information barrier between producers and consumers, leading to

  8. Fungi producing significant mycotoxins.

    Science.gov (United States)

    2012-01-01

    Mycotoxins are secondary metabolites of microfungi that are known to cause sickness or death in humans or animals. Although many such toxic metabolites are known, it is generally agreed that only a few are significant in causing disease: aflatoxins, fumonisins, ochratoxin A, deoxynivalenol, zearalenone, and ergot alkaloids. These toxins are produced by just a few species from the common genera Aspergillus, Penicillium, Fusarium, and Claviceps. All Aspergillus and Penicillium species either are commensals, growing in crops without obvious signs of pathogenicity, or invade crops after harvest and produce toxins during drying and storage. In contrast, the important Fusarium and Claviceps species infect crops before harvest. The most important Aspergillus species, occurring in warmer climates, are A. flavus and A. parasiticus, which produce aflatoxins in maize, groundnuts, tree nuts, and, less frequently, other commodities. The main ochratoxin A producers, A. ochraceus and A. carbonarius, commonly occur in grapes, dried vine fruits, wine, and coffee. Penicillium verrucosum also produces ochratoxin A but occurs only in cool temperate climates, where it infects small grains. F. verticillioides is ubiquitous in maize, with an endophytic nature, and produces fumonisins, which are generally more prevalent when crops are under drought stress or suffer excessive insect damage. It has recently been shown that Aspergillus niger also produces fumonisins, and several commodities may be affected. F. graminearum, which is the major producer of deoxynivalenol and zearalenone, is pathogenic on maize, wheat, and barley and produces these toxins whenever it infects these grains before harvest. Also included is a short section on Claviceps purpurea, which produces sclerotia among the seeds in grasses, including wheat, barley, and triticale. The main thrust of the chapter contains information on the identification of these fungi and their morphological characteristics, as well as factors

  9. Agricultural Producer Certificates

    Data.gov (United States)

    Montgomery County of Maryland — A Certified Agricultural Producer, or representative thereof, is an individual who wishes to sell regionally-grown products in the public right-of-way. A Certified...

  10. Expanding the concepts and tools of metabolic engineering to elucidate cancer metabolism.

    Science.gov (United States)

    Keibler, Mark A; Fendt, Sarah-Maria; Stephanopoulos, Gregory

    2012-01-01

    The metabolic engineer's toolbox, comprising stable isotope tracers, flux estimation and analysis, pathway identification, and pathway kinetics and regulation, among other techniques, has long been used to elucidate and quantify pathways primarily in the context of engineering microbes for producing small molecules of interest. Recently, these tools are increasingly finding use in cancer biology due to their unparalleled capacity for quantifying intracellular metabolism of mammalian cells. Here, we review basic concepts that are used to derive useful insights about the metabolism of tumor cells, along with a number of illustrative examples highlighting the fundamental contributions of these methods to elucidating cancer cell metabolism. This area presents unique opportunities for metabolic engineering to expand its portfolio of applications into the realm of cancer biology and help develop new cancer therapies based on a new class of metabolically derived targets. Copyright © 2012 American Institute of Chemical Engineers (AIChE).

  11. Yeast: A new oil producer?

    Directory of Open Access Journals (Sweden)

    Beopoulos Athanasios

    2012-01-01

    Full Text Available The increasing demand of plant oils or animal fat for biodiesel and specific lipid derivatives for the oleochemical field (such as lubricants, adhesives or plastics have created price imbalance in both the alimentary and energy field. Moreover, the lack of non-edible oil feedstock has given rise to concerns on land-use practices and on oil production strategies. Recently, much attention has been paid to the exploitation of microbial oils. Most of them present lipid profiles similar in type and composition to plants and could therefore have many advantages as are no competitive with food, have short process cycles and their cultivation is independent of climate factors. Among microorganisms, yeasts seem to be very promising as they can be easily genetically enhanced, are suitable for large-scale fermentation and are devoid of endotoxins. This review will focus on the recent understanding of yeasts lipid metabolism, the succeeding genetic engineering of the lipid pathways and the recent developments on fermentation techniques that pointed out yeasts as promising alternative producers for oil or plastic.

  12. Producing superhydrophobic roof tiles

    International Nuclear Information System (INIS)

    Carrascosa, Luis A M; Facio, Dario S; Mosquera, Maria J

    2016-01-01

    Superhydrophobic materials can find promising applications in the field of building. However, their application has been very limited because the synthesis routes involve tedious processes, preventing large-scale application. A second drawback is related to their short-term life under outdoor conditions. A simple and low-cost synthesis route for producing superhydrophobic surfaces on building materials is developed and their effectiveness and their durability on clay roof tiles are evaluated. Specifically, an organic–inorganic hybrid gel containing silica nanoparticles is produced. The nanoparticles create a densely packed coating on the roof tile surface in which air is trapped. This roughness produces a Cassie–Baxter regime, promoting superhydrophobicity. A surfactant, n-octylamine, was also added to the starting sol to catalyze the sol–gel process and to coarsen the pore structure of the gel network, preventing cracking. The application of ultrasound obviates the need to use volatile organic compounds in the synthesis, thereby making a ‘green’ product. It was also demonstrated that a co-condensation process effective between the organic and inorganic species is crucial to obtain durable and effective coatings. After an aging test, high hydrophobicity was maintained and water absorption was completely prevented for the roof tile samples under study. However, a transition from a Cassie–Baxter to a Wenzel state regime was observed as a consequence of the increase in the distance between the roughness pitches produced by the aging of the coating. (paper)

  13. Producing superhydrophobic roof tiles.

    Science.gov (United States)

    Carrascosa, Luis A M; Facio, Dario S; Mosquera, Maria J

    2016-03-04

    Superhydrophobic materials can find promising applications in the field of building. However, their application has been very limited because the synthesis routes involve tedious processes, preventing large-scale application. A second drawback is related to their short-term life under outdoor conditions. A simple and low-cost synthesis route for producing superhydrophobic surfaces on building materials is developed and their effectiveness and their durability on clay roof tiles are evaluated. Specifically, an organic-inorganic hybrid gel containing silica nanoparticles is produced. The nanoparticles create a densely packed coating on the roof tile surface in which air is trapped. This roughness produces a Cassie-Baxter regime, promoting superhydrophobicity. A surfactant, n-octylamine, was also added to the starting sol to catalyze the sol-gel process and to coarsen the pore structure of the gel network, preventing cracking. The application of ultrasound obviates the need to use volatile organic compounds in the synthesis, thereby making a 'green' product. It was also demonstrated that a co-condensation process effective between the organic and inorganic species is crucial to obtain durable and effective coatings. After an aging test, high hydrophobicity was maintained and water absorption was completely prevented for the roof tile samples under study. However, a transition from a Cassie-Baxter to a Wenzel state regime was observed as a consequence of the increase in the distance between the roughness pitches produced by the aging of the coating.

  14. TRIAL: Producing Media Catalogs.

    Science.gov (United States)

    McWeeney, Mark G.

    TRIAL (Technique for Retrieving Information from Abstracts of Literature) is an information storage and retrieval system which can be used by school media specialists to produce indexes of non-print materials. This manual provides a step by step approach for media specialists to automate their non-print holdings. These procedures can also be…

  15. Methods for producing diterpenes

    DEFF Research Database (Denmark)

    2015-01-01

    The present invention discloses that by combining different di TPS enzymes of class I and class II different diterpenes may be produced including diterpenes not identified in nature. Surprisingly it is revealed that a di TPS enzyme of class I of one species may be combined with a di TPS enzyme...

  16. Producing Civil Society

    DEFF Research Database (Denmark)

    Feldt, Liv Egholm; Hein Jessen, Mathias

    ’ and as such dominates our way of thinking about civil society. Yet, this view hinders the understanding of how civil society is not a pre-existing or given sphere, but a sphere which is constantly produced both discursively, conceptually and practically. Through two examples; 1,the case of philanthropy in the beginning...

  17. (PHB)-producing bacteria

    African Journals Online (AJOL)

    Isolation and characterization of two novel polyhydroxybutyrate (PHB)-producing bacteria. ... subsequently studied using phenotype microarray panels which allowed the testing of the effect of more than 90 different carbon, nitrogen, sulfur and phosphorus sources as well as pH on the growth characteristics of these strains.

  18. Inborn errors of metabolism

    Science.gov (United States)

    Metabolism - inborn errors of ... Bodamer OA. Approach to inborn errors of metabolism. In: Goldman L, Schafer AI, eds. Goldman-Cecil Medicine . 25th ed. Philadelphia, PA: Elsevier Saunders; 2016:chap 205. Rezvani I, Rezvani GA. An ...

  19. Lipid Metabolism Disorders

    Science.gov (United States)

    ... metabolic disorder, something goes wrong with this process. Lipid metabolism disorders, such as Gaucher disease and Tay-Sachs disease, involve lipids. Lipids are fats or fat-like substances. They ...

  20. Cold-induced metabolism

    NARCIS (Netherlands)

    Lichtenbelt, W. van Marken; Daanen, H.A.M.

    2003-01-01

    Purpose of review Cold response can be insulative (drop in peripheral temperature) or metabolic (increase in energy expenditure). Nonshivering thermogenesis by sympathetic, norepinephrine-induced mitochondrial heat production in brown adipose tissue is a well known component of this metabolic

  1. Investigation of metabolic encephalopathy

    African Journals Online (AJOL)

    , and. Table 1. Confirmed IMD cases associated with metabolic encephalopathy diagnosed at Red Cross Children's Hospital Metabolic Disease. Laboratory, 2006 - 2012. Name of disorder. Number of cases. Glutaric aciduria type 1 (GA1)*. 23.

  2. [Regulation of terpene metabolism

    Energy Technology Data Exchange (ETDEWEB)

    Croteau, R.

    1989-11-09

    Terpenoid oils, resins, and waxes from plants are important renewable resources. The objective of this project is to understand the regulation of terpenoid metabolism using the monoterpenes (C[sub 10]) as a model. The pathways of monoterpene biosynthesis and catabolism have been established, and the relevant enzymes characterized. Developmental studies relating enzyme levels to terpene accumulation within the oil gland sites of synthesis, and work with bioregulators, indicate that monoterpene production is controlled by terpene cyclases, the enzymes catalyzing the first step of the monoterpene pathway. As the leaf oil glands mature, cyclase levels decline and monoterpene biosynthesis ceases. Yield then decreases as the monoterpenes undergo catabolism by a process involving conversion to a glycoside and transport from the leaf glands to the root. At this site, the terpenoid is oxidatively degraded to acetate that is recycled into other lipid metabolites. During the transition from terpene biosynthesis to catabolism, the oil glands undergo dramatic ultrastructural modification. Degradation of the producing cells results in mixing of previously compartmentized monoterpenes with the catabolic enzymes, ultimately leading to yield decline. This regulatory model is being applied to the formation of other terpenoid classes (C[sub 15] C[sub 20], C[sub 30], C[sub 40]) within the oil glands. Preliminary investigations on the formation of sesquiterpenes (C[sub 15]) suggest that the corresponding cyclases may play a lesser role in determining yield of these products, but that compartmentation effects are important. From these studies, a comprehensive scheme for the regulation of terpene metabolism is being constructed. Results from this project wail have important consequences for the yield and composition of terpenoid natural products that can be made available for industrial exploitation.

  3. Neuroendocrine Regulation of Metabolism

    OpenAIRE

    Cornejo, Maria P.; Hentges, Shane T.; Maliqueo, Manuel; Coirini, Hector; Becu-Villalobos, Damasia; Elias, Carol F.

    2016-01-01

    Given the current environment in most developed countries, it is a challenge to maintain a good balance between calories consumed and calories burned, although maintenance of metabolic balance is key to good health. Therefore, understanding how metabolic regulation is achieved and how the dysregulation of metabolism affects health is an area of intense research. Most studies are focused on the hypothalamus, which is a brain area that acts as a key regulator of metabolism. Among the nuclei tha...

  4. Metabolic Engineering X Conference

    Energy Technology Data Exchange (ETDEWEB)

    Flach, Evan [American Institute of Chemical Engineers

    2015-05-07

    The International Metabolic Engineering Society (IMES) and the Society for Biological Engineering (SBE), both technological communities of the American Institute of Chemical Engineers (AIChE), hosted the Metabolic Engineering X Conference (ME-X) on June 15-19, 2014 at the Westin Bayshore in Vancouver, British Columbia. It attracted 395 metabolic engineers from academia, industry and government from around the globe.

  5. Producing colloids with microfluidics

    Science.gov (United States)

    Pannacci, Nicolas; Willaime, Herve; Tabeling, Patrick

    2008-11-01

    Submicronic emulsions are commonly used in pharmaceutical, food, cosmetic and material industries. Standard microfluidic tool is particularly convenient to produce in a very controlled way either droplets of typical diameter ranging from 10 to 300 microns with a perfect monodispersity (nanodrops in a way that is slightly dependent on the fluids used. The control on such a flow authorizes the adjustment of the diameter of the colloids formed. We will show brownian particles from 860 nm to 1.3 μm in diameter obtained in such way and their clustering into crystals thanks to their high monodispersity. These first experimental results are very promising and make evident the great potential of micro and nano-fluidics to produce nano-emulsions or colloids with very controlled size that metamaterials can require.

  6. Means for producing gas

    Energy Technology Data Exchange (ETDEWEB)

    Reichhelm, G.L.

    1929-01-22

    This patent describes a gas-generating apparatus which works in combination with a gas-generating receptacle. The process requires a means for supplying finely divided carbon to said receptable, means for supplying a flame under pressure to hold said carbon in suspension, a conduit for conducting the combustible gas produced from said receptacle, and synchronously operating mechanical means for controlling said carbon-supplying means and said flame-supplying means.

  7. Renal Ammonia Metabolism and Transport

    Science.gov (United States)

    Weiner, I. David; Verlander, Jill W.

    2015-01-01

    Renal ammonia metabolism and transport mediates a central role in acid-base homeostasis. In contrast to most renal solutes, the majority of renal ammonia excretion derives from intrarenal production, not from glomerular filtration. Renal ammoniagenesis predominantly results from glutamine metabolism, which produces 2 NH4+ and 2 HCO3− for each glutamine metabolized. The proximal tubule is the primary site for ammoniagenesis, but there is evidence for ammoniagenesis by most renal epithelial cells. Ammonia produced in the kidney is either excreted into the urine or returned to the systemic circulation through the renal veins. Ammonia excreted in the urine promotes acid excretion; ammonia returned to the systemic circulation is metabolized in the liver in a HCO3−-consuming process, resulting in no net benefit to acid-base homeostasis. Highly regulated ammonia transport by renal epithelial cells determines the proportion of ammonia excreted in the urine versus returned to the systemic circulation. The traditional paradigm of ammonia transport involving passive NH3 diffusion, protonation in the lumen and NH4+ trapping due to an inability to cross plasma membranes is being replaced by the recognition of limited plasma membrane NH3 permeability in combination with the presence of specific NH3-transporting and NH4+-transporting proteins in specific renal epithelial cells. Ammonia production and transport are regulated by a variety of factors, including extracellular pH and K+, and by several hormones, such as mineralocorticoids, glucocorticoids and angiotensin II. This coordinated process of regulated ammonia production and transport is critical for the effective maintenance of acid-base homeostasis. PMID:23720285

  8. Altered metabolism in cancer

    Directory of Open Access Journals (Sweden)

    Locasale Jason W

    2010-06-01

    Full Text Available Abstract Cancer cells have different metabolic requirements from their normal counterparts. Understanding the consequences of this differential metabolism requires a detailed understanding of glucose metabolism and its relation to energy production in cancer cells. A recent study in BMC Systems Biology by Vasquez et al. developed a mathematical model to assess some features of this altered metabolism. Here, we take a broader look at the regulation of energy metabolism in cancer cells, considering their anabolic as well as catabolic needs. See research article: http://www.biomedcentral.com/1752-0509/4/58/

  9. Cancer stem cell metabolism.

    Science.gov (United States)

    Peiris-Pagès, Maria; Martinez-Outschoorn, Ubaldo E; Pestell, Richard G; Sotgia, Federica; Lisanti, Michael P

    2016-05-24

    Cancer is now viewed as a stem cell disease. There is still no consensus on the metabolic characteristics of cancer stem cells, with several studies indicating that they are mainly glycolytic and others pointing instead to mitochondrial metabolism as their principal source of energy. Cancer stem cells also seem to adapt their metabolism to microenvironmental changes by conveniently shifting energy production from one pathway to another, or by acquiring intermediate metabolic phenotypes. Determining the role of cancer stem cell metabolism in carcinogenesis has become a major focus in cancer research, and substantial efforts are conducted towards discovering clinical targets.

  10. Systems Biology of Metabolism.

    Science.gov (United States)

    Nielsen, Jens

    2017-06-20

    Metabolism is highly complex and involves thousands of different connected reactions; it is therefore necessary to use mathematical models for holistic studies. The use of mathematical models in biology is referred to as systems biology. In this review, the principles of systems biology are described, and two different types of mathematical models used for studying metabolism are discussed: kinetic models and genome-scale metabolic models. The use of different omics technologies, including transcriptomics, proteomics, metabolomics, and fluxomics, for studying metabolism is presented. Finally, the application of systems biology for analyzing global regulatory structures, engineering the metabolism of cell factories, and analyzing human diseases is discussed.

  11. Producing images by ionography

    International Nuclear Information System (INIS)

    Pullan, B.R.; Dovas, T.; Mootes, B.M.

    1983-01-01

    A method and system for producing images by ionography and recording and storing same for display, comprising means for forming and recording a latent ionographic image on an electrically insulating film within a gas ionisation chamber between electrodes, scanning the latent image formed by an X-ray source, by means of an array of scanning electrodes movable on a platform to scan the latent image, the output signals from said scanning electrodes being amplified and digitised and thereafter placed in a digital storage and display device. (author)

  12. Acyl-Lipid Metabolism

    Science.gov (United States)

    Li-Beisson, Yonghua; Shorrosh, Basil; Beisson, Fred; Andersson, Mats X.; Arondel, Vincent; Bates, Philip D.; Baud, Sébastien; Bird, David; DeBono, Allan; Durrett, Timothy P.; Franke, Rochus B.; Graham, Ian A.; Katayama, Kenta; Kelly, Amélie A.; Larson, Tony; Markham, Jonathan E.; Miquel, Martine; Molina, Isabel; Nishida, Ikuo; Rowland, Owen; Samuels, Lacey; Schmid, Katherine M.; Wada, Hajime; Welti, Ruth; Xu, Changcheng; Zallot, Rémi; Ohlrogge, John

    2013-01-01

    Acyl lipids in Arabidopsis and all other plants have a myriad of diverse functions. These include providing the core diffusion barrier of the membranes that separates cells and subcellular organelles. This function alone involves more than 10 membrane lipid classes, including the phospholipids, galactolipids, and sphingolipids, and within each class the variations in acyl chain composition expand the number of structures to several hundred possible molecular species. Acyl lipids in the form of triacylglycerol account for 35% of the weight of Arabidopsis seeds and represent their major form of carbon and energy storage. A layer of cutin and cuticular waxes that restricts the loss of water and provides protection from invasions by pathogens and other stresses covers the entire aerial surface of Arabidopsis. Similar functions are provided by suberin and its associated waxes that are localized in roots, seed coats, and abscission zones and are produced in response to wounding. This chapter focuses on the metabolic pathways that are associated with the biosynthesis and degradation of the acyl lipids mentioned above. These pathways, enzymes, and genes are also presented in detail in an associated website (ARALIP: http://aralip.plantbiology.msu.edu/). Protocols and methods used for analysis of Arabidopsis lipids are provided. Finally, a detailed summary of the composition of Arabidopsis lipids is provided in three figures and 15 tables. PMID:23505340

  13. [Regulation of terpene metabolism

    Energy Technology Data Exchange (ETDEWEB)

    Croteau, R.

    1991-01-01

    During the last grant period, we have completed studies on the key pathways of monoterpene biosynthesis and catabolism in sage and peppermint, and have, by several lines of evidence, deciphered the rate-limiting step of each pathway. We have at least partially purified and characterized the relevant enzymes of each pathway. We have made a strong case, based on analytical, in vivo, and in vitro studies, that terpene accumulation depends upon the balance between biosynthesis and catabolism, and provided supporting evidence that these processes are developmentally-regulated and very closely associated with senescence of the oil glands. Oil gland ontogeny has been characterized at the ultrastructural level. We have exploited foliar-applied bioregulators to delay gland senescence, and have developed tissue explant and cell culture systems to study several elusive aspects of catabolism. We have isolated pure gland cell clusters and localized monoterpene biosynthesis and catabolism within these structures, and have used these preparations as starting materials for the purification to homogeneity of target regulatory'' enzymes. We have thus developed the necessary background knowledge, based on a firm understanding of enzymology, as well as the necessary experimental tools for studying the regulation of monoterpene metabolism at the molecular level. Furthermore, we are now in a position to extend our systematic approach to other terpenoid classes (C[sub 15]-C[sub 30]) produced by oil glands.

  14. Producing x-rays

    International Nuclear Information System (INIS)

    Mallozzi, P.J.; Epstein, H.M.; Jung, R.G.; Applebaum, D.C.; Fairand, B.P.; Gallagher, W.J.

    1977-01-01

    A method of producing x-rays by directing radiant energy from a laser onto a target is described. Conversion efficiency of at least about 3 percent is obtained by providing the radiant energy in a low-power precursor pulse of approximately uniform effective intensity focused onto the surface of the target for about 1 to 30 nanoseconds so as to generate an expanding unconfined coronal plasma having less than normal solid density throughout and comprising a low-density (underdense) region wherein the plasma frequency is less than the laser radiation frequency and a higher-density (overdense) region wherein the plasma frequency is greater than the laser radiation frequency and, about 1 to 30 nanoseconds after the precursor pulse strikes the target, a higher-power main pulse focused onto the plasma for about 10 -3 to 30 nanoseconds and having such power density and total energy that the radiant energy is absorbed in the underdense region and conducted into the overdense region to heat it and thus to produce x-rays therefrom with the plasma remaining substantially below normal solid density and thus facilitating the substantial emission of x-rays in the form of spectral lines arising from nonequilibrium ionization states

  15. Roles of homocysteine in cell metabolism: old and new functions.

    Science.gov (United States)

    Medina, M; Urdiales, J L; Amores-Sánchez, M I

    2001-07-01

    Mild hyperhomocysteinemia has been suggested as a new, independent risk factor for cardiovascular disease. This fact has produced a new, increased interest in the study of homocysteine metabolism and its relation to pathogenesis. This emergent area of biomedical research is reviewed here, stressing the biochemical and metabolic basis of the pathogenicity of increased levels of homocysteine.

  16. Insulin Resistance: Causes And Metabolic Implications | Igharo ...

    African Journals Online (AJOL)

    Insulin is an anabolic hormone that plays key roles in glucose metabolism. Insulin resistance is a decreased biological response to normal concentration of circulating insulin. In insulin resistance, normal amounts of insulin are inadequate to produce a normal insulin response from fat, muscle and liver cells. Insulin ...

  17. 92 INSULIN RESISTANCE: CAUSES AND METABOLIC ...

    African Journals Online (AJOL)

    drclement

    2009-12-01

    Dec 1, 2009 ... ABSTRACT. Insulin is an anabolic hormone that plays key roles in glucose metabolism. Insulin resistance is a decreased biological response to normal concentration of circulating insulin. In insulin resistance, normal amounts of insulin are inadequate to produce a normal insulin response from fat, muscle ...

  18. Colorectal adenomas produce lysozyme.

    Science.gov (United States)

    Rubio, C A

    2003-01-01

    Lysozyme is an innate non-immunologic antibacterial enzyme produced by the Paneth cells of the upper intestinal tract. Lysozyme is not normally secreted in the lower intestinal tract. Previous reports indicate, however, that lysozyme may be secreted by colorectal neoplasias. The aim was to audit lysozyme expression in colorectal diseases including neoplasias. For that purpose, sections were stained with lysozyme (Muramidase), Ki67 (MIB1) and CD 68. Intense lysozyme overexpression (+++) was compared among 177 colorectal tissues: 35 having normal mucosa, 20 regenerative mucosa in inflammatory bowel disease (IBD), 2 inflammatory polyps, 3 collagenous colitis, 2 melanosis coli, 21 hyperplastic polyps, 42 tubular adenomas, 9 serrated adenomas, 30 villous adenomas and 13 invasive carcinomas. Intense lysozyme overexpression (+++) was found in 9.5% of the hyperplastic polyps, in 97.6% of the tubular adenomas, in 88.9% of the serrated adenomas, in 93.3% of the villous adenomas, in 76.9% of the carcinomas, but in none of the other tissues investigated. Neoplastic colorectal cells may acquire the capacity to produce lysozyme. The presence of that enzyme may not be a haphazard, capricious event in mutated colorectal epithelial cells but part of a more elaborate molecular behavior, not necessarily antibacterial. Recently, it was demonstrated that patients having lysozyme-secreting breast carcinomas were associated with a favorable prognosis. Whether lysozyme expression has any bearing on the biological behavior of colorectal carcinomas remains to be elucidated. Lysozyme overexpression (+++) also occurred in 2 of the 21 hyperplastic polyps, suggesting that intense lysozyme production might herald a possible dysplastic evolution in some hyperplastic polyps.

  19. DREAMS of metabolism.

    Science.gov (United States)

    Soh, Keng Cher; Hatzimanikatis, Vassily

    2010-10-01

    Metabolic networks have been studied for several decades, and sophisticated computational frameworks are needed to augment experimental approaches to harness these complex networks. BNICE (Biochemical Network Integrated Computational Explorer), a computational approach for the discovery of novel biochemical pathways that is based on biochemical transformations, overcomes many of the current limitations. BNICE and similar frameworks can be used in several different areas: (i) 'Design' of novel pathways for metabolic engineering; (ii) 'Retrosynthesis' of metabolic compounds; (iii) 'Evolution' analysis between metabolic pathways of different organisms; (iv) 'Analysis' of metabolic pathways; (v) 'Mining' of omics data; and (vi) 'Selection' of targets for enzyme engineering. Here, we discuss the issues and challenges in building such frameworks as well as the gamut of applications in biotechnology, metabolic engineering and synthetic biology. Copyright © 2010 Elsevier Ltd. All rights reserved.

  20. [Menopause and metabolic syndrome].

    Science.gov (United States)

    Meirelles, Ricardo M R

    2014-03-01

    The incidence of cardiovascular disease increases considerably after the menopause. One reason for the increased cardiovascular risk seems to be determined by metabolic syndrome, in which all components (visceral obesity, dyslipidemia, hypertension, and glucose metabolism disorder) are associated with higher incidence of coronary artery disease. After menopause, metabolic syndrome is more prevalent than in premenopausal women, and may plays an important role in the occurrence of myocardial infarction and other atherosclerotic and cardiovascular morbidities. Obesity, an essential component of the metabolic syndrome, is also associated with increased incidence of breast, endometrial, bowel, esophagus, and kidney cancer. The treatment of metabolic syndrome is based on the change in lifestyle and, when necessary, the use of medication directed to its components. In the presence of symptoms of the climacteric syndrome, hormonal therapy, when indicated, will also contribute to the improvement of the metabolic syndrome.

  1. A network perspective on metabolic inconsistency

    Directory of Open Access Journals (Sweden)

    Sonnenschein Nikolaus

    2012-05-01

    Full Text Available Abstract Background Integrating gene expression profiles and metabolic pathways under different experimental conditions is essential for understanding the coherence of these two layers of cellular organization. The network character of metabolic systems can be instrumental in developing concepts of agreement between expression data and pathways. A network-driven interpretation of gene expression data has the potential of suggesting novel classifiers for pathological cellular states and of contributing to a general theoretical understanding of gene regulation. Results Here, we analyze the coherence of gene expression patterns and a reconstruction of human metabolism, using consistency scores obtained from network and constraint-based analysis methods. We find a surprisingly strong correlation between the two measures, demonstrating that a substantial part of inconsistencies between metabolic processes and gene expression can be understood from a network perspective alone. Prompted by this finding, we investigate the topological context of the individual biochemical reactions responsible for the observed inconsistencies. On this basis, we are able to separate the differential contributions that bear physiological information about the system, from the unspecific contributions that unravel gaps in the metabolic reconstruction. We demonstrate the biological potential of our network-driven approach by analyzing transcriptome profiles of aldosterone producing adenomas that have been obtained from a cohort of Primary Aldosteronism patients. We unravel systematics in the data that could not have been resolved by conventional microarray data analysis. In particular, we discover two distinct metabolic states in the adenoma expression patterns. Conclusions The methodology presented here can help understand metabolic inconsistencies from a network perspective. It thus serves as a mediator between the topology of metabolic systems and their dynamical

  2. Metabolic syndrome and menopause

    OpenAIRE

    Jouyandeh, Zahra; Nayebzadeh, Farnaz; Qorbani, Mostafa; Asadi, Mojgan

    2013-01-01

    Abstract Background The metabolic syndrome is defined as an assemblage of risk factors for cardiovascular diseases, and menopause is associated with an increase in metabolic syndrome prevalence. The aim of this study was to assess the prevalence of metabolic syndrome and its components among postmenopausal women in Tehran, Iran. Methods In this cross-sectional study in menopause clinic in Tehran, 118 postmenopausal women were investigated. We used the adult treatment panel 3 (ATP3) criteria t...

  3. Nutrition and metabolic syndrome.

    OpenAIRE

    Albornoz López, Raúl; Pérez Rodrigo, Iciar

    2012-01-01

    The metabolic syndrome comprises a cluster of metabolic abnormalities that increase the risk for cardiovascular disease and type 2 diabetes mellitus. The exact etiology is unclear, although it is known thatthere is a complex interaction between genetic, metabolic and environmental factors. Among the environmental factors, dietary habits play an important role in the treatment and prevention of this condition. General classic recommendations include control of obesity, increased physical activ...

  4. Diet-dependent shifts in ruminal butyrate producing bacteria

    Czech Academy of Sciences Publication Activity Database

    Mrázek, Jakub; Tepšič, K.; Avguštin, G.; Kopečný, Jan

    2006-01-01

    Roč. 51, č. 4 (2006), s. 294-298 ISSN 0015-5632 R&D Projects: GA AV ČR IBS5045112 Institutional research plan: CEZ:AV0Z50450515 Keywords : butyrate -producing bacteria Subject RIV: FB - Endocrinology, Diabetology, Metabolism, Nutrition Impact factor: 0.963, year: 2006

  5. producing dairy cows fed conventional forages, wheat straw

    African Journals Online (AJOL)

    Chewing activity, metabolic profile and performance of high- producing dairy cows fed conventional forages, wheat straw or rice straw. ... South African Journal of Animal Science ... Twelve lactating Holstein cows were used in a replicated (n = 4) 3 × 3 Latin square design experiment with three periods of 21 days. Cows were ...

  6. Development of Producibility Evaluation Criteria

    National Research Council Canada - National Science Library

    Wilkins, Jr., James R; Kraine, Gilbert L; Thompson, Daniel H; Borchers, Kenneth H; Borchers, Marilyn M

    1993-01-01

    .... To accept this definition is to equate producibility with productivity, and normally leads to consideration of many more elements than should be taken into account for evaluating producibility...

  7. Fluoroacetylcarnitine: metabolism and metabolic effects in mitochondria

    Energy Technology Data Exchange (ETDEWEB)

    Bremer, J.; Davis, E.J.

    1973-01-01

    The metabolism and metabolic effects of fluoroacetylcarnitine have been investigated. Carnitineacetyltransferase transfers the fluoro-acetyl group of fluoroacetylcarnitine nearly as rapidly to CoA as the acetyl group of acetylcarnitine. Fluorocitrate is then formed by citrate synthase, but this second reaction is relatively slow. The fluorocitrate formed intramitochondrially inhibits the metabolism of citrate. In heart and skeletal muscle mitochondria the accumulated citrate inhibits citrate synthesis and the ..beta..-oxidation of fatty acids. Free acetate is formed, presumably because accumulated acetyl-CoA is hydrolyzed. In liver mitochondria the accumulation of citrate leads to a relatively increased rate of ketogenesis. Increased ketogenesis is obtained also upon the addition of citrate to the reaction mixture.

  8. Power Producer Production Valuation

    Directory of Open Access Journals (Sweden)

    M. Kněžek

    2008-01-01

    Full Text Available The ongoing developments in the electricity market, in particular the establishment of the Prague Energy Exchange (PXE and the associated transfer from campaign-driven sale to continuous trading, represent a significant change for power companies.  Power producing companies can now optimize the sale of their production capacities with the objective of maximizing profit from wholesale electricity and supporting services. The Trading Departments measure the success rate of trading activities by the gross margin (GM, calculated by subtracting the realized sales prices from the realized purchase prices and the production cost, and indicate the profit & loss (P&L to be subsequently calculated by the Control Department. The risk management process is set up on the basis of a business strategy defining the volumes of electricity that have to be sold one year and one month before the commencement of delivery. At the same time, this process defines the volume of electricity to remain available for spot trading (trading limits. 

  9. Respiration of Chemodenervated Goats in Acute Metabolic Acidosis,

    Science.gov (United States)

    1983-08-02

    metabolic ) alkalosis . Furthermore, the ventilatory responses to increase in PaCO2 produced by CO2 inhalation are shifted to lower values of PaCO2 in...the presence of metabolic acidosis, and to higher PaCO2 vaiues in metabolic alkalosis (Fencl et al. [1966]). The roles played by the carotid bodies (CB...and J.A. Broch (1969). Respiration and cerebral blood flow in metabolic acidosis and alkalosis in humans. J. Appl. Physiol. 27: 67-76. Gabel, R.A

  10. Genetic and metabolic engineering in diatoms.

    Science.gov (United States)

    Huang, Weichao; Daboussi, Fayza

    2017-09-05

    Diatoms have attracted considerable attention due to their success in diverse environmental conditions, which probably is a consequence of their complex origins. Studies of their metabolism will provide insight into their adaptation capacity and are a prerequisite for metabolic engineering. Several years of investigation have led to the development of the genome engineering tools required for such studies, and a profusion of appropriate tools is now available for exploring and exploiting the metabolism of these organisms. Diatoms are highly prized in industrial biotechnology, due to both their richness in natural lipids and carotenoids and their ability to produce recombinant proteins, of considerable value in diverse markets. This review provides an overview of recent advances in genetic engineering methods for diatoms, from the development of gene expression cassettes and gene delivery methods, to cutting-edge genome-editing technologies. It also highlights the contributions of these rapid developments to both basic and applied research: they have improved our understanding of key physiological processes; and they have made it possible to modify the natural metabolism to favour the production of specific compounds or to produce new compounds for green chemistry and pharmaceutical applications.This article is part of the themed issue 'The peculiar carbon metabolism in diatoms'. © 2017 The Author(s).

  11. Fatty acid metabolism: target for metabolic syndrome

    OpenAIRE

    Wakil, Salih J.; Abu-Elheiga, Lutfi A.

    2009-01-01

    Fatty acids are a major energy source and important constituents of membrane lipids, and they serve as cellular signaling molecules that play an important role in the etiology of the metabolic syndrome. Acetyl-CoA carboxylases 1 and 2 (ACC1 and ACC2) catalyze the synthesis of malonyl-CoA, the substrate for fatty acid synthesis and the regulator of fatty acid oxidation. They are highly regulated and play important roles in the energy metabolism of fatty acids in animals, including humans. They...

  12. The compositional and evolutionary logic of metabolism

    International Nuclear Information System (INIS)

    Braakman, Rogier; Smith, Eric

    2013-01-01

    within biochemistry. Module boundaries provide the interfaces where change is concentrated, when we catalogue extant diversity of metabolic phenotypes. The same modules that organize the compositional diversity of metabolism are argued, with many explicit examples, to have governed long-term evolution. Early evolution of core metabolism, and especially of carbon-fixation, appears to have required very few innovations, and to have used few rules of composition of conserved modules, to produce adaptations to simple chemical or energetic differences of environment without diverse solutions and without historical contingency. We demonstrate these features of metabolism at each of several levels of hierarchy, beginning with the small-molecule metabolic substrate and network architecture, continuing with cofactors and key conserved reactions, and culminating in the aggregation of multiple diverse physical and biochemical processes in cells. (topical review)

  13. PPARa governs glycerol metabolism

    NARCIS (Netherlands)

    Patsouris, D.A.; Mandard, S.J.; Voshol, P.J.; Escher, P.; Tan, N.S.; Havekes, L.M.; Koenig, W.; März, W.; Müller, M.R.; Kersten, A.H.

    2004-01-01

    Glycerol, a product of adipose tissue lipolysis, is an important substrate for hepatic glucose synthesis. However, little is known about the regulation of hepatic glycerol metabolism. Here we show that several genes involved in the hepatic metabolism of glycerol, i.e., cytosolic and mitochondrial

  14. Metabolic syndrome and menopause

    Directory of Open Access Journals (Sweden)

    Jouyandeh Zahra

    2013-01-01

    Full Text Available Abstract Background The metabolic syndrome is defined as an assemblage of risk factors for cardiovascular diseases, and menopause is associated with an increase in metabolic syndrome prevalence. The aim of this study was to assess the prevalence of metabolic syndrome and its components among postmenopausal women in Tehran, Iran. Methods In this cross-sectional study in menopause clinic in Tehran, 118 postmenopausal women were investigated. We used the adult treatment panel 3 (ATP3 criteria to classify subjects as having metabolic syndrome. Results Total prevalence of metabolic syndrome among our subjects was 30.1%. Waist circumference, HDL-cholesterol, fasting blood glucose, diastolic blood pressure ,Systolic blood pressure, and triglyceride were significantly higher among women with metabolic syndrome (P-value Conclusions Our study shows that postmenopausal status is associated with an increased risk of metabolic syndrome. Therefore, to prevent cardiovascular disease there is a need to evaluate metabolic syndrome and its components from the time of the menopause.

  15. Circadian Systems and Metabolism

    NARCIS (Netherlands)

    Roenneberg, Till; Merrow, Martha

    1999-01-01

    Circadian systems direct many metabolic parameters and, at the same time, they appear to be exquisitely shielded from metabolic variations. Although the recent decade of circadian research has brought insights into how circadian periodicity may be generated at the molecular level, little is known

  16. Comprehensive metabolic panel

    Science.gov (United States)

    Metabolic panel - comprehensive; Chem-20; SMA20; Sequential multi-channel analysis with computer-20; SMAC20; Metabolic panel 20 ... Normal values for the panel tests are: Albumin : 3.4 to 5.4 g/dL (34 to 54 g/L) Alkaline phosphatase : 44 to 147 ...

  17. Metabolic theory predicts animal self-thinning.

    Science.gov (United States)

    Jonsson, Tomas

    2017-05-01

    The metabolic theory of ecology (MTE) predicts observed patterns in ecology based on metabolic rates of individuals. The theory is influential but also criticized for a lack of firm empirical evidence confirming MTE's quantitative predictions of processes, e.g. outcome of competition, at population or community level. Self-thinning is a well-known population level phenomenon among plants, but a much less studied phenomenon in animal populations and no consensus exists on what a universal thinning slope for animal populations might be, or if it exists. The goal of this study was to use animal self-thinning as a tool to test population-level predictions from MTE, by analysing (i) if self-thinning can be induced in populations of house crickets (Acheta domesticus) and (ii) if the resulting thinning trajectories can be predicted from metabolic theory, using estimates of the species-specific metabolic rate of A. domesticus. I performed a laboratory study where the growth of A. domesticus was followed, from hatching until emergence as adults, in 71 cohorts of five different starting densities. Ninety-six per cent of all cohorts in the three highest starting densities showed evidence of self-thinning, with estimated thinning slopes in general being remarkably close to that expected under metabolic constraints: A cross-sectional analysis of all data showing evidence of self-thinning produced an ordinary least square (OLS) slope of -1·11, exactly that predicted from specific metabolic allometry of A. domesticus. This result is furthermore supported by longitudinal analyses, allowing for independent responses within cohorts, producing a mean OLS slope across cohorts of -1·13 and a fixed effect linear mixed effects models slope of -1·09. Sensitivity analysis showed that these results are robust to how the criterion for on-going self-thinning was defined. Finally, also as predicted by metabolic theory, temperature had a negative effect on the thinning intercept, producing

  18. It must be my metabolism: Metabolic control of mind

    Directory of Open Access Journals (Sweden)

    Dana M Small

    2014-07-01

    relationship between the reinforcing potency of sugared solutions and the metabolic effects that follow their consumption (16, also see the abstract of I. de Araujo. We therefore hypothesized that metabolic response provides the critical signal necessary to condition preference. To test this prediction in humans we designed a flavor nutrient conditioning study in which participants first rated their liking for novel flavored beverages and then, over a three week-long conditioning protocol, alternately ingested one of the flavored beverages with 112.5 kcal from maltodextrin, a tasteless and odorless polysaccharide that breaks down into glucose, and another flavored beverage with no calories added. Plasma glucose was measured before and after each of the drinks’ consumption as a proxy measure of metabolic response, assuming that glucose oxidation depends upon the level of circulating glucose. For each participant flavor-calorie pairings were held constant but the identity of the conditioned flavors were counterbalanced across participants. Following the exposure phase, participants’ liking of, and brain responses to, non-caloric versions of the flavors were assessed. We predicted that change in plasma glucose produced by beverage consumption during the exposure sessions would be associated with neural responses in dopamine source and target regions to the calorie predictive flavor. As predicted, response in the ventral striatum and hypothalamus to the calorie-predictive flavor (CS+ vs. non the noncaloric-predictive flavor (CS- was strongly associated with the changes in plasma glucose levels produced by ingestion of these same beverages when consumed previously either with (CS+ or without (CS- calories (17. Specifically, the greater the increase in circulating glucose occurring post ingestion of the beverage containing 112.5 kcal from maltodextrin versus the noncaloric drink, the stronger was the brain response to the CS+ compared to the CS- flavor. Importantly, because each

  19. Radiation produced biomaterials

    International Nuclear Information System (INIS)

    Rosiak, J.M.

    1998-01-01

    radiation technique. Immobilization of biologically active species in hydrogel matrices, their use as drug delivery systems and enzyme traps as well as modification of material surfaces to improve their biocompatibility and ability to bond antigens and antibodies have been the main subject of their investigations. The rising interest in the field of application of radiation to bioengineering was also recognized by the International Atoimc Energy Agency, which has initiated the international programs relating to those studies. In these lectures some directions of investigations on the formation of hydrogels and their applications for biomedical purposes have been specified. Also, some examples of commercialized products being produced by means of radiation technique have been presented

  20. Mycobacterium tuberculosis Metabolism

    Science.gov (United States)

    Warner, Digby F.

    2015-01-01

    Metabolism underpins the physiology and pathogenesis of Mycobacterium tuberculosis. However, although experimental mycobacteriology has provided key insights into the metabolic pathways that are essential for survival and pathogenesis, determining the metabolic status of bacilli during different stages of infection and in different cellular compartments remains challenging. Recent advances—in particular, the development of systems biology tools such as metabolomics—have enabled key insights into the biochemical state of M. tuberculosis in experimental models of infection. In addition, their use to elucidate mechanisms of action of new and existing antituberculosis drugs is critical for the development of improved interventions to counter tuberculosis. This review provides a broad summary of mycobacterial metabolism, highlighting the adaptation of M. tuberculosis as specialist human pathogen, and discusses recent insights into the strategies used by the host and infecting bacillus to influence the outcomes of the host–pathogen interaction through modulation of metabolic functions. PMID:25502746

  1. Metabolic Engineering VII Conference

    Energy Technology Data Exchange (ETDEWEB)

    Kevin Korpics

    2012-12-04

    The aims of this Metabolic Engineering conference are to provide a forum for academic and industrial researchers in the field; to bring together the different scientific disciplines that contribute to the design, analysis and optimization of metabolic pathways; and to explore the role of Metabolic Engineering in the areas of health and sustainability. Presentations, both written and oral, panel discussions, and workshops will focus on both applications and techniques used for pathway engineering. Various applications including bioenergy, industrial chemicals and materials, drug targets, health, agriculture, and nutrition will be discussed. Workshops focused on technology development for mathematical and experimental techniques important for metabolic engineering applications will be held for more in depth discussion. This 2008 meeting will celebrate our conference tradition of high quality and relevance to both industrial and academic participants, with topics ranging from the frontiers of fundamental science to the practical aspects of metabolic engineering.

  2. Regulation of Glucose Metabolism - A Perspective From Cell Bioprocessing.

    Science.gov (United States)

    Mulukutla, Bhanu Chandra; Yongky, Andrew; Le, Tung; Mashek, Douglas G; Hu, Wei-Shou

    2016-08-01

    Cultured mammalian cells are the main workhorses for producing biologics. The performance of these cell culture processes, in terms of both productivity and product quality attributes, is significantly influenced by cellular metabolism. Glucose is the major carbon source for cellular biosynthesis and energy generation. We summarize here recent advances in our understanding of the regulation of glucose metabolism in cultured cells. The versatility of cells to sustain homeostatic states under widely varying environments is made possible by allosteric regulation of the metabolic network, interplay between the signaling pathways, and transcription factors. Understanding the regulation of metabolism holds the key to altering the metabolic regulatory circuit and implementing direct metabolic control over cell culture processes. Copyright © 2016 Elsevier Ltd. All rights reserved.

  3. The divergence and natural selection of autocatalytic primordial metabolic systems.

    Science.gov (United States)

    Marakushev, Sergey A; Belonogova, Ol'ga V

    2013-06-01

    The diversity of the central metabolism of modern organisms is caused by the existence of a few metabolic modules, combination of which produces multiple metabolic pathways. This paper analyzes biomimetically reconstructed coupled autocatalytic cycles as the basis of ancestral metabolic systems. The mechanism for natural selection and evolution in autocatalytic chemical systems may be affected by natural homeostatic parameters such as ambient chemical potentials, temperature, and pressure. Competition between separate parts of an autocatalytic network with positive-plus-negative feedback resulted in the formation of primordial autotrophic, mixotrophic, and heterotrophic metabolic systems. This work examined the last common ancestor of a set of coupled metabolic cycles in a population of protocells. Physical-chemical properties of these cycles determined the main principles of natural selection for the ancestral Bacteria and Archaea taxa.

  4. The Divergence and Natural Selection of Autocatalytic Primordial Metabolic Systems

    Science.gov (United States)

    Marakushev, Sergey A.; Belonogova, Ol'ga V.

    2013-06-01

    The diversity of the central metabolism of modern organisms is caused by the existence of a few metabolic modules, combination of which produces multiple metabolic pathways. This paper analyzes biomimetically reconstructed coupled autocatalytic cycles as the basis of ancestral metabolic systems. The mechanism for natural selection and evolution in autocatalytic chemical systems may be affected by natural homeostatic parameters such as ambient chemical potentials, temperature, and pressure. Competition between separate parts of an autocatalytic network with positive-plus-negative feedback resulted in the formation of primordial autotrophic, mixotrophic, and heterotrophic metabolic systems. This work examined the last common ancestor of a set of coupled metabolic cycles in a population of protocells. Physical-chemical properties of these cycles determined the main principles of natural selection for the ancestral Bacteria and Archaea taxa.

  5. Aspergillus mulundensis sp. nov., a new species for the fungus producing the antifungal echinocandin lipopeptides, mulundocandins

    DEFF Research Database (Denmark)

    Bills, Gerald F.; Yue, Qun; Chen, Li

    2016-01-01

    The invalidly published name Aspergillus sydowii var. mulundensis was proposed for a strain of Aspergillus that produced new echinocandin metabolites designated as the mulundocadins. Reinvestigation of this strain (Y-30462=DSMZ 5745) using phylogenetic, morphological, and metabolic data indicated...

  6. Topics in Xenobiochemistry: do metabolic pathways exist for xenobiotics? The micro-metabolism hypothesis.

    Science.gov (United States)

    Wilson, I D; Nicholson, J K

    2003-09-01

    1. The relevance of the concept of 'the metabolic pathway' for the understanding of xenobiotic metabolism is discussed in the light of advances in modern analytical methods that have enabled the detection and identification of minor metabolites present at ever lower concentrations. 2. A model is suggested where the overall metabolic fate of a xenobiotic is the sum of all the possible metabolic reactions permitted by the solution chemistry of the compound modulated by factors such as the metabolizing enzyme complement of the organism, the affinity of those enzymes for the xenobiotic substrates and the probabilities of all of these processes. 3. In this probabilistic, rather than deterministic, system, the resulting proportions of particular metabolites will, therefore, depend on the sums of the probabilities of particular biotransformation reactions occurring and the stability (chemical or metabolic) of the resulting metabolite. 4. In this model, all the potential metabolic possibilities that could result for any individual xenobiotic will occur to some extent. However, in actuality, many of the resulting metabolites will be produced or excreted in such small quantities as to defy ready detection with current methods.

  7. Cytotoxicity of lapachol metabolites produced by probiotics.

    Science.gov (United States)

    Oliveira Silva, E; Cruz de Carvalho, T; Parshikov, I A; Alves dos Santos, R; Silva Emery, F; Jacometti Cardoso Furtado, N A

    2014-07-01

    Probiotics are currently added to a variety of functional foods to provide health benefits to the host and are commonly used by patients with gastrointestinal complaints or diseases. The therapeutic effects of lapachol continue to inspire studies to obtain derivatives with improved bioactivity and lower unwanted effects. Therefore, the general goal of this study was to show that probiotics are able to convert lapachol and are important to assess the effects of bacterial metabolism on drug performance and toxicity. The microbial transformations of lapachol were carried out by Bifidobacterium sp. and Lactobacillus acidophilus and different metabolites were produced in mixed and isolated cultures. The cytotoxic activities against breast cancer and normal fibroblast cell lines of the isolated metabolites (4α-hydroxy-2,2-dimethyl-5-oxo-2,3,4,4α,5,9β-hexahydroindeno[1,2-β]pyran-9β-carboxilic acid, a new metabolite produced by mixed culture and dehydro-α-lapachone produced by isolated cultures) were assessed and compared with those of lapachol. The new metabolite displayed a lower activity against a breast cancer cell line (IC50 = 532.7 μmol l(-1) ) than lapachol (IC50 = 72.3 μmol l(-1) ), while dehydro-α-lapachone (IC50 = 10.4 μmol l(-1) ) displayed a higher activity than lapachol. The present study is the first to demonstrate that probiotics are capable of converting lapachol into the most effective cytotoxic compound against a breast cancer cell line. Probiotics have been used in dairy products to promote human health and have the ability to metabolize drugs and other xenobiotics. Naphthoquinones, such as lapachol, are considered privileged scaffolds due to their high propensity to interact with biological targets. The present study is the first to demonstrate that probiotics are capable of converting lapachol into the most effective cytotoxic compound against a breast cancer cell line. The developed approach highlights the importance of probiotics to assess

  8. Metabolic disorders in menopause.

    Science.gov (United States)

    Stachowiak, Grzegorz; Pertyński, Tomasz; Pertyńska-Marczewska, Magdalena

    2015-03-01

    Metabolic disorders occurring in menopause, including dyslipidemia, disorders of carbohydrate metabolism (impaired glucose tolerance - IGT, type 2 diabetes mellitus - T2DM) or components of metabolic syndrome, constitute risk factors for cardiovascular disease in women. A key role could be played here by hyperinsulinemia, insulin resistance and visceral obesity, all contributing to dyslipidemia, oxidative stress, inflammation, alter coagulation and atherosclerosis observed during the menopausal period. Undiagnosed and untreated, metabolic disorders may adversely affect the length and quality of women's life. Prevention and treatment preceded by early diagnosis should be the main goal for the physicians involved in menopausal care. This article represents a short review of the current knowledge concerning metabolic disorders (e.g. obesity, polycystic ovary syndrome or thyroid diseases) in menopause, including the role of a tailored menopausal hormone therapy (HT). According to current data, HT is not recommend as a preventive strategy for metabolic disorders in menopause. Nevertheless, as part of a comprehensive strategy to prevent chronic diseases after menopause, menopausal hormone therapy, particularly estrogen therapy may be considered (after balancing benefits/risks and excluding women with absolute contraindications to this therapy). Life-style modifications, with moderate physical activity and healthy diet at the forefront, should be still the first choice recommendation for all patients with menopausal metabolic abnormalities.

  9. Metabolic disorders in menopause

    Directory of Open Access Journals (Sweden)

    Grzegorz Stachowiak

    2015-04-01

    Full Text Available Metabolic disorders occurring in menopause, including dyslipidemia, disorders of carbohydrate metabolism (impaired glucose tolerance – IGT, type 2 diabetes mellitus – T2DM or components of metabolic syndrome, constitute risk factors for cardiovascular disease in women. A key role could be played here by hyperinsulinemia, insulin resistance and visceral obesity, all contributing to dyslipidemia, oxidative stress, inflammation, alter coagulation and atherosclerosis observed during the menopausal period. Undiagnosed and untreated, metabolic disorders may adversely affect the length and quality of women’s life. Prevention and treatment preceded by early diagnosis should be the main goal for the physicians involved in menopausal care. This article represents a short review of the current knowledge concerning metabolic disorders (e.g. obesity, polycystic ovary syndrome or thyroid diseases in menopause, including the role of a tailored menopausal hormone therapy (HT. According to current data, HT is not recommend as a preventive strategy for metabolic disorders in menopause. Nevertheless, as part of a comprehensive strategy to prevent chronic diseases after menopause, menopausal hormone therapy, particularly estrogen therapy may be considered (after balancing benefits/risks and excluding women with absolute contraindications to this therapy. Life-style modifications, with moderate physical activity and healthy diet at the forefront, should be still the first choice recommendation for all patients with menopausal metabolic abnormalities.

  10. Lipid metabolism in experimental animals

    Directory of Open Access Journals (Sweden)

    Sánchez-Muñiz, Francisco J.

    1998-08-01

    Full Text Available Publications are scarce in the way in chich metabolic processes are affected by the ingestion of heated fats used to prepare food. Similarly studies measuring metabolic effects of the consumption on fried food are poorly known. The purpose of this presentation is to summarize information on frying fats and frying foods upon lipid metabolism in experimental animals. Food consumption is equivalent or even higher when oils or the fat content of frying foods are poorly alterated decreasing their acceptability when their alteration degree increase. After 4hr. experiment the digestibility and absorption coefficients of a single dosis of thermooxidized oils were significantly decreased in rats, however the digestive utilization of frying thermooxidized oils included in diets showed very little change in comparison with unused oils by feeding trials on rats. Feeding rats different frying fats induced a slight hypercholesterolemic effect being the magnitude of this effect related to the linoleic decrease in diet produced by frying. However HDL, the main rat-cholesterol carrier, also increased, thus the serum cholesterol/HDL-cholesterol ratio did not change. Results suggest that rats fed frying fats adapt their lipoprotein metabolism increasing the number of HDL particles. Deep fat frying deeply changed the fatty acid composition of foods, being possible to increase their n-9 or n-6 fatty acid and to decrease the saturated fatty acid contents by frying. When olive oil-and sunflower oil-fried sardines were used as the only protein and fat sources of rats-diets in order to prevent the dietary hypercholesterolemia it was provided that both fried-sardine diets showed a powerful check effect on the cholesterol raising effect induced by dietary cholesterol. The negative effect of feeding rats cholesterol plus bovine bile to induce hypercholesterolemia on some cell-damage markers such as lactate dehydrogenase, transaminases, alkaline phosphatase, was

  11. Comparative genome-scale metabolic modeling of actinomycetes : The topology of essential core metabolism

    NARCIS (Netherlands)

    Alam, Mohammad Tauqeer; Medema, Marnix H.; Takano, Eriko; Breitling, Rainer; Gojobori, Takashi

    2011-01-01

    Actinomycetes are highly important bacteria. On one hand, some of them cause severe human and plant diseases, on the other hand, many species are known for their ability to produce antibiotics. Here we report the results of a comparative analysis of genome-scale metabolic models of 37 species of

  12. Comparative genome-scale metabolic modeling of actinomycetes: the topology of essential core metabolism.

    NARCIS (Netherlands)

    Alam, M.T.; Medema, M.H.; Takano, E.; Breitling, R.

    2011-01-01

    Actinomycetes are highly important bacteria. On one hand, some of them cause severe human and plant diseases, on the other hand, many species are known for their ability to produce antibiotics. Here we report the results of a comparative analysis of genome-scale metabolic models of 37 species of

  13. Fundamentals of cancer metabolism

    Science.gov (United States)

    DeBerardinis, Ralph J.; Chandel, Navdeep S.

    2016-01-01

    Tumors reprogram pathways of nutrient acquisition and metabolism to meet the bioenergetic, biosynthetic, and redox demands of malignant cells. These reprogrammed activities are now recognized as hallmarks of cancer, and recent work has uncovered remarkable flexibility in the specific pathways activated by tumor cells to support these key functions. In this perspective, we provide a conceptual framework to understand how and why metabolic reprogramming occurs in tumor cells, and the mechanisms linking altered metabolism to tumorigenesis and metastasis. Understanding these concepts will progressively support the development of new strategies to treat human cancer. PMID:27386546

  14. Novel metabolic pathways for linoleic and arachidonic acid metabolism.

    Science.gov (United States)

    Moghaddam, M; Motoba, K; Borhan, B; Pinot, F; Hammock, B D

    1996-08-13

    Mouse liver microsomes oxidized linoleic acid to form 9,10- or 12,13-epoxyoctadecenoate. These monoepoxides were subsequently hydrolyzed to their corresponding diols in the absence of the microsomal epoxide hydrolase inhibitor, 1,2-epoxy-3,3,3-trichloropropane. Furthermore, both 9,10- and 12,13-epoxyoctadecenoates were oxidized to diepoxyoctadecanoate at apparently identical rates by mouse liver microsomal P-450 epoxidation. Both epoxyoctadecanoates and diepoxyoctadecanoates were converted to tetrahydrofuran-diols by microsomes. Tetrahydroxides of linoleate were produced as minor metabolites. Arachidonic acid was metabolized to epoxyeicosatrienoates, dihydroxyeicosatrienoates, and monohydroxyeicosatetraenoates by the microsomes. Microsomes prepared from clofibrate (but not phenobarbital) -treated mice exhibited much higher production rates for epoxyeicosatrienoates and vic-dihydroxyeicosatrienoates. This indicated an induction of P-450 epoxygenase(s) and microsomal epoxide hydrolase in mice by clofibrate and not by phenobarbital. Incubation of synthetic epoxyeicosatrienoates with microsomes led to the production of diepoxyeicosadienoates. Among chemically generated diepoxyeicosadienoate isomers, three of them possessing adjacent diepoxides were hydrolyzed to their diol epoxides which cyclized to the corresponding tetrahydrofuran-diols by microsomes as well as soluble epoxide hydrolase at a much higher rate. Larger cyclic products from non-adjacent diepoxides were not observed. The results of our in vitro experiments suggest that linoleic and arachidonic acid can be metabolized to their tetrahydrofuran-diols by two consecutive microsomal cytochrome P-450 epoxidations followed by microsomal or soluble epoxide hydrolase catalyzed hydrolysis of the epoxides. Incubation experiments with the S-9 fractions indicate that the soluble epoxide hydrolase is more important in this conversion. This manuscript is the first report of techniques for the separation and

  15. Antidepressants Alter Cerebrovascular Permeability and Metabolic Rate in Primates

    Science.gov (United States)

    Preskorn, Sheldon H.; Raichle, Marcus E.; Hartman, Boyd K.

    1982-07-01

    External detection of the annihilation radiation produced by water labeled with oxygen-15 was used to measure cerebrovascular permeability and cerebral blood flow in six rhesus monkeys. Use of oxygen-15 also permitted assessment of cerebral metabolic rate in two of the monkeys. Amitriptyline produced a dose-dependent, reversible increase in permeability at plasma drug concentrations which are therapeutic for depressed patients. At the same concentrations the drug also produced a 20 to 30 percent reduction in cerebral metabolic rate. At higher doses normal autoregulation of cerebral blood flow was suspended, but responsivity to arterial carbon dioxide was normal.

  16. Metabolic Imaging of Infection

    NARCIS (Netherlands)

    Lawal, Ismaheel; Zeevaart, JanRijn; Ebenhan, Thomas; Ankrah, Alfred; Vorster, Mariza; Kruger, Hendrik G.; Govender, Thavendran; Sathekge, Mike

    2017-01-01

    Metabolic imaging has come to occupy a prominent place in the diagnosis and management of microbial infection. Molecular probes available for infection imaging have undergone a rapid evolution starting with nonspecific agents that accumulate similarly in infection, sterile inflammation, and

  17. Epigenetics and Cellular Metabolism

    Directory of Open Access Journals (Sweden)

    Wenyi Xu

    2016-01-01

    Full Text Available Living eukaryotic systems evolve delicate cellular mechanisms for responding to various environmental signals. Among them, epigenetic machinery (DNA methylation, histone modifications, microRNAs, etc. is the hub in transducing external stimuli into transcriptional response. Emerging evidence reveals the concept that epigenetic signatures are essential for the proper maintenance of cellular metabolism. On the other hand, the metabolite, a main environmental input, can also influence the processing of epigenetic memory. Here, we summarize the recent research progress in the epigenetic regulation of cellular metabolism and discuss how the dysfunction of epigenetic machineries influences the development of metabolic disorders such as diabetes and obesity; then, we focus on discussing the notion that manipulating metabolites, the fuel of cell metabolism, can function as a strategy for interfering epigenetic machinery and its related disease progression as well.

  18. Galactose metabolism and health.

    Science.gov (United States)

    Coelho, Ana I; Berry, Gerard T; Rubio-Gozalbo, M Estela

    2015-07-01

    Galactose - a key source of energy and a crucial structural element in complex molecules - is particularly important for early human development. However, galactose metabolism might be important not only for fetal and neonatal development but also for adulthood, as evidenced by the inherited disorders of galactose metabolism. The purpose of this review is to summarize the current evidence of galactose metabolism in health and disease. The biological importance of galactose goes beyond its importance as a nutrient and a metabolite. Galactose has been selected by evolutionary pressure to exert also a crucial structural role in macromolecules. Additionally, galactose has recently been reported as beneficial in a number of diseases, particularly in those affecting the brain. Galactose is crucial for human metabolism, with an established role in energy delivery and galactosylation of complex molecules, and evidence for other roles is emerging.

  19. Metabolism. Part III: Lipids.

    Science.gov (United States)

    Bodner, George M.

    1986-01-01

    Describes the metabolic processes of complex lipids, including saponification, activation and transport, and the beta-oxidation spiral. Discusses fatty acid degradation in regard to biochemical energy and ketone bodies. (TW)

  20. What is Nutrition & Metabolism?

    Directory of Open Access Journals (Sweden)

    Feinman Richard D

    2004-08-01

    Full Text Available Abstract A new Open Access journal, Nutrition & Metabolism (N&M will publish articles that integrate nutrition with biochemistry and molecular biology. The open access process is chosen to provide rapid and accessible dissemination of new results and perspectives in a field that is of great current interest. Manuscripts in all areas of nutritional biochemistry will be considered but three areas of particular interest are lipoprotein metabolism, amino acids as metabolic signals, and the effect of macronutrient composition of diet on health. The need for the journal is identified in the epidemic of obesity, diabetes, dyslipidemias and related diseases, and a sudden increase in popular diets, as well as renewed interest in intermediary metabolism.

  1. Basic metabolic panel

    Science.gov (United States)

    ... Alternative Names SMAC7; Sequential multi-channel analysis with computer-7; SMA7; Metabolic panel 7; CHEM-7 References ... M. is also a founding member of Hi-Ethics and subscribes to the principles of the Health ...

  2. Comprehensive Metabolic Panel

    Science.gov (United States)

    ... and Iron-binding Capacity (TIBC, UIBC) Trichomonas Testing Triglycerides Troponin Tryptase Tumor Markers Uric Acid Urinalysis Urine ... information about the current status of a person's metabolism, including the health of the kidneys and liver, ...

  3. BMP (Basic Metabolic Panel)

    Science.gov (United States)

    ... and Iron-binding Capacity (TIBC, UIBC) Trichomonas Testing Triglycerides Troponin Tryptase Tumor Markers Uric Acid Urinalysis Urine ... your healthcare provider important information about your body's metabolism , including the current status of your kidneys as ...

  4. Approach to metabolic alkalosis.

    Science.gov (United States)

    Soifer, Jennifer T; Kim, Hyung T

    2014-05-01

    Metabolic alkalosis is a common disorder, accounting for half of all acid-base disturbances in hospitalized patients. It is the result of an increase in bicarbonate production, a decrease in bicarbonate excretion, or a loss of hydrogen ions. Most causes of metabolic alkalosis can be divided into 4 categories: chloride depletion alkalosis, mineralocorticoid excess syndromes, apparent mineralocorticoid excess syndromes, and excess alkali administration. Treatment is usually supportive and based on cause of the alkalosis. Copyright © 2014 Elsevier Inc. All rights reserved.

  5. Metabolism of fluoroacetate in lettuce

    Energy Technology Data Exchange (ETDEWEB)

    Ward, P.F.V.; Huskisson, N.S.

    1972-01-01

    Whole lettuce plants were incubated with (1) (l-/sup 14/C)acetate, (2) fluoroacetate followed by (l-/sup 14/C)acetate, (3) fluoro(l-/sup 14/C)acetate, (4) fluoro(2-/sup 14/C)acetate or (5) S-carboxy-(/sup 14/C)methylglutathione. 2. Fluoroacetate did not affect the expiration of /sup 14/CO/sub 2/ from (l-/sup 14/C)acetate and only a small amount of /sup 14/CO/sub 2/ was produced from either fluoro(l-/sup 14/C)-acetate or fluoro(2-/sup 14/C)acetate in 43 h. 3. Fluoroacetate at 50 mg/kg wet wt. doubled the plant citrate concentration after 43 h incubation, and depending on the age and size of the plant 50-100% of the compound was metabolized. 4. With both fluoro(l-/sup 14/C)acetate and fluoro(2-/sup 14/C)acetate all the radioactivity except that in the CO/sub 2/ was found in the water-soluble fraction. About 2% was in fluorocitrate and the remainder, apart from unchanged fluoroacetate, was in a number of compounds devoid of fluorine but containing nitrogen and sulphur. These were peptide-like and could be separated by chromatography on an amino acid analyser. 5. Identical compounds were obtained from the spontaneous reaction between iodo(2-/sup 14/C)acetate and glutathione, the major product being S-carboxy-methylglutathione. 6. S-Carboxymethylcysteine was also isolated and its mass spectrum compared with a commercial sample. 7. Reaction rates of all the monohaloacetates with glutathione were studied at pH 7 at 25/sup 0/C. No reaction was observed with fluoroacetate. 8. The metabolism of fluoroacetate by lettuce is discussed in relation to that of aliphatic and aromatic halogen compounds, including fluoroacetate, by mammalian liver and to the metabolism of fluoroacetate by different plants reported by other workers.

  6. Producers give prices a boost

    International Nuclear Information System (INIS)

    Anon.

    1992-01-01

    Uranium producers came alive in August, helping spot prices crack the $8.00 barrier for the first time since March. The upper end of NUKEM's price range actually finished the month at $8.20. Scrambling to fulfill their long-term delivery contracts, producers dominate the market. In the span of three weeks, five producers came out for 2 million lbs U3O8, ultimately buying nearly 1.5 million lbs. One producer accounted for over half this volume. The major factor behind rising prices was that producers required specific origins to meet contract obligations. Buyers willing to accept open origins created the lower end of NUKEM's price range

  7. [Aging and metabolism: changes and regulation].

    Science.gov (United States)

    Ortiz, Genaro Gabriel; Arias-Merino, Elva D; Velázquez-Brizuela, Irma E; Pacheco-Moisés, Fermín P; Flores-Alvarado, Luis J; Torres-Sánchez, Erandis D; Cortés-Enríquez, Fernando; González-Renovato, Erika D; Ortiz-Velázquez, Irma G

    2012-09-01

    Studies about the effects of aging in the physiology and metabolism are increasingly, one of its objectives is to help implement programs to improve the quality of life and prevent disability in elderly. It is relevant to mention that, during aging, there is a natural metabolic deceleration, a series of changes in the regulation of energy are produced, which contributes to loss of weight and fat; the changes in the regulation of caloric intake contribute to increase the susceptibility to energy imbalance both positive and negative, which is associated with a deterioration in health. However, to grow old, is not a death sentence for metabolism, on the other hand, it can be controlled by maintaining an active lifestyle, coupled with this, research has shown that the metabolism'can be regulated by a synchronized clock (circadian rhythms), which is mediated by regulatory proteins, this relationship ensures the proper functioning of the cells and therefore good health. The aim of this review is to provide updated information on the energy- metabolism-regulation and its relationship with the great variety of components involved in energy expenditure that accompany aging, to analyze the regulation of this system to improve the quality of life and maintenance of health in old age.

  8. Gut microbiota and host metabolism: what relationship?

    Science.gov (United States)

    Mithieux, Gilles

    2017-10-24

    A large number of genomic studies have reported associations between the gut microbiota composition and metabolic diseases such as obesity or type 2 diabetes. This led to the widespread idea that a causal relationship could exist between intestinal microbiota and metabolic diseases. At odds with this idea, some compelling studies reported that global changes in microbiota composition have no effect on the host metabolism in obese mice or humans. However, specific bacteria are able to confer host metabolic benefits, such as Akkermansia muciniphila or Prevotella copri, when they are given by gavage in obese mice. A crucial link by which gut bacteria communicate with the host mucosa is based on metabolites or low molecular weight compounds. Among them, short chain fatty acids produced from the fermentation of dietary fibers initiate beneficial effects on the host metabolism via the activation of intestinal gluconeogenesis. This mucosal function exerts anti-diabetic and anti-obesity effects through the activation of gut-brain neural circuits. ©2017S. Karger AG, Basel.

  9. Triglyceride metabolism in exercising muscle.

    Science.gov (United States)

    Watt, Matthew J; Cheng, Yunsheng

    2017-10-01

    Triglycerides are stored within lipid droplets in skeletal muscle and can be hydrolyzed to produce fatty acids for energy production through β-oxidation and oxidative phosphorylation. While there was some controversy regarding the quantitative importance of intramyocellular triglyceride (IMTG) as a metabolic substrate, recent advances in proton magnetic resonance spectroscopy and confocal microscopy support earlier tracer and biopsy studies demonstrating a substantial contribution of IMTG to energy production, particularly during moderate-intensity endurance exercise. This review provides an update on the understanding of IMTG utilization during exercise, with a focus on describing the key regulatory proteins that control IMTG breakdown and how these proteins respond to acute exercise and in the adaptation to exercise training. This article is part of a Special Issue entitled: Recent Advances in Lipid Droplet Biology edited by Rosalind Coleman and Matthijs Hesselink. Copyright © 2017 Elsevier B.V. All rights reserved.

  10. Evolutionary dynamics of metabolic adaptation

    NARCIS (Netherlands)

    van Hoek, M.J.A.

    2008-01-01

    In this thesis we study how organisms adapt their metabolism to a changing environment. Metabolic adaptation occurs at different timescales. Organisms adapt their metabolism via metabolic regulation, which happens in the order of minutes to hours and via evolution, which takes many generations. Here

  11. Advancing metabolic engineering through systems biology of industrial microorganisms.

    Science.gov (United States)

    Dai, Zongjie; Nielsen, Jens

    2015-12-01

    Development of sustainable processes to produce bio-based compounds is necessary due to the severe environmental problems caused by the use of fossil resources. Metabolic engineering can facilitate the development of highly efficient cell factories to produce these compounds from renewable resources. The objective of systems biology is to gain a comprehensive and quantitative understanding of living cells and can hereby enhance our ability to characterize and predict cellular behavior. Systems biology of industrial microorganisms is therefore valuable for metabolic engineering. Here we review the application of systems biology tools for the identification of metabolic engineering targets which may lead to reduced development time for efficient cell factories. Finally, we present some perspectives of systems biology for advancing metabolic engineering further. Copyright © 2015 Elsevier Ltd. All rights reserved.

  12. Corynebacterium glutamicum for Sustainable Bioproduction: From Metabolic Physiology to Systems Metabolic Engineering.

    Science.gov (United States)

    Becker, Judith; Gießelmann, Gideon; Hoffmann, Sarah Lisa; Wittmann, Christoph

    Since its discovery 60 years ago, Corynebacterium glutamicum has evolved into a workhorse for industrial biotechnology. Traditionally well known for its remarkable capacity to produce amino acids, this Gram-positive soil bacterium, has become a flexible, efficient production platform for various bulk and fine chemicals, materials, and biofuels. The central turnstile of all these achievements is our excellent understanding of its metabolism and physiology. This knowledge base, together with innovative systems metabolic engineering concepts, which integrate systems and synthetic biology into strain engineering, has upgraded C. glutamicum into one of the most successful industrial microorganisms in the world.

  13. Control of fluxes towards antibiotics and the role of primary metabolism in production of antibiotics

    DEFF Research Database (Denmark)

    Gunnarsson, Nina; Eliasson Lantz, Anna; Nielsen, Jacob

    2004-01-01

    Yield improvements in antibiotic-producing strains have classically been obtained through random mutagenesis and screening. An attractive alternative to this strategy is the rational design of producer strains via metabolic engineering, an approach that offers the possibility to increase yields...... in the metabolic network. Here we describe and discuss available methods for identification of these steps, both in antibiotic biosynthesis pathways and in the primary metabolism, which serves as the supplier of precursors and cofactors for the secondary metabolism. Finally, the importance of precursor...... and cofactor supply from primary metabolism in the biosynthesis of different types of antibiotics is discussed and recent developments in metabolic engineering towards increased product yields in antibiotic producing strains are reviewed....

  14. Control of fluxes towards antibiotics and the role of primary metabolism in production of antibiotics

    DEFF Research Database (Denmark)

    Gunnarsson, Nina; Eliasson Lantz, Anna; Nielsen, Jacob

    2004-01-01

    in the metabolic network. Here we describe and discuss available methods for identification of these steps, both in antibiotic biosynthesis pathways and in the primary metabolism, which serves as the supplier of precursors and cofactors for the secondary metabolism. Finally, the importance of precursor...... and cofactor supply from primary metabolism in the biosynthesis of different types of antibiotics is discussed and recent developments in metabolic engineering towards increased product yields in antibiotic producing strains are reviewed.......Yield improvements in antibiotic-producing strains have classically been obtained through random mutagenesis and screening. An attractive alternative to this strategy is the rational design of producer strains via metabolic engineering, an approach that offers the possibility to increase yields...

  15. Robustness of metabolic networks

    Science.gov (United States)

    Jeong, Hawoong

    2009-03-01

    We investigated the robustness of cellular metabolism by simulating the system-level computational models, and also performed the corresponding experiments to validate our predictions. We address the cellular robustness from the ``metabolite''-framework by using the novel concept of ``flux-sum,'' which is the sum of all incoming or outgoing fluxes (they are the same under the pseudo-steady state assumption). By estimating the changes of the flux-sum under various genetic and environmental perturbations, we were able to clearly decipher the metabolic robustness; the flux-sum around an essential metabolite does not change much under various perturbations. We also identified the list of the metabolites essential to cell survival, and then ``acclimator'' metabolites that can control the cell growth were discovered. Furthermore, this concept of ``metabolite essentiality'' should be useful in developing new metabolic engineering strategies for improved production of various bioproducts and designing new drugs that can fight against multi-antibiotic resistant superbacteria by knocking-down the enzyme activities around an essential metabolite. Finally, we combined a regulatory network with the metabolic network to investigate its effect on dynamic properties of cellular metabolism.

  16. Vertigo and metabolic disorders.

    Science.gov (United States)

    Santos, Maruska D' Aparecida; Bittar, Roseli Saraiva Moreira

    2012-01-01

    Metabolic disorders are accepted by many authors as being responsible for balance disorders. Because of the importance of metabolic disorders in the field of labyrinthine dysfunction, we decided to assess the prevalence of carbohydrates, lipids and thyroid hormones disorders in our patients with vestibular diseases. The study evaluates the metabolic profile of 325 patients with vertigo who sought the Otolaryngology Department of the University of São Paulo in the Hospital das Clínicas da Universidade de São Paulo. The laboratory tests ordered according to the classical research protocol were: low-density lipoprotein cholesterol fraction, TSH, T3, T4 and fasting blood sugar level. The metabolic disorders found and the ones that were observed in the general population were compared. The high level of low-density lipoprotein cholesterol, the altered levels of thyroid hormones, the higher prevalence of diabetes mellitus were the most significant changes found in the group of study. The higher amount of metabolic disorders in patients with vertigo disease reinforces the hypothesis of its influence on the etiopathogenesis of cochleovestibular symptoms.

  17. Metabolic surgery: quo vadis?

    Science.gov (United States)

    Ramos-Leví, Ana M; Rubio Herrera, Miguel A

    2014-01-01

    The impact of bariatric surgery beyond its effect on weight loss has entailed a change in the way of regarding it. The term metabolic surgery has become more popular to designate those interventions that aim at resolving diseases that have been traditionally considered as of exclusive medical management, such as type 2 diabetes mellitus (T2D). Recommendations for metabolic surgery have been largely addressed and discussed in worldwide meetings, but no definitive consensus has been reached yet. Rates of diabetes remission after metabolic surgery have been one of the most debated hot topics, with heterogeneity being a current concern. This review aims to identify and clarify controversies regarding metabolic surgery, by focusing on a critical analysis of T2D remission rates achieved with different bariatric procedures, and using different criteria for its definition. Indications for metabolic surgery for patients with T2D who are not morbidly obese are also discussed. Copyright © 2013 SEEN. Published by Elsevier Espana. All rights reserved.

  18. Metabolic engineering of cyanobacteria for the synthesis of commodity products.

    Science.gov (United States)

    Angermayr, S Andreas; Gorchs Rovira, Aleix; Hellingwerf, Klaas J

    2015-06-01

    Through metabolic engineering cyanobacteria can be employed in biotechnology. Combining the capacity for oxygenic photosynthesis and carbon fixation with an engineered metabolic pathway allows carbon-based product formation from CO(2), light, and water directly. Such cyanobacterial 'cell factories' are constructed to produce biofuels, bioplastics, and commodity chemicals. Efforts of metabolic engineers and synthetic biologists allow the modification of the intermediary metabolism at various branching points, expanding the product range. The new biosynthesis routes 'tap' the metabolism ever more efficiently, particularly through the engineering of driving forces and utilization of cofactors generated during the light reactions of photosynthesis, resulting in higher product titers. High rates of carbon rechanneling ultimately allow an almost-complete allocation of fixed carbon to product above biomass. Copyright © 2015 Elsevier Ltd. All rights reserved.

  19. Metabolic Engineering: Techniques for analysis of targets for genetic manipulations

    DEFF Research Database (Denmark)

    Nielsen, Jens Bredal

    1998-01-01

    enzymes. Despite the prospect of obtaining major improvement through metabolic engineering, this approach is, however, not expected to completely replace the classical approach to strain improvement-random mutagenesis followed by screening. Identification of the optimal genetic changes for improvement......Metabolic engineering has been defined as the purposeful modification of intermediary metabolism using recombinant DNA techniques. With this definition metabolic engineering includes: (1) inserting new pathways in microorganisms with the aim of producing novel metabolites, e.g., production...... of polyketides by Streptomyces; (2) production of heterologous peptides, e.g., production of human insulin, erythropoitin, and tPA; and (3) improvement of both new and existing processes, e.g., production of antibiotics and industrial enzymes. Metabolic engineering is a multidisciplinary approach, which involves...

  20. Systems metabolic engineering strategies for the production of amino acids.

    Science.gov (United States)

    Ma, Qian; Zhang, Quanwei; Xu, Qingyang; Zhang, Chenglin; Li, Yanjun; Fan, Xiaoguang; Xie, Xixian; Chen, Ning

    2017-06-01

    Systems metabolic engineering is a multidisciplinary area that integrates systems biology, synthetic biology and evolutionary engineering. It is an efficient approach for strain improvement and process optimization, and has been successfully applied in the microbial production of various chemicals including amino acids. In this review, systems metabolic engineering strategies including pathway-focused approaches, systems biology-based approaches, evolutionary approaches and their applications in two major amino acid producing microorganisms: Corynebacterium glutamicum and Escherichia coli, are summarized.

  1. Design Constraints on a Synthetic Metabolism

    Science.gov (United States)

    Bilgin, Tugce; Wagner, Andreas

    2012-01-01

    A metabolism is a complex network of chemical reactions that converts sources of energy and chemical elements into biomass and other molecules. To design a metabolism from scratch and to implement it in a synthetic genome is almost within technological reach. Ideally, a synthetic metabolism should be able to synthesize a desired spectrum of molecules at a high rate, from multiple different nutrients, while using few chemical reactions, and producing little or no waste. Not all of these properties are achievable simultaneously. We here use a recently developed technique to create random metabolic networks with pre-specified properties to quantify trade-offs between these and other properties. We find that for every additional molecule to be synthesized a network needs on average three additional reactions. For every additional carbon source to be utilized, it needs on average two additional reactions. Networks able to synthesize 20 biomass molecules from each of 20 alternative sole carbon sources need to have at least 260 reactions. This number increases to 518 reactions for networks that can synthesize more than 60 molecules from each of 80 carbon sources. The maximally achievable rate of biosynthesis decreases by approximately 5 percent for every additional molecule to be synthesized. Biochemically related molecules can be synthesized at higher rates, because their synthesis produces less waste. Overall, the variables we study can explain 87 percent of variation in network size and 84 percent of the variation in synthesis rate. The constraints we identify prescribe broad boundary conditions that can help to guide synthetic metabolism design. PMID:22768162

  2. Microbiota-Produced Succinate Improves Glucose Homeostasis via Intestinal Gluconeogenesis

    DEFF Research Database (Denmark)

    De Vadder, Filipe; Kovatcheva-Datchary, Petia; Zitoun, Carine

    2016-01-01

    Beneficial effects of dietary fiber on glucose and energy homeostasis have long been described, focusing mostly on the production of short-chain fatty acids by the gut commensal bacteria. However, bacterial fermentation of dietary fiber also produces large amounts of succinate and, to date...... homeostasis. Accordingly, dietary succinate improved glucose and insulin tolerance in wild-type mice, but those effects were absent in mice deficient in IGN. Conventional mice colonized with the succinate producer Prevotella copri exhibited metabolic benefits, which could be related to succinate-activated IGN...

  3. Urea metabolism in plants.

    Science.gov (United States)

    Witte, Claus-Peter

    2011-03-01

    Urea is a plant metabolite derived either from root uptake or from catabolism of arginine by arginase. In agriculture, urea is intensively used as a nitrogen fertilizer. Urea nitrogen enters the plant either directly, or in the form of ammonium or nitrate after urea degradation by soil microbes. In recent years various molecular players of plant urea metabolism have been investigated: active and passive urea transporters, the nickel metalloenzyme urease catalyzing the hydrolysis of urea, and three urease accessory proteins involved in the complex activation of urease. The degradation of ureides derived from purine breakdown has long been discussed as a possible additional metabolic source for urea, but an enzymatic route for the complete hydrolysis of ureides without a urea intermediate has recently been described for Arabidopsis thaliana. This review focuses on the proteins involved in plant urea metabolism and the metabolic sources of urea but also addresses open questions regarding plant urea metabolism in a physiological and agricultural context. The contribution of plant urea uptake and metabolism to fertilizer urea usage in crop production is still not investigated although globally more than half of all nitrogen fertilizer is applied to crops in the form of urea. Nitrogen use efficiency in crop production is generally well below 50% resulting in economical losses and creating ecological problems like groundwater pollution and emission of nitric oxides that can damage the ozone layer and function as greenhouse gasses. Biotechnological approaches to improve fertilizer urea usage bear the potential to increase crop nitrogen use efficiency. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

  4. DOES ELECTRIC CAR PRODUCE EMISSIONS?

    Directory of Open Access Journals (Sweden)

    Vladimír RIEVAJ

    2017-03-01

    Full Text Available This article focuses on the comparison of the amount of emissions produced by vehicles with a combustion engine and electric cars. The comparison, which is based on the LCA factor results, indicates that an electric car produces more emissions than a vehicle with combustion engine. The implementation of electric cars will lead to an increase in the production of greenhouse gases.

  5. Method of producing molybdenum-99

    Science.gov (United States)

    Pitcher, Eric John

    2013-05-28

    Method of producing molybdenum-99, comprising accelerating ions by means of an accelerator; directing the ions onto a metal target so as to generate neutrons having an energy of greater than 10 MeV; directing the neutrons through a converter material comprising techentium-99 to produce a mixture comprising molybdenum-99; and, chemically extracting the molybdenum-99 from the mixture.

  6. Producing energy efficiently; Energieeffizient produzieren

    Energy Technology Data Exchange (ETDEWEB)

    Blass, H.W.; Schumacher, M.; Coy, C; Pfister, J.; Finkbeiner, M.; Kuehnle, J.; Kiel, E.; Duerrschmidt, R.; Diede, J.; Scheffels, G.; Kranz, H.; Simon, J.; Diebold, K.; Koch, H.R.; Lehnhardt, M.

    2008-04-07

    Producing energy efficiently means saving much energy and money. Drives are responsible for the accounting of power for companies. The fair shows examples on the complete field of producing sector, hits the advantages of heat recovery and an efficient cooling. (GL)

  7. Positron emission tomography for measuring metabolism in vivo

    International Nuclear Information System (INIS)

    Feinendegen, L.E.

    1985-01-01

    Nuclear medical imaging always relates to changes at the cellular or molecular level of organization of the body. For years, such changes, summarily called metabolism, permitted radionuclides as tracers to produce information on rather gross organ structure and function. Yet, more recently, increasing emphasis is placed on metabolic reactions themselves; this development is of considerable promise to the clinician, because disease begins and nearly always expresses itself by alterations of metabolism. PET greatly helps to investigate and describe in vivo individual steps within the complex network of enzyme catalized reactions that maintain life; in fact, PET allows studies of biochemistry in vivo. (Author)

  8. Metabolic Imaging of Infection.

    Science.gov (United States)

    Lawal, Ismaheel; Zeevaart, JanRijn; Ebenhan, Thomas; Ankrah, Alfred; Vorster, Mariza; Kruger, Hendrik G; Govender, Thavendran; Sathekge, Mike

    2017-11-01

    Metabolic imaging has come to occupy a prominent place in the diagnosis and management of microbial infection. Molecular probes available for infection imaging have undergone a rapid evolution starting with nonspecific agents that accumulate similarly in infection, sterile inflammation, and neoplastic tissue and then extending to more targeted probes that seek to identify specific microbial species. This focus review describes the metabolic and molecular imaging techniques currently available for clinical use in infection imaging and those that have demonstrated promising results in preclinical studies with the potential for clinical applications. © 2017 by the Society of Nuclear Medicine and Molecular Imaging.

  9. Transplacental metabolic alkalosis.

    Science.gov (United States)

    Schimert, Patrik; Bernet-Buettiker, Vera; Rutishauser, Christoph; Schams, Mohammed; Frey, Bernhard

    2007-12-01

    We present a newborn with hypochloraemic metabolic alkalosis due to severe metabolic alkalosis of his mother. Hypoventilation as a leading symptom resolved quickly with treatment but may be life-threatening if not detected. In this case, the mother had a probable eating disorder. Little is known about transplacentally acquired electrolyte disorders in this setting. In the absence of symptoms, most of the cases might be undetected. The usual neonatal outcome of anorexia and/or bulimia nervosa in pregnancy is a lower birthweight and a lower risk for instrumental delivery.

  10. Rewriting the Metabolic Blueprint: Advances in Pathway Diversification in Microorganisms

    Directory of Open Access Journals (Sweden)

    Gazi Sakir Hossain

    2018-02-01

    Full Text Available Living organisms have evolved over millions of years to fine tune their metabolism to create efficient pathways for producing metabolites necessary for their survival. Advancement in the field of synthetic biology has enabled the exploitation of these metabolic pathways for the production of desired compounds by creating microbial cell factories through metabolic engineering, thus providing sustainable routes to obtain value-added chemicals. Following the past success in metabolic engineering, there is increasing interest in diversifying natural metabolic pathways to construct non-natural biosynthesis routes, thereby creating possibilities for producing novel valuable compounds that are non-natural or without elucidated biosynthesis pathways. Thus, the range of chemicals that can be produced by biological systems can be expanded to meet the demands of industries for compounds such as plastic precursors and new antibiotics, most of which can only be obtained through chemical synthesis currently. Herein, we review and discuss novel strategies that have been developed to rewrite natural metabolic blueprints in a bid to broaden the chemical repertoire achievable in microorganisms. This review aims to provide insights on recent approaches taken to open new avenues for achieving biochemical production that are beyond currently available inventions.

  11. Context-specific metabolic networks are consistent with experiments.

    Directory of Open Access Journals (Sweden)

    Scott A Becker

    2008-05-01

    Full Text Available Reconstructions of cellular metabolism are publicly available for a variety of different microorganisms and some mammalian genomes. To date, these reconstructions are "genome-scale" and strive to include all reactions implied by the genome annotation, as well as those with direct experimental evidence. Clearly, many of the reactions in a genome-scale reconstruction will not be active under particular conditions or in a particular cell type. Methods to tailor these comprehensive genome-scale reconstructions into context-specific networks will aid predictive in silico modeling for a particular situation. We present a method called Gene Inactivity Moderated by Metabolism and Expression (GIMME to achieve this goal. The GIMME algorithm uses quantitative gene expression data and one or more presupposed metabolic objectives to produce the context-specific reconstruction that is most consistent with the available data. Furthermore, the algorithm provides a quantitative inconsistency score indicating how consistent a set of gene expression data is with a particular metabolic objective. We show that this algorithm produces results consistent with biological experiments and intuition for adaptive evolution of bacteria, rational design of metabolic engineering strains, and human skeletal muscle cells. This work represents progress towards producing constraint-based models of metabolism that are specific to the conditions where the expression profiling data is available.

  12. Draft Genome Sequence of Hoeflea sp. Strain BAL378, a Potential Producer of Bioactive Compounds

    DEFF Research Database (Denmark)

    Bentzon-Tilia, Mikkel; Riemann, Lasse; Gram, Lone

    2014-01-01

    Some phytoplankton-associated marine bacteria produce bioactive compounds. Members of the genus Hoeflea may be examples of such bacteria; however, data describing their metabolisms are scarce. Here, we report the draft genome sequence of Hoeflea sp. strain BAL378, a putative producer of bacterioc...... of bacteriocins, polyketides, and auxins, as demonstrated by genome mining....

  13. Redirection of metabolism for hydrogen production

    Energy Technology Data Exchange (ETDEWEB)

    Harwood, Caroline S.

    2011-11-28

    This project is to develop and apply techniques in metabolic engineering to improve the biocatalytic potential of the bacterium Rhodopseudomonas palustris for nitrogenase-catalyzed hydrogen gas production. R. palustris, is an ideal platform to develop as a biocatalyst for hydrogen gas production because it is an extremely versatile microbe that produces copious amounts of hydrogen by drawing on abundant natural resources of sunlight and biomass. Anoxygenic photosynthetic bacteria, such as R. palustris, generate hydrogen and ammonia during a process known as biological nitrogen fixation. This reaction is catalyzed by the enzyme nitrogenase and normally consumes nitrogen gas, ATP and electrons. The applied use of nitrogenase for hydrogen production is attractive because hydrogen is an obligatory product of this enzyme and is formed as the only product when nitrogen gas is not supplied. Our challenge is to understand the systems biology of R. palustris sufficiently well to be able to engineer cells to produce hydrogen continuously, as fast as possible and with as high a conversion efficiency as possible of light and electron donating substrates. For many experiments we started with a strain of R. palustris that produces hydrogen constitutively under all growth conditions. We then identified metabolic pathways and enzymes important for removal of electrons from electron-donating organic compounds and for their delivery to nitrogenase in whole R. palustris cells. For this we developed and applied improved techniques in 13C metabolic flux analysis. We identified reactions that are important for generating electrons for nitrogenase and that are yield-limiting for hydrogen production. We then increased hydrogen production by blocking alternative electron-utilizing metabolic pathways by mutagenesis. In addition we found that use of non-growing cells as biocatalysts for hydrogen gas production is an attractive option, because cells divert all resources away from growth and

  14. Something Old, Something New: Conserved Enzymes and the Evolution of Novelty in Plant Specialized Metabolism1

    Science.gov (United States)

    Moghe, Gaurav D.; Last, Robert L.

    2015-01-01

    Plants produce hundreds of thousands of small molecules known as specialized metabolites, many of which are of economic and ecological importance. This remarkable variety is a consequence of the diversity and rapid evolution of specialized metabolic pathways. These novel biosynthetic pathways originate via gene duplication or by functional divergence of existing genes, and they subsequently evolve through selection and/or drift. Studies over the past two decades revealed that diverse specialized metabolic pathways have resulted from the incorporation of primary metabolic enzymes. We discuss examples of enzyme recruitment from primary metabolism and the variety of paths taken by duplicated primary metabolic enzymes toward integration into specialized metabolism. These examples provide insight into processes by which plant specialized metabolic pathways evolve and suggest approaches to discover enzymes of previously uncharacterized metabolic networks. PMID:26276843

  15. Something Old, Something New: Conserved Enzymes and the Evolution of Novelty in Plant Specialized Metabolism.

    Science.gov (United States)

    Moghe, Gaurav D; Last, Robert L

    2015-11-01

    Plants produce hundreds of thousands of small molecules known as specialized metabolites, many of which are of economic and ecological importance. This remarkable variety is a consequence of the diversity and rapid evolution of specialized metabolic pathways. These novel biosynthetic pathways originate via gene duplication or by functional divergence of existing genes, and they subsequently evolve through selection and/or drift. Studies over the past two decades revealed that diverse specialized metabolic pathways have resulted from the incorporation of primary metabolic enzymes. We discuss examples of enzyme recruitment from primary metabolism and the variety of paths taken by duplicated primary metabolic enzymes toward integration into specialized metabolism. These examples provide insight into processes by which plant specialized metabolic pathways evolve and suggest approaches to discover enzymes of previously uncharacterized metabolic networks. © 2015 American Society of Plant Biologists. All Rights Reserved.

  16. Interdependence of nutrient metabolism and the circadian clock system: Importance for metabolic health

    Science.gov (United States)

    Ribas-Latre, Aleix; Eckel-Mahan, Kristin

    2016-01-01

    Background While additional research is needed, a number of large epidemiological studies show an association between circadian disruption and metabolic disorders. Specifically, obesity, insulin resistance, cardiovascular disease, and other signs of metabolic syndrome all have been linked to circadian disruption in humans. Studies in other species support this association and generally reveal that feeding that is not in phase with the external light/dark cycle, as often occurs with night or rotating shift workers, is disadvantageous in terms of energy balance. As food is a strong driver of circadian rhythms in the periphery, understanding how nutrient metabolism drives clocks across the body is important for dissecting out why circadian misalignment may produce such metabolic effects. A number of circadian clock proteins as well as their accessory proteins (such as nuclear receptors) are highly sensitive to nutrient metabolism. Macronutrients and micronutrients can function as zeitgebers for the clock in a tissue-specific way and can thus impair synchrony between clocks across the body, or potentially restore synchrony in the case of circadian misalignment. Circadian nuclear receptors are particularly sensitive to nutrient metabolism and can alter tissue-specific rhythms in response to changes in the diet. Finally, SNPs in human clock genes appear to be correlated with diet-specific responses and along with chronotype eventually may provide valuable information from a clinical perspective on how to use diet and nutrition to treat metabolic disorders. Scope of review This article presents a background of the circadian clock components and their interrelated metabolic and transcriptional feedback loops, followed by a review of some recent studies in humans and rodents that address the effects of nutrient metabolism on the circadian clock and vice versa. We focus on studies in which results suggest that nutrients provide an opportunity to restore or, alternatively

  17. Sleep and Metabolism: An Overview

    Directory of Open Access Journals (Sweden)

    Sunil Sharma

    2010-01-01

    Full Text Available Sleep and its disorders are increasingly becoming important in our sleep deprived society. Sleep is intricately connected to various hormonal and metabolic processes in the body and is important in maintaining metabolic homeostasis. Research shows that sleep deprivation and sleep disorders may have profound metabolic and cardiovascular implications. Sleep deprivation, sleep disordered breathing, and circadian misalignment are believed to cause metabolic dysregulation through myriad pathways involving sympathetic overstimulation, hormonal imbalance, and subclinical inflammation. This paper reviews sleep and metabolism, and how sleep deprivation and sleep disorders may be altering human metabolism.

  18. Macrophage Polarization in Metabolism and Metabolic Disease

    Directory of Open Access Journals (Sweden)

    Anna Meiliana

    2013-08-01

    Full Text Available BACKGROUND: Obesity is now recognized as the main cause of the worldwide epidemic of type 2 diabetes. Obesity-associated chronic inflammation is a contributing key factor for type 2 diabetes and cardiovascular disease. Numbers of studies have clearly demonstrated that the immune system and metabolism are highly integrated. CONTENT: Macrophages are an essential component of innate immunity and play a central role in inflammation and host defense. Moreover, these cells have homeostatic functions beyond defense, including tissue remodeling in ontogenesis and orchestration of metabolic functions. Diversity and plasticity are hallmarks of cells of the monocyte-macrophage lineage. In response to interferons (IFNs, toll-like receptor (TLR, or interleukin (IL-4/IL-13 signals, macrophages undergo M1 (classical or M2 (alternative activation. Progress has now been made in defining the signaling pathways, transcriptional networks, and epigenetic mechanisms underlying M1, M2 or M2-like polarized activation. SUMMARY: In response to various signals, macrophages may undergo classical M1 activation (stimulated by TLR ligands and IFN-γ or alternative M2 activation (stimulated by IL-4/IL-13; these states mirror the T helper (Th1–Th2 polarization of T cells. Pathology is frequently associated with dynamic changes in macrophage activation, with classically activated M1 cells implicate in initiating and sustaining inflammation, meanwhile M2 or M2-like activated cells associated with resolution or smoldering chronic inflammation. Identification of the mechanisms and molecules that are associated with macrophage plasticity and polarized activation provides a basis for macrophage centered diagnostic and therapeutic strategies. KEYWORDS: obesity, adipose tissue, inflammation, macrophage polarization.

  19. DISTURBANCES OF LIPID METABOLISM

    Directory of Open Access Journals (Sweden)

    P. F. Litvitskii

    2012-01-01

    Full Text Available The article contains modern data on etiology, pathogenesis, manifestations and mechanisms of development of the most common forms of lipid metabolism disturbances in humans, such as obesity, emaciation, lipodystrophy, lipidosis, dyslipoproteinemia and atherosclerosis. The authors give the informative materials for self-testing and correction of the knowledge level.

  20. Neonatal nutrition and metabolism

    National Research Council Canada - National Science Library

    Thureen, Patti J; Hay, William W

    2006-01-01

    ..., the volume highlights the important longterm effects of fetal and neonatal growth on health in later life. In addition, there are very practical chapters on methods and techniques for assessing nutritional status, body composition, and evaluating metabolic function. Written by an authoritative, international team of cont...

  1. Vitamin D metabolism

    Energy Technology Data Exchange (ETDEWEB)

    Holick, M.F.; DeLuca, H.F.

    1974-01-01

    Studies on the metabolism of vitamin D in experimental animals are reviewed. It can be demonstrated that vitamin D/sub 3/ first must be hydroxylated on carbon 25 in the liver and subsequently on carbon 1 in the kidney before it can stimulate intestinal calcium absorption and bone calcium mobilization. The resultant 1,25-(OH)/sub 2/D/sub 3/ can be regarded as a hormone derived from vitamin D, whose synthesis is feedback regulated in a complex manner involving serum calcium, phosphorus, and parathyroid hormone. Evidence in experimental animals suggests that patients suffering from chronic renal disease, vitamin D-dependency disease, and hypoparathyroidism have a failure in the l-hydroxylating mechanism. The findings of vitamin D metabolism in experimental animals has led to the initiation of a search for similar systems in man. In addition, metabolites of vitamin D and their analogs are now being studied for potential use in the treatment of vitamin D-resistant bone disease. It seems likely that basic investigation into the metabolism and function of vitamin D will lead to new understanding of metabolic bone disease and to practical new methods of management in the clinics. (auth)

  2. Ghrelin and Metabolic Surgery

    Directory of Open Access Journals (Sweden)

    Dimitrios J. Pournaras

    2010-01-01

    Full Text Available Metabolic surgery is the most effective treatment for morbid obesity. Ghrelin has been implicated to play a role in the success of these procedures. Furthermore, these operations have been used to study the gut-brain axis. This article explores this interaction, reviewing the available data on changes in ghrelin levels after different surgical procedures.

  3. Synthetic Metabolic Pathways

    DEFF Research Database (Denmark)

    topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and tips on troubleshooting and avoiding known pitfalls. Authoritative and practical, Synthetic Metabolic Pathways: Methods and Protocols aims to ensure successful results in the further study...

  4. Neuroendocrine Regulation of Metabolism.

    Science.gov (United States)

    Cornejo, M P; Hentges, S T; Maliqueo, M; Coirini, H; Becu-Villalobos, D; Elias, C F

    2016-07-01

    Given the current environment in most developed countries, it is a challenge to maintain a good balance between calories consumed and calories burned, although maintenance of metabolic balance is key to good health. Therefore, understanding how metabolic regulation is achieved and how the dysregulation of metabolism affects health is an area of intense research. Most studies focus on the hypothalamus, which is a brain area that acts as a key regulator of metabolism. Among the nuclei that comprise the hypothalamus, the arcuate nucleus is one of the major mediators in the regulation of food intake. The regulation of energy balance is also a key factor ensuring the maintenance of any species as a result of the dependence of reproduction on energy stores. Adequate levels of energy reserves are necessary for the proper functioning of the hypothalamic-pituitary-gonadal axis. This review discusses valuable data presented in the 2015 edition of the International Workshop of Neuroendocrinology concerning the fundamental nature of the hormonal regulation of the hypothalamus and the impact on energy balance and reproduction. © 2016 British Society for Neuroendocrinology.

  5. Methanogenesis: Syntrophic metabolism

    NARCIS (Netherlands)

    Sieber, J.R.; McInerney, M.J.; Plugge, C.M.; Schink, B.; Gunsales, R.P.

    2009-01-01

    "Water is life!" All active cellular systems require water as the medium and solvent of their metabolic activities. Hydrophobic compounds and structures, which tend to exclude water, though providing inter alia excellent sources of energy and a means of biological compartmentalization, present

  6. The War Against Drug Producers

    OpenAIRE

    Herschel I. Grossman; Daniel Mejia

    2005-01-01

    This paper develops a model of a war against the producers of illegal hard drugs. This war occurs on two fronts. First, to prevent the cultivation of crops that are the raw material for producing drugs the state engages the drug producers in conflict over the control of arable land. Second, to impede further the production and exportation of drugs the state attempts to eradicate crops and to interdict drug shipments. The model also includes an interested outsider who uses both a stick and a c...

  7. Producing colour pictures from SCAN

    International Nuclear Information System (INIS)

    Robichaud, K.

    1982-01-01

    The computer code SCAN.TSK has been written for use on the Interdata 7/32 minicomputer which will convert the pictures produced by the SCAN program into colour pictures on a colour graphics VDU. These colour pictures are a more powerful aid to detecting errors in the MONK input data than the normal lineprinter pictures. This report is intended as a user manual for using the program on the Interdata 7/32, and describes the method used to produce the pictures and gives examples of JCL, input data and of the pictures that can be produced. (U.K.)

  8. Producing new radionuclides for medicine

    International Nuclear Information System (INIS)

    Michaut, C.

    2009-01-01

    The Arronax cyclotron, a new particle accelerator dedicated to the production of radionuclides for medicine and research has been commissioned in Nantes (France). Because of its unique features: an energy of 70 MeV and an intensity of 750 μA, Arronax will produce radionuclides that can not be produce in present cyclotrons. Among others it will produce Strontium-82 and Germanium-68 that are the precursors for Rubidium-82 and Gallium-68 respectively. 20 per cent of the research works will be dedicated to other domains like radioactive wastes, the radiation biological damage and the radiation damage on electronic devices. (A.C.)

  9. Metabolic and Inflammatory Adaptation of Reactive Astrocytes: Role of PPARs.

    Science.gov (United States)

    Iglesias, José; Morales, Ludis; Barreto, George E

    2017-05-01

    Astrocyte-mediated inflammation is associated with degenerative pathologies such as Alzheimer's and Parkinson's diseases and multiple sclerosis. The acute inflammation and morphological and metabolic changes that astrocytes develop after the insult are known as reactive astroglia or astrogliosis that is an important response to protect and repair the lesion. Astrocytes optimize their metabolism to produce lactate, glutamate, and ketone bodies in order to provide energy to the neurons that are deprived of nutrients upon insult. Firstly, we review the basis of inflammation and morphological changes of the different cell population implicated in reactive gliosis. Next, we discuss the more active metabolic pathways in healthy astrocytes and explain the metabolic response of astrocytes to the insult in different pathologies and which metabolic alterations generate complications in these diseases. We emphasize the role of peroxisome proliferator-activated receptors isotypes in the inflammatory and metabolic adaptation of astrogliosis developed in ischemia or neurodegenerative diseases. Based on results reported in astrocytes and other cells, we resume and hypothesize the effect of peroxisome proliferator-activated receptor (PPAR) activation with ligands on different metabolic pathways in order to supply energy to the neurons. The activation of selective PPAR isotype activity may serve as an input to better understand the role played by these receptors on the metabolic and inflammatory compensation of astrogliosis and might represent an opportunity to develop new therapeutic strategies against traumatic brain injuries and neurodegenerative diseases.

  10. Dysregulated metabolism contributes to oncogenesis

    Science.gov (United States)

    Hirschey, Matthew D.; DeBerardinis, Ralph J.; Diehl, Anna Mae E.; Drew, Janice E.; Frezza, Christian; Green, Michelle F.; Jones, Lee W.; Ko, Young H.; Le, Anne; Lea, Michael A.; Locasale, Jason W.; Longo, Valter D.; Lyssiotis, Costas A.; McDonnell, Eoin; Mehrmohamadi, Mahya; Michelotti, Gregory; Muralidhar, Vinayak; Murphy, Michael P.; Pedersen, Peter L.; Poore, Brad; Raffaghello, Lizzia; Rathmell, Jeffrey C.; Sivanand, Sharanya; Vander Heiden, Matthew G.; Wellen, Kathryn E.

    2015-01-01

    Cancer is a disease characterized by unrestrained cellular proliferation. In order to sustain growth, cancer cells undergo a complex metabolic rearrangement characterized by changes in metabolic pathways involved in energy production and biosynthetic processes. The relevance of the metabolic transformation of cancer cells has been recently included in the updated version of the review “Hallmarks of Cancer”, where the dysregulation of cellular metabolism was included as an emerging hallmark. While several lines of evidence suggest that metabolic rewiring is orchestrated by the concerted action of oncogenes and tumor suppressor genes, in some circumstances altered metabolism can play a primary role in oncogenesis. Recently, mutations of cytosolic and mitochondrial enzymes involved in key metabolic pathways have been associated with hereditary and sporadic forms of cancer. Together, these results suggest that aberrant metabolism, once seen just as an epiphenomenon of oncogenic reprogramming, plays a key role in oncogenesis with the power to control both genetic and epigenetic events in cells. In this review, we discuss the relationship between metabolism and cancer, as part of a larger effort to identify a broad-spectrum of therapeutic approaches. We focus on major alterations in nutrient metabolism and the emerging link between metabolism and epigenetics. Finally, we discuss potential strategies to manipulate metabolism in cancer and tradeoffs that should be considered. More research on the suite of metabolic alterations in cancer holds the potential to discover novel approaches to treat it. PMID:26454069

  11. A Metabolic Race

    Directory of Open Access Journals (Sweden)

    A.M.S. Costa et al.

    2017-07-01

    Full Text Available Metabolic Syndrome describes a set of metabolic risk factors that manifest in an individual and some aspects contribute to its appearance: genetic, overweight and the absence of physical activity. So, a board game was created to simulate the environment and routine experienced by UFF students that could contribute  to the development of Metabolic Syndrome. Players move along a simplified map of Niterói city, where places as Antônio Pedro Hospital (HUAP are pointed out. OBJECTIVES: This project aimed to develop an educational game to consolidate Metabolic Syndrome biochemical events. MATERIAL E METHODS: Each group receives a board, pins, dice, question, challenge and diagnostics cards. One student performs the family doctor function, responsable for delivering cards, reading activities and providing diagnosis to players when game is over.The scoring system is based on 3 criteria for Metabolic Syndrome diagnosis: glycemia, abdominal obesity and HDL cholesterol. At the end of game, it is possible to calculate the rates of each player and provide proportional diagnosis. The winner is the healthiest that first arrives at HUAP. RESULTS AND DISCUSSION: The game was applied to 50 students and only 10% classified the subject-matter as difficult. This finding highlight the need to establish new methods to enhance the teaching and learning process and decrease the students’ dificulties. Students evaluated the game as an important educational support and 85% of them agreed it complements  and consolidate the content discussed in classroom. Finally, the game was very highly rated by students according to their perception about their own performance while playing.  In addition, 95 % students pointed they would play again and 98% said they think games are able to optimize learning. CONCLUSIONS: It was possible not only to approximate biochemical phenomena to the students’ daily life, but also to solidify the theoretical concepts in a dynamic and fun

  12. Remnants of an Ancient Metabolism without Phosphate.

    Science.gov (United States)

    Goldford, Joshua E; Hartman, Hyman; Smith, Temple F; Segrè, Daniel

    2017-03-09

    Phosphate is essential for all living systems, serving as a building block of genetic and metabolic machinery. However, it is unclear how phosphate could have assumed these central roles on primordial Earth, given its poor geochemical accessibility. We used systems biology approaches to explore the alternative hypothesis that a protometabolism could have emerged prior to the incorporation of phosphate. Surprisingly, we identified a cryptic phosphate-independent core metabolism producible from simple prebiotic compounds. This network is predicted to support the biosynthesis of a broad category of key biomolecules. Its enrichment for enzymes utilizing iron-sulfur clusters, and the fact that thermodynamic bottlenecks are more readily overcome by thioester rather than phosphate couplings, suggest that this network may constitute a "metabolic fossil" of an early phosphate-free nonenzymatic biochemistry. Our results corroborate and expand previous proposals that a putative thioester-based metabolism could have predated the incorporation of phosphate and an RNA-based genetic system. PAPERCLIP. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  13. Glucose Transporters in Cardiac Metabolism and Hypertrophy

    Science.gov (United States)

    Shao, Dan; Tian, Rong

    2016-01-01

    The heart is adapted to utilize all classes of substrates to meet the high-energy demand, and it tightly regulates its substrate utilization in response to environmental changes. Although fatty acids are known as the predominant fuel for the adult heart at resting stage, the heart switches its substrate preference toward glucose during stress conditions such as ischemia and pathological hypertrophy. Notably, increasing evidence suggests that the loss of metabolic flexibility associated with increased reliance on glucose utilization contribute to the development of cardiac dysfunction. The changes in glucose metabolism in hypertrophied hearts include altered glucose transport and increased glycolysis. Despite the role of glucose as an energy source, changes in other nonenergy producing pathways related to glucose metabolism, such as hexosamine biosynthetic pathway and pentose phosphate pathway, are also observed in the diseased hearts. This article summarizes the current knowledge regarding the regulation of glucose transporter expression and translocation in the heart during physiological and pathological conditions. It also discusses the signaling mechanisms governing glucose uptake in cardiomyocytes, as well as the changes of cardiac glucose metabolism under disease conditions. PMID:26756635

  14. User producer interaction in context

    NARCIS (Netherlands)

    Nahuis, R.; Moors, E.H.M.; Smits, R.E.H.M.

    2012-01-01

    User producer interaction (UPI) increases chances for successful innovations. It is not always clear, however, what type of interaction is necessary in a particular context. This article identifies seven different types of UPI: constructing linkages, broadening, characterizing users, upstream

  15. ESBL-Producing Escherichia coli

    DEFF Research Database (Denmark)

    Hertz, Frederik Boetius

    in E.coli is increasing and especially isolates producing Extended-Spectrum Beta-Lactamases (ESBL) have been reported worldwide. Treatment of UTI is usually initiated by the general practitioners and a significant proportion of clinical isolates are now resistant to first line antibiotics. The global...... dissemination of resistant E.coli has in particular been driven by the spread of a few specific E.coli-lineages and it seems that there is a difference between the sequence types found among resistant E.coli, ESBL-producing E.coli and antibiotic susceptible E.coli. The overall objectives of this thesis were...... to investigate (i) antibiotics involved in selection of ESBL-producing E.coli, in an experimental mouse model in vivo, (ii) risk factors for UTI with ESBL-producing E.coli and (iii) to describe the phylogenetic composition of E.coli populations with different resistance patterns. We found that different...

  16. Ecological network analysis of China's societal metabolism.

    Science.gov (United States)

    Zhang, Yan; Liu, Hong; Li, Yating; Yang, Zhifeng; Li, Shengsheng; Yang, Naijin

    2012-01-01

    Uncontrolled socioeconomic development has strong negative effects on the ecological environment, including pollution and the depletion and waste of natural resources. These serious consequences result from the high flows of materials and energy through a socioeconomic system produced by exchanges between the system and its surroundings, causing the disturbance of metabolic processes. In this paper, we developed an ecological network model for a societal system, and used China in 2006 as a case study to illustrate application of the model. We analyzed China's basic metabolic processes and used ecological network analysis to study the network relationships within the system. Basic components comprised the internal environment, five sectors (agriculture, exploitation, manufacturing, domestic, and recycling), and the external environment. We defined 21 pairs of ecological relationships in China's societal metabolic system (excluding self-mutualism within a component). Using utility and throughflow analysis, we found that exploitation, mutualism, and competition relationships accounted for 76.2, 14.3, and 9.5% of the total relationships, respectively. In our trophic level analysis, the components were divided into producers, consumers, and decomposers according to their positions in the system. Our analyses revealed ways to optimize the system's structure and adjust its functions, thereby promoting healthier socioeconomic development, and suggested ways to apply ecological network analysis in future socioeconomic research. Copyright © 2011 Elsevier Ltd. All rights reserved.

  17. Autophagy research Lessons from metabolism

    NARCIS (Netherlands)

    Meijer, Alfred J.

    2009-01-01

    Autophagy research continues to expand exponentially. Clearly autophagy and metabolism are intimately connected; however, the rapid expansion of research into this topic inevitably brings the risk that important basic knowledge of metabolism will be overlooked when considering experimental data.

  18. Human drug metabolism: an introduction

    National Research Council Canada - National Science Library

    Coleman, Michael D

    2010-01-01

    ... metabolism and its impact on patient welfare. After underlining the relationship between efficacy, toxicity and drug concentration, the book then considers how metabolizing systems operate and how they impact upon drug concentration...

  19. Metabolic Syndrome, Androgens, and Hypertension

    OpenAIRE

    Moulana, Mohadetheh; Lima, Roberta; Reckelhoff, Jane F.

    2011-01-01

    Obesity is one of the constellation of factors that make up the definition of the metabolic syndrome. Metabolic syndrome is also associated with insulin resistance, dyslipidemia, hypertriglyceridemia, and type 2 diabetes mellitus. The presence of obesity and metabolic syndrome in men and women is also associated with increased risk of cardiovascular disease and hypertension. In men, obesity and metabolic syndrome are associated with reductions in testosterone levels. In women, obesity and met...

  20. Metabolic Flux Analysis of Shewanella spp. Reveals Evolutionary Robustness in Central Carbon Metabolism

    Energy Technology Data Exchange (ETDEWEB)

    Tang, Yinjie J.; Martin, Hector Garcia; Dehal, Paramvir S.; Deutschbauer, Adam; Llora, Xavier; Meadows, Adam; Arkin, Adam; Keasling, Jay D.

    2009-08-19

    Shewanella spp. are a group of facultative anaerobic bacteria widely distributed in marine and fresh-water environments. In this study, we profiled the central metabolic fluxes of eight recently sequenced Shewanella species grown under the same condition in minimal med-ium with [3-13C] lactate. Although the tested Shewanella species had slightly different growth rates (0.23-0.29 h31) and produced different amounts of acetate and pyruvate during early exponential growth (pseudo-steady state), the relative intracellular metabolic flux distributions were remarkably similar. This result indicates that Shewanella species share similar regulation in regard to central carbon metabolic fluxes under steady growth conditions: the maintenance of metabolic robustness is not only evident in a single species under genetic perturbations (Fischer and Sauer, 2005; Nat Genet 37(6):636-640), but also observed through evolutionary related microbial species. This remarkable conservation of relative flux profiles through phylogenetic differences prompts us to introduce the concept of metabotype as an alternative scheme to classify microbial fluxomics. On the other hand, Shewanella spp. display flexibility in the relative flux profiles when switching their metabolism from consuming lactate to consuming pyruvate and acetate.

  1. Lipid metabolism and body composition in Gclm(-/-) mice

    Energy Technology Data Exchange (ETDEWEB)

    Kendig, Eric L. [Department of Environmental Health, University of Cincinnati Medical Center, P.O. Box 670056, Cincinnati, OH 45267 (United States); Center for Environmental Genetics, University of Cincinnati Medical Center, P.O. Box 670056, Cincinnati, OH 45267 (United States); Chen, Ying [Department of Pharmaceutical Sciences, School of Pharmacy, University of Colorado Denver, Aurora, CO 80045 (United States); Krishan, Mansi; Johansson, Elisabet; Schneider, Scott N. [Department of Environmental Health, University of Cincinnati Medical Center, P.O. Box 670056, Cincinnati, OH 45267 (United States); Genter, Mary Beth; Nebert, Daniel W. [Department of Environmental Health, University of Cincinnati Medical Center, P.O. Box 670056, Cincinnati, OH 45267 (United States); Center for Environmental Genetics, University of Cincinnati Medical Center, P.O. Box 670056, Cincinnati, OH 45267 (United States); Shertzer, Howard G., E-mail: shertzhg@ucmail.uc.edu [Department of Environmental Health, University of Cincinnati Medical Center, P.O. Box 670056, Cincinnati, OH 45267 (United States); Center for Environmental Genetics, University of Cincinnati Medical Center, P.O. Box 670056, Cincinnati, OH 45267 (United States)

    2011-12-15

    In humans and experimental animals, high fat diets (HFD) are associated with risk factors for metabolic diseases, such as excessive weight gain and adiposity, insulin resistance and fatty liver. Mice lacking the glutamate-cysteine ligase modifier subunit gene (Gclm(-/-)) and deficient in glutathione (GSH), are resistant to HFD-mediated weight gain. Herein, we evaluated Gclm-associated regulation of energy metabolism, oxidative stress, and glucose and lipid homeostasis. C57BL/6J Gclm(-/-) mice and littermate wild-type (WT) controls received a normal diet or an HFD for 11 weeks. HFD-fed Gclm(-/-) mice did not display a decreased respiratory quotient, suggesting that they are unable to process lipid for metabolism. Although dietary energy consumption and intestinal lipid absorption were unchanged in Gclm(-/-) mice, feeding these mice an HFD did not produce excess body weight nor fat storage. Gclm(-/-) mice displayed higher basal metabolic rates resulting from higher activities of liver mitochondrial NADH-CoQ oxidoreductase, thus elevating respiration. Although Gclm(-/-) mice exhibited strong systemic and hepatic oxidative stress responses, HFD did not promote glucose intolerance or insulin resistance. Furthermore, HFD-fed Gclm(-/-) mice did not develop fatty liver, likely resulting from very low expression levels of genes encoding lipid metabolizing enzymes. We conclude that Gclm is involved in the regulation of basal metabolic rate and the metabolism of dietary lipid. Although Gclm(-/-) mice display a strong oxidative stress response, they are protected from HFD-induced excessive weight gain and adipose deposition, insulin resistance and steatosis. -- Highlights: Black-Right-Pointing-Pointer A high fat diet does not produce body weight and fat gain in Gclm(-/-) mice. Black-Right-Pointing-Pointer A high fat diet does not induce steatosis or insulin resistance in Gclm(-/-) mice. Black-Right-Pointing-Pointer Gclm(-/-) mice have high basal metabolism and mitochondrial

  2. Human drug metabolism: an introduction

    National Research Council Canada - National Science Library

    Coleman, Michael D

    2010-01-01

    ..., both under drug pressure and during inhibition. Factors affecting drug metabolism, such as genetic polymorphisms, age and diet are discussed and how metabolism can lead to toxicity is explained. The book concludes with the role of drug metabolism in the commercial development of therapeutic agents as well as the pharmacology of some illicit drugs.

  3. Quantitative 1H NMR metabolomics reveals extensive metabolic reprogramming of primary and secondary metabolism in elicitor-treated opium poppy cell cultures

    OpenAIRE

    Zulak, Katherine G; Weljie, Aalim M; Vogel, Hans J; Facchini, Peter J

    2008-01-01

    Abstract Background Opium poppy (Papaver somniferum) produces a diverse array of bioactive benzylisoquinoline alkaloids and has emerged as a model system to study plant alkaloid metabolism. The plant is cultivated as the only commercial source of the narcotic analgesics morphine and codeine, but also produces many other alkaloids including the antimicrobial agent sanguinarine. Modulations in plant secondary metabolism as a result of environmental perturbations are often associated with the al...

  4. Human body may produce bacteria.

    Science.gov (United States)

    Salerian, Alen J

    2017-06-01

    "Human body may produce bacteria" proposes that human body may produce bacteria and represent an independent source of infections contrary to the current paradigm of infectious disorders proposed by Louis Pasteur in 1880. The following observations are consistent with this hypothesis: A. Bidirectional transformations of both living and nonliving things have been commonly observed in nature. B. Complex multicellular organisms harbor the necessary properties to produce bacteria (water, nitrogen and oxygen). C. Physical laws suggest any previously observed phenomenon or action will occur again (life began on earth; a non living thing). D. Animal muscle cells may generate energy (fermentation). E. Sterilized food products (i.e. boiled eggs), may produce bacteria and fungus under special conditions and without any exposure to foreign living cells. "Human body may produce bacteria" may challenge the current medical paradigm that views human infectious disorders as the exclusive causative byproducts of invading foreign cells. It may also introduce new avenues to treat infectious disorders. Copyright © 2017 Elsevier Ltd. All rights reserved.

  5. [Microbiota and metabolic syndrome].

    Science.gov (United States)

    Altuntaş, Yüksel; Batman, Adnan

    2017-04-01

    The role of gut bacteria in the pathogenesis and treatment of various diseases has been a focus of attention in the last 10 years. Prevalence of diabetes, obesity, and cardiovascular diseases continues to increase, in spite of technological developments and treatment alternatives. Microbial dysbiosis, described as the decrease of useful bacteria and the increase of harmful bacteria, has been associated with diabetes, obesity, atherosclerosis, and metabolic syndrome. In microbial dysbiosis, increase of harmful metabolites and changes to composition of bile acids occur via carbohydrate and protein fermentation. As a result, insulin resistance pathways are activated, which initiate the processes of obesity, diabetes, and atherosclerosis. Healthy diet recommendations, including prebiotic and probiotic foods and the use of probiotic agents, look promising for future treatment of metabolic syndrome and cardiovascular diseases.

  6. GALACTOSE METABOLISM I.

    Science.gov (United States)

    Fukuyama, T. T.; O'Kane, D. J.

    1962-01-01

    Fukuyama T. T. (University of Pennsylvania, Philadelphia) and D. J. O'Kane. Galactose metabolism. I. Pathway of carbon in fermentation by Streptococcus faecalis. J. Bacteriol. 84:793–796. 1962.—The pathway by which galactose-1-C14 is fermented in Streptococcus faecalis was investigated using dried-cell preparations. Lactic acid, acetic acid, formic acid, ethanol, and carbon dioxide were the end products formed, with lactic acid representing approximately 50% of the sugar fermented. The distribution of radio-activity indicated that the fermentation follows the Embden-Meyerhof route, suggesting that the difference in the formation of the products of glucose and galactose fermentation must be attributed to alternate routes of pyruvic acid metabolism. Differences in pH did not account for the dissimilar fermentation patterns. PMID:13960210

  7. Scaling metabolic rate fluctuations

    OpenAIRE

    Labra, Fabio A.; Marquet, Pablo A.; Bozinovic, Francisco

    2007-01-01

    Complex ecological and economic systems show fluctuations in macroscopic quantities such as exchange rates, size of companies or populations that follow non-Gaussian tent-shaped probability distributions of growth rates with power-law decay, which suggests that fluctuations in complex systems may be governed by universal mechanisms, independent of particular details and idiosyncrasies. We propose here that metabolic rate within individual organisms may be considered as an example of an emerge...

  8. Spectrum of metabolic myopathies.

    Science.gov (United States)

    Angelini, Corrado

    2015-04-01

    Metabolic myopathies are disorders of utilization of carbohydrates or fat in muscles. The acute nature of energy failure is manifested either by a metabolic crisis with weakness, sometimes associated with respiratory failure, or by myoglobinuria. A typical disorder where permanent weakness occurs is glycogenosis type II (GSDII or Pompe disease) both in infantile and late-onset forms, where respiratory insufficiency is manifested by a large number of cases. In GSDII the pathogenetic mechanism is still poorly understood, and has to be attributed more to structural muscle alterations, possibly in correlation to macro-autophagy, rather than to energetic failure. This review is focused on recent advances about GSDII and its treatment, and the most recent notions about the management and treatment of other metabolic myopathies will be briefly reviewed, including glycogenosis type V (McArdle disease), glycogenosis type III (debrancher enzyme deficiency or Cori disease), CPT-II deficiency, and ETF-dehydrogenase deficiency (also known as riboflavin-responsive multiple acyl-CoA dehydrogenase deficiency or RR-MADD). The discovery of the genetic defect in ETF dehydrogenase confirms the etiology of this syndrome. Other metabolic myopathies with massive lipid storage and weakness are carnitine deficiency, neutral lipid storage-myopathy (NLSD-M), besides RR-MADD. Enzyme replacement therapy is presented with critical consideration and for each of the lipid storage disorders, representative cases and their response to therapy is included. This article is part of a Special Issue entitled: Neuromuscular Diseases: Pathology and Molecular Pathogenesis. Copyright © 2014. Published by Elsevier B.V.

  9. Autophagy, Metabolism, and Cancer.

    Science.gov (United States)

    White, Eileen; Mehnert, Janice M; Chan, Chang S

    2015-11-15

    Macroautophagy (autophagy hereafter) captures intracellular proteins and organelles and degrades them in lysosomes. The degradation breakdown products are released from lysosomes and recycled into metabolic and biosynthetic pathways. Basal autophagy provides protein and organelle quality control by eliminating damaged cellular components. Starvation-induced autophagy recycles intracellular components into metabolic pathways to sustain mitochondrial metabolic function and energy homeostasis. Recycling by autophagy is essential for yeast and mammals to survive starvation through intracellular nutrient scavenging. Autophagy suppresses degenerative diseases and has a context-dependent role in cancer. In some models, cancer initiation is suppressed by autophagy. By preventing the toxic accumulation of damaged protein and organelles, particularly mitochondria, autophagy limits oxidative stress, chronic tissue damage, and oncogenic signaling, which suppresses cancer initiation. This suggests a role for autophagy stimulation in cancer prevention, although the role of autophagy in the suppression of human cancer is unclear. In contrast, some cancers induce autophagy and are dependent on autophagy for survival. Much in the way that autophagy promotes survival in starvation, cancers can use autophagy-mediated recycling to maintain mitochondrial function and energy homeostasis to meet the elevated metabolic demand of growth and proliferation. Thus, autophagy inhibition may be beneficial for cancer therapy. Moreover, tumors are more autophagy-dependent than normal tissues, suggesting that there is a therapeutic window. Despite these insights, many important unanswered questions remain about the exact mechanisms of autophagy-mediated cancer suppression and promotion, how relevant these observations are to humans, and whether the autophagy pathway can be modulated therapeutically in cancer. See all articles in this CCR Focus section, "Cell Death and Cancer Therapy." ©2015

  10. Produced water - composition and analysis

    International Nuclear Information System (INIS)

    Kvernheim, Arne Lund

    1998-01-01

    Produced water can be defined as ''High volume waste-water separated from oil and gas that is produced from subsurface formations''. The water contains aliphatic and aromatic hydrocarbons, particulate matter and soluble salts as well as elements originating from formations and from sea water injections. Residues of chemicals may also be present. The accepted North Sea discharge limit is 40 ppm. In this presentation the focus will be on the chemical composition of produced water and on the challenges involved in developing and implementing analytical methods. The focus will also be on the development of a new oil-in-water analytical method as a replacement for the Freon method. 7 refs., 1 tab

  11. Hypothalamic Hormones and Metabolism

    Science.gov (United States)

    Thio, Liu Lin

    2011-01-01

    Summary The ketogenic diet is an effective treatment for medically intractable epilepsy and may have antiepileptogenic, neuroprotective, and antitumor properties. While on a ketogenic diet, the body obtains most of its calories from fat rather than carbohydrates. This dramatic change in caloric composition results in a unique metabolic state. In turn, these changes in caloric composition and metabolism alter some of the neurohormones that participate in the complex neuronal network regulating energy homeostasis. Two observed changes are an increase in serum leptin and a decrease in serum insulin. These opposing changes in leptin and insulin are unique compared to other metabolic stimuli and may modify the activity of several cell signaling cascades including phosphoinositidyl-3 kinase (PI3K), adenosine monophosphate activated protein kinase (AMPK), and mammalian target of rapamycin (mTOR). These cell signaling pathways may mediate the anticonvulsant and other beneficial effects of the diet, though the neurohormonal changes induced by the ketogenic diet and the physiological consequences of these changes remain poorly characterized. PMID:21856125

  12. Identification of the Entner-Doudoroff pathway in an antibiotic-producing actinomycete species

    DEFF Research Database (Denmark)

    Gunnarsson, Nina; Mortensen, Uffe Hasbro; Sosio, M.

    2004-01-01

    the primary metabolic pathways of the poorly characterized antibiotic-producing actinomycete Nonomuraea sp. ATCC 39727. Surprisingly, it was found that Nonomuraea sp. ATCC 39272 predominantly metabolizes glucose via the Entner-Doudoroff (ED) pathway. This represents the first time that the ED pathway has been...... recognized as the main catabolic pathway in an actinomycete. The Nonomuraea genes encoding the key enzymes of the ED pathway were subsequently identified, sequenced and functionally described....

  13. Maternal cardiac metabolism in pregnancy

    Science.gov (United States)

    Liu, Laura X.; Arany, Zolt

    2014-01-01

    Pregnancy causes dramatic physiological changes in the expectant mother. The placenta, mostly foetal in origin, invades maternal uterine tissue early in pregnancy and unleashes a barrage of hormones and other factors. This foetal ‘invasion’ profoundly reprogrammes maternal physiology, affecting nearly every organ, including the heart and its metabolism. We briefly review here maternal systemic metabolic changes during pregnancy and cardiac metabolism in general. We then discuss changes in cardiac haemodynamic during pregnancy and review what is known about maternal cardiac metabolism during pregnancy. Lastly, we discuss cardiac diseases during pregnancy, including peripartum cardiomyopathy, and the potential contribution of aberrant cardiac metabolism to disease aetiology. PMID:24448314

  14. Population FBA predicts metabolic phenotypes in yeast.

    Directory of Open Access Journals (Sweden)

    Piyush Labhsetwar

    2017-09-01

    Full Text Available Using protein counts sampled from single cell proteomics distributions to constrain fluxes through a genome-scale model of metabolism, Population flux balance analysis (Population FBA successfully described metabolic heterogeneity in a population of independent Escherichia coli cells growing in a defined medium. We extend the methodology to account for correlations in protein expression arising from the co-regulation of genes and apply it to study the growth of independent Saccharomyces cerevisiae cells in two different growth media. We find the partitioning of flux between fermentation and respiration predicted by our model agrees with recent 13C fluxomics experiments, and that our model largely recovers the Crabtree effect (the experimentally known bias among certain yeast species toward fermentation with the production of ethanol even in the presence of oxygen, while FBA without proteomics constraints predicts respirative metabolism almost exclusively. The comparisons to the 13C study showed improvement upon inclusion of the correlations and motivated a technique to systematically identify inconsistent kinetic parameters in the literature. The minor secretion fluxes for glycerol and acetate are underestimated by our method, which indicate a need for further refinements to the metabolic model. For yeast cells grown in synthetic defined (SD medium, the calculated broad distribution of growth rates matches experimental observations from single cell studies, and we characterize several metabolic phenotypes within our modeled populations that make use of diverse pathways. Fast growing yeast cells are predicted to perform significant amount of respiration, use serine-glycine cycle and produce ethanol in mitochondria as opposed to slow growing cells. We use a genetic algorithm to determine the proteomics constraints necessary to reproduce the growth rate distributions seen experimentally. We find that a core set of 51 constraints are essential but

  15. Producing deep-water hydrocarbons

    International Nuclear Information System (INIS)

    Pilenko, Thierry

    2011-01-01

    Several studies relate the history and progress made in offshore production from oil and gas fields in relation to reserves and the techniques for producing oil offshore. The intention herein is not to review these studies but rather to argue that the activities of prospecting and producing deep-water oil and gas call for a combination of technology and project management and, above all, of devotion and innovation. Without this sense of commitment motivating men and women in this industry, the human adventure of deep-water production would never have taken place

  16. Tumor Metabolism of Malignant Gliomas

    Energy Technology Data Exchange (ETDEWEB)

    Ru, Peng; Williams, Terence M.; Chakravarti, Arnab; Guo, Deliang, E-mail: deliang.guo@osumc.edu [Department of Radiation Oncology, Ohio State University Comprehensive Cancer Center & Arthur G James Cancer Hospital, Columbus, OH 43012 (United States)

    2013-11-08

    Constitutively activated oncogenic signaling via genetic mutations such as in the EGFR/PI3K/Akt and Ras/RAF/MEK pathways has been recognized as a major driver for tumorigenesis in most cancers. Recent insights into tumor metabolism have further revealed that oncogenic signaling pathways directly promote metabolic reprogramming to upregulate biosynthesis of lipids, carbohydrates, protein, DNA and RNA, leading to enhanced growth of human tumors. Therefore, targeting cell metabolism has become a novel direction for drug development in oncology. In malignant gliomas, metabolism pathways of glucose, glutamine and lipid are significantly reprogrammed. Moreover, molecular mechanisms causing these metabolic changes are just starting to be unraveled. In this review, we will summarize recent studies revealing critical gene alterations that lead to metabolic changes in malignant gliomas, and also discuss promising therapeutic strategies via targeting the key players in metabolic regulation.

  17. Disturbances of lipoprotein metabolism in metabolic syndro

    Directory of Open Access Journals (Sweden)

    Marta Czyżewska

    2010-01-01

    Full Text Available Dyslipidemia in metabolic syndrome (MS, called the atherogenic triad, includes elevated levels of plasma triglycerides (TGs, low levels of HDL-cholesterol (HDL-CH, and the presence of small dense low-density lipoproteins (sdLDLs with normal or slightly elevated LDL-CH levels. Insulin resistance drives the increase in the three main sources of TG for VLDL synthesis: fatty-acid flux from adipose tissue, de novo lipogenesis, and uptake of remnant lipoproteins. Overproduction of VLDL, predominantly triglyceride-rich large VLDL1 particles, induces the cascade of events which lead to abnormalities of other plasma lipoproteins. The accumulation of VLDL in plasma and decreased activity of lipoprotein lipase (LPL impair the catabolism of chylomicrons. Moreover, hyperinsulinemia induces increased intestinal production of chylomicrons. These factors cause augmented postprandial lipemia. Hepatic overproduction of VLDL leads to an increased level of VLDL remnants in plasma. Highly atherogenic sdLDLs are generated from VLDL1 particles by the action of LPL, cholesterol ester transfer protein (CETP, and hepatic lipase (HL. In the presence of hypertriglyceridemia, accelerated CETP-mediated lipid transfer generates TG-enriched HDL particles. This enhances HDL catabolism mediated by HL and endothelial lipase (EL. The assessment of risk of atherosclerotic cardiovascular disease in MS related to low HDL-CH and the presence of sdLDL particles may be improved by the incorporation of measurements of apolipoproteins (apo-B and apoA-I into clinical practice. In addition, the concentration of non-HDL-CH may be useful in quantifying apo-B-containing atherogenic lipoproteins.

  18. Smoke producing and inflammable materials

    NARCIS (Netherlands)

    Wilms EB; van Xanten NHW; Meulenbelt J

    1990-01-01

    On behalf of the AMGB (Afdeling Militair Geneeskundig Beleid) toxicological reviews have been made about several smoke producing and inflammable materials. The reviews have been made after a literature search and are meant to complete or to replace the concerning chapters in the NATO handbook on

  19. Process for producing chalcogenide semiconductors

    Science.gov (United States)

    Noufi, R.; Chen, Y.W.

    1985-04-30

    A process for producing chalcogenide semiconductor material is disclosed. The process includes forming a base metal layer and then contacting this layer with a solution having a low pH and containing ions from at least one chalcogen to chalcogenize the layer and form the chalcogenide semiconductor material.

  20. Marketing Hardwoods to Furniture Producers

    Science.gov (United States)

    Steven A. Sinclair; Robert J. Bush; Philip A. Araman

    1989-01-01

    This paper discusses some of the many problems in developing marketing programs for small wood products manufacturers. It examines the problems of using price as a dominant means for getting and attracting customers. The marketing of hardwood lumber to furniture producers is then used as an example. Data from 36 furniture lumber buyers is presented to illustrate...

  1. Cattle producers' perceptions of biosecurity.

    Science.gov (United States)

    Brennan, Marnie L; Christley, Robert M

    2013-04-10

    The limited use of biosecurity practices by many in the farming community is likely to be due to a range of factors; further understanding of this issue is required. In this study, attitudes and behaviours of producers relating to selected biosecurity practices and the farming industry were studied by interviewing cattle farmers within a 100 km2 study area in north-west England using an interview-based questionnaire. Most producers appeared to be familiar with the broad concept of the term biosecurity, although risks due to indirect contacts, rather than direct (animal) contacts, were more frequently highlighted. Most producers felt the nominated biosecurity practices were in some way useful, however there was not always agreement between the usefulness of a practice and it being undertaken, and vice versa. In agreement with other studies conducted in the UK, farmers most preferred to obtain information and advice on biosecurity from private veterinarians, but also highlighted DEFRA as a source. This study highlights the importance of understanding the motivators and barriers behind the uptake of biosecurity practices on farms, as perceptions are variable. Further understanding of these issues is needed in order to more effectively communicate information in regards to herd health and disease prevention. By identifying differences in producers' attitudes, programs can be tailored specifically to individuals' needs.

  2. Importance of producing impactful research

    CSIR Research Space (South Africa)

    Nienaber, S

    2010-11-01

    Full Text Available from the more pragmatic issue of funding. Funding agencies, organisational leadership and policymakers need scientists to prove that the science we produce makes enough of an impact to merit further funding in future. This emphasis and pressure around...

  3. Producing Talent and Variety Shows.

    Science.gov (United States)

    Szabo, Chuck

    1995-01-01

    Identifies key aspects of producing talent shows and outlines helpful hints for avoiding pitfalls and ensuring a smooth production. Presents suggestions concerning publicity, scheduling, and support personnel. Describes types of acts along with special needs and problems specific to each act. Includes a list of resources. (MJP)

  4. Method of producing vegetable puree

    DEFF Research Database (Denmark)

    2004-01-01

    A process for producing a vegetable puree, comprising the sequential steps of: a)crushing, chopping or slicing the vegetable into pieces of 1 to 30 mm; b) blanching the vegetable pieces at a temperature of 60 to 90°C; c) contacted the blanched vegetable pieces with a macerating enzyme activity; d......) blending the macerated vegetable pieces and obtaining a puree....

  5. Metabolic engineering of biosynthetic pathway for production of renewable biofuels.

    Science.gov (United States)

    Singh, Vijai; Mani, Indra; Chaudhary, Dharmendra Kumar; Dhar, Pawan Kumar

    2014-02-01

    Metabolic engineering is an important area of research that involves editing genetic networks to overproduce a certain substance by the cells. Using a combination of genetic, metabolic, and modeling methods, useful substances have been synthesized in the past at industrial scale and in a cost-effective manner. Currently, metabolic engineering is being used to produce sufficient, economical, and eco-friendly biofuels. In the recent past, a number of efforts have been made towards engineering biosynthetic pathways for large scale and efficient production of biofuels from biomass. Given the adoption of metabolic engineering approaches by the biofuel industry, this paper reviews various approaches towards the production and enhancement of renewable biofuels such as ethanol, butanol, isopropanol, hydrogen, and biodiesel. We have also identified specific areas where more work needs to be done in the future.

  6. Computational methods in metabolic engineering for strain design.

    Science.gov (United States)

    Long, Matthew R; Ong, Wai Kit; Reed, Jennifer L

    2015-08-01

    Metabolic engineering uses genetic approaches to control microbial metabolism to produce desired compounds. Computational tools can identify new biological routes to chemicals and the changes needed in host metabolism to improve chemical production. Recent computational efforts have focused on exploring what compounds can be made biologically using native, heterologous, and/or enzymes with broad specificity. Additionally, computational methods have been developed to suggest different types of genetic modifications (e.g. gene deletion/addition or up/down regulation), as well as suggest strategies meeting different criteria (e.g. high yield, high productivity, or substrate co-utilization). Strategies to improve the runtime performances have also been developed, which allow for more complex metabolic engineering strategies to be identified. Future incorporation of kinetic considerations will further improve strain design algorithms. Copyright © 2015 Elsevier Ltd. All rights reserved.

  7. Mitochondria: The ketogenic diet--A metabolism-based therapy.

    Science.gov (United States)

    Vidali, Silvia; Aminzadeh, Sepideh; Lambert, Bridget; Rutherford, Tricia; Sperl, Wolfgang; Kofler, Barbara; Feichtinger, René G

    2015-06-01

    Mitochondria are the energy-producing organelles of the cell, generating ATP via oxidative phosphorylation mainly by using pyruvate derived from glycolytic processing of glucose. Ketone bodies generated by fatty acid oxidation can serve as alternative metabolites for aerobic energy production. The ketogenic diet, which is high in fat and low in carbohydrates, mimics the metabolic state of starvation, forcing the body to utilize fat as its primary source of energy. The ketogenic diet is used therapeutically for pharmacoresistant epilepsy and for "rare diseases" of glucose metabolism (glucose transporter type 1 and pyruvate dehydrogenase deficiency). As metabolic reprogramming from oxidative phosphorylation toward increased glycolysis is a hallmark of cancer cells; there is increasing evidence that the ketogenic diet may also be beneficial as an adjuvant cancer therapy by potentiating the antitumor effect of chemotherapy and radiation treatment. This article is part of a Directed Issue entitled: Energy Metabolism Disorders and Therapies. Copyright © 2015 Elsevier Ltd. All rights reserved.

  8. Metabolic rates of giant pandas inform conservation strategies

    Science.gov (United States)

    Fei, Yuxiang; Hou, Rong; Spotila, James R.; Paladino, Frank V.; Qi, Dunwu; Zhang, Zhihe

    2016-06-01

    The giant panda is an icon of conservation and survived a large-scale bamboo die off in the 1980s in China. Captive breeding programs have produced a large population in zoos and efforts continue to reintroduce those animals into the wild. However, we lack sufficient knowledge of their physiological ecology to determine requirements for survival now and in the face of climate change. We measured resting and active metabolic rates of giant pandas in order to determine if current bamboo resources were sufficient for adding additional animals to populations in natural reserves. Resting metabolic rates were somewhat below average for a panda sized mammal and active metabolic rates were in the normal range. Pandas do not have exceptionally low metabolic rates. Nevertheless, there is enough bamboo in natural reserves to support both natural populations and large numbers of reintroduced pandas. Bamboo will not be the limiting factor in successful reintroduction.

  9. Bystander signaling via oxidative metabolism

    Directory of Open Access Journals (Sweden)

    Sawal HA

    2017-08-01

    Full Text Available Humaira Aziz Sawal,1 Kashif Asghar,2 Matthias Bureik,3 Nasir Jalal4 1Healthcare Biotechnology Department, Atta-ur-Rahman School of Applied Biosciences, National University of Sciences and Technology, Islamabad, 2Basic Sciences Research, Shaukat Khanum Memorial Cancer Hospital and Research Centre, Lahore, Pakistan; 3Health Science Platform, School of Pharmaceutical Science and Technology, Tianjin University, Tianjin, China; 4Health Science Platform, Department of Molecular and Cellular Pharmacology, Tianjin University, Tianjin, China Abstract: The radiation-induced bystander effect (RIBE is the initiation of biological end points in cells (bystander cells that are not directly traversed by an incident-radiation track, but are in close proximity to cells that are receiving the radiation. RIBE has been indicted of causing DNA damage via oxidative stress, besides causing direct damage, inducing tumorigenesis, producing micronuclei, and causing apoptosis. RIBE is regulated by signaling proteins that are either endogenous or secreted by cells as a means of communication between cells, and can activate intracellular or intercellular oxidative metabolism that can further trigger signaling pathways of inflammation. Bystander signals can pass through gap junctions in attached cell lines, while the suspended cell lines transmit these signals via hormones and soluble proteins. This review provides the background information on how reactive oxygen species (ROS act as bystander signals. Although ROS have a very short half-life and have a nanometer-scale sphere of influence, the wide variety of ROS produced via various sources can exert a cumulative effect, not only in forming DNA adducts but also setting up signaling pathways of inflammation, apoptosis, cell-cycle arrest, aging, and even tumorigenesis. This review outlines the sources of the bystander effect linked to ROS in a cell, and provides methods of investigation for researchers who would like to

  10. Central carbon metabolism influences cellulase production in Bacillus licheniformis.

    Science.gov (United States)

    Wang, J; Liu, S; Li, Y; Wang, H; Xiao, S; Li, C; Liu, B

    2018-01-01

    Bacillus licheniformis that can produce cellulase including endo glucanase and glucosidase is an important industrial microbe for cellulose degradation. The purpose of this research was to assess the effect of endo glucanase gene bglC and glucosidase gene bglH on the central metabolic flux in B. licheniformis. bglC and bglH were knocked out using homologous recombination method, respectively, and the corresponding knockout strains were obtained for 13 C metabolic flux analysis. A significant change was observed in metabolic fluxes after 13 C metabolic flux ratio analysis. In both of the knockout strains, the increased fluxes of the pentose phosphate pathway and malic enzyme reaction enabled an elevated supply of NADPH which provided enough reducing power for the in vivo synthesis reactions. The fluxes through tricarboxylic acid cycle and anaplerotic reactions increased fast in the two knockout strains, which meant more energy generated. The changed fluxes in central carbon metabolism provided a holistic view of the physiological status in B. licheniformis and possible targets for further strain engineering. Cellulase is very important in the field of agriculture and bioenergy because of its degrading effect on cellulosic biomass. This study presented the effect of central carbon metabolism on cellulase production in Bacillus licheniformis. The study also provided a holistic view of the physiological status in B. licheniformis. The shifted metabolism provided a quantitative evaluation of the biosynthesis of cellulase and a priority ranked target list for further strain engineering. © 2017 The Society for Applied Microbiology.

  11. Peroxisome Proliferators-Activated Receptor (PPAR Modulators and Metabolic Disorders

    Directory of Open Access Journals (Sweden)

    Min-Chul Cho

    2008-01-01

    Full Text Available Overweight and obesity lead to an increased risk for metabolic disorders such as impaired glucose regulation/insulin resistance, dyslipidemia, and hypertension. Several molecular drug targets with potential to prevent or treat metabolic disorders have been revealed. Interestingly, the activation of peroxisome proliferator-activated receptor (PPAR, which belongs to the nuclear receptor superfamily, has many beneficial clinical effects. PPAR directly modulates gene expression by binding to a specific ligand. All PPAR subtypes (α,γ, and σ are involved in glucose metabolism, lipid metabolism, and energy balance. PPAR agonists play an important role in therapeutic aspects of metabolic disorders. However, undesired effects of the existing PPAR agonists have been reported. A great deal of recent research has focused on the discovery of new PPAR modulators with more beneficial effects and more safety without producing undesired side effects. Herein, we briefly review the roles of PPAR in metabolic disorders, the effects of PPAR modulators in metabolic disorders, and the technologies with which to discover new PPAR modulators.

  12. DDT increases hepatic testosterone metabolism in rats

    Energy Technology Data Exchange (ETDEWEB)

    Sierra-Santoyo, Adolfo; Albores, Arnulfo; Cebrian, Mariano E. [Cinvestav-IPN, Seccion de Toxicologia, Mexico (Mexico); Hernandez, Manuel [Cinvestav-IPN, Departamento de Biologia Celular (Mexico)

    2005-01-01

    DDT and its metabolites are considered as endocrine disruptors able to promote hormone-dependent pathologies. We studied the effects of technical-grade DDT on hepatic testosterone metabolism and testosterone hydroxylase activity ratios in the rat. Male and female Wistar rats were treated by gavage with a single dose of technical-grade DDT (0, 0.1, 1, 10, and 100 mg/kg body weight) and killed 24 h later. Hepatic microsomes were incubated with [4-{sup 14}C]-testosterone and the metabolites were separated by thin-layer chromatography and quantified by radio scanning. DDT increased testosterone biotransformation and modified the profile of metabolites produced in a sex-dependent manner. Males treated with a representative dose (10 mg/kg) produced relatively less androstenedione (AD), 2{alpha}-hydroxytestosterone (OHT), and 16{alpha}-OHT but higher 6{beta}-OHT whereas treated females produced less 7{alpha}-OHT and AD but higher 6{beta}-OHT and 6{alpha}-OHT than their respective controls. In both sexes DDT decreased the relative proportion of AD and increased that of 6{beta}-OHT suggesting that the androgen-saving pathway was affected. The testosterone 6{alpha}-/15{alpha}-OHT ratio, a proposed indicator of demasculinization, was increased in treated males. This effect was in agreement with the demasculinizing ability proposed for DDT. The effects on 6{alpha}-/16{alpha}-OHT and 6-dehydrotestosterone/16{alpha}-OHT ratios followed a similar tendency, with the ratio 6{alpha}-/16{alpha}-OHT being the most sensitive marker. Interestingly, these ratios were reduced in treated females suggesting that technical-grade DDT shifted testosterone hydroxylations toward a more masculine pattern. Thus, technical-grade DDT altered the hepatic sexual dimorphism in testosterone metabolism and decreased the metabolic differences between male and female rats. (orig.)

  13. METABOLIC WAR: A VARIATION FOR METABOLIC BIOCHEMISTRY LEARNING OF A WORLDLY KNOWN BOARD GAME

    Directory of Open Access Journals (Sweden)

    C. M. Anjos

    2008-05-01

    Full Text Available Biomedical careers are highly wished by young students in Brazil. Although future jobs,  academic knowledge and higher earnings  are tempting reasons for this life choice, few of them are aware  of  the difficult path through the  basic classes. Advanced and specific disciplines  are easier to associate with the professional career itself, but few students can identify the importance  of the basic knowledge for their future work. Biochemistry is one of the most difficult  disciplines  for Brazilian students, probably due to the level of abstraction needed to fully learn and understand the topics. Some recent experimental tools, such as bioinformatics, are now helping students with the learning process, providing visual data for understanding biomolecule structure.  In addition to this, biochemical reactions  could be even tougher because of the many variables involved.  To facilitate the learning process for metabolic biochemistry, we created a game based on the board game WAR®,  using Photoshop software. Named Metabolic War, it keeps the same basic rules of WAR®, but with some minor changes. The continents are metabolic pathways (citric acid cycle, glycolysis, beta-oxidation, etc and the countries are metabolic intermediates. Similarly to the original game, players must conquer an objective (one or more metabolic pathways by dominating intermediates. But the desired intermediate must be a possible product from an intermediate the player already owns. This  and other  games were produced by Biomedicine  undergraduate  students  in Metabolic Biochemistry classes. It was presented to other students, who tested and acknowledged it as a great help in understanding metabolic biochemistry,  giving a great understanding of integrative metabolism. Keywords: game; Biochemistry; Metabolic Biochemistry learning; science learning; playful learning.

  14. Nonstarter lactic acid bacteria volatilomes produced using cheese components.

    Science.gov (United States)

    Sgarbi, E; Lazzi, C; Tabanelli, G; Gatti, M; Neviani, E; Gardini, F

    2013-07-01

    In long-ripened cheese, flavor formation occurs during ripening. The metabolism of lactic acid bacteria (LAB) leads to the production of different compounds that contribute to the flavor of cheese. The contribution of LAB to the formation of cheese flavor has previously been studied. However, the specific nonstarter LAB (NSLAB) metabolic reactions in ripened cheese that lead to the formation of flavor compounds remain unclear. In ripened cheese, the nutrient sources available include small peptides or amino acids, citrate, lactate, free fatty acids, and starter LAB cell lysis products. Thus, the aim of this study was to evaluate the ability of NSLAB to produce volatile flavor compounds by using an in vitro system that used only the nutrients available in ripened cheese as the energy source. Moreover, the potential contribution of the NSLAB volatilome on total cheese flavor is discussed. For this purpose, the production of volatile compounds on cheese-based medium (CBM) and on starter LAB lysed cell medium (LCM) by 2 Lactobacillus casei and 2 Lactobacillus rhamnosus strains, previously isolated from ripened Parmigiano Reggiano cheese, was investigated. The generated volatile compounds were analyzed with head-space gas chromatography mass spectrometry. Overall, ketones, aldehydes, alcohols, and acids were the most abundant compounds produced. Differences in volatilome production were found between NSLAB grown in LCM and CBM. The catabolic metabolism of amino acids and fatty acids were required for NSLAB growth on LCM. Conversely, pyruvate metabolism was the main catabolic pathway that supported growth of NSLAB in CBM. This study can be considered a first step toward a better understanding of how microbiota involved in the long ripening of cheese may contribute to the development of cheese flavor. Copyright © 2013 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

  15. A reverse Warburg metabolism in oral squamous cell carcinoma is not dependent upon myofibroblasts

    DEFF Research Database (Denmark)

    Jensen, David Hebbelstrup; Therkildsen, Marianne Hamilton; Dabelsteen, Erik

    2015-01-01

    The reverse Warburg effect describes the phenomenon that epithelial cancer cells take advantage of the metabolic machinery from nearby cancer-associated fibroblast, inducing them to produce lactate and ketones to fuel the high metabolic demands of the epithelial tumour tissues. This is in breast...

  16. Metabolic characterization of high- and low-yielding strains of Penicillium chrysogenum

    DEFF Research Database (Denmark)

    Christensen, Bjarke; Thykær, Jette; Nielsen, Jens

    2000-01-01

    A recently developed method for analyzing metabolic networks using C-13-labels was employed for investigating the metabolism of a high- and a low-yielding strain of Penicillium chrysogenum. Under penicillin-producing conditions, the flux through the pentose phosphate (PP) pathway in the high- and...

  17. Flux balance analysis of genome-scale metabolic model of rice ...

    Indian Academy of Sciences (India)

    2015-09-28

    Sep 28, 2015 ... producing vitamin A–enriched golden rice (Beyer et al. 2002). On the other hand, metabolic engineering has been proven as a powerful technique for over or less production of specific metabolites in microbes (Peralta-Yahya et al. 2012). Modelling and analysis of the cellular metabolism is a key step in the ...

  18. The effect of selected metals on the central metabolic pathways in ...

    African Journals Online (AJOL)

    2006-10-04

    Oct 4, 2006 ... Furthermore, metals also produce an affect carbohydrate, pro- tein and lipid metabolism (Almeida et al., 2001) .... industry alloys, in planting, in batteries and in pigments used in paints, inks, plastic, and enamels ..... complexes inhibit cyanobacterial metabolism by binding at the phosphate binding sites.

  19. Metabolic effects of spices, teas, and caffeine.

    Science.gov (United States)

    Westerterp-Plantenga, Margriet; Diepvens, Kristel; Joosen, Annemiek M C P; Bérubé-Parent, Sonia; Tremblay, Angelo

    2006-08-30

    Consumption of spiced foods or herbal drinks leads to greater thermogenesis and in some cases to greater satiety. In this regard, capsaicin, black pepper, ginger, mixed spices, green tea, black tea and caffeine are relevant examples. These functional ingredients have the potential to produce significant effects on metabolic targets such as satiety, thermogenesis, and fat oxidation. A significant clinical outcome sometimes may appear straightforwardly but also depends too strongly on full compliance of subjects. Nevertheless, thermogenic ingredients may be considered as functional agents that could help in preventing a positive energy balance and obesity.

  20. Uncovering transcriptional regulation of metabolism by using metabolic network topology

    DEFF Research Database (Denmark)

    Patil, Kiran Raosaheb; Nielsen, Jens

    2005-01-01

    therefore developed an algorithm that is based on hypothesis-driven data analysis to uncover the transcriptional regulatory architecture of metabolic networks. By using information on the metabolic network topology from genome-scale metabolic reconstruction, we show that it is possible to reveal patterns...... changes induced by complex regulatory mechanisms coordinating the activity of different metabolic pathways. It is difficult to map such global transcriptional responses by using traditional methods, because many genes in the metabolic network have relatively small changes at their transcription level. We...... in the metabolic network that follow a common transcriptional response. Thus, the algorithm enables identification of so-called reporter metabolites (metabolites around which the most significant transcriptional changes occur) and a set of connected genes with significant and coordinated response to genetic...

  1. Engineering biofuel tolerance in non-native producing microorganisms.

    Science.gov (United States)

    Jin, Hu; Chen, Lei; Wang, Jiangxin; Zhang, Weiwen

    2014-01-01

    Large-scale production of renewable biofuels through microbiological processes has drawn significant attention in recent years, mostly due to the increasing concerns on the petroleum fuel shortages and the environmental consequences of the over-utilization of petroleum-based fuels. In addition to native biofuel-producing microbes that have been employed for biofuel production for decades, recent advances in metabolic engineering and synthetic biology have made it possible to produce biofuels in several non-native biofuel-producing microorganisms. Compared to native producers, these non-native systems carry the advantages of fast growth, simple nutrient requirements, readiness for genetic modifications, and even the capability to assimilate CO2 and solar energy, making them competitive alternative systems to further decrease the biofuel production cost. However, the tolerance of these non-native microorganisms to toxic biofuels is naturally low, which has restricted the potentials of their application for high-efficiency biofuel production. To address the issues, researches have been recently conducted to explore the biofuel tolerance mechanisms and to construct robust high-tolerance strains for non-native biofuel-producing microorganisms. In this review, we critically summarize the recent progress in this area, focusing on three popular non-native biofuel-producing systems, i.e. Escherichia coli, Lactobacillus and photosynthetic cyanobacteria. Copyright © 2014 Elsevier Inc. All rights reserved.

  2. Enumeration of minimal stoichiometric precursor sets in metabolic networks

    NARCIS (Netherlands)

    Andrade, R.; Wannagat, M.; Coimbra Klein, C.; Acuna, V.; Marchetti Spaccamela, A.; Vieira Milreu, P.; Stougie, L.; Sagot, M.-F.

    2016-01-01

    Background: What an organism needs at least from its environment to produce a set of metabolites, e.g. target(s) of interest and/or biomass, has been called a minimal precursor set. Early approaches to enumerate all minimal precursor sets took into account only the topology of the metabolic network

  3. Phylogeny of metabolic networks: A spectral graph theoretical ...

    Indian Academy of Sciences (India)

    The eigenvalues of this matrix reflect not only the global architecture of a network but also the local topologies that are produced by different graph evolutionary processes like motif duplication or joining. A divergence measure on spectral densities is used to quantify the distances between various metabolic networks, and a ...

  4. Metabolic markers as possible diagnostic tools to distinguish ...

    African Journals Online (AJOL)

    No metabolic markers could distinguish between gram positive and gram negative septicemia. α-Amino-adipic acid, citramalic acid and xanthurenic acid, produced only by bacteria, show promise. Alanine and glycine increased significantly over 24 h and can be used as diagnostic markers and perhaps as markers of ...

  5. Relation between usual daily walking time and metabolic syndrome ...

    African Journals Online (AJOL)

    Background: There are several studies about the positive relation between physical inactivity or low cardio respiratory fitness with development of metabolic syndrome (MS). In contrast, physical activity had favourable effects on all components of MS but the quantity and the frequency of physical activity necessary to produce ...

  6. The Effects of Breakfast Consumption and Composition on Metabolic Wellness with a Focus on Carbohydrate Metabolism.

    Science.gov (United States)

    Maki, Kevin C; Phillips-Eakley, Alyssa K; Smith, Kristen N

    2016-05-01

    Findings from epidemiologic studies indicate that there are associations between breakfast consumption and a lower risk of type 2 diabetes mellitus (T2DM) and metabolic syndrome, prompting interest in the influence of breakfast on carbohydrate metabolism and indicators of T2DM risk. The objective of this review was to summarize the available evidence from randomized controlled trials assessing the impact of breakfast on variables related to carbohydrate metabolism and metabolic wellness. Consuming compared with skipping breakfast appeared to improve glucose and insulin responses throughout the day. Breakfast composition may also be important. Dietary patterns high in rapidly available carbohydrate were associated with elevated T2DM risk. Therefore, partial replacement of rapidly available carbohydrate with other dietary components, such as whole grains and cereal fibers, proteins, and unsaturated fatty acids (UFAs), at breakfast may be a useful strategy for producing favorable metabolic outcomes. Consumption of fermentable and viscous dietary fibers at breakfast lowers glycemia and insulinemia. Fermentable fibers likely act through enhancing insulin sensitivity later in the day, and viscous fibers have an acute effect to slow the rate of carbohydrate absorption. Partially substituting protein for rapidly available carbohydrate enhances satiety and diet-induced thermogenesis, and also favorably affects lipoprotein lipids and blood pressure. Partially substituting UFA for carbohydrate has been associated with improved insulin sensitivity, lipoprotein lipids, and blood pressure. Overall, the available evidence suggests that consuming breakfast foods high in whole grains and cereal fiber, while limiting rapidly available carbohydrate, is a promising strategy for metabolic health promotion. © 2016 American Society for Nutrition.

  7. Metabolic Diseases of Muscle

    Science.gov (United States)

    ... disease, composes and produces music in his home studio. He moved from Michigan to California to pursue ... helps recruit and coordinate in-home help MDA’s public health education program helps you stay abreast of ...

  8. Microbiota-Produced Succinate Improves Glucose Homeostasis via Intestinal Gluconeogenesis.

    Science.gov (United States)

    De Vadder, Filipe; Kovatcheva-Datchary, Petia; Zitoun, Carine; Duchampt, Adeline; Bäckhed, Fredrik; Mithieux, Gilles

    2016-07-12

    Beneficial effects of dietary fiber on glucose and energy homeostasis have long been described, focusing mostly on the production of short-chain fatty acids by the gut commensal bacteria. However, bacterial fermentation of dietary fiber also produces large amounts of succinate and, to date, no study has focused on the role of succinate on host metabolism. Here, we fed mice a fiber-rich diet and found that succinate was the most abundant carboxylic acid in the cecum. Dietary succinate was identified as a substrate for intestinal gluconeogenesis (IGN), a process that improves glucose homeostasis. Accordingly, dietary succinate improved glucose and insulin tolerance in wild-type mice, but those effects were absent in mice deficient in IGN. Conventional mice colonized with the succinate producer Prevotella copri exhibited metabolic benefits, which could be related to succinate-activated IGN. Thus, microbiota-produced succinate is a previously unsuspected bacterial metabolite improving glycemic control through activation of IGN. Copyright © 2016 Elsevier Inc. All rights reserved.

  9. Polyamine metabolism revisited.

    Science.gov (United States)

    Urdiales, J L; Medina MA; Sánchez-Jiménez, F

    2001-09-01

    The natural polyamines putrescine, spermidine and spermine play an essential role in cell growth and differentiation. Cellular polyamine depletion results in inhibition of growth, whereas its accumulation appears to be toxic. Intracellular levels of polyamines are regulated by a multitude of mechanisms affecting their synthesis, degradation, uptake and excretion. The three key enzymes in the regulation of polyamine metabolism have short half-lives and are inducible. Ornithine and S-adenosylmethionine decarboxylases regulate polyamine biosynthesis whereas spermidine/spermine acetyltransferase regulates polyamine interconvertion and degradation.

  10. Metal metabolism and toxicity

    International Nuclear Information System (INIS)

    Bhattacharyya, M.H.; Larsen, R.P.; Whelton, B.D.; Moretti, E.S.; Peterson, D.P.; Oldham, R.D.

    1985-01-01

    This research focuses on the role of pregnancy and lactation in susceptibility to the toxic effects of cadmium and lead. Responses under investigation include lead-induced changes in pathways for vitamin D and calcium metabolism and cadmium-induced alterations in kidney function and skeletal structure. The second area focuses on the gastrointestinal absorption of plutonium and other actinide elements. Studies currently being conducted in nonhuman primates to develop a procedure to determine GI absorption values of uranium and plutonium that does not require sacrifice of the animal. 6 refs

  11. Crassulacean acid metabolism

    Directory of Open Access Journals (Sweden)

    Thomas David Geydan

    2005-07-01

    Full Text Available A review of Crassulacean acid metabolism is presented, characterized by showing the occurrence, activity and plasticity of these complex mechanism at the physiological, biochemical and molecular level, framed by the presence of the denominated four phases in CAM and its repercussion and expression due to different stresses in an ecological context. The basic enzymes, and metabolites necessary for the optional functioning of CAM are presented as well as their mode of action and cellular control. Finally, it is shown how environmental conditions and molecular signalling mediate the phenotypic plasticity.

  12. Method for producing carbon nanotubes

    Science.gov (United States)

    Phillips, Jonathan [Santa Fe, NM; Perry, William L [Jemez Springs, NM; Chen, Chun-Ku [Albuquerque, NM

    2006-02-14

    Method for producing carbon nanotubes. Carbon nanotubes were prepared using a low power, atmospheric pressure, microwave-generated plasma torch system. After generating carbon monoxide microwave plasma, a flow of carbon monoxide was directed first through a bed of metal particles/glass beads and then along the outer surface of a ceramic tube located in the plasma. As a flow of argon was introduced into the plasma through the ceramic tube, ropes of entangled carbon nanotubes, attached to the surface of the tube, were produced. Of these, longer ropes formed on the surface portion of the tube located in the center of the plasma. Transmission electron micrographs of individual nanotubes revealed that many were single-walled.

  13. Metabolic network reconstruction, growth characterization and 13C-metabolic flux analysis of the extremophile Thermus thermophilus HB8.

    Science.gov (United States)

    Swarup, Aditi; Lu, Jing; DeWoody, Kathleen C; Antoniewicz, Maciek R

    2014-07-01

    Thermus thermophilus is an extremely thermophilic bacterium with significant biotechnological potential. In this work, we have characterized aerobic growth characteristics of T. thermophilus HB8 at temperatures between 50 and 85°C, constructed a metabolic network model of its central carbon metabolism and validated the model using (13)C-metabolic flux analysis ((13)C-MFA). First, cells were grown in batch cultures in custom constructed mini-bioreactors at different temperatures to determine optimal growth conditions. The optimal temperature for T. thermophilus grown on defined medium with glucose was 81°C. The maximum growth rate was 0.25h(-1). Between 50 and 81°C the growth rate increased by 7-fold and the temperature dependence was described well by an Arrhenius model with an activation energy of 47kJ/mol. Next, we performed a (13)C-labeling experiment with [1,2-(13)C] glucose as the tracer and calculated intracellular metabolic fluxes using (13)C-MFA. The results provided support for the constructed network model and highlighted several interesting characteristics of T. thermophilus metabolism. We found that T. thermophilus largely uses glycolysis and TCA cycle to produce biosynthetic precursors, ATP and reducing equivalents needed for cells growth. Consistent with its proposed metabolic network model, we did not detect any oxidative pentose phosphate pathway flux or Entner-Doudoroff pathway activity. The biomass precursors erythrose-4-phosphate and ribose-5-phosphate were produced via the non-oxidative pentose phosphate pathway, and largely via transketolase, with little contribution from transaldolase. The high biomass yield on glucose that was measured experimentally was also confirmed independently by (13)C-MFA. The results presented here provide a solid foundation for future studies of T. thermophilus and its metabolic engineering applications. Copyright © 2014 International Metabolic Engineering Society. Published by Elsevier Inc. All rights reserved.

  14. SU-E-J-102: Separation of Metabolic Supply and Demand: From Power Grid Economics to Cancer Metabolism

    International Nuclear Information System (INIS)

    Epstein, T; Xu, L; Gillies, R; Gatenby, R

    2014-01-01

    Purpose: To study a new model of glucose metabolism which is primarily governed by the timescale of the energetic demand and not by the oxygen level, and its implication on cancer metabolism (Warburg effect) Methods: 1) Metabolic profiling of membrane transporters activity in several cell lines, which represent the spectrum from normal breast epithelium to aggressive, metastatic cancer, using Seahorse XF reader.2) Spatial localization of oxidative and non-oxidative metabolic components using immunocytochemical imaging of the glycolytic ATP-producing enzyme, pyruvate kinase and mitochondria. 3) Finite element simulations of coupled partial differential equations using COMSOL and MATLAB. Results: Inhibition or activation of pumps on the cell membrane led to reduction or increase in aerobic glycolysis, respectively, while oxidative phosphorylation remained unchanged. These results were consistent with computational simulations of changes in short-timescale demand for energy by cell membrane processes. A specific model prediction was that the spatial distribution of ATP-producing enzymes in the glycolytic pathway must be primarily localized adjacent to the cell membrane, while mitochondria should be predominantly peri-nuclear. These predictions were confirmed experimentally. Conclusion: The results in this work support a new model for glucose metabolism in which glycolysis and oxidative phosphorylation supply different types of energy demand. Similar to power grid economics, optimal metabolic control requires the two pathways, even in normoxic conditions, to match two different types of energy demands. Cells use aerobic metabolism to meet baseline, steady energy demand and glycolytic metabolism to meet short-timescale energy demands, mainly from membrane transport activities, even in the presence of oxygen. This model provides a mechanism for the origin of the Warburg effect in cancer cells. Here, the Warburg effect emerges during carcinogenesis is a physiological

  15. SU-E-J-102: Separation of Metabolic Supply and Demand: From Power Grid Economics to Cancer Metabolism

    Energy Technology Data Exchange (ETDEWEB)

    Epstein, T; Xu, L; Gillies, R; Gatenby, R [Moffitt Cancer Center and Research Institute, Tampa, FL (United States)

    2014-06-01

    Purpose: To study a new model of glucose metabolism which is primarily governed by the timescale of the energetic demand and not by the oxygen level, and its implication on cancer metabolism (Warburg effect) Methods: 1) Metabolic profiling of membrane transporters activity in several cell lines, which represent the spectrum from normal breast epithelium to aggressive, metastatic cancer, using Seahorse XF reader.2) Spatial localization of oxidative and non-oxidative metabolic components using immunocytochemical imaging of the glycolytic ATP-producing enzyme, pyruvate kinase and mitochondria. 3) Finite element simulations of coupled partial differential equations using COMSOL and MATLAB. Results: Inhibition or activation of pumps on the cell membrane led to reduction or increase in aerobic glycolysis, respectively, while oxidative phosphorylation remained unchanged. These results were consistent with computational simulations of changes in short-timescale demand for energy by cell membrane processes. A specific model prediction was that the spatial distribution of ATP-producing enzymes in the glycolytic pathway must be primarily localized adjacent to the cell membrane, while mitochondria should be predominantly peri-nuclear. These predictions were confirmed experimentally. Conclusion: The results in this work support a new model for glucose metabolism in which glycolysis and oxidative phosphorylation supply different types of energy demand. Similar to power grid economics, optimal metabolic control requires the two pathways, even in normoxic conditions, to match two different types of energy demands. Cells use aerobic metabolism to meet baseline, steady energy demand and glycolytic metabolism to meet short-timescale energy demands, mainly from membrane transport activities, even in the presence of oxygen. This model provides a mechanism for the origin of the Warburg effect in cancer cells. Here, the Warburg effect emerges during carcinogenesis is a physiological

  16. Nonlinear Pricing to Produce Information

    OpenAIRE

    David J. Braden; Shmuel S. Oren

    1994-01-01

    We investigate the firm's dynamic nonlinear pricing problem when facing consumers whose tastes vary according to a scalar index. We relax the standard assumption that the firm knows the distribution of this index. In general the firm should determine its marginal price schedule as if it were myopic, and produce information by lowering the price schedule; “bunching” consumers at positive purchase levels should be avoided. As a special case we also consider a market characterized by homogeneous...

  17. Soybean biomass produced in Argentina

    DEFF Research Database (Denmark)

    Semino, Stella Maris; Paul, Helena; Tomei, Julia

    2009-01-01

    Soybean biomass for biodiesel, produced in Argentina amongst other places, is considered by some to reduce greenhouse gas emissions and mitigate climate change when compared with fossil fuel. To ensure that the production of biofuels is ‘sustainable', EU institutions and national governments are ...... for environmental sustainability. This is exemplified by soy, whose cultivation undermines the climate benefit claimed for soy-based biodiesel. This paper concludes that to certify soy monocultures as sustainable would exacerbate existing climatic and environmental problems....

  18. Method for producing metallic nanoparticles

    Science.gov (United States)

    Phillips, Jonathan; Perry, William L.; Kroenke, William J.

    2004-02-10

    Method for producing metallic nanoparticles. The method includes generating an aerosol of solid metallic microparticles, generating non-oxidizing plasma with a plasma hot zone at a temperature sufficiently high to vaporize the microparticles into metal vapor, and directing the aerosol into the hot zone of the plasma. The microparticles vaporize in the hot zone to metal vapor. The metal vapor is directed away from the hot zone and to the plasma afterglow where it cools and condenses to form solid metallic nanoparticles.

  19. Method for producing metallic microparticles

    Science.gov (United States)

    Phillips, Jonathan; Perry, William L.; Kroenke, William J.

    2004-06-29

    Method for producing metallic particles. The method converts metallic nanoparticles into larger, spherical metallic particles. An aerosol of solid metallic nanoparticles and a non-oxidizing plasma having a portion sufficiently hot to melt the nanoparticles are generated. The aerosol is directed into the plasma where the metallic nanoparticles melt, collide, join, and spheroidize. The molten spherical metallic particles are directed away from the plasma and enter the afterglow where they cool and solidify.

  20. Extended producer responsibility in oligopoly

    OpenAIRE

    Hiroaki Ino

    2007-01-01

    I investigate the optimal environmental tax under a policy based on extended producer responsibility (EPR) in oligopoly markets. I introduce the recycling market and explicitly consider how these policies affect the incentive for recycling. I derive the optimal tax rule, which depends on the weighted sum of the markup in the product market and the markdown in the recycling market. In contrast to the existing works that emphasize that the optimal tax rate is lower than the marginal external da...

  1. Metabolic syndrome, diet and exercise.

    Science.gov (United States)

    De Sousa, Sunita M C; Norman, Robert J

    2016-11-01

    Polycystic ovary syndrome (PCOS) is associated with a range of metabolic complications including insulin resistance (IR), obesity, dyslipidaemia, hypertension, obstructive sleep apnoea (OSA) and non-alcoholic fatty liver disease. These compound risks result in a high prevalence of metabolic syndrome and possibly increased cardiovascular (CV) disease. As the cardiometabolic risk of PCOS is shared amongst the different diagnostic systems, all women with PCOS should undergo metabolic surveillance though the precise approach differs between guidelines. Lifestyle interventions consisting of increased physical activity and caloric restriction have been shown to improve both metabolic and reproductive outcomes. Pharmacotherapy and bariatric surgery may be considered in resistant metabolic disease. Issues requiring further research include the natural history of PCOS-associated metabolic disease, absolute CV risk and comparative efficacy of lifestyle interventions. Copyright © 2016 Elsevier Ltd. All rights reserved.

  2. Cancer metabolism at a glance.

    Science.gov (United States)

    Vazquez, Alexei; Kamphorst, Jurre J; Markert, Elke K; Schug, Zachary T; Tardito, Saverio; Gottlieb, Eyal

    2016-09-15

    A defining hallmark of cancer is uncontrolled cell proliferation. This is initiated once cells have accumulated alterations in signaling pathways that control metabolism and proliferation, wherein the metabolic alterations provide the energetic and anabolic demands of enhanced cell proliferation. How these metabolic requirements are satisfied depends, in part, on the tumor microenvironment, which determines the availability of nutrients and oxygen. In this Cell Science at a Glance paper and the accompanying poster, we summarize our current understanding of cancer metabolism, emphasizing pathways of nutrient utilization and metabolism that either appear or have been proven essential for cancer cells. We also review how this knowledge has contributed to the development of anticancer therapies that target cancer metabolism. © 2016. Published by The Company of Biologists Ltd.

  3. Metabolic impact of shift work.

    Science.gov (United States)

    Zimberg, Ioná Zalcman; Fernandes Junior, Silvio A; Crispim, Cibele Aparecida; Tufik, Sergio; de Mello, Marco Tulio

    2012-01-01

    In developing countries, shift work represents a considerable contingent workforce. Recently, studies have shown that overweight and obesity are more prevalent in shift workers than day workers. In addition, shift work has been associated with a higher propensity for the development of many metabolic disorders, such as insulin resistance, diabetes, dislipidemias and metabolic syndrome. Recent data have pointed that decrease of the sleep time, desynchronization of circadian rhythm and alteration of environmental aspects are the main factors related to such problems. Shortened or disturbed sleep is among the most common health-related effects of shift work. The plausible physiological and biological mechanisms are related to the activation of the autonomic nervous system, inflammation, changes in lipid and glucose metabolism, and related changes in the risk for atherosclerosis, metabolic syndrome, and type II diabetes. The present review will discuss the impact of shift work on obesity and metabolic disorders and how disruption of sleep and circadian misalignment may contribute to these metabolic dysfunctions.

  4. Metabolic Reprogramming in Thyroid Carcinoma

    Directory of Open Access Journals (Sweden)

    Raquel Guimaraes Coelho

    2018-03-01

    Full Text Available Among all the adaptations of cancer cells, their ability to change metabolism from the oxidative to the glycolytic phenotype is a hallmark called the Warburg effect. Studies on tumor metabolism show that improved glycolysis and glutaminolysis are necessary to maintain rapid cell proliferation, tumor progression, and resistance to cell death. Thyroid neoplasms are common endocrine tumors that are more prevalent in women and elderly individuals. The incidence of thyroid cancer has increased in the Past decades, and recent findings describing the metabolic profiles of thyroid tumors have emerged. Currently, several drugs are in development or clinical trials that target the altered metabolic pathways of tumors are undergoing. We present a review of the metabolic reprogramming in cancerous thyroid tissues with a focus on the factors that promote enhanced glycolysis and the possible identification of promising metabolic targets in thyroid cancer.

  5. Metabolic Reprogramming in Thyroid Carcinoma

    Science.gov (United States)

    Coelho, Raquel Guimaraes; Fortunato, Rodrigo S.; Carvalho, Denise P.

    2018-01-01

    Among all the adaptations of cancer cells, their ability to change metabolism from the oxidative to the glycolytic phenotype is a hallmark called the Warburg effect. Studies on tumor metabolism show that improved glycolysis and glutaminolysis are necessary to maintain rapid cell proliferation, tumor progression, and resistance to cell death. Thyroid neoplasms are common endocrine tumors that are more prevalent in women and elderly individuals. The incidence of thyroid cancer has increased in the Past decades, and recent findings describing the metabolic profiles of thyroid tumors have emerged. Currently, several drugs are in development or clinical trials that target the altered metabolic pathways of tumors are undergoing. We present a review of the metabolic reprogramming in cancerous thyroid tissues with a focus on the factors that promote enhanced glycolysis and the possible identification of promising metabolic targets in thyroid cancer. PMID:29629339

  6. Bacterial chemotaxis: introverted or extroverted? A comparison of the advantages and disadvantages of basic forms of metabolism-based and metabolism-independent behavior using a computational model.

    Science.gov (United States)

    Egbert, Matthew D

    2013-01-01

    Using a minimal model of metabolism, we examine the limitations of behavior that is (a) solely in response to environmental phenomena or (b) solely in response to metabolic dynamics, showing that basic forms of each of these kinds of behavior are incapable of driving survival-prolonging behavior in certain situations. Inspired by experimental evidence of concurrent metabolism-based and metabolism-independent chemotactic mechanisms in Escherichia coli and Rhodobacter sphaeroides, we then investigate how metabolism-independent and metabolism-based sensitivities can be integrated into a single behavioral response, demonstrating that a simple switching mechanism can be sufficient to effectively integrate metabolism-based and metabolism-independent behaviors. Finally, we use a spatial simulation of bacteria to show that the investigated forms of behavior produce different spatio-temporal patterns that are influenced by the metabolic-history of the bacteria. We suggest that these patterns could be a way to experimentally derive insight into the relationship between metabolism and chemotaxis in real bacteria.

  7. Magnesium Oxide Induced Metabolic Alkalosis in Cattle

    Science.gov (United States)

    Ogilvie, T.H.; Butler, D.G.; Gartley, C.J.; Dohoo, I.R.

    1983-01-01

    A study was designed to compare the metabolic alkalosis produced in cattle from the use of an antacid (magnesium oxide) and a saline cathartic (magnesium sulphate). Six, mature, normal cattle were treated orally with a magnesium oxide (MgO) product and one week later given a comparable cathartic dose of magnesium sulphate (MgSO4). The mean percent dry matter content of the cattle feces changed significantly (Pmetabolic alkalosis as determined by base excess values. The base excess values remained elevated for 24 hours in the MgO treated group compared to only 12 hours after MgSO4 administration. Following MgO administration, mean hydrogen ion concentration (pH), bicarbonate ion concentration ([HCO3-]) and base excess were 7.44, 33.3 mmol/L and +8.0 respectively compared to 7.38, 27 mmol/L and +3.0 after MgSO4. Since the oral use of MgO in normal cattle causes a greater and more prolonged metabolic alkalosis compared to MgSO4, MgO is contraindicated as a cathartic in normal cattle or in cattle with abomasal abnormalities characterized by pyloric obstruction and metabolic alkalosis. PMID:6883181

  8. Biochemical research elucidating metabolic pathways in Pneumocystis*

    Directory of Open Access Journals (Sweden)

    Kaneshiro E.S.

    2010-12-01

    Full Text Available Advances in sequencing the Pneumocystis carinii genome have helped identify potential metabolic pathways operative in the organism. Also, data from characterizing the biochemical and physiological nature of these organisms now allow elucidation of metabolic pathways as well as pose new challenges and questions that require additional experiments. These experiments are being performed despite the difficulty in doing experiments directly on this pathogen that has yet to be subcultured indefinitely and produce mass numbers of cells in vitro. This article reviews biochemical approaches that have provided insights into several Pneumocystis metabolic pathways. It focuses on 1 S-adenosyl-L-methionine (AdoMet; SAM, which is a ubiquitous participant in numerous cellular reactions; 2 sterols: focusing on oxidosqualene cyclase that forms lanosterol in P. carinii; SAM:sterol C-24 methyltransferase that adds methyl groups at the C-24 position of the sterol side chain; and sterol 14α-demethylase that removes a methyl group at the C-14 position of the sterol nucleus; and 3 synthesis of ubiquinone homologs, which play a pivotal role in mitochondrial inner membrane and other cellular membrane electron transport.

  9. Probiotics as Complementary Treatment for Metabolic Disorders

    Directory of Open Access Journals (Sweden)

    Mélanie Le Barz

    2015-08-01

    Full Text Available Over the past decade, growing evidence has established the gut microbiota as one of the most important determinants of metabolic disorders such as obesity and type 2 diabetes. Indeed, obesogenic diet can drastically alter bacterial populations (i.e., dysbiosis leading to activation of pro-inflammatory mechanisms and metabolic endotoxemia, therefore promoting insulin resistance and cardiometabolic disorders. To counteract these deleterious effects, probiotic strains have been developed with the aim of reshaping the microbiome to improve gut health. In this review, we focus on benefits of widely used probiotics describing their potential mechanisms of action, especially their ability to decrease metabolic endotoxemia by restoring the disrupted intestinal mucosal barrier. We also discuss the perspective of using new bacterial strains such as butyrate-producing bacteria and the mucolytic Akkermansia muciniphila, as well as the use of prebiotics to enhance the functionality of probiotics. Finally, this review introduces the notion of genetically engineered bacterial strains specifically developed to deliver anti-inflammatory molecules to the gut.

  10. Metabolic regulation of yeast

    Science.gov (United States)

    Fiechter, A.

    1982-12-01

    Metabolic regulation which is based on endogeneous and exogeneous process variables which may act constantly or time dependently on the living cell is discussed. The observed phenomena of the regulation are the result of physical, chemical, and biological parameters. These parameters are identified. Ethanol is accumulated as an intermediate product and the synthesis of biomass is reduced. This regulatory effect of glucose is used for the aerobic production of ethanol. Very high production rates are thereby obtained. Understanding of the regulation mechanism of the glucose effect has improved. In addition to catabolite repression, several other mechanisms of enzyme regulation have been described, that are mostly governed by exogeneous factors. Glucose also affects the control of respiration in a third class of yeasts which are unable to make use of ethanol as a substrate for growth. This is due to the lack of any anaplerotic activity. As a consequence, diauxic growth behavior is reduced to a one-stage growth with a drastically reduced cell yield. The pulse chemostat technique, a systematic approach for medium design is developed and medium supplements that are essential for metabolic control are identified.

  11. Biochemical Hypermedia: Galactose Metabolism.

    Directory of Open Access Journals (Sweden)

    J.K. Sugai

    2013-05-01

    Full Text Available Introduction: Animations of biochemical processes and virtual laboratory environments lead to true molecular simulations. The use of interactive software’s in education can improve cognitive capacity, better learning and, mainly, it makes information acquisition easier. Material and Methods: This work presents the development of a biochemical hypermedia to understanding of the galactose metabolism. It was developed with the help of concept maps, ISIS Draw, ADOBE Photoshop and FLASH MX Program. Results and Discussion: A step by step animation process shows the enzymatic reactions of galactose conversion to glucose-1-phosphate (to glycogen synthesis, glucose-6-phosphate (glycolysis intermediary, UDP-galactose (substrate to mucopolysaccharides synthesis and collagen’s glycosylation. There are navigation guide that allow scrolling the mouse over the names of the components of enzymatic reactions of via the metabolism of galactose. Thus, explanatory text box, chemical structures and animation of the actions of enzymes appear to navigator. Upon completion of the module, the user’s response to the proposed exercise can be checked immediately through text box with interactive content of the answer. Conclusion: This hypermedia was presented for undergraduate students (UFSC who revealed that it was extremely effective in promoting the understanding of the theme.

  12. Metabolic topography of Parkinsonism

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Jae Seung [Asan Medical Center, University of Ulsan College of Medicine, Seoul (Korea, Republic of)

    2007-04-15

    Parkinson's disease is one of the most frequent neurodegenerative diseases, which mainly affects the elderly. Parkinson's disease is often difficult to differentiate from atypical parkinson disorder such as progressive supranuclear palsy, multiple system atrophy, dementia with Lewy body, and corticobasal ganglionic degeneration, based on the clinical findings because of the similarity of phenotypes and lack of diagnostic markers. The accurate diagnosis of Parkinson's disease and atypical Parkinson disorders is not only important for deciding on treatment regimens and providing prognosis, but also it is critical for studies designed to investigate etiology and pathogenesis of parkinsonism and to develop new therapeutic strategies. Although degeneration of the nigrostriatal dopamine system results in marked loss of striatal dopamine content in most of the diseases causing parkinsonism, pathologic studies revealed different topographies of the neuronal cell loss in Parkinsonism. Since the regional cerebral glucose metabolism is a marker of integrated local synaptic activity and as such is sensitive to both direct neuronal/synaptic damage and secondary functional disruption at synapses distant from the primary site of pathology, and assessment of the regional cerebral glucose metabolism with F-18 FDG PET is useful in the differential diagnosis of parkinsonism and evaluating the pathophysiology of Parkinsonism.

  13. Metabolic topography of Parkinsonism

    International Nuclear Information System (INIS)

    Kim, Jae Seung

    2007-01-01

    Parkinson's disease is one of the most frequent neurodegenerative diseases, which mainly affects the elderly. Parkinson's disease is often difficult to differentiate from atypical parkinson disorder such as progressive supranuclear palsy, multiple system atrophy, dementia with Lewy body, and corticobasal ganglionic degeneration, based on the clinical findings because of the similarity of phenotypes and lack of diagnostic markers. The accurate diagnosis of Parkinson's disease and atypical Parkinson disorders is not only important for deciding on treatment regimens and providing prognosis, but also it is critical for studies designed to investigate etiology and pathogenesis of parkinsonism and to develop new therapeutic strategies. Although degeneration of the nigrostriatal dopamine system results in marked loss of striatal dopamine content in most of the diseases causing parkinsonism, pathologic studies revealed different topographies of the neuronal cell loss in Parkinsonism. Since the regional cerebral glucose metabolism is a marker of integrated local synaptic activity and as such is sensitive to both direct neuronal/synaptic damage and secondary functional disruption at synapses distant from the primary site of pathology, and assessment of the regional cerebral glucose metabolism with F-18 FDG PET is useful in the differential diagnosis of parkinsonism and evaluating the pathophysiology of Parkinsonism

  14. Mitochondrial Metabolism in Aging Heart

    OpenAIRE

    Lesnefsky, Edward J.; Chen, Qun; Hoppel, Charles L.

    2016-01-01

    Altered mitochondrial metabolism is the underlying basis for the increased sensitivity in the aged heart to stress. The aged heart exhibits impaired metabolic flexibility, with a decreased capacity to oxidize fatty acids and enhanced dependence on glucose metabolism. Aging impairs mitochondrial oxidative phosphorylation, with a greater role played by the mitochondria located between the myofibrils, the interfibrillar mitochondria. With aging, there is a decrease in activity of complexes III a...

  15. Severe metabolic alkalosis in pregnancy

    Science.gov (United States)

    Frise, Charlotte; Noori, Muna

    2013-01-01

    Summary Metabolic alkalosis is uncommon in pregnancy and is most often the result of severe vomiting. If this is present at the time of delivery, transient metabolic derangement in the fetus can occur, potentially requiring additional organ support. A 22-year-old woman is described, who presented at 37 weeks gestation with a severe metabolic alkalosis, vomiting and acute renal and hepatic impairment. The investigations, management options and maternal and fetal outcome are described. PMID:27708709

  16. Testosterone and the metabolic syndrome

    OpenAIRE

    Muraleedharan, Vakkat; Jones, T. Hugh

    2010-01-01

    Metabolic syndrome and testosterone deficiency in men are closely Linked. Epidemiological studies have shown that Low testosterone Levels are associated with obesity, insulin resistance and an adverse Lipid profile in men. Conversely in men with metabolic syndrome and type 2 diabetes have a high prevalence of hypogonadism. Metabolic syndrome and Low testosterone status are both independently associated with increased all-cause and cardiovascular mortality. Observational and experimental data ...

  17. From prebiotic chemistry to cellular metabolism--the chemical evolution of metabolism before Darwinian natural selection.

    Science.gov (United States)

    Meléndez-Hevia, Enrique; Montero-Gómez, Nancy; Montero, Francisco

    2008-06-07

    It is generally assumed that the complex map of metabolism is a result of natural selection working at the molecular level. However, natural selection can only work on entities that have three basic features: information, metabolism and membrane. Metabolism must include the capability of producing all cellular structures, as well as energy (ATP), from external sources; information must be established on a material that allows its perpetuity, in order to safeguard the goals achieved; and membranes must be able to preserve the internal material, determining a selective exchange with external material in order to ensure that both metabolism and information can be individualized. It is not difficult to understand that protocellular entities that boast these three qualities can evolve through natural selection. The problem is rather to explain the origin of such features under conditions where natural selection could not work. In the present work we propose that these protocells could be built by chemical evolution, starting from the prebiotic primordial soup, by means of chemical selection. This consists of selective increases of the rates of certain specific reactions because of the kinetic or thermodynamic features of the process, such as stoichiometric catalysis or autocatalysis, cooperativity and others, thereby promoting their prevalence among the whole set of chemical possibilities. Our results show that all chemical processes necessary for yielding the basic materials that natural selection needs to work may be achieved through chemical selection, thus suggesting a way for life to begin.

  18. Metabolic Engineering for Substrate Co-utilization

    Science.gov (United States)

    Gawand, Pratish

    Production of biofuels and bio-based chemicals is being increasingly pursued by chemical industry to reduce its dependence on petroleum. Lignocellulosic biomass (LCB) is an abundant source of sugars that can be used for producing biofuels and bio-based chemicals using fermentation. Hydrolysis of LCB results in a mixture of sugars mainly composed of glucose and xylose. Fermentation of such a sugar mixture presents multiple technical challenges at industrial scale. Most industrial microorganisms utilize sugars in a sequential manner due to the regulatory phenomenon of carbon catabolite repression (CCR). Due to sequential utilization of sugars, the LCB-based fermentation processes suffer low productivities and complicated operation. Performance of fermentation processes can be improved by metabolic engineering of microorganisms to obtain superior characteristics such as high product yield. With increased computational power and availability of complete genomes of microorganisms, use of model-based metabolic engineering is now a common practice. The problem of sequential sugar utilization, however, is a regulatory problem, and metabolic models have never been used to solve such regulatory problems. The focus of this thesis is to use model-guided metabolic engineering to construct industrial strains capable of co-utilizing sugars. First, we develop a novel bilevel optimization algorithm SimUp, that uses metabolic models to identify reaction deletion strategies to force co-utilization of two sugars. We then use SimUp to identify reaction deletion strategies to force glucose-xylose co-utilization in Escherichia coli. To validate SimUp predictions, we construct three mutants with multiple gene knockouts and test them for glucose-xylose utilization characteristics. Two mutants, designated as LMSE2 and LMSE5, are shown to co-utilize glucose and xylose in agreement with SimUp predictions. To understand the molecular mechanism involved in glucose-xylose co-utilization of the

  19. Gut Microbiota and Metabolic Disorders

    Directory of Open Access Journals (Sweden)

    Kyu Yeon Hur

    2015-06-01

    Full Text Available Gut microbiota plays critical physiological roles in the energy extraction and in the control of local or systemic immunity. Gut microbiota and its disturbance also appear to be involved in the pathogenesis of diverse diseases including metabolic disorders, gastrointestinal diseases, cancer, etc. In the metabolic point of view, gut microbiota can modulate lipid accumulation, lipopolysaccharide content and the production of short-chain fatty acids that affect food intake, inflammatory tone, or insulin signaling. Several strategies have been developed to change gut microbiota such as prebiotics, probiotics, certain antidiabetic drugs or fecal microbiota transplantation, which have diverse effects on body metabolism and on the development of metabolic disorders.

  20. Artificial Promoters for Metabolic Optimization

    DEFF Research Database (Denmark)

    Jensen, Peter Ruhdal; Hammer, Karin

    1998-01-01

    In this article, we review some of the expression systems that are available for Metabolic Control Analysis and Metabolic Engineering, and examine their advantages and disadvantages in different contexts. In a recent approach, artificial promoters for modulating gene expression in micro-organisms......In this article, we review some of the expression systems that are available for Metabolic Control Analysis and Metabolic Engineering, and examine their advantages and disadvantages in different contexts. In a recent approach, artificial promoters for modulating gene expression in micro...

  1. Clinical update on metabolic syndrome

    Directory of Open Access Journals (Sweden)

    Juan Diego Hernández-Camacho

    2017-12-01

    Full Text Available Metabolic syndrome has been defined as a global issue since it affects a lot of people. Numerous factors are involved in metabolic syndrome development. It has been described that metabolic syndrome has negative consequences on health. Consequently, a lot of treatments have been proposed to palliate it such as drugs, surgery or life style changes where nutritional habits have shown to be an important point in its management. The current study reviews the literature existing about the actual epidemiology of metabolic syndrome, the components involucrate in its appearance and progression, the clinical consequences of metabolic syndrome and the nutritional strategies reported in its remission. A bibliographic search in PubMed and Medline was performed to identify eligible studies. Authors obtained that metabolic syndrome is present in population from developed and undeveloped areas in a huge scale. Environmental and genetic elements are involucrate in metabolic syndrome development. Metabolic syndrome exponentially increased risk of cardiovascular disease, some types of cancers, diabetes mellitus type 2, sleep disturbances, etc. Nutritional treatments play a crucial role in metabolic syndrome prevention, treatment and recovery.

  2. Metabolic requirements for fetal growth.

    Science.gov (United States)

    Milley, J R; Simmons, M A

    1979-09-01

    Table 1 outlines a metabolic balance sheet for the sheep fetus. It is clear that maternal substrate concentrations as well as placental function are important in assuring the provision of adequate substrate to meet fetal metabolic and growth requirements. It is intriguing that the fetus appears to use substrates not usually regarded as important in extrauterine diets (lactate) and to use substrates for catabolic purposes normally thought to be primarily anabolic substrates (amino acids). This information emphasizes the hazards of extrapolating metabolic and nutritional patterns seen in extrauterine life in reaching conclusions concerning the fetus. It likewise emphasizes the importance of ongoing studies in maternal and fetal nutrition and metabolism.

  3. Regulatory Biology: Depressed Metabolic States

    Science.gov (United States)

    Holton, E. M. (Editor)

    1973-01-01

    Exobiological aspects of depressed metabolism and thermoregulation are discussed for subsequent development of biological space flight experiments. Included is a brief description of differential hypothermia in cancer chemotherapy.

  4. Atrazine Metabolism and Herbicidal Selectivity

    Science.gov (United States)

    Shimabukuro, R. H.

    1967-01-01

    Metabolism of the herbicide 2-chloro-4-ethylamino-6-isopropylamino-s-triazine (atrazine) was investigated in resistant corn (Zea mays L.) and sorghum (Sorghum vulgare Pers.), intermediately susceptible pea (Pisum sativum L.), and highly susceptible wheat (Triticum vulgare Vill.) and soybean (Glycine max Merril.). This study revealed that 2 possible pathways for atrazine metabolism exist in higher plants. All species studied were able to metabolize atrazine initially by N-dealkylation of either of the 2 substituted alkylamine groups. Corn and wheat, which contain benzoxazinone, also metabolized atrazine initially by hydrolysis in the 2-position of the s-triazine ring to form hydroxyatrazine. Subsequent metabolism by both pathways resulted in the conversion of the parent atrazine to more polar compounds and eventually into methanol-insoluble plant residue. No evidence for s-triazine ring cleavage was obtained. Both pathways for atrazine metabolism appear to detoxify atrazine. The hydroxylation pathway results in a direct conversion of a highly phytotoxic compound to a completely non-phytotoxic derivative. The dealkylation pathway leads to detoxication through one or more partially detoxified, stable intermediates. Therefore, the rate and pathways of atrazine metabolism are important in determining the tolerance of plants to the herbicide. Both quantitative and qualitative differences in atrazine metabolism were detected between resistant, intermediately susceptible, and susceptible species. The ability of plants to metabolize atrazine by N-dealkylation and the influence of this pathway in determining tolerance of plants to atrazine are discussed. Images PMID:16656648

  5. Producing biofuels using polyketide synthases

    Science.gov (United States)

    Katz, Leonard; Fortman, Jeffrey L; Keasling, Jay D

    2013-04-16

    The present invention provides for a non-naturally occurring polyketide synthase (PKS) capable of synthesizing a carboxylic acid or a lactone, and a composition such that a carboxylic acid or lactone is included. The carboxylic acid or lactone, or derivative thereof, is useful as a biofuel. The present invention also provides for a recombinant nucleic acid or vector that encodes such a PKS, and host cells which also have such a recombinant nucleic acid or vector. The present invention also provides for a method of producing such carboxylic acids or lactones using such a PKS.

  6. How Mobility Systems Produce Inequality

    DEFF Research Database (Denmark)

    Richardson, Tim; Jensen, Ole B.

    2008-01-01

    This paper explores a crucial aspect of sustainable mobility: the production of social inequality in mobility systems. The approach taken is to focus on how, as new transit infrastructures create alternative ways of traveling in and accessing the city, they create changed conditions for the forma...... are constructed and how social inequality is materially produced.......This paper explores a crucial aspect of sustainable mobility: the production of social inequality in mobility systems. The approach taken is to focus on how, as new transit infrastructures create alternative ways of traveling in and accessing the city, they create changed conditions...

  7. Fatty acid-producing hosts

    Science.gov (United States)

    Pfleger, Brian F; Lennen, Rebecca M

    2013-12-31

    Described are hosts for overproducing a fatty acid product such as a fatty acid. The hosts include an exogenous nucleic acid encoding a thioesterase and, optionally, an exogenous nucleic acid encoding an acetyl-CoA carboxylase, wherein an acyl-CoA synthetase in the hosts are functionally delected. The hosts prefereably include the nucleic acid encoding the thioesterase at an intermediate copy number. The hosts are preferably recominantly stable and growth-competent at 37.degree. C. Methods of producing a fatty acid product comprising culturing such hosts at 37.degree. C. are also described.

  8. Uranium producers foresee new boom

    International Nuclear Information System (INIS)

    McIntyre, H.

    1979-01-01

    The status of uranium production in Canada is reviewed. Uranium resources in Saskatchewan and Ontario are described and the role of the Cluff Lake inquiry in securing a government decision in favour of further uranium development is mentioned. There have been other uranium strikes near Kelowna, British Columbia and in the Northwest Territories. Increasing uranium demand and favourable prices are making the development of northern resources economically attractive. In fact, all uranium currently produced has been committed to domestic and export contracts so that there is considerable room for expanding the production of uranium in Canada. (T.I.)

  9. Electromagnetic pulses produced by expanding laser-produced Au plasma

    Czech Academy of Sciences Publication Activity Database

    De Marco, Massimo; Cikhardt, J.; Krása, Josef; Velyhan, Andriy; Pfeifer, Miroslav; Krouský, Eduard; Klír, D.; Řezáč, K.; Limpouch, J.; Margarone, Daniele; Ullschmied, Jiří

    2015-01-01

    Roč. 60, č. 2 (2015), s. 239-243 ISSN 0029-5922 R&D Projects: GA MŠk EE2.3.20.0279; GA ČR GAP205/12/0454; GA MŠk(CZ) LD14089; GA MŠk LM2010014 Grant - others:LaserZdroj (OP VK 3)(XE) CZ.1.07/2.3.00/20.0279 Institutional support: RVO:68378271 ; RVO:61389021 Keywords : laser-produced plasma * electromagnetic pulse (EMP) * return target current * Moebius loop antenna * inductive target probe Subject RIV: BL - Plasma and Gas Discharge Physics; BH - Optics, Masers, Lasers (UFP-V) Impact factor: 0.546, year: 2015

  10. [Nutrition and metabolic syndrome].

    Science.gov (United States)

    Matía Martín, Pilar; Lecumberri Pascual, Edurne; Calle Pascual, Alfonso L

    2007-01-01

    Sufficient evidence exists in relation to the association in clinical practice between disorders in the metabolism of glucose, lipoproteins, insulin action, arterial hypertension and centrally-distributed obesity. This association is named Metabolic Syndrome. Despite the existence thereof had been questioned by the ADA and EASD, it is a useful tool affording the possibility of identifying individuals at high risk of developing cardiovascular disease. Metabolic syndrome and/or its individual components are associated with a high incidence rate of cardiovascular disease. Obesity and a sedentary lifestyle are underlying risk factors along this syndrome's pathway to disease, changes in living habits therefore being a first-line intervention in the prevention and treatment of insulin resistance, hyperglycemia, aterogenic dyslipemia and arterial hypertension. Weight loss and exercise are the keys to the overall plan, one of the most important non-pharmacological cardiovascular risk reduction strategies however still being diet. Epidemiological studies have found a high intake of simple sugars, of foods having a glycemic index and of diets with a high glycemic load to be associated to insulin resistance, type II diabetes mellitus, hypertriglyceridemia and low HDL-cholesterol figures. Los saturated fat intake in favor of polyunsaturated and monounsaturated fatty acids has been implied in a reduction of the incidence of type II diabetes mellitus and dyslipemia, although the debate is ongoing. Unrefined grain fiber in the diet has been beneficial in reducing the risk of diabetes. Among the diet patterns, the Mediterranean diet has been related to a lower incidence of diabetes and a reduction in the risk of death. Studies for intervention in the prevention of type II diabetes have suggested low-fat diets (reducing saturated and trans-fats), with a high degree of fiber and low glycemic index. Clinical trials have shown diets with small amounts of carbohydrates, low glycemic

  11. ANAEROBIC ENDOGENOUS METABOLISM IN STREPTOCOCCUS FAECALIS.

    Science.gov (United States)

    WALKER, D J; FORREST, W W

    1964-02-01

    Walker, D. J. (CSIRO, University of Adelaide, Adelaide, South Australia), and W. W. Forrest. Endogenous metabolism in Streptococcus faecalis. J. Bacteriol. 87:256-262. 1964.-Washed suspensions of Streptococcus faecalis incubated in phosphate buffer (pH 6.0) under anaerobic conditions released amino acids into the suspending medium. Little or no carbohydrate was released in soluble form, and no acid production could be detected. Cell lipid was stable, and only a small amount of nucleotide (material absorbing at 260 mmu) was released. Estimates of total carbon produced in soluble form showed that this could be almost entirely accounted for as amino acid. Over the short period during which amino acid was produced (up to 5 hr), the glycolytic activity of the cells remained fairly constant, and fell slowly thereafter to low values in 24 to 48 hr; the rate of fall depended on cell concentration. Whereas exogenous sources of energy protected against loss of glycolytic activity, arsenate, hydroxylamine, or replacement of phosphate by other buffers accelerated loss of glycolytic activity. Restoration of glycolytic activity in aged cells could be achieved by incubation with amino acids plus an energy source, with concurrent synthesis of protein but no apparent growth. Ammonium ion was not effective in protecting or restoring glycolytic activity. The nature of changes which took place during endogenous metabolism are discussed.

  12. CLAs, nature, origin and some metabolic aspects

    Directory of Open Access Journals (Sweden)

    Chardigny Jean-Michel

    2005-01-01

    Full Text Available CLA (conjugated linoleic acid is a generic term for several isomers of linoleic acid with conjugated double bonds. They have been reported since 1935 in butter fat, but the major natural isomer (9cis,11trans-18 :2 was identified in 1977 and further named « rumenic acid ». This fatty acid is formed in the rumen as a product of biohydrogenation. Tissues may also produce rumenic acid from vaccenic acid, which is a further intermediate of ruminal biohydrogenation. Interest for CLAs started with a report on beneficial effects of CLA from grilled beef on skin tumours. CLA was produced as mixtures of isomers from chemically modified vegetable oil. As a metabolic point of view, it has been shown that rumenic acid is bioconverted like linoleic acid and beta-oxidised. CLA isomers may also interfere with the metabolism of other fatty acids. Other targets than skin tumours have also been identified. These aspects will be developed in other sections of the present issue.

  13. Apolipoprotein B metabolism: tracer kinetics, models, and metabolic studies.

    Science.gov (United States)

    Burnett, John R; Barrett, P Hugh R

    2002-04-01

    The study of apolipoprotein (apo) B metabolism is central to our understanding of lipoprotein metabolism. However, the assembly and secretion of apoB-containing lipoproteins is a complex process. Specialized techniques, developed and applied to in vitro and in vivo studies of apoB metabolism, have provided insights into the mechanisms involved in the regulation of this process. Moreover, these studies have important implications for understanding both the pathophysiology as well as the therapeutic options for the dyslipidemias. The purpose of this review is to examine the role of apoB in lipoprotein metabolism and to explore the applications of kinetic analysis and multicompartmental modeling to the study of apoB metabolism. New developments and significant advances over the last decade are discussed.

  14. Concrete produced with recycled aggregates

    Directory of Open Access Journals (Sweden)

    J. J. L. Tenório

    Full Text Available This paper presents the analysis of the mechanical and durable properties of recycled aggregate concrete (RAC for using in concrete. The porosity of recycled coarse aggregates is known to influence the fresh and hardened concrete properties and these properties are related to the specific mass of the recycled coarse aggregates, which directly influences the mechanical properties of the concrete. The recycled aggregates were obtained from construction and demolition wastes (CDW, which were divided into recycled sand (fine and coarse aggregates. Besides this, a recycled coarse aggregate of a specific mass with a greater density was obtained by mixing the recycled aggregates of the CDW with the recycled aggregates of concrete wastes (CW. The concrete was produced in laboratory by combining three water-cement ratios, the ratios were used in agreement with NBR 6118 for structural concretes, with each recycled coarse aggregates and recycled sand or river sand, and the reference concrete was produced with natural aggregates. It was observed that recycled aggregates can be used in concrete with properties for structural concrete. In general, the use of recycled coarse aggregate in combination with recycled sand did not provide good results; but when the less porous was used, or the recycled coarse aggregate of a specific mass with a greater density, the properties of the concrete showed better results. Some RAC reached bigger strengths than the reference concrete.

  15. Aspects of energetic substrate metabolism of in vitro and in vivo bovine embryos

    Directory of Open Access Journals (Sweden)

    D.K. de Souza

    2015-03-01

    Full Text Available Although the metabolism of early bovine embryos has not been fully elucidated, several publications have addressed this important issue to improve culture conditions for cattle reproductive biotechnologies, with the ultimate goal of producing in vitro embryos similar in quality to those developing in vivo. Here, we review general aspects of bovine embryo metabolism in vitro and in vivo, and discuss the use of metabolic analysis of embryos produced in vitro to assess viability and predict a viable pregnancy after transference to the female tract.

  16. Aspects of energetic substrate metabolism of in vitro and in vivo bovine embryos

    International Nuclear Information System (INIS)

    Souza, D.K. de; Salles, L.P.; Rosa e Silva, A.A.M.

    2015-01-01

    Although the metabolism of early bovine embryos has not been fully elucidated, several publications have addressed this important issue to improve culture conditions for cattle reproductive biotechnologies, with the ultimate goal of producing in vitro embryos similar in quality to those developing in vivo. Here, we review general aspects of bovine embryo metabolism in vitro and in vivo, and discuss the use of metabolic analysis of embryos produced in vitro to assess viability and predict a viable pregnancy after transference to the female tract

  17. Aspects of energetic substrate metabolism of in vitro and in vivo bovine embryos

    Energy Technology Data Exchange (ETDEWEB)

    Souza, D.K. de [Laboratório de Biotecnologia da Saúde, Faculdade de Medicina, Universidade de Brasília, Brasília, DF (Brazil); Faculdade da Ceilândia, Universidade de Brasília, Brasília, DF (Brazil); Salles, L.P. [Laboratório de Biotecnologia da Saúde, Faculdade de Medicina, Universidade de Brasília, Brasília, DF (Brazil); Departamento de Biologia Molecular, Instituto de Biologia, Universidade de Brasília, Brasília, DF (Brazil); Rosa e Silva, A.A.M. [Laboratório de Biotecnologia da Saúde, Faculdade de Medicina, Universidade de Brasília, Brasília, DF (Brazil)

    2015-01-23

    Although the metabolism of early bovine embryos has not been fully elucidated, several publications have addressed this important issue to improve culture conditions for cattle reproductive biotechnologies, with the ultimate goal of producing in vitro embryos similar in quality to those developing in vivo. Here, we review general aspects of bovine embryo metabolism in vitro and in vivo, and discuss the use of metabolic analysis of embryos produced in vitro to assess viability and predict a viable pregnancy after transference to the female tract.

  18. Regulation of Terpene Metabolism

    Energy Technology Data Exchange (ETDEWEB)

    Rodney Croteau

    2004-03-14

    OAK-B135 Research over the last four years has progressed fairly closely along the lines initially proposed, with progress-driven expansion of Objectives 1, 2 and 3. Recent advances have developed from three research thrusts: 1. Random sequencing of an enriched peppermint oil gland cDNA library has given access to a large number of potential pathway and regulatory genes for test of function; 2. The availability of new DNA probes and antibodies has permitted investigation of developmental regulation and organization of terpenoid metabolism; and 3. The development of a transformation system for peppermint by colleagues at Purdue University has allowed direct transgenic testing of gene function and added a biotechnological component to the project. The current status of each of the original research objectives is outlined below.

  19. Early anaerobic metabolisms

    DEFF Research Database (Denmark)

    Canfield, Donald Eugene; Rosing, Minik T; Bjerrum, Christian

    2006-01-01

    probably driven by the cycling of H2 and Fe2+ through primary production conducted by anoxygenic phototrophs. Interesting and dynamic ecosystems would have also been driven by the microbial cycling of sulphur and nitrogen species, but their activity levels were probably not so great. Despite the diversity......Before the advent of oxygenic photosynthesis, the biosphere was driven by anaerobic metabolisms. We catalogue and quantify the source strengths of the most probable electron donors and electron acceptors that would have been available to fuel early-Earth ecosystems. The most active ecosystems were...... of potential early ecosystems, rates of primary production in the early-Earth anaerobic biosphere were probably well below those rates observed in the marine environment. We shift our attention to the Earth environment at 3.8Gyr ago, where the earliest marine sediments are preserved. We calculate, consistent...

  20. The metabolic syndrome.

    Science.gov (United States)

    Harris, Mark F

    2013-08-01

    The metabolic syndrome (MetSy) is increasingly common in Australia. It is associated with the rise in obesity and lifestyle risk behaviours. It is also controversial - its value in predicting cardiovascular disease and diabetes risk and in guiding therapy has been challenged. This article aims to provide advice on the diagnosis of the MetSy and the principles for its prevention and management in the context of primary care, taking into consideration aetiological factors and the complexity of managing its constituent risk factors. Diagnosis of the MetSy is useful in focusing attention on central adiposity and insulin resistance as risk factors both for the syndrome, and cardiovascular and diabetes morbidity and mortality. Its assessment requires measurement of waist circumference - a simple but seldom performed procedure in general practice. The most essential components for the prevention and management of the MetSy are measures to change diet and physical activity in order to achieve and sustain weight loss.

  1. Metabolism during hypodynamia

    Science.gov (United States)

    Federov, I. V.

    1980-01-01

    Physical immobilization, inaction due to space travel, a sedentary occupation, or bed confinement due to a chronic illness elicit similar alternations in the metabolism of man and animals (rat, rabbit, dog, mouse). After a preliminary period of weight loss, there is eventually weight gain due to increased lipid storage. Protein catabolism is enhanced and anabolism depressed, with elevated urinary excretion of amino acids, creatine, and ammonia. Glycogen stores are depleted and glyconeogenesis is accelerated. Polyuria develops with subsequent redistribution of body fluids in which the blood volume of the systemic circulation is decreased and that of pulmonary circulation increased. This results in depressed production of vasopressin by the posterior pituitary which further enhances urinary water and salt loss.

  2. Cytochrome P450-dependent metabolism of caffeine in Drosophila melanogaster.

    Directory of Open Access Journals (Sweden)

    Alexandra Coelho

    Full Text Available Caffeine (1, 3, 7-trimethylxanthine, an alkaloid produced by plants, has antioxidant and insecticide properties that can affect metabolism and cognition. In vertebrates, the metabolites derived from caffeine have been identified, and their functions have been characterized. However, the metabolites of caffeine in insects remain unknown. Thus, using radiolabelled caffeine, we have identified some of the primary caffeine metabolites produced in the body of Drosophila melanogaster males, including theobromine, paraxanthine and theophylline. In contrast to mammals, theobromine was the predominant metabolite (paraxanthine in humans; theophylline in monkeys; 1, 3, 7-trimethyluric acid in rodents. A transcriptomic screen of Drosophila flies exposed to caffeine revealed the coordinated variation of a large set of genes that encode xenobiotic-metabolizing proteins, including several cytochromes P450s (CYPs that were highly overexpressed. Flies treated with metyrapone--an inhibitor of CYP enzymes--showed dramatically decreased caffeine metabolism, indicating that CYPs are involved in this process. Using interference RNA genetic silencing, we measured the metabolic and transcriptomic effect of three candidate CYPs. Silencing of CYP6d5 completely abolished theobromine synthesis, whereas CYP6a8 and CYP12d1 silencing induced different consequences on metabolism and gene expression. Therefore, we characterized several metabolic products and some enzymes potentially involved in the degradation of caffeine. In conclusion, this pioneer approach to caffeine metabolism in insects opens novel perspectives for the investigation of the physiological effects of caffeine metabolites. It also indicates that caffeine could be used as a biomarker to evaluate CYP phenotypes in Drosophila and other insects.

  3. Genome scale metabolic modeling of cancer

    DEFF Research Database (Denmark)

    Nilsson, Avlant; Nielsen, Jens

    2017-01-01

    of metabolism which allows simulation and hypotheses testing of metabolic strategies. It has successfully been applied to many microorganisms and is now used to study cancer metabolism. Generic models of human metabolism have been reconstructed based on the existence of metabolic genes in the human genome......Cancer cells reprogram metabolism to support rapid proliferation and survival. Energy metabolism is particularly important for growth and genes encoding enzymes involved in energy metabolism are frequently altered in cancer cells. A genome scale metabolic model (GEM) is a mathematical formalization...

  4. Metabolism of endocannabinoids.

    Science.gov (United States)

    Biernacki, Michał; Skrzydlewska, Elżbieta

    2016-08-11

    Endocannabinoids belong to a group of ester, ether and amide derivatives of fatty acids, which are endogenous ligands of receptors CB1, CB2, TRPV1 and GPR55 that are included in the endocannabinoid system of the animal organism. The best known endocannabinoids are: N-arachidonylethanolamide called anandamide (AEA) and 2-arachidonoylglycerol (2-AG). They occur in all organisms, and their highest level is observed in the brain. In this review the mechanisms of synthesis and degradation of both AEA and 2-AG are shown. Endocannabinoids are synthesized from phospholipids (mainly phosphatidylethanolamine, phosphatidylcholine, and phosphatidylinositol) located in the cell membrane. As a result of arachidonic acid transfer from phosphatidylcholine to phosphatidylethanolamine, N-arachidonoyl phosphatidylethanolamine is formed, which is hydrolyzed to AEA by phospholipase D, C and A2. However, 2-AG is formed during the hydrolysis of phosphatidylinositol catalyzed mainly by DAGL. The primary role of endocannabinoids is the activation of cannabinoid receptors. Both AEA and 2-AG are primarily agonists of the CB1 receptor and to a lower degree CB2 and TRPV1r eceptors, but 2-AG has stronger affinity for these receptors. Through activation of receptors, endocannabinoids affect cellular metabolism and participate in the metabolic processes by receptor-independent pathways. Endocannabinoids which are not bound to the receptors are degraded. The main enzymes responsible for the hydrolysis of AEA and 2-AG are FAAH and MAGL, respectively. Apart from hydrolytic degradation, endocannabinoids may also be oxidized by cyclooxygenase-2, lipoxygenases, and cytochrome P450. It has been shown that the metabolites of both endocannabinoids also have biological significance.

  5. Metabolism of endocannabinoids

    Directory of Open Access Journals (Sweden)

    Michał Biernacki

    2016-08-01

    Full Text Available Endocannabinoids belong to a group of ester, ether and amide derivatives of fatty acids, which are endogenous ligands of receptors CB1, CB2, TRPV1 and GPR55 that are included in the endocannabinoid system of the animal organism. The best known endocannabinoids are: N-arachidonylethanolamide called anandamide (AEA and 2-arachidonoylglycerol (2-AG. They occur in all organisms, and their highest level is observed in the brain. In this review the mechanisms of synthesis and degradation of both AEA and 2-AG are shown. Endocannabinoids are synthesized from phospholipids (mainly phosphatidylethanolamine, phosphatidylcholine, and phosphatidylinositol located in the cell membrane. As a result of arachidonic acid transfer from phosphatidylcholine to phosphatidylethanolamine, N-arachidonoyl phosphatidylethanolamine is formed, which is hydrolyzed to AEA by phospholipase D, C and A2. However, 2-AG is formed during the hydrolysis of phosphatidylinositol catalyzed mainly by DAGL. The primary role of endocannabinoids is the activation of cannabinoid receptors. Both AEA and 2-AG are primarily agonists of the CB1 receptor and to a lower degree CB2 and TRPV1r eceptors, but 2-AG has stronger affinity for these receptors. Through activation of receptors, endocannabinoids affect cellular metabolism and participate in the metabolic processes by receptor-independent pathways. Endocannabinoids which are not bound to the receptors are degraded. The main enzymes responsible for the hydrolysis of AEA and 2-AG are FAAH and MAGL, respectively. Apart from hydrolytic degradation, endocannabinoids may also be oxidized by cyclooxygenase-2, lipoxygenases, and cytochrome P450. It has been shown that the metabolites of both endocannabinoids also have biological significance.

  6. Activation of murine pre-proglucagon-producing neurons reduces food intake and body weight.

    Science.gov (United States)

    Gaykema, Ronald P; Newmyer, Brandon A; Ottolini, Matteo; Raje, Vidisha; Warthen, Daniel M; Lambeth, Philip S; Niccum, Maria; Yao, Ting; Huang, Yiru; Schulman, Ira G; Harris, Thurl E; Patel, Manoj K; Williams, Kevin W; Scott, Michael M

    2017-03-01

    Peptides derived from pre-proglucagon (GCG peptides) act in both the periphery and the CNS to change food intake, glucose homeostasis, and metabolic rate while playing a role in anxiety behaviors and physiological responses to stress. Although the actions of GCG peptides produced in the gut and pancreas are well described, the role of glutamatergic GGC peptide-secreting hindbrain neurons in regulating metabolic homeostasis has not been investigated. Here, we have shown that chemogenetic stimulation of GCG-producing neurons reduces metabolic rate and food intake in fed and fasted states and suppresses glucose production without an effect on glucose uptake. Stimulation of GCG neurons had no effect on corticosterone secretion, body weight, or conditioned taste aversion. In the diet-induced obese state, the effects of GCG neuronal stimulation on gluconeogenesis were lost, while the food intake-lowering effects remained, resulting in reductions in body weight and adiposity. Our work suggests that GCG peptide-expressing neurons can alter feeding, metabolic rate, and glucose production independent of their effects on hypothalamic pituitary-adrenal (HPA) axis activation, aversive conditioning, or insulin secretion. We conclude that GCG neurons likely stimulate separate populations of downstream cells to produce a change in food intake and glucose homeostasis and that these effects depend on the metabolic state of the animal.

  7. Integration of Sweet Taste and Metabolism Determines Carbohydrate Reward.

    Science.gov (United States)

    Veldhuizen, Maria Geraldine; Babbs, Richard Keith; Patel, Barkha; Fobbs, Wambura; Kroemer, Nils B; Garcia, Elizabeth; Yeomans, Martin R; Small, Dana M

    2017-08-21

    Post-ingestive signals related to nutrient metabolism are thought to be the primary drivers of reinforcement potency of energy sources. Here, in a series of neuroimaging and indirect calorimetry human studies, we examine the relative roles of caloric load and perceived sweetness in driving metabolic, perceptual, and brain responses to sugared beverages. Whereas caloric load was manipulated using the tasteless carbohydrate maltodextrin, sweetness levels were manipulated using the non-nutritive sweetener sucralose. By formulating beverages that contain different amounts of maltodextrin+sucralose, we demonstrate a non-linear association between caloric load, metabolic response, and reinforcement potency, which is driven in part by the extent to which sweetness is proportional to caloric load. In particular, we show that (1) lower-calorie beverages can produce greater metabolic response and condition greater brain response and liking than higher-calorie beverages and (2) when sweetness is proportional to caloric load, greater metabolic responses are observed. These results demonstrate a non-linear association between caloric load and reward and describe an unanticipated role for sweet taste in regulating carbohydrate metabolism, revealing a novel mechanism by which sugar-sweetened beverages influence physiological responses to carbohydrate ingestion. Copyright © 2017 Elsevier Ltd. All rights reserved.

  8. Deranged Cardiac Metabolism and the Pathogenesis of Heart Failure

    Science.gov (United States)

    2016-01-01

    Activation of the neuro-hormonal system is a pathophysiological consequence of heart failure. Neuro-hormonal activation promotes metabolic changes, such as insulin resistance, and determines an increased use of non-carbohydrate substrates for energy production. Fasting blood ketone bodies as well as fat oxidation are increased in patients with heart failure, yielding a state of metabolic inefficiency. The net result is additional depletion of myocardial adenosine triphosphate, phosphocreatine and creatine kinase levels with further decreased efficiency of mechanical work. In this context, manipulation of cardiac energy metabolism by modification of substrate use by the failing heart has produced positive clinical results. The results of current research support the concept that shifting the energy substrate preference away from fatty acid metabolism and towards glucose metabolism could be an effective adjunctive treatment in patients with heart failure. The additional use of drugs able to partially inhibit fatty acids oxidation in patients with heart failure may therefore yield a significant protective effect for clinical symptoms and cardiac function improvement, and simultaneously ameliorate left ventricular remodelling. Certainly, to clarify the exact therapeutic role of metabolic therapy in heart failure, a large multicentre, randomised controlled trial should be performed. PMID:28785448

  9. Schizophrenia: metabolic aspects of aetiology, diagnosis and future treatment strategies.

    Science.gov (United States)

    Harris, Laura W; Guest, Paul C; Wayland, Matthew T; Umrania, Yagnesh; Krishnamurthy, Divya; Rahmoune, Hassan; Bahn, Sabine

    2013-06-01

    Despite decades of research, the pathophysiology and aetiology of schizophrenia remains incompletely understood. The disorder is frequently accompanied by metabolic symptoms including dyslipidaemia, hyperinsulinaemia, type 2 diabetes and obesity. These symptoms are a common side effect of currently available antipsychotic medications. However, reports of metabolic dysfunction in schizophrenia predate the antipsychotic era and have also been observed in first onset patients prior to antipsychotic treatment. Here, we review the evidence for abnormalities in metabolism in schizophrenia patients, both in the central nervous system and periphery. Molecular analysis of post mortem brain tissue has pointed towards alterations in glucose metabolism and insulin signalling pathways, and blood-based molecular profiling analyses have demonstrated hyperinsulinaemia and abnormalities in secretion of insulin and co-released factors at first presentation of symptoms. Nonetheless, such features are not observed for all subjects with the disorder and not all individuals with such abnormalities suffer the symptoms of schizophrenia. One interpretation of these data is the presence of an underlying metabolic vulnerability in a subset of individuals which interacts with environmental or genetic factors to produce the overt symptoms of the disorder. Further investigation of metabolic aspects of schizophrenia may prove critical for diagnosis, improvement of existing treatment based on patient stratification/personalised medicine strategies and development of novel antipsychotic agents. Copyright © 2012 Elsevier Ltd. All rights reserved.

  10. Newborn Screening for inherited metabolic disorders; news and views

    Directory of Open Access Journals (Sweden)

    Morteza Pourfarzam

    2013-01-01

    Full Text Available Newborn screening is important for the early detection of many congenital genetic and metabolic disorders, aimed at the earliest possible recognition and management of affected newborns, to prevent the morbidity, mortality, and disabilities associated with an inherited metabolic disorder. This comprehensive system includes; testing, education, follow up, diagnosis, treatment, management, and evaluation. There are major differences among many of the disorders being considered for inclusion in newborn screening programs. In recent times, advances in laboratory technology such as tandem mass spectrometry (MS/MS, which is more specific, sensitive, reliable, and comprehensive than traditional assays, has increased the number of genetic conditions that can be diagnosed through neonatal screening programs at birth. With a single dried filter paper blood spot, MS/MS can identify more than 30 inherited metabolic disorders in around two to three minutes. Advances in the diagnosis and treatment and an increased understanding of the natural history of inborn errors of metabolism have produced pressure to implement expanded newborn screening programs in many countries. Even as many countries throughout the world have made newborn screening mandatory, in Iran, nationwide newborn screening for inherited metabolic disorders other than hypothyroidism has not been initiated, hence, there is little information about these diseases. This article aims to review the recent advances in newborn metabolic screening and its situation in Iran and other countries.

  11. Intestinal Crosstalk between Bile Acids and Microbiota and Its Impact on Host Metabolism

    DEFF Research Database (Denmark)

    Wahlström, Annika; Sayin, Sama I; Marschall, Hanns-Ulrich

    2016-01-01

    , is produced in the liver from cholesterol and metabolized in the intestine by the gut microbiota. These bioconversions modulate the signaling properties of bile acids via the nuclear farnesoid X receptor and the G protein-coupled membrane receptor 5, which regulate numerous metabolic pathways in the host......The gut microbiota is considered a metabolic "organ" that not only facilitates harvesting of nutrients and energy from the ingested food but also produces numerous metabolites that signal through their cognate receptors to regulate host metabolism. One such class of metabolites, bile acids....... Conversely, bile acids can modulate gut microbial composition both directly and indirectly through activation of innate immune genes in the small intestine. Thus, host metabolism can be affected through microbial modifications of bile acids, which lead to altered signaling via bile acid receptors, but also...

  12. L-Cysteine Metabolism and Fermentation in Microorganisms.

    Science.gov (United States)

    Takagi, Hiroshi; Ohtsu, Iwao

    L-Cysteine is an important amino acid both biologically and commercially. Although most amino acids are industrially produced by microbial fermentation, L-cysteine has been mainly produced by protein hydrolysis. Due to environmental and safety problems, synthetic or biotechnological products have been preferred in the market. Here, we reviewed L-cysteine metabolism, including biosynthesis, degradation, and transport, and biotechnological production (including both enzymatic and fermentation processes) of L-cysteine. The metabolic regulation of L-cysteine including novel sulfur metabolic pathways found in microorganisms is also discussed. Recent advancement in biochemical studies, genome sequencing, structural biology, and metabolome analysis has enabled us to use various approaches to achieve direct fermentation of L-cysteine from glucose. For example, worldwide companies began to supply L-cysteine and its derivatives produced by bacterial fermentation. These companies successfully optimized the original metabolism of their private strains. Basically, a combination of three factors should be required for improving L-cysteine fermentation: that is, (1) enhancing biosynthesis: overexpression of the altered cysE gene encoding feedback inhibition-insensitive L-serine O-acetyltransferase (SAT), (2) weakening degradation: knockout of the genes encoding L-cysteine desulfhydrases, and (3) exploiting export system: overexpression of the gene involved in L-cysteine transport. Moreover, we found that "thiosulfate" is much more effective sulfur source than commonly used "sulfate" for L-cysteine production in Escherichia coli, because thiosulfate is advantageous for saving consumption of NADPH and relating energy molecules.

  13. Gait Dynamics and Locomotor Metabolism

    Science.gov (United States)

    2014-12-01

    26 47. Taylor CR, Heglund NC, Maloiy GMO . Energetics and mechanics of terrestrial locomotion. I. Metabolic energy consumption as a function of...San Diego, CA: Academic Press, 1994. 110 47. Taylor CR, Heglund NC, Maloiy GMO . Energetics and mechanics of terrestrial locomotion. I. Metabolic

  14. Sex steroids and lipoprotein metabolism

    NARCIS (Netherlands)

    Gevers Leuven, J.A.

    1994-01-01

    Lipoprotein metabolism is involved in atherogenesis. Female sex-hormones have substantial effects on both lipoprotein metabolism and the vessel wall. Cholesterol, one of the major lipids in lipoproteins, is both the substrate for, and the target of, the steroidal sex hormones.

  15. Cancer Metabolism: A Modeling Perspective

    DEFF Research Database (Denmark)

    Ghaffari, Pouyan; Mardinoglu, Adil; Nielsen, Jens

    2015-01-01

    Tumor cells alter their metabolism to maintain unregulated cellular proliferation and survival, but this transformation leaves them reliant on constant supply of nutrients and energy. In addition to the widely studied dysregulated glucose metabolism to fuel tumor cell growth, accumulating evidences...

  16. Multidimensional optimality of microbial metabolism

    NARCIS (Netherlands)

    Schuetz, Robert; Zamboni, Nicola; Zampieri, Mattia; Heinemann, Matthias; Sauer, Uwe

    2012-01-01

    Although the network topology of metabolism is well known, understanding the principles that govern the distribution of fluxes through metabolism lags behind. Experimentally, these fluxes can be measured by (13)C-flux analysis, and there has been a long-standing interest in understanding this

  17. Metabolic syndrome and acute pancreatitis.

    Science.gov (United States)

    Mikolasevic, I; Milic, S; Orlic, L; Poropat, G; Jakopcic, I; Franjic, N; Klanac, A; Kristo, N; Stimac, D

    2016-07-01

    The aim of our study was to investigate the influence of metabolic syndrome on the course of acute pancreatitis determined by disease severity, the presence of local and systemic complications and survival rate. 609 patients admitted to our hospital in the period from January 1, 2008 up to June 31, 2015 with the diagnosis of acute pancreatitis were analyzed. The diagnosis and the severity of acute pancreatitis were made according to the revised Atlanta classification criteria from 2012. Of 609 patients with acute pancreatitis, 110 fulfilled the criteria for metabolic syndrome. Patients with metabolic syndrome had statistically significantly higher incidence of moderately severe (38.2% vs. 28.5%; p=0.05) and severe (22.7% vs. 12.8%; p=0.01) acute pancreatitis in comparison to those without metabolic syndrome, while patients without metabolic syndrome had higher incidence of mild acute pancreatitis in comparison to those patients with metabolic syndrome (58.7% vs. 39.1%; pacute pancreatitis. Comparing survival rates, patients suffering from metabolic syndrome had a higher death rate compared to patients without metabolic syndrome (16% vs. 4.5%; pacute pancreatitis, as well as higher mortality rate. Copyright © 2016 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.

  18. Conducting nanofibres produced by electrospinning

    Science.gov (United States)

    Sen, S.; Davis, F. J.; Mitchell, G. R.; Robinson, E.

    2009-08-01

    Electrospun fibres based on polypyrrole have been prepared. The incorporation of preformed polypyrrole into fibres electrospun from a carrier polymer can only be achieved when materials are prepared with particulates smaller than the cross-section of the fibre; even so there are some problems, with the substantial loss of material from the electrode tip. As an alternative approach, soluble polypyrroles can be prepared but these are not of sufficient viscosity to prepare electrospun fibres, once again a carrier polymer must be employed. More effective loadings are gained by the process of coating the outer surface of a pre-spun fibre; in this way electrospun fibres coated with polypyrrole can be prepared. This approach has been adapted to produce silver coated polymer fibres by the use of copolymers of styrene and 3-vinyl benzaldehyde.

  19. Conducting nanofibres produced by electrospinning

    International Nuclear Information System (INIS)

    Sen, S; Mitchell, G R; Robinson, E; Davis, F J

    2009-01-01

    Electrospun fibres based on polypyrrole have been prepared. The incorporation of preformed polypyrrole into fibres electrospun from a carrier polymer can only be achieved when materials are prepared with particulates smaller than the cross-section of the fibre; even so there are some problems, with the substantial loss of material from the electrode tip. As an alternative approach, soluble polypyrroles can be prepared but these are not of sufficient viscosity to prepare electrospun fibres, once again a carrier polymer must be employed. More effective loadings are gained by the process of coating the outer surface of a pre-spun fibre; in this way electrospun fibres coated with polypyrrole can be prepared. This approach has been adapted to produce silver coated polymer fibres by the use of copolymers of styrene and 3-vinyl benzaldehyde.

  20. Metabolic Engineering of Chemical Defence Pathways in Plant Disease Control

    DEFF Research Database (Denmark)

    Rook, Frederik

    2016-01-01

    with antimicrobial properties for use in crop protection. It presents an overview of the metabolic engineering efforts made in the area of plant chemical defence. For in-depth information on the characteristics of a specific class of chemical defence compounds, the reader is referred to the specialized reviews......Plants produce a wide variety of specialized (or secondary) metabolites that function as chemical defence compounds and provide protection against microbial pathogens or herbivores. This chapter focuses on the metabolic engineering of biosynthetic pathways for plant chemical defence compounds...

  1. [Update on acute management of inborn errors of metabolism].

    Science.gov (United States)

    Bravo J, Paulina; Castro C H, Gabriela

    2014-07-01

    Inborn metabolic disorders are genetic diseases which are uncommon each one, but together they are not. They are characterized by an enzimatic defect that blocks a metabolic pathway, producing specific signs and symptoms. The current article pretends be an updated guideline for their acute management which is based on: 1) Inmediate life support, hydroelectrolyte balance and sample procurement, 2) Avoiding the production of toxic endogenous metabolites and anabolism promotion, 3) The supplementation of substrates and 4) The removal of toxic substances. Their prompt suspicious, identification and treatment starting will be crucial for neurological prognosis and prevention of death.

  2. A Metabolic Therapy for Malignant Glioma Requires a Clinical Measure.

    Science.gov (United States)

    Corbin, Zachary; Spielman, Daniel; Recht, Lawrence

    2017-11-02

    Cancers are "reprogrammed" to use a much higher rate of glycolysis (GLY) relative to oxidative phosphorylation (OXPHOS), even in the presence of adequate amounts of oxygenation. Originally identified by Nobel Laureate Otto Warburg, this hallmark of cancer has recently been termed metabolic reprogramming and represents a way for the cancer tissue to divert carbon skeletons to produce biomass. Understanding the mechanisms that underlie this metabolic shift should lead to better strategies for cancer treatments. Malignant gliomas, cancers that are very resistant to conventional treatments, are highly glycolytic and seem particularly suited to approaches that can subvert this phenotype.

  3. Metabolic impact of an NADH-producing glucose-6-phosphate dehydrogenase in Escherichia coli

    DEFF Research Database (Denmark)

    Olavarria, K.; De Ingeniis, J.; Zielinski, D. C.

    2014-01-01

    In Escherichia coli, the oxidative branch of the pentose phosphate pathway (oxPPP) is one of the major sources of NADPH when glucose is the sole carbon nutrient. However, unbalanced NADPH production causes growth impairment as observed in a strain lacking phosphoglucoisomerase (Δpgi). In this work......PDH(R46E,Q47E). Through homologous recombination, the zwf loci (encoding G6PDH) in the chromosomes of WT and Δpgi E. coli strains were replaced by DNA encoding LmG6PDH(R46E,Q47E). Contrary to some predictions performed with flux balance analysis, the replacements caused a substantial effect...

  4. Effect of heat stress on polyamine metabolism in proline-over-producing tobacco plants

    Czech Academy of Sciences Publication Activity Database

    Cvikrová, Milena; Gemperlová, Lenka; Dobrá, Jana; Martincová, Olga; Prášil, I.T.; Gubiš, J.; Vaňková, Radomíra

    2012-01-01

    Roč. 182, Sp.Issue (2012), s. 49-58 ISSN 0168-9452 R&D Projects: GA MŠk OC08013 Institutional research plan: CEZ:AV0Z50380511 Keywords : Heat stress * Polyamines * Proline Subject RIV: ED - Physiology Impact factor: 2.922, year: 2012

  5. Retinoid Metabolism and Diabetes Mellitus

    Directory of Open Access Journals (Sweden)

    Eun-Jung Rhee

    2012-06-01

    Full Text Available Retinoid acid is a metabolite of vitamin A and functions as an important factor in cell survival, differentiation and death. Most previous studies on retinoid metabolism have focused on its association with cancer, hematologic and dermatologic disorders. Given the special concern over the recent increase in the prevalence of diabetes worldwide, the role of retinoid metabolism on glucose metabolism and insulin resistance in the human body is of marked importance. Therefore, in this issue, we review the literature on the association of retinoid metabolism with glucose tolerance, with regard to insulin secretion, pancreatic autoimmunity, insulin sensitivity and lipid metabolism. Further, we tried to assess the possibility of using retinoids as a novel therapeutic strategy for diabetes.

  6. Vasomotor symptoms and metabolic syndrome.

    Science.gov (United States)

    Tuomikoski, Pauliina; Savolainen-Peltonen, Hanna

    2017-03-01

    A vast majority of menopausal women suffer from vasomotor symptoms, such as hot flushes and night sweats, the mean duration of which may be up to 7-10 years. In addition to a decreased quality of life, vasomotor symptoms may have an impact on overall health. Vasomotor symptoms are associated with overactivity of the sympathetic nervous system, and sympathetic overdrive in turn is associated with metabolic syndrome, which is a known risk factor for cardiovascular disease. Menopausal hot flushes have a complex relationship to different features of the metabolic syndrome and not all data point towards an association between vasomotor symptoms and metabolic syndrome. Thus, it is still unclear whether vasomotor symptoms are an independent risk factor for metabolic syndrome. Research in this area is constantly evolving and we present here the most recent data on the possible association between menopausal vasomotor symptoms and the metabolic syndrome. Copyright © 2017 Elsevier B.V. All rights reserved.

  7. [Hypovitaminosis D and metabolic syndrome].

    Science.gov (United States)

    Miñambres, Inka; de Leiva, Alberto; Pérez, Antonio

    2014-12-23

    Metabolic syndrome and hypovitaminosis D are 2 diseases with high prevalence that share several risk factors, while epidemiological evidence shows they are associated. Although the mechanisms involved in this association are not well established, hypovitaminosis D is associated with insulin resistance, decreased insulin secretion and activation of the renin-angiotensin system, mechanisms involved in the pathophysiology of metabolic syndrome. However, the apparent ineffectiveness of vitamin D supplementation on metabolic syndrome components, as well as the limited information about the effect of improving metabolic syndrome components on vitamin D concentrations, does not clarify the direction and the mechanisms involved in the causal relationship between these 2 pathologies. Overall, because of the high prevalence and the epidemiological association between both diseases, hypovitaminosis D could be considered a component of the metabolic syndrome. Copyright © 2013 Elsevier España, S.L.U. All rights reserved.

  8. Possible mechanisms involved in the vasorelaxant effect produced by clobenzorex in aortic segments of rats

    OpenAIRE

    Lozano-Cuenca, J.; González-Hernández, A.; López-Canales, O.A.; Villagrana-Zesati, J.R.; Rodríguez-Choreão, J.D.; Morín-Zaragoza, R.; Castillo-Henkel, E.F.; López-Canales, J.S.

    2017-01-01

    Clobenzorex is a metabolic precursor of amphetamine indicated for the treatment of obesity. Amphetamines have been involved with cardiovascular side effects such as hypertension and pulmonary arterial hypertension. The aim of the present study was to investigate whether the direct application of 10?9?10?5 M clobenzorex on isolated phenylephrine-precontracted rat aortic rings produces vascular effects, and if so, what mechanisms may be involved. Clobenzorex produced an immediate concentration-...

  9. Crosstalk of metabolic factors and neurogenic signaling in adult neurogenesis: Implication of metabolic regulation for mental and neurological diseases.

    Science.gov (United States)

    Gao, Chong; Wang, Qi; Chung, Sookja K; Shen, Jiangang

    2017-06-01

    Metabolic disorders like diabetes and obesity are commonly companied with neurological diseases and psychiatric disorders. Accumulating evidences indicated that cellular metabolic factors affect adult neurogenesis and have modulating effects on neurodegenerative disorders and psychiatric diseases. Adult neurogenesis contains multiple steps including proliferation of neural stem cells, lineage commitments of neural progenitor cells, maturation into functional neurons, and integration into neuronal network. Many intrinsic and extrinsic factors produced from neural stem/progenitor cells and their microenvironment or neurogenic niche take roles in modulating neurogenesis and contribute to the brain repair and functional recoveries in many neurological diseases and psychiatric disorders. In this article, we review current progress about how different growth factors, neurotrophin, neurotransmitters and transcriptional factors work on regulating neurogenic process. In particular, we emphasize the roles of the cellular metabolic factors, such as insulin/IGF signaling, incretins, and lipid metabolic signaling molecules in modulating adult neurogenesis, and discuss their impacts on neurological behaviors. We propose that the metabolic factors could be the new therapeutic targets for adult neurogenesis. Plus, the metabolism-regulating drugs have the potentials for treatment of neurodegenerative diseases and mental disorders. Copyright © 2017 Elsevier Ltd. All rights reserved.

  10. The Effects of Breakfast Consumption and Composition on Metabolic Wellness with a Focus on Carbohydrate Metabolism1234

    Science.gov (United States)

    Maki, Kevin C; Phillips-Eakley, Alyssa K; Smith, Kristen N

    2016-01-01

    Findings from epidemiologic studies indicate that there are associations between breakfast consumption and a lower risk of type 2 diabetes mellitus (T2DM) and metabolic syndrome, prompting interest in the influence of breakfast on carbohydrate metabolism and indicators of T2DM risk. The objective of this review was to summarize the available evidence from randomized controlled trials assessing the impact of breakfast on variables related to carbohydrate metabolism and metabolic wellness. Consuming compared with skipping breakfast appeared to improve glucose and insulin responses throughout the day. Breakfast composition may also be important. Dietary patterns high in rapidly available carbohydrate were associated with elevated T2DM risk. Therefore, partial replacement of rapidly available carbohydrate with other dietary components, such as whole grains and cereal fibers, proteins, and unsaturated fatty acids (UFAs), at breakfast may be a useful strategy for producing favorable metabolic outcomes. Consumption of fermentable and viscous dietary fibers at breakfast lowers glycemia and insulinemia. Fermentable fibers likely act through enhancing insulin sensitivity later in the day, and viscous fibers have an acute effect to slow the rate of carbohydrate absorption. Partially substituting protein for rapidly available carbohydrate enhances satiety and diet-induced thermogenesis, and also favorably affects lipoprotein lipids and blood pressure. Partially substituting UFA for carbohydrate has been associated with improved insulin sensitivity, lipoprotein lipids, and blood pressure. Overall, the available evidence suggests that consuming breakfast foods high in whole grains and cereal fiber, while limiting rapidly available carbohydrate, is a promising strategy for metabolic health promotion. PMID:27184288

  11. Engineering plant metabolism into microbes: from systems biology to synthetic biology.

    Science.gov (United States)

    Xu, Peng; Bhan, Namita; Koffas, Mattheos A G

    2013-04-01

    Plant metabolism represents an enormous repository of compounds that are of pharmaceutical and biotechnological importance. Engineering plant metabolism into microbes will provide sustainable solutions to produce pharmaceutical and fuel molecules that could one day replace substantial portions of the current fossil-fuel based economy. Metabolic engineering entails targeted manipulation of biosynthetic pathways to maximize yields of desired products. Recent advances in Systems Biology and the emergence of Synthetic Biology have accelerated our ability to design, construct and optimize cell factories for metabolic engineering applications. Progress in predicting and modeling genome-scale metabolic networks, versatile gene assembly platforms and delicate synthetic pathway optimization strategies has provided us exciting opportunities to exploit the full potential of cell metabolism. In this review, we will discuss how systems and synthetic biology tools can be integrated to create tailor-made cell factories for efficient production of natural products and fuel molecules in microorganisms. Copyright © 2012 Elsevier Ltd. All rights reserved.

  12. Metabolic memory: Evolving concepts.

    Science.gov (United States)

    Misra, Anoop; Bloomgarden, Zachary

    2018-03-01

    The relationships of glycemic control over time with the development of complications have been investigated in several studies, but new areas of debate continue to arise. Does glycemic control have greater benefit when attained earlier than when attained later in the natural history of diabetes? Is it simply the duration of better or worse levels of glycemia that lead a given individual to have fewer or greater levels of complications? Might glycemic control have similar benefit throughout the duration of diabetes until irreversible damage occurs, perhaps varying by organ system (neurologic, renal, retinal, cardiovascular)? Specific benefits or adverse effects of treatment agents may further complicate the interpretation of what has been characterized as "metabolic memory." The notion of metabolic memory was based on findings of the Diabetes Control and Complications Trial (DCCT) of type 1 diabetes (T1D), in which the initial 2% HbA1c separation between the groups of patients randomized to intensive or conventional control was lost during the follow up Epidemiology of Diabetes Interventions and Complications (EDIC) study, when the two groups of participants returned to standard treatment and showed similar HbA1c levels but the initial intensively treated group continued to have lower rates of development of microvascular and, subsequently, macrovascular complications. Similarly, a decade after the conclusion of the UK Prospective Diabetes Study (UKPDS), patients with type 2 diabetes (T2D) in the intensive therapy group, despite showing similar levels of glycemic control to those receiving standard care, continued to have significant reductions in microvascular endpoints and reductions in myocardial infarction and all-cause mortality. A 6-year follow up of the Veteran's Administration Diabetes Trial suggested that the formerly intensively controlled subset were more likely to maintain an estimated glomerular filtration rate >60 ml/min/1.73m 2 than those randomized

  13. A Status Report on the Global Research in Microbial Metabolic Engineering

    International Nuclear Information System (INIS)

    Joe, Min Ho; Lim, Sang Yong; Kim, Dong Ho

    2008-09-01

    Biotechnology industry is now a global 'Mega-Trend' and metabolic engineering technology has important role is this area. Therefore, many countries has made efforts in this field to produce top value added bio-products efficiently using microorganisms. It has been applied to increase the production of chemicals that are already produced by the host organism, to produce desired chemical substances from less expensive feedstock, and to generate products that are new to the host organism. Recent experimental advances, the so-called '-omics' technologies, mainly functional genomics, proteomics and metabolomics, have enabled wholesale generation of new genomic, transcriptomic, proteomic, and metabolomic data. This report provides the insights of the integrated view of metabolism generated by metabolic engineering for biotechnological applications of microbial metabolic engineering

  14. A Status Report on the Global Research in Microbial Metabolic Engineering

    Energy Technology Data Exchange (ETDEWEB)

    Joe, Min Ho; Lim, Sang Yong; Kim, Dong Ho

    2008-09-15

    Biotechnology industry is now a global 'Mega-Trend' and metabolic engineering technology has important role is this area. Therefore, many countries has made efforts in this field to produce top value added bio-products efficiently using microorganisms. It has been applied to increase the production of chemicals that are already produced by the host organism, to produce desired chemical substances from less expensive feedstock, and to generate products that are new to the host organism. Recent experimental advances, the so-called '-omics' technologies, mainly functional genomics, proteomics and metabolomics, have enabled wholesale generation of new genomic, transcriptomic, proteomic, and metabolomic data. This report provides the insights of the integrated view of metabolism generated by metabolic engineering for biotechnological applications of microbial metabolic engineering.

  15. Pyrrolizidine alkaloids--genotoxicity, metabolism enzymes, metabolic activation, and mechanisms.

    Science.gov (United States)

    Fu, Peter P; Xia, Qingsu; Lin, Ge; Chou, Ming W

    2004-02-01

    Pyrrolizidine alkaloid-containing plants are widely distributed in the world and are probably the most common poisonous plants affecting livestock, wildlife, and humans. Because of their abundance and potent toxicities, the mechanisms by which pyrrolizidine alkaloids induce genotoxicities, particularly carcinogenicity, were extensively studied for several decades but not exclusively elucidated until recently. To date, the pyrrolizidine alkaloid-induced genotoxicities were revealed to be elicited by the hepatic metabolism of these naturally occurring toxins. In this review, we present updated information on the metabolism, metabolizing enzymes, and the mechanisms by which pyrrolizidine alkaloids exert genotoxicity and tumorigenicity.

  16. Galacto-oligosaccharide hydrolysis by genetically-engineered alpha-galactosidase-producing Pseudomonas chlororaphis strains

    Science.gov (United States)

    Various Pseudomonas chlororaphis strains have been shown to produce rhamnolipid (a biosurfactant), poly(hydroxyalkanoate) (PHA; a biopolymer), and/or antifungal compounds for plants. An ability to metabolize galacto-oligosaccharides in soy molasses would allow P. chlororaphis to use the byproduct as...

  17. Design of homo-organic acid producing strains using multi-objective optimization

    DEFF Research Database (Denmark)

    Kim, Tae Yong; Park, Jong Myoung; Kim, Hyun Uk

    2015-01-01

    Production of homo-organic acids without byproducts is an important challenge in bioprocess engineering to minimize operation cost for separation processes. In this study, we used multi-objective optimization to design Escherichia coli strains with the goals of maximally producing target organic ...... for the production of a homo-organic acid. The systems metabolic engineering-based approach reported here should be...

  18. Draft Genome Sequence of Clostridium aceticum DSM 1496, a Potential Butanol Producer through Syngas Fermentation

    OpenAIRE

    Song, Yoseb; Hwang, Soonkyu; Cho, Byung-Kwan

    2015-01-01

    Clostridium aceticum DSM 1496 is a Gram-negative anaerobic chemolithoautotrophic acetogenic bacterium that is capable of producing commodity chemicals from syngas fermentation. In this study, we report the draft genome sequence of the C.?aceticum DSM 1496 strain (4.16?Mb) to elucidate the syngas fermentation metabolic pathway.

  19. Draft Genome Sequence of Clostridium aceticum DSM 1496, a Potential Butanol Producer through Syngas Fermentation

    Science.gov (United States)

    Song, Yoseb; Hwang, Soonkyu

    2015-01-01

    Clostridium aceticum DSM 1496 is a Gram-negative anaerobic chemolithoautotrophic acetogenic bacterium that is capable of producing commodity chemicals from syngas fermentation. In this study, we report the draft genome sequence of the C. aceticum DSM 1496 strain (4.16 Mb) to elucidate the syngas fermentation metabolic pathway. PMID:25931594

  20. Draft Genome Sequence of Acetobacterium bakii DSM 8239, a Potential Psychrophilic Chemical Producer through Syngas Fermentation

    Science.gov (United States)

    Hwang, Soonkyu; Song, Yoseb

    2015-01-01

    Acetobacterium bakii DSM 8239 is an anaerobic, psychrophilic, and chemolithoautotrophic bacterium that is a potential platform for producing commodity chemicals from syngas fermentation. We report here the draft genome sequence of A. bakii DSM 8239 (4.14 Mb) to elucidate its physiological and metabolic properties related to syngas fermentation. PMID:26404601

  1. Manual for reactor produced radioisotopes

    International Nuclear Information System (INIS)

    2003-01-01

    numerous new developments that have taken place since then. Hence in this manual it was decided to focus only on reactor produced radioisotopes. This manual contains procedures for 48 important reactor-produced isotopes. These were contributed by major radioisotope producers from different parts of the world and are based on their practical experience. In case of widely used radioisotopes such as 131 I, 32 P and 99 Mo, information from more than one centre is included so that the users can compare the procedures. As in the earlier two versions, a general introductory write-up is included covering basic information on related aspects such as target irradiation, handling facilities, radiation protection and transportation, but in less detail. Relevant IAEA publications on such matters, particularly related to radiation protection and transportation, should be referred to for guidelines. Similarly, the nuclear data contained in the manual are only indicative and the relevant databases should be referred to for more authentic values. It is hoped that the manual will be a useful source of information for those working in radioisotope production laboratories as well as those intending to initiate such activities

  2. Elucidating and reprogramming Escherichia coli metabolisms for obligate anaerobic n-butanol and isobutanol production

    Energy Technology Data Exchange (ETDEWEB)

    Trinh, Cong T. [Tennessee Univ., Knoxville, TN (United States). Dept. of Chemical and Biomolecular Engineering

    2012-08-15

    Elementary mode (EM) analysis based on the constraint-based metabolic network modeling was applied to elucidate and compare complex fermentative metabolisms of Escherichia coli for obligate anaerobic production of n-butanol and isobutanol. The result shows that the n-butanol fermentative metabolism was NADH-deficient, while the isobutanol fermentative metabolism was NADH redundant. E. coli could grow and produce n-butanol anaerobically as the sole fermentative product but not achieve the maximum theoretical n-butanol yield. In contrast, for the isobutanol fermentative metabolism, E. coli was required to couple with either ethanol- or succinate-producing pathway to recycle NADH. To overcome these ''defective'' metabolisms, EM analysis was implemented to reprogram the native fermentative metabolism of E. coli for optimized anaerobic production of n-butanol and isobutanol through multiple gene deletion ({proportional_to}8-9 genes), addition ({proportional_to}6-7 genes), up- and downexpression ({proportional_to}6-7 genes), and cofactor engineering (e.g., NADH, NADPH). The designed strains were forced to couple both growth and anaerobic production of n-butanol and isobutanol, which is a useful characteristic to enhance biofuel production and tolerance through metabolic pathway evolution. Even though the n-butanol and isobutanol fermentative metabolisms were quite different, the designed strains could be engineered to have identical metabolic flux distribution in ''core'' metabolic pathways mainly supporting cell growth and maintenance. Finally, the model prediction in elucidating and reprogramming the native fermentative metabolism of E. coli for obligate anaerobic production of n-butanol and isobutanol was validated with published experimental data. (orig.)

  3. MARKETING STRATEGIES OF SMARTPHONES PRODUCERS

    Directory of Open Access Journals (Sweden)

    Markova V.

    2017-12-01

    Full Text Available Smartphones global market is one of the most dynamically developing markets that can be characterized by high level of competition. The growth of smartphones homogeneity, which is a reduction in difference between technical and functional parameters of smartphones produced by various manufacturers, can be considered the market’s specific feature. The unique situation of high-tech product homogeneity in a fast-growing market is scantily described in specialized literature. The article shows changeability of smartphones global market leaders and explains that the key success factor in such a mature market is marketing. Based on secondary information, marketing strategies of long standing market leader in sales Samsung and overtaking Apple companies are determined as well as strategies of contenders for leadership - Chinese companies Huawei and Lenovo. It is shown on Lenovo case that inexplicit positioning leads to a loss of the growing market share due to offensive marketing strategies of other Chinese companies. The research results broaden the knowledge of methodical potential of marketing strategies in companies’ activities in competitive markets of homogeneous high-tech products.

  4. PPARs in Rhythmic Metabolic Regulation and Implications in Health and Disease

    Directory of Open Access Journals (Sweden)

    Purin Charoensuksai

    2010-01-01

    Full Text Available The circadian rhythm, controlled by a complex network of cellular transcription factors, orchestrates behavior and physiology in the vast majority of animals. The circadian system is comprised of a master clock located in central nervous system with 24-hour rotation and periphery clocks to ensure optimal timing of physiology in peripheral tissues. Circadian expression of peroxisome proliferator-activated receptors (PPARs, members of the nuclear receptor superfamily and key mediators of energy homeostasis and metabolism, is regulated by clock genes. PPARs serve as sensors of nutrient and energy/metabolism status to temporally entrain peripheral clock. Metabolism and circadian clocks are tightly intertwined: clock genes drive metabolism, and various metabolic parameters affect clock genes, producing a reciprocal feedback relationship. Due to PPARs' robust relationship with energy status and metabolism, the aberration of PPARs in the biological clock system leads to abnormal expression of genes in metabolic pathways, thus, contributing to etiology of metabolic syndrome. Studying PPARs' functions under the context of the mammalian circadian system could advance our understanding of how energy and metabolic status are maintained in the body, which may ultimately lead to rhythmic medical treatment against metabolic syndrome.

  5. Metabolic syndrome in androgenic alopecia.

    Science.gov (United States)

    Gopinath, Hima; Upadya, Gatha M

    2016-01-01

    Androgenic alopecia has been associated with an increased risk of coronary heart disease in various studies. The relationship between androgenic alopecia and metabolic syndrome, a known risk factor for atherosclerotic cardiovascular disease, is still poorly understood. To study the association between metabolic syndrome and early-onset androgenic alopecia. A hospital-based analytical cross-sectional study was done on men in the age group of 18-55 years. Eighty five clinically diagnosed cases with early-onset (alopecia of Norwood grade III or above, and 85 controls without androgenic alopecia were included. Data collected included anthropometric measurements, arterial blood pressure and history of chronic diseases. Fasting blood and lipid profile were determined. Metabolic syndrome was diagnosed as per the new International Diabetes Federation criteria. Chi-square and Student's t-test were used for statistical analysis using Statistical Package for the Social Sciences (SPSS) version 17.00. Metabolic syndrome was seen in 19 (22.4%) patients with androgenic alopecia and 8 (9.4%) controls (P = 0.021). Abdominal obesity, hypertension and lowered high-density lipoprotein were significantly higher in patients with androgenic alopecia versus their respective controls. The limitations of our study include small sample size in subgroups and the lack of evidence of a temporal relationship between metabolic syndrome and androgenic alopecia. A higher prevalence of metabolic syndrome is seen in men with early-onset androgenic alopecia. Early screening for metabolic syndrome and its components is beneficial in patients with early-onset androgenic alopecia.

  6. Xenobiotic Metabolism and Gut Microbiomes

    Science.gov (United States)

    Das, Anubhav; Srinivasan, Meenakshi; Ghosh, Tarini Shankar; Mande, Sharmila S.

    2016-01-01

    Humans are exposed to numerous xenobiotics, a majority of which are in the form of pharmaceuticals. Apart from human enzymes, recent studies have indicated the role of the gut bacterial community (microbiome) in metabolizing xenobiotics. However, little is known about the contribution of the plethora of gut microbiome in xenobiotic metabolism. The present study reports the results of analyses on xenobiotic metabolizing enzymes in various human gut microbiomes. A total of 397 available gut metagenomes from individuals of varying age groups from 8 nationalities were analyzed. Based on the diversities and abundances of the xenobiotic metabolizing enzymes, various bacterial taxa were classified into three groups, namely, least versatile, intermediately versatile and highly versatile xenobiotic metabolizers. Most interestingly, specific relationships were observed between the overall drug consumption profile and the abundance and diversity of the xenobiotic metabolizing repertoire in various geographies. The obtained differential abundance patterns of xenobiotic metabolizing enzymes and bacterial genera harboring them, suggest their links to pharmacokinetic variations among individuals. Additional analyses of a few well studied classes of drug modifying enzymes (DMEs) also indicate geographic as well as age specific trends. PMID:27695034

  7. Cancer metabolism: a modeling perspective

    Directory of Open Access Journals (Sweden)

    Pouyan eGhaffari Nouran

    2015-12-01

    Full Text Available Tumor cells alter their metabolism to maintain unregulated cellular proliferation and survival, but this transformation leaves them reliant on constant supply of nutrients and energy. In addition to the widely studied dysregulated glucose metabolism to fuel tumor cell growth, accumulating evidences suggest that utilization of amino acids and lipids contributes significantly to cancer cell metabolism. Also recent progresses in our understanding of carcinogenesis have revealed that cancer is a complex disease and cannot be understood through simple investigation of genetic mutations of cancerous cells. Cancer cells present in complex tumor tissues communicate with the surrounding microenvironment and develop traits which promote their growth, survival and metastasis. Decoding the full scope and targeting dysregulated metabolic pathways that support neoplastic transformations and their preservation requires both the advancement of experimental technologies for more comprehensive measurement of omics as well as the advancement of robust computational methods for accurate analysis of the generated data. Here, we review cancer-associated reprogramming of metabolism and highlight the capability of genome-scale metabolic modeling approaches in perceiving a system-level perspective of cancer metabolism and in detecting novel selective drug targets

  8. Xenobiotic Metabolism and Gut Microbiomes.

    Directory of Open Access Journals (Sweden)

    Anubhav Das

    Full Text Available Humans are exposed to numerous xenobiotics, a majority of which are in the form of pharmaceuticals. Apart from human enzymes, recent studies have indicated the role of the gut bacterial community (microbiome in metabolizing xenobiotics. However, little is known about the contribution of the plethora of gut microbiome in xenobiotic metabolism. The present study reports the results of analyses on xenobiotic metabolizing enzymes in various human gut microbiomes. A total of 397 available gut metagenomes from individuals of varying age groups from 8 nationalities were analyzed. Based on the diversities and abundances of the xenobiotic metabolizing enzymes, various bacterial taxa were classified into three groups, namely, least versatile, intermediately versatile and highly versatile xenobiotic metabolizers. Most interestingly, specific relationships were observed between the overall drug consumption profile and the abundance and diversity of the xenobiotic metabolizing repertoire in various geographies. The obtained differential abundance patterns of xenobiotic metabolizing enzymes and bacterial genera harboring them, suggest their links to pharmacokinetic variations among individuals. Additional analyses of a few well studied classes of drug modifying enzymes (DMEs also indicate geographic as well as age specific trends.

  9. Aerobic glucose metabolism of Saccharomyces kluyveri: Growth, metabolite production, and quantification of metabolic fluxes

    DEFF Research Database (Denmark)

    Møller, Kasper; Christensen, B.; Förster, Jochen

    2002-01-01

    The growth and product formation of Saccharomyces kluyveri was characterized in aerobic batch cultivation on glucose. At these conditions it was found that ethyl acetate was a major overflow metabolite in S. kluyveri. During the exponential-growth phase on glucose ethyl acetate was produced...... at a constant specific rate of 0.12 g ethyl acetate per g dry weight per hour. The aerobic glucose metabolism in S. kluyveri was found to be less fermentative than in S. cerevisiae, as illustrated by the comparably low yield of ethanol on glucose (0.08 +/- 0.02 g/g), and high yield of biomass on glucose (0...

  10. Equine metabolic syndrome

    Science.gov (United States)

    Morgan, R.; Keen, J.; McGowan, C.

    2015-01-01

    Laminitis is one of the most common and frustrating clinical presentations in equine practice. While the principles of treatment for laminitis have not changed for several decades, there have been some important paradigm shifts in our understanding of laminitis. Most importantly, it is essential to consider laminitis as a clinical sign of disease and not as a disease in its own right. Once this shift in thinking has occurred, it is logical to then question what disease caused the laminitis. More than 90 per cent of horses presented with laminitis as their primary clinical sign will have developed it as a consequence of endocrine disease; most commonly equine metabolic syndrome (EMS). Given the fact that many horses will have painful protracted and/or chronic recurrent disease, a good understanding of the predisposing factors and how to diagnose and manage them is crucial. Current evidence suggests that early diagnosis and effective management of EMS should be a key aim for practising veterinary surgeons to prevent the devastating consequences of laminitis. This review will focus on EMS, its diagnosis and management. PMID:26273009

  11. Nitrogen metabolism meets phytopathology.

    Science.gov (United States)

    Fagard, Mathilde; Launay, Alban; Clément, Gilles; Courtial, Julia; Dellagi, Alia; Farjad, Mahsa; Krapp, Anne; Soulié, Marie-Christine; Masclaux-Daubresse, Céline

    2014-10-01

    Nitrogen (N) is essential for life and is a major limiting factor of plant growth. Because soils frequently lack sufficient N, large quantities of inorganic N fertilizers are added to soils for crop production. However, nitrate, urea, and ammonium are a major source of global pollution, because much of the N that is not taken up by plants enters streams, groundwater, and lakes, where it affects algal production and causes an imbalance in aquatic food webs. Many agronomical data indicate that the higher use of N fertilizers during the green revolution had an impact on the incidence of crop diseases. In contrast, examples in which a decrease in N fertilization increases disease severity are also reported, indicating that there is a complex relationship linking N uptake and metabolism and the disease infection processes. Thus, although it is clear that N availability affects disease, the underlying mechanisms remain unclear. The aim of this review is to describe current knowledge of the mechanisms that link plant N status to the plant's response to pathogen infection and to the virulence and nutritional status of phytopathogens. © The Author 2014. Published by Oxford University Press on behalf of the Society for Experimental Biology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  12. Revisiting the metabolic syndrome.

    Science.gov (United States)

    Chew, Gerard T; Gan, Seng Khee; Watts, Gerald F

    2006-10-16

    Metabolic syndrome (MS) refers to the clustering of cardiometabolic risk factors - including abdominal obesity, hyperglycaemia, dyslipidaemia and elevated blood pressure - that are thought to be linked to insulin resistance. MS is associated with increased risk of cardiovascular disease and type 2 diabetes. MS is common, affecting a quarter to a third of adults, and its prevalence is rising, in parallel with increasing obesity and population ageing. Operational definitions of MS have been proposed by the World Health Organization and the National Cholesterol Education Program. Recently, the International Diabetes Federation proposed a global definition that emphasised the importance of central adiposity. In cardiovascular risk assessment, MS encapsulates the contribution of non-traditional risk factors and provides a clinically useful framework for early identification of people at increased long-term risk. It should be used in conjunction with standard algorithms based on conventional risk factors, which better predict short-term risk. Management of MS should emphasise lifestyle interventions (eg, physical activity, healthy diet and weight reduction) to reduce long-term risk of cardiovascular disease and diabetes. Those at increased short-term risk should also have individual risk factors treated according to established guidelines.

  13. Early anaerobic metabolisms

    Science.gov (United States)

    Canfield, Don E; Rosing, Minik T; Bjerrum, Christian

    2006-01-01

    Before the advent of oxygenic photosynthesis, the biosphere was driven by anaerobic metabolisms. We catalogue and quantify the source strengths of the most probable electron donors and electron acceptors that would have been available to fuel early-Earth ecosystems. The most active ecosystems were probably driven by the cycling of H2 and Fe2+ through primary production conducted by anoxygenic phototrophs. Interesting and dynamic ecosystems would have also been driven by the microbial cycling of sulphur and nitrogen species, but their activity levels were probably not so great. Despite the diversity of potential early ecosystems, rates of primary production in the early-Earth anaerobic biosphere were probably well below those rates observed in the marine environment. We shift our attention to the Earth environment at 3.8 Gyr ago, where the earliest marine sediments are preserved. We calculate, consistent with the carbon isotope record and other considerations of the carbon cycle, that marine rates of primary production at this time were probably an order of magnitude (or more) less than today. We conclude that the flux of reduced species to the Earth surface at this time may have been sufficient to drive anaerobic ecosystems of sufficient activity to be consistent with the carbon isotope record. Conversely, an ecosystem based on oxygenic photosynthesis was also possible with complete removal of the oxygen by reaction with reduced species from the mantle. PMID:17008221

  14. Physics of metabolic organization

    Science.gov (United States)

    Jusup, Marko; Sousa, Tânia; Domingos, Tiago; Labinac, Velimir; Marn, Nina; Wang, Zhen; Klanjšček, Tin

    2017-03-01

    We review the most comprehensive metabolic theory of life existing to date. A special focus is given to the thermodynamic roots of this theory and to implications that the laws of physics-such as the conservation of mass and energy-have on all life. Both the theoretical foundations and biological applications are covered. Hitherto, the foundations were more accessible to physicists or mathematicians, and the applications to biologists, causing a dichotomy in what always should have been a single body of work. To bridge the gap between the two aspects of the same theory, we (i) adhere to the theoretical formalism, (ii) try to minimize the amount of information that a reader needs to process, but also (iii) invoke examples from biology to motivate the introduction of new concepts and to justify the assumptions made, and (iv) show how the careful formalism of the general theory enables modular, self-consistent extensions that capture important features of the species and the problem in question. Perhaps the most difficult among the introduced concepts, the utilization (or mobilization) energy flow, is given particular attention in the form of an original and considerably simplified derivation. Specific examples illustrate a range of possible applications-from energy budgets of individual organisms, to population dynamics, to ecotoxicology.

  15. Purine and pyrimidine metabolism in man V

    International Nuclear Information System (INIS)

    Nyhan, W.L.; Thompson, L.F.; Watts, R.W.E.

    1986-01-01

    This book comprises the proceedings of the Fifth International Symposium on Human Purine and Pyrimidine Metabolism. Its papers are organized under the following categories: adenosine receptors; purine receptors and the central nervous system; nucleoside and base transport; studies with antimetabolites; deoxynucleotide and nucleoside toxicity and metabolism; enzymes; purine and pyrimidine metabolism during lymphocyte differentiation; purine metabolism in skeletal muscle; purine nucleotide metabolism in the heart; purine and pyrimidine metabolism in primary cell cultures and in parasites; nucleoside kinases and drug activation; phosphoribosylpyrophosphate; S-adenosylmethionine metabolism; and the metabolic effects of interferon

  16. Cancer as a metabolic disease

    Directory of Open Access Journals (Sweden)

    Shelton Laura M

    2010-01-01

    Full Text Available Abstract Emerging evidence indicates that impaired cellular energy metabolism is the defining characteristic of nearly all cancers regardless of cellular or tissue origin. In contrast to normal cells, which derive most of their usable energy from oxidative phosphorylation, most cancer cells become heavily dependent on substrate level phosphorylation to meet energy demands. Evidence is reviewed supporting a general hypothesis that genomic instability and essentially all hallmarks of cancer, including aerobic glycolysis (Warburg effect, can be linked to impaired mitochondrial function and energy metabolism. A view of cancer as primarily a metabolic disease will impact approaches to cancer management and prevention.

  17. Serotonergic Control of Metabolic Homeostasis

    Directory of Open Access Journals (Sweden)

    Steven C. Wyler

    2017-09-01

    Full Text Available New treatments are urgently needed to address the current epidemic of obesity and diabetes. Recent studies have highlighted multiple pathways whereby serotonin (5-HT modulates energy homeostasis, leading to a renewed interest in the identification of 5-HT-based therapies for metabolic disease. This review aims to synthesize pharmacological and genetic studies that have found diverse functions of both central and peripheral 5-HT in the control of food intake, thermogenesis, and glucose and lipid metabolism. We also discuss the potential benefits of targeting the 5-HT system to combat metabolic disease.

  18. Genetic-Metabolic Coupling for Targeted Metabolic Engineering

    DEFF Research Database (Denmark)

    Cardinale, Stefano; Tueros Farfan, Felipe Gonzalo; Sommer, Morten Otto Alexander

    2017-01-01

    Production of chemicals in microbes often employs potent biosynthetic enzymes, which can interact with the microbial native metabolism to affect cell fitness and product yield. However, production optimization largely relies on data collected from wild-type strains in the absence of metabolic per...... for the reliable high-throughput identification of genetic targets of both known and unknown function that are directly relevant to a specific biosynthetic process....

  19. Equine metabolic syndrome in Colombian creole horse: case report

    Directory of Open Access Journals (Sweden)

    C.A. Castillo

    Full Text Available ABSTRACT The equine metabolic syndrome is a condition that can be recognized because of obesity, insulin resistance and laminitis. Genetic factors could play a role in the occurrence of this syndrome. Certain breeds such as ponies (including the South American creole horses have a lower sensibility to insulin and a higher prevalence of hyperinsulinemia. The environment and management conditions, such as overfeeding and lack of exercise are factors that bring a propensity for obesity. The adipose tissue works as an endocrine organ producing hormones (adipokines or adipocytokines that affect the horse´s metabolism. The objective of this report is to describe the first case report of a Colombian creole mare with a metabolic syndrome, diagnosed by means of the combined test of glucose-insulin and clinical signs. Early diagnosis of this entity and an adequate treatment are useful for improving the life and the zootechnical conditions of the patient.

  20. Control of Lipid Metabolism by Tachykinin in Drosophila

    Directory of Open Access Journals (Sweden)

    Wei Song

    2014-10-01

    Full Text Available The intestine is a key organ for lipid uptake and distribution, and abnormal intestinal lipid metabolism is associated with obesity and hyperlipidemia. Although multiple regulatory gut hormones secreted from enteroendocrine cells (EEs regulate systemic lipid homeostasis, such as appetite control and energy balance in adipose tissue, their respective roles regarding lipid metabolism in the intestine are not well understood. We demonstrate that tachykinins (TKs, one of the most abundant secreted peptides expressed in midgut EEs, regulate intestinal lipid production and subsequently control systemic lipid homeostasis in Drosophila and that TKs repress lipogenesis in enterocytes (ECs associated with TKR99D receptor and protein kinase A (PKA signaling. Interestingly, nutrient deprivation enhances the production of TKs in the midgut. Finally, unlike the physiological roles of TKs produced from the brain, gut-derived TKs do not affect behavior, thus demonstrating that gut TK hormones specifically regulate intestinal lipid metabolism without affecting neuronal functions.

  1. One-Carbon Metabolism in Health and Disease.

    Science.gov (United States)

    Ducker, Gregory S; Rabinowitz, Joshua D

    2017-01-10

    One-carbon (1C) metabolism, mediated by the folate cofactor, supports multiple physiological processes. These include biosynthesis (purines and thymidine), amino acid homeostasis (glycine, serine, and methionine), epigenetic maintenance, and redox defense. Both within eukaryotic cells and across organs, 1C metabolic reactions are compartmentalized. Here we review the fundamentals of mammalian 1C metabolism, including the pathways active in different compartments, cell types, and biological states. Emphasis is given to recent discoveries enabled by modern genetics, analytical chemistry, and isotope tracing. An emerging theme is the biological importance of mitochondrial 1C reactions, both for producing 1C units that are exported to the cytosol and for making additional products, including glycine and NADPH. Increased clarity regarding differential folate pathway usage in cancer, stem cells, development, and adult physiology is reviewed and highlights new opportunities for selective therapeutic intervention. Copyright © 2017. Published by Elsevier Inc.

  2. Effects of kinins on glucose metabolism in vivo.

    Science.gov (United States)

    Hartl, W H; Jauch, K W; Wolfe, R R; Schildberg, F W

    1990-01-01

    Current concepts of the physiological importance of the kinin/prostaglandin system view these tissue factors as part of a defense system, which protects tissues from potentially noxious factors, such as hypoxia or destructive inflammatory reactions. This kinin-triggered defense reaction includes an improvement in cellular energy metabolism. The latter is brought about in peripheral tissues by an increased availability of glucose for anaerobic and aerobic glycolysis, whereas in liver tissue, energy-consuming reactions such as gluconeogenesis are attenuated. There is evidence that such favorable effects can also be produced in man when kinins are administered systemically. Prostaglandins are most likely the second messengers of kinin-induced metabolic effects. Thus, it may be advantageous to increase the availability of kinins either by exogenous infusion or by inhibiting endogenous degradation during postoperative stress or in diseases such as diabetes mellitus, in which glucose metabolism is severely disturbed.

  3. Reactor-produced therapeutic radioisotopes

    International Nuclear Information System (INIS)

    Knapp, F.F. Jr.

    2002-01-01

    The significant worldwide increase in therapeutic radioisotope applications in nuclear medicine, oncology and interventional cardiology requires the dependable production of sufficient levels of radioisotopes for these applications (Reba, 2000; J. Nucl. Med., 1998; Nuclear News, 1999; Adelstein and Manning, 1994). The issues associated with both accelerator- and reactor-production of therapeutic radioisotopes is important. Clinical applications of therapeutic radioisotopes include the use of both sealed sources and unsealed radiopharmaceutical sources. Targeted radiopharmaceutical agents include those for cancer therapy and palliation of bone pain from metastatic disease, ablation of bone marrow prior to stem cell transplantation, treatment modalities for mono and oligo- and polyarthritis, for cancer therapy (including brachytherapy) and for the inhibition of the hyperplastic response following coronary angioplasty and other interventional procedures (For example, see Volkert and Hoffman, 1999). Sealed sources involve the use of radiolabeled devices for cancer therapy (brachytherapy) and also for the inhibition of the hyperplasia which is often encountered after angioplasty, especially with the exponential increase in the use of coronary stents and stents for the peripheral vasculature and other anatomical applications. Since neutron-rich radioisotopes often decay by beta decay or decay to beta-emitting daughter radioisotopes which serve as the basis for radionuclide generator systems, reactors are expected to play an increasingly important role for the production of a large variety of therapeutic radioisotopes required for these and other developing therapeutic applications. Because of the importance of the availability of reactor-produced radioisotopes for these applications, an understanding of the contribution of neutron spectra for radioisotope production and determination of those cross sections which have not yet been established is important. This

  4. Interaction between stress responses and circadian metabolism in metabolic disease.

    Science.gov (United States)

    Yang, Zhao; Kim, Hyunbae; Ali, Arushana; Zheng, Ze; Zhang, Kezhong

    2017-09-01

    Circadian rhythms play crucial roles in orchestrating diverse physiological processes that are critical for health and disease. Dysregulated circadian rhythms are closely associated with various human metabolic diseases, including type 2 diabetes, cardiovascular disease, and non-alcoholic fatty liver disease. Modern lifestyles are frequently associated with an irregular circadian rhythm, which poses a significant risk to public health. While the central clock has a set periodicity, circadian oscillators in peripheral organs, particularly in the liver, can be entrained by metabolic alterations or stress cues. At the molecular level, the signal transduction pathways that mediate stress responses interact with, and are often integrated with, the key determinants of circadian oscillation, to maintain metabolic homeostasis under physiological or pathological conditions. In the liver, a number of nuclear receptors or transcriptional regulators, which are regulated by metabolites, hormones, the circadian clock, or environmental stressors, serve as direct links between stress responses and circadian metabolism. In this review, we summarize recent advances in the understanding of the interactions between stress responses (the endoplasmic reticulum (ER) stress response, the oxidative stress response, and the inflammatory response) and circadian metabolism, and the role of these interactions in the development of metabolic diseases.

  5. Proteome Analysis of the Penicillin Producer Penicillium chrysogenum

    Science.gov (United States)

    Jami, Mohammad-Saeid; Barreiro, Carlos; García-Estrada, Carlos; Martín, Juan-Francisco

    2010-01-01

    Proteomics is a powerful tool to understand the molecular mechanisms causing the production of high penicillin titers by industrial strains of the filamentous fungus Penicillium chrysogenum as the result of strain improvement programs. Penicillin biosynthesis is an excellent model system for many other bioactive microbial metabolites. The recent publication of the P. chrysogenum genome has established the basis to understand the molecular processes underlying penicillin overproduction. We report here the proteome reference map of P. chrysogenum Wisconsin 54-1255 (the genome project reference strain) together with an in-depth study of the changes produced in three different strains of this filamentous fungus during industrial strain improvement. Two-dimensional gel electrophoresis, peptide mass fingerprinting, and tandem mass spectrometry were used for protein identification. Around 1000 spots were visualized by “blue silver” colloidal Coomassie staining in a non-linear pI range from 3 to 10 with high resolution, which allowed the identification of 950 proteins (549 different proteins and isoforms). Comparison among the cytosolic proteomes of the wild-type NRRL 1951, Wisconsin 54-1255 (an improved, moderate penicillin producer), and AS-P-78 (a penicillin high producer) strains indicated that global metabolic reorganizations occurred during the strain improvement program. The main changes observed in the high producer strains were increases of cysteine biosynthesis (a penicillin precursor), enzymes of the pentose phosphate pathway, and stress response proteins together with a reduction in virulence and in the biosynthesis of other secondary metabolites different from penicillin (pigments and isoflavonoids). In the wild-type strain, we identified enzymes to utilize cellulose, sorbitol, and other carbon sources that have been lost in the high penicillin producer strains. Changes in the levels of a few specific proteins correlated well with the improved penicillin

  6. Plant Metabolic Modeling: Achieving New Insight into Metabolism and Metabolic Engineering

    Science.gov (United States)

    Baghalian, Kambiz; Hajirezaei, Mohammad-Reza; Schreiber, Falk

    2014-01-01

    Models are used to represent aspects of the real world for specific purposes, and mathematical models have opened up new approaches in studying the behavior and complexity of biological systems. However, modeling is often time-consuming and requires significant computational resources for data development, data analysis, and simulation. Computational modeling has been successfully applied as an aid for metabolic engineering in microorganisms. But such model-based approaches have only recently been extended to plant metabolic engineering, mainly due to greater pathway complexity in plants and their highly compartmentalized cellular structure. Recent progress in plant systems biology and bioinformatics has begun to disentangle this complexity and facilitate the creation of efficient plant metabolic models. This review highlights several aspects of plant metabolic modeling in the context of understanding, predicting and modifying complex plant metabolism. We discuss opportunities for engineering photosynthetic carbon metabolism, sucrose synthesis, and the tricarboxylic acid cycle in leaves and oil synthesis in seeds and the application of metabolic modeling to the study of plant acclimation to the environment. The aim of the review is to offer a current perspective for plant biologists without requiring specialized knowledge of bioinformatics or systems biology. PMID:25344492

  7. Serum uric acid levels and metabolic syndrome.

    Science.gov (United States)

    Ciarla, Sara; Struglia, Manuela; Giorgini, Paolo; Striuli, Rinaldo; Necozione, Stefano; Properzi, Giuliana; Ferri, Claudio

    2014-07-01

    To investigate the relationship among serum uric acid levels and metabolic syndrome. Anthropometric parameters, serum uric acid and metabolic parameters were evaluated in 139 subjects. Serum uric acid levels were significantly higher in subjects with than without metabolic syndrome (p metabolic syndrome components (p for trend uric acid significantly correlated with various anthropometric and serum metabolic parameters. Serum uric acid levels were higher in individuals with rather than without metabolic syndrome and raised gradually as the number of metabolic syndrome components increased. The relationship between serum uric acid levels and various metabolic parameters suggests that uric acid might be considered as a component of metabolic syndrome. Hyperuricemia is a common finding in patients with the metabolic syndrome. Recent studies indicated that hyperuricemia may be also a predictor of metabolic syndrome development.

  8. Mass-producing B mesons

    International Nuclear Information System (INIS)

    Aleksan, Roy; Ali, Ahmed

    1993-01-01

    Since the discovery of the upsilon resonances in 1977 the physics of the fifth quark - beauty - has played a vital role in establishing and consolidating today's Standard Model of particle physics. In recent years, a wealth of data on B particle (containing the beauty quark) has emerged from the detectors ARGUS (at the DORIS ring, DESY, Hamburg) and CLEO (at the Cornell CESR ring) as well as from CERN's LEP electron-positron collider and the proton-antiproton colliders at CERN and Fermilab. But the most challenging goal of this physics is to explore the mystery of CP violation, so far only seen in neutral kaon decays. This subtle mechanism - a disregard for the combined symmetry of particle antiparticle switching and left-right reflection - possibly moulded the evolution of the Universe after the Big Bang, providing a world dominated by matter, rather than one where matter and antimatter play comparable roles. To fully explore CP violation in the laboratory needs a dedicated machine - a particle 'factory' - to mass produce B mesons. Only when this full picture of CP violation has been revealed will physicists finally be able to solve its mysteries. As well as major proposals in the US and Japan, several ideas have been launched in Europe. Over the years, many working groups have accumulated an impressive amount of data and knowledge on the physics as well as on the machine and detectors. The spearheads of experimental B physics are the ARGUS and CLEO collaborations. Highlights include the determination of the parameters of the (Cabibbo-Kobayashi-Maskawa, CKM) quark mixing matrix, testing the consistency of the Standard Model with six quarks and three leptons, and giving the first indirect hint that the as yet unseen sixth ('top') quark is very heavy, together with initial indications of how it should decay. Valuable complementary information has come from proton-antiproton collider data and particularly from the LEP experiments at the

  9. Glycogen metabolism in humans.

    Science.gov (United States)

    Adeva-Andany, María M; González-Lucán, Manuel; Donapetry-García, Cristóbal; Fernández-Fernández, Carlos; Ameneiros-Rodríguez, Eva

    2016-06-01

    In the human body, glycogen is a branched polymer of glucose stored mainly in the liver and the skeletal muscle that supplies glucose to the blood stream during fasting periods and to the muscle cells during muscle contraction. Glycogen has been identified in other tissues such as brain, heart, kidney, adipose tissue, and erythrocytes, but glycogen function in these tissues is mostly unknown. Glycogen synthesis requires a series of reactions that include glucose entrance into the cell through transporters, phosphorylation of glucose to glucose 6-phosphate, isomerization to glucose 1-phosphate, and formation of uridine 5'-diphosphate-glucose, which is the direct glucose donor for glycogen synthesis. Glycogenin catalyzes the formation of a short glucose polymer that is extended by the action of glycogen synthase. Glycogen branching enzyme introduces branch points in the glycogen particle at even intervals. Laforin and malin are proteins involved in glycogen assembly but their specific function remains elusive in humans. Glycogen is accumulated in the liver primarily during the postprandial period and in the skeletal muscle predominantly after exercise. In the cytosol, glycogen breakdown or glycogenolysis is carried out by two enzymes, glycogen phosphorylase which releases glucose 1-phosphate from the linear chains of glycogen, and glycogen debranching enzyme which untangles the branch points. In the lysosomes, glycogen degradation is catalyzed by α-glucosidase. The glucose 6-phosphatase system catalyzes the dephosphorylation of glucose 6-phosphate to glucose, a necessary step for free glucose to leave the cell. Mutations in the genes encoding the enzymes involved in glycogen metabolism cause glycogen storage diseases.

  10. Metabolic Syndrome in Nurses

    Directory of Open Access Journals (Sweden)

    María Escasany

    2014-01-01

    Full Text Available Objectives: To estimate the prevalence of metabolic syndrome (MS in female nurses in the Hospital Juan A. Fernandez (HJAF, Buenos Aires, Argentina, and to determine whether work, rest, diet, and health, are predictive of it.Materials and methods: For the first objective, a descriptive, observational and cross-sectional study was conducted, and for the second, a multivariate cross-sectional observational multivariate analysis was made comparing independent samples. A total of 192 nurses were studied between October 2008 and March 2009. They completed a questionnaire that include indicators that could be predictors of MS. Anthropometric measurements, including blood pressure were taken, was well as a blood sample to analyze fasting glucose, HDL-C and plasma triglycerides.Results: It was found that 35% and 41% of nurses were overweight and obese, respectively. A total of 92% had centro-abdominal obesity. The prevalence of MS found was 33.3% (95%CI, 26.7 to 40.5. Those who had this disease were between 53±9 years. Statistically significant differences were found in the bivariate analysis between MS and the variables, age, length of service, time worked during night shift, and academic studies.Conclusions: The prevalence of MS was 64/192 in HJAF nurses (33.3% I 95%CI, 26.7-40.5. There were no statistically significant differences with the indicators of, age, “time worked during night shift”, and “studies”. These results suggest that age is the most important variable in predicting the onset of MS in the population of nurses.

  11. Testosterone and metabolic syndrome.

    Science.gov (United States)

    Cunningham, Glenn R

    2015-01-01

    Controversies surround the usefulness of identifying patients with the metabolic syndrome (MetS). Many of the components are accepted risk factors for cardiovascular disease (CVD). Although the MetS as defined includes many men with insulin resistance, insulin resistance is not universal. The low total testosterone (TT) and sex hormone binding globulin (SHBG) levels in these men are best explained by the hyperinsulinism and increased inflammatory cytokines that accompany obesity and increased waist circumference. It is informative that low SHBG levels predict future development of the MetS. Evidence is strong relating low TT levels to CVD in men with and without the MetS; however, the relationship may not be causal. The recommendations of the International Diabetes Federation for managing the MetS include cardiovascular risk assessment, lifestyle changes in diet, exercise, weight reduction and treatment of individual components of the MetS. Unfortunately, it is uncommon to see patients with the MetS lose and maintain a 10% weight loss. Recent reports showing testosterone treatment induced dramatic changes in weight, waist circumference, insulin sensitivity, hemoglobin A1c levels and improvements in each of the components of the MetS are intriguing. While some observational studies have reported that testosterone replacement therapy increases cardiovascular events, the Food and Drug Administration in the United States has reviewed these reports and found them to be seriously flawed. Large, randomized, placebo-controlled trials are needed to provide more definitive data regarding the efficacy and safety of this treatment in middle and older men with the MetS and low TT levels.

  12. Testosterone and metabolic syndrome

    Directory of Open Access Journals (Sweden)

    Glenn R Cunningham

    2015-04-01

    Full Text Available Controversies surround the usefulness of identifying patients with the metabolic syndrome (MetS. Many of the components are accepted risk factors for cardiovascular disease (CVD. Although the MetS as defined includes many men with insulin resistance, insulin resistance is not universal. The low total testosterone (TT and sex hormone binding globulin (SHBG levels in these men are best explained by the hyperinsulinism and increased inflammatory cytokines that accompany obesity and increased waist circumference. It is informative that low SHBG levels predict future development of the MetS. Evidence is strong relating low TT levels to CVD in men with and without the MetS; however, the relationship may not be causal. The recommendations of the International Diabetes Federation for managing the MetS include cardiovascular risk assessment, lifestyle changes in diet, exercise, weight reduction and treatment of individual components of the MetS. Unfortunately, it is uncommon to see patients with the MetS lose and maintain a 10% weight loss. Recent reports showing testosterone treatment induced dramatic changes in weight, waist circumference, insulin sensitivity, hemoglobin A1c levels and improvements in each of the components of the MetS are intriguing. While some observational studies have reported that testosterone replacement therapy increases cardiovascular events, the Food and Drug Administration in the United States has reviewed these reports and found them to be seriously flawed. Large, randomized, placebo-controlled trials are needed to provide more definitive data regarding the efficacy and safety of this treatment in middle and older men with the MetS and low TT levels.

  13. Inborn Errors of Metabolism.

    Science.gov (United States)

    Ezgu, Fatih

    2016-01-01

    Inborn errors of metabolism are single gene disorders resulting from the defects in the biochemical pathways of the body. Although these disorders are individually rare, collectively they account for a significant portion of childhood disability and deaths. Most of the disorders are inherited as autosomal recessive whereas autosomal dominant and X-linked disorders are also present. The clinical signs and symptoms arise from the accumulation of the toxic substrate, deficiency of the product, or both. Depending on the residual activity of the deficient enzyme, the initiation of the clinical picture may vary starting from the newborn period up until adulthood. Hundreds of disorders have been described until now and there has been a considerable clinical overlap between certain inborn errors. Resulting from this fact, the definite diagnosis of inborn errors depends on enzyme assays or genetic tests. Especially during the recent years, significant achievements have been gained for the biochemical and genetic diagnosis of inborn errors. Techniques such as tandem mass spectrometry and gas chromatography for biochemical diagnosis and microarrays and next-generation sequencing for the genetic diagnosis have enabled rapid and accurate diagnosis. The achievements for the diagnosis also enabled newborn screening and prenatal diagnosis. Parallel to the development the diagnostic methods; significant progress has also been obtained for the treatment. Treatment approaches such as special diets, enzyme replacement therapy, substrate inhibition, and organ transplantation have been widely used. It is obvious that by the help of the preclinical and clinical research carried out for inborn errors, better diagnostic methods and better treatment approaches will high likely be available. © 2016 Elsevier Inc. All rights reserved.

  14. Metabolic Resistance in Bed Bugs

    Directory of Open Access Journals (Sweden)

    Omprakash Mittapalli

    2011-03-01

    Full Text Available Blood-feeding insects have evolved resistance to various insecticides (organochlorines, pyrethroids, carbamates, etc. through gene mutations and increased metabolism. Bed bugs (Cimex lectularius are hematophagous ectoparasites that are poised to become one of the major pests in households throughout the United States. Currently, C. lectularius has attained a high global impact status due to its sudden and rampant resurgence. Resistance to pesticides is one factor implicated in this phenomenon. Although much emphasis has been placed on target sensitivity, little to no knowledge is available on the role of key metabolic players (e.g., cytochrome P450s and glutathione S-transferases towards pesticide resistance in C. lectularius. In this review, we discuss different modes of resistance (target sensitivity, penetration resistance, behavioral resistance, and metabolic resistance with more emphasis on metabolic resistance.

  15. Metabolic engineering: past and future.

    Science.gov (United States)

    Woolston, Benjamin M; Edgar, Steven; Stephanopoulos, Gregory

    2013-01-01

    We present here a broad overview of the field of metabolic engineering, describing in the first section the key fundamental principles that define and distinguish it, as well as the technological and intellectual developments over the past approximately 20 years that have led to the current state of the art. Discussion of concepts such as metabolic flux analysis, metabolic control analysis, and rational and combinatorial methods is facilitated by illustrative examples of their application drawn from the extensive metabolic engineering literature. In the second section, we present some of the rapidly emerging technologies that we think will play pivotal roles in the continued growth of the field, from improving production metrics to expanding the range of attainable compounds.

  16. Neuroinflammatory basis of metabolic syndrome.

    Science.gov (United States)

    Purkayastha, Sudarshana; Cai, Dongsheng

    2013-10-05

    Inflammatory reaction is a fundamental defense mechanism against threat towards normal integrity and physiology. On the other hand, chronic diseases such as obesity, type 2 diabetes, hypertension and atherosclerosis, have been causally linked to chronic, low-grade inflammation in various metabolic tissues. Recent cross-disciplinary research has led to identification of hypothalamic inflammatory changes that are triggered by overnutrition, orchestrated by hypothalamic immune system, and sustained through metabolic syndrome-associated pathophysiology. While continuing research is actively trying to underpin the identity and mechanisms of these inflammatory stimuli and actions involved in metabolic syndrome disorders and related diseases, proinflammatory IκB kinase-β (IKKβ), the downstream nuclear transcription factor NF-κB and some related molecules in the hypothalamus were discovered to be pathogenically significant. This article is to summarize recent progresses in the field of neuroendocrine research addressing the central integrative role of neuroinflammation in metabolic syndrome components ranging from obesity, glucose intolerance to cardiovascular dysfunctions.

  17. Histone variants and lipid metabolism

    NARCIS (Netherlands)

    Borghesan, Michela; Mazzoccoli, Gianluigi; Sheedfar, Fareeba; Oben, Jude; Pazienza, Valerio; Vinciguerra, Manlio

    2014-01-01

    Within nucleosomes, canonical histones package the genome, but they can be opportunely replaced with histone variants. The incorporation of histone variants into the nucleosome is a chief cellular strategy to regulate transcription and cellular metabolism. In pathological terms, cellular steatosis

  18. Metabolic Acidosis: Diagnostics and Treatment

    Directory of Open Access Journals (Sweden)

    R. F. Tepaev

    2016-01-01

    Full Text Available Metabolic acidosis is the most common child acid-base balance disorder. This condition accompanies a variety of diseases, and the degree of its severity correlates with the patients’ survival: although not a separate disease in itself, metabolic acidosis, however, can worsen the disease course and even lead to death. The pathology causes are various (in connection with life-threatening changes in various organs and systems — lungs, heart and blood vessels, kidneys, and also due to a violation of lipid metabolism, in case of diabetes, poisoning, etc., which determines the fact that a wide range of specialists are interested in the issue. Approaches to the diagnosis simplify the search for the etiology of metabolic acidosis. This study presents data on the physiological basis of acid-base balance regulation, and its etiology and pathophysiology; the principles of therapy are observed.

  19. Complex systems in metabolic engineering.

    Science.gov (United States)

    Winkler, James D; Erickson, Keesha; Choudhury, Alaksh; Halweg-Edwards, Andrea L; Gill, Ryan T

    2015-12-01

    Metabolic engineers manipulate intricate biological networks to build efficient biological machines. The inherent complexity of this task, derived from the extensive and often unknown interconnectivity between and within these networks, often prevents researchers from achieving desired performance. Other fields have developed methods to tackle the issue of complexity for their unique subset of engineering problems, but to date, there has not been extensive and comprehensive examination of how metabolic engineers use existing tools to ameliorate this effect on their own research projects. In this review, we examine how complexity affects engineering at the protein, pathway, and genome levels within an organism, and the tools for handling these issues to achieve high-performing strain designs. Quantitative complexity metrics and their applications to metabolic engineering versus traditional engineering fields are also discussed. We conclude by predicting how metabolic engineering practices may advance in light of an explicit consideration of design complexity. Copyright © 2015 Elsevier Ltd. All rights reserved.

  20. Metabolic Effects of Ketogenic Diets

    OpenAIRE

    J Gordon Millichap

    1989-01-01

    The results of 24 metabolic profiles performed on 55 epileptic children receiving the classical ketogenic diet, the MCT diet, a modified MCT diet, and normal diets are reported from the University Department of Paediatrics, John Radcliffe Hospital, Oxford, England.

  1. The metabolic syndrome in HIV

    DEFF Research Database (Denmark)

    Worm, Signe W; Lundgren, Jens D

    2011-01-01

    The metabolic syndrome (MS) is a term used to describe the clustering of risk factors for cardiovascular disease (CVD), including elevated triglyceride (TG), low high density lipoprotein cholesterol (HDL), hypertension, hyperglycemia/ insulin resistance and intra-abdominal obesity. This paper...

  2. Human drug metabolism: an introduction

    National Research Council Canada - National Science Library

    Coleman, Michael D

    2010-01-01

    Human Drug Metabolism, An Introduction, Second Edition provides an accessible introduction to the subject and will be particularly invaluable to those who already have some understanding of the life sciences...

  3. Metabolic Responses to Weight Lifting

    Directory of Open Access Journals (Sweden)

    Arnold Nelson

    2017-04-01

    Full Text Available Editor's Note, The ability to lift heavy loads while performing multiple repetitions is not only highly correlated with muscle mass or the total number actomyosin interactions, but also metabolic functions that includes substrate concentrations and by-product removal.  Muscles use adenosine triphosphate (ATP in at least three locations during exercise; to run the actomyosin interaction, operate sarcoplasmic reticulum calcium pumps, and operate sarcolemma sodium and potassium pumps.  Weight lifting sessions are considered to be an intermittent activity that includes only a few second bursts of high force and/or velocity movements followed by rest periods of up to several minutes. Therefore, the anaerobic pathways such as the phosphagen and glycolytic systems are the initial pathways to respond due in part to the ability to match the increased rates of ATP depletion by increasing ATP production. After the initial resting ATP stores are used up, the phosphagen system starts contributing to ATP replenishment.  This system consists of reactions from the creatine kinase (CK pathway and the adenylate kinase (AK pathway.  However, the CK pathway can only work at max capacity for a short period for resting phosphocreatine (PCr concentrations are only about 4-6 times the amount of resting ATP stores.  Once the PCr concentrations are depleted, the AK reaction will begin by using two adenosine diphosphate (ADP to form one ATP and one adenosine monophosphate (AMP. Although ATP is produced in this pathway, this production of ATP does coincide with an increased concentration of AMP. This is problematic because increased AMP levels will in turn stimulate the adenylate deaminase reaction, which will produce ammonia (NH3. This conversion of AMP into NH3 will result in the muscle cell having a net loss of total adenine nucleotides available to resynthesize ATP.  Glycolysis is the next reaction in line, which increases its role in ATP replenishment as PCr

  4. Multiple metabolic pathways for metabolism of l-tryptophan in Fusarium graminearum.

    Science.gov (United States)

    Luo, Kun; DesRoches, Caro-Lyne; Johnston, Anne; Harris, Linda J; Zhao, Hui-Yan; Ouellet, Thérèse

    2017-11-01

    Fusarium graminearum is a plant pathogen that can cause the devastating cereal grain disease fusarium head blight in temperate regions of the world. Previous studies have shown that F. graminearum can synthetize indole-3-acetic acid (auxin) using l-tryptophan (L-TRP)-dependent pathways. In the present study, we have taken a broader approach to examine the metabolism of L-TRP in F. graminearum liquid culture. Our results showed that F. graminearum was able to transiently produce the indole tryptophol when supplied with L-TRP. Comparative gene expression profiling between L-TRP-treated and control cultures showed that L-TRP treatment induced the upregulation of a series of genes with predicted function in the metabolism of L-TRP via anthranilic acid and catechol towards the tricarboxylic acid cycle. It is proposed that this metabolic activity provides extra energy for 15-acetyldeoxynivalenol production, as observed in our experiments. This is the first report of the use of L-TRP to increase energy resources in a Fusarium species.

  5. The metabolic cost of communicative sound production in bottlenose dolphins (Tursiops truncatus).

    Science.gov (United States)

    Noren, Dawn P; Holt, Marla M; Dunkin, Robin C; Williams, Terrie M

    2013-05-01

    Bottlenose dolphins (Tursiops truncatus) produce various communicative sounds that are important for social behavior, maintaining group cohesion and coordinating foraging. For example, whistle production increases during disturbances, such as separations of mother-calf pairs and vessel approaches. It is clear that acoustic communication is important to the survival of these marine mammals, yet the metabolic cost of producing whistles and other socials sounds and the energetic consequences of modifying these sounds in response to both natural and anthropogenic disturbance are unknown. We used flow-through respirometry to determine whether the metabolic cost of sound production could be quantified in two captive dolphins producing social sounds (whistles and squawks). On average, we found that metabolic rates measured during 2 min periods of sound production were 1.2 times resting values. Up to 7 min were required for metabolism to return to resting values following vocal periods. The total metabolic cost (over resting values) of the 2 min vocal period plus the required recovery period (163.3 to 2995.9 ml O2 or 3279.6 to 60,166.7 J) varied by individual as well as by mean duration of sounds produced within the vocal period. Observed variation in received cumulative sound energy levels of vocalizations was not related to total metabolic costs. Furthermore, our empirical findings did not agree with previous theoretical estimates of the metabolic cost of whistles. This study provides the first empirical data on the metabolic cost of sound production in dolphins, which can be used to estimate metabolic costs of vocal responses to environmental perturbations in wild dolphins.

  6. Effectiveness of Hydrogen Rich Water on Antioxidant Status of Subjects with Potential Metabolic Syndrome?An Open Label Pilot Study

    OpenAIRE

    Nakao, Atsunori; Toyoda, Yoshiya; Sharma, Prachi; Evans, Malkanthi; Guthrie, Najla

    2010-01-01

    Metabolic syndrome is characterized by cardiometabolic risk factors that include obesity, insulin resistance, hypertension and dyslipidemia. Oxidative stress is known to play a major role in the pathogenesis of metabolic syndrome. The objective of this study was to examine the effectiveness of hydrogen rich water (1.5?2?L/day) in an open label, 8-week study on 20 subjects with potential metabolic syndrome. Hydrogen rich water was produced, by placing a metallic magnesium stick into drinking w...

  7. Investigation of cerebral metabolism by positron CT in Japanese following musical stimulation

    International Nuclear Information System (INIS)

    Wakasugi, Naotoshi

    1994-01-01

    Cerebral metabolic responses to Japanese and Western instrumental music were examined using 11 C-glucose and positron CT. Eight right-handed subjects were studied in both Japanese and Western music-stimulated states. Biaural musical stimulation with a Japanese instrument, the 'shakuhachi', produced diffuse metabolic changes in the left temporal lobe in all subjects. Biaural musical stimulation with a Western instrument, the 'violin', produced metabolic changes in the right temporal lobe in 3 subjects, changes in the left in 4, and changes on both sides in one. It was considered previously that all musical stimulation led to hypermetabolism in the right hemisphere of human beings. However, the present results indicated that Japanese music produced activation of the left hemisphere in Japanese. On the other hand, Western music produced right hemispheric hypermetabolism in Japanese with no emotion. The laterality of the hemisphere stimulated by Western music was apparently incidentally changed according to the state of mind the Japanese subjects. (author)

  8. Evolution of metabolic network organization

    Directory of Open Access Journals (Sweden)

    Bonchev Danail

    2010-05-01

    Full Text Available Abstract Background Comparison of metabolic networks across species is a key to understanding how evolutionary pressures shape these networks. By selecting taxa representative of different lineages or lifestyles and using a comprehensive set of descriptors of the structure and complexity of their metabolic networks, one can highlight both qualitative and quantitative differences in the metabolic organization of species subject to distinct evolutionary paths or environmental constraints. Results We used a novel representation of metabolic networks, termed network of interacting pathways or NIP, to focus on the modular, high-level organization of the metabolic capabilities of the cell. Using machine learning techniques we identified the most relevant aspects of cellular organization that change under evolutionary pressures. We considered the transitions from prokarya to eukarya (with a focus on the transitions among the archaea, bacteria and eukarya, from unicellular to multicellular eukarya, from free living to host-associated bacteria, from anaerobic to aerobic, as well as the acquisition of cell motility or growth in an environment of various levels of salinity or temperature. Intuitively, we expect organisms with more complex lifestyles to have more complex and robust metabolic networks. Here we demonstrate for the first time that such organisms are not only characterized by larger, denser networks of metabolic pathways but also have more efficiently organized cross communications, as revealed by subtle changes in network topology. These changes are unevenly distributed among metabolic pathways, with specific categories of pathways being promoted to more central locations as an answer to environmental constraints. Conclusions Combining methods from graph theory and machine learning, we have shown here that evolutionary pressures not only affects gene and protein sequences, but also specific details of the complex wiring of functional modules

  9. Microelements and inherited metabolic diseases.

    Science.gov (United States)

    Marklová, Eliska

    2002-01-01

    In addition to the main groups of inherited metabolic diseases, including mitochondrial, peroxisomal and lysosomal defects, organic acidurias, porphyrias, defects of amino acids, saccharides and fatty acids metabolism, disorders of transport and utilisation of microelements have also been recognized. Recent findings concerning hereditary hemochromatosis (iron), Wilson and Menkes diseases (copper), molybdenum cofactor deficiency (molybdenum), defects of cobalamine synthesis (cobalt) and acrodermatitis enteropathica (zinc) are reviewed.

  10. DNA methylation in metabolic disorders

    DEFF Research Database (Denmark)

    Barres, Romain; Zierath, Juleen R

    2011-01-01

    DNA methylation is a major epigenetic modification that controls gene expression in physiologic and pathologic states. Metabolic diseases such as diabetes and obesity are associated with profound alterations in gene expression that are caused by genetic and environmental factors. Recent reports h...... a mechanism by which environmental factors, including diet and exercise, can modify genetic predisposition to disease. This article considers the current evidence that defines a role for DNA methylation in metabolic disorders....

  11. A computational model of liver iron metabolism.

    Directory of Open Access Journals (Sweden)

    Simon Mitchell

    Full Text Available Iron is essential for all known life due to its redox properties; however, these same properties can also lead to its toxicity in overload through the production of reactive oxygen species. Robust systemic and cellular control are required to maintain safe levels of iron, and the liver seems to be where this regulation is mainly located. Iron misregulation is implicated in many diseases, and as our understanding of iron metabolism improves, the list of iron-related disorders grows. Recent developments have resulted in greater knowledge of the fate of iron in the body and have led to a detailed map of its metabolism; however, a quantitative understanding at the systems level of how its components interact to produce tight regulation remains elusive. A mechanistic computational model of human liver iron metabolism, which includes the core regulatory components, is presented here. It was constructed based on known mechanisms of regulation and on their kinetic properties, obtained from several publications. The model was then quantitatively validated by comparing its results with previously published physiological data, and it is able to reproduce multiple experimental findings. A time course simulation following an oral dose of iron was compared to a clinical time course study and the simulation was found to recreate the dynamics and time scale of the systems response to iron challenge. A disease state simulation of haemochromatosis was created by altering a single reaction parameter that mimics a human haemochromatosis gene (HFE mutation. The simulation provides a quantitative understanding of the liver iron overload that arises in this disease. This model supports and supplements understanding of the role of the liver as an iron sensor and provides a framework for further modelling, including simulations to identify valuable drug targets and design of experiments to improve further our knowledge of this system.

  12. Metabolic Flexibility of Sulfate Reducing Bacteria

    Directory of Open Access Journals (Sweden)

    Caroline M. Plugge

    2011-05-01

    Full Text Available Dissimilatory sulfate-reducing prokaryotes (SRB are a very diverse group of anaerobic bacteria that are omnipresent in nature and play an imperative role in the global cycling of carbon and sulfur. In anoxic marine sediments sulfate reduction accounts for up to 50% of the entire organic mineralization in coastal and shelf ecosystems where sulfate diffuses several meters deep into the sediment. As a consequence, SRB would be expected in the sulfate-containing upper sediment layers, whereas methanogenic Archaea would be expected to succeed in the deeper sulfate-depleted layers of the sediment. Where sediments are high in organic matter, sulfate is depleted at shallow sediment depths, and biogenic methane production will occur. In the absence of sulfate, many SRB ferment organic acids and alcohols, producing hydrogen, acetate, and carbon dioxide, and may even rely on hydrogen- and acetate-scavenging methanogens to convert organic compounds to methane. SRB can establish two different life styles, and these can be termed as sulfidogenic and acetogenic, hydrogenogenic metabolism. The advantage of having different metabolic capabilities is that it raises the chance of survival in environments when electron acceptors become depleted. In marine sediments, SRB and methanogens do not compete but rather complement each other in the degradation of organic matter.Also in freshwater ecosystems with sulfate concentrations of only 10-200 μM, sulfate is consumed efficiently within the top several cm of the sediments. Here, many of the δ-Proteobacteria present have the genetic machinery to perform dissimilatory sulfate reduction, yet they have an acetogenic, hydrogenogenic way of life.In this review we evaluate the physiology and metabolic mode of SRB in relation with their environment.

  13. Metabolic surgery and nutritional deficiencies.

    Science.gov (United States)

    Stroh, Christine; Manger, Thomas; Benedix, Frank

    2017-10-01

    The increasing prevalence of morbid obesity in Germany is associated with an increasing number of metabolic surgical interventions. Short-term surgical and long-term metabolic complications such as nutrient deficiencies can be considered as the main risks of metabolic surgery with its malabsorptive but also restrictive procedures. The aim of this review was to characterize the most relevant metabolic complications specific for the various bariatric procedures, which, subsequently, require a permanent surveillance and supplementation, respectively. Furthermore, we aimed to identify if there are diagnostic and therapeutic measures that can prevent those complications. Restrictive bariatric surgery such as "gastric banding" and "sleeve gastrectomy" can be associated with deficiencies related to B-vitamins whereas iron, folate, vitamin B1, B12 and D deficiencies are associated with the malabsorptive procedure such as "biliopancreatic diversion," "duodenal switch" and "Roux-en-Y gastric bypass". Due to possible metabolic and surgical complications after bariatric surgery, patients need to undergo life-long medical and dietetic surveillance. The recently published guidelines of the "American Association of Bariatric and Metabolic Surgery" are the basis for recommendations on supplementation and treatment following weight loss surgery.

  14. Metabolic management of brain cancer.

    Science.gov (United States)

    Seyfried, Thomas N; Kiebish, Michael A; Marsh, Jeremy; Shelton, Laura M; Huysentruyt, Leanne C; Mukherjee, Purna

    2011-06-01

    Malignant brain tumors are a significant health problem in children and adults. Conventional therapeutic approaches have been largely unsuccessful in providing long-term management. As primarily a metabolic disease, malignant brain cancer can be managed through changes in metabolic environment. In contrast to normal neurons and glia, which readily transition to ketone bodies (β-hydroxybutyrate) for energy under reduced glucose, malignant brain tumors are strongly dependent on glycolysis for energy. The transition from glucose to ketone bodies as a major energy source is an evolutionary conserved adaptation to food deprivation that permits the survival of normal cells during extreme shifts in nutritional environment. Only those cells with a flexible genome and normal mitochondria can effectively transition from one energy state to another. Mutations restrict genomic and metabolic flexibility thus making tumor cells more vulnerable to energy stress than normal cells. We propose an alternative approach to brain cancer management that exploits the metabolic flexibility of normal cells at the expense of the genetically defective and metabolically challenged tumor cells. This approach to brain cancer management is supported from recent studies in mice and humans treated with calorie restriction and the ketogenic diet. Issues of implementation and use protocols are presented for the metabolic management of brain cancer. Copyright © 2010. Published by Elsevier B.V.

  15. Metabolic syndrome and cardiovascular risk

    Directory of Open Access Journals (Sweden)

    Abdullah M Alshehri

    2010-11-01

    Full Text Available The constellation of dyslipidemia (hypertriglyceridemia and low levels of high-density lipoprotein cholesterol, elevated blood pressure, impaired glucose tolerance, and central obesity is now classified as metabolic syndrome, also called syndrome X. In the past few years, several expert groups have attempted to set forth simple diagnostic criteria for use in clinical practice to identify patients who manifest the multiple components of the metabolic syndrome. These criteria have varied somewhat in specific elements, but in general, they include a combination of multiple and metabolic risk factors. The most widely recognized of the metabolic risk factors are atherogenic dyslipidemia, elevated blood pressure, and elevated plasma glucose. Individuals with these characteristics, commonly manifest a prothrombotic state as well as and a proinflammatory state. Atherogenic dyslipidemia consists of an aggregation of lipoprotein abnormalities including elevated serum triglyceride and apolipoprotein B (apoB, increased small LDL particles, and a reduced level of HDL cholesterol (HDL-C. The metabolic syndrome is often referred to as if it were a discrete entity with a single cause. Available data suggest that it truly is a syndrome, ie, a grouping of atherosclerotic cardiovascular disease (ASCVD risk factors, that probably has more than one cause. Regardless of cause, the syndrome identifies individuals at an elevated risk for ASCVD. The magnitude of the increased risk can vary according to the components of the syndrome present as well as the other, non-metabolic syndrome risk factors in a particular person.

  16. Drug treatment of metabolic syndrome.

    Science.gov (United States)

    Altabas, Velimir

    2013-08-01

    The metabolic syndrome is a constellation of risk factors for cardiovascular diseases including: abdominal obesity, a decreased ability to metabolize glucose (increased blood glucose levels and/or presence of insulin resistance), dyslipidemia, and hypertension. Patients who have developed this syndrome have been shown to be at an increased risk of developing cardiovascular disease and/or type 2 diabetes. Genetic factors and the environment both are important in the development of the metabolic syndrome, influencing all single components of this syndrome. The goals of therapy are to treat the underlying cause of the syndrome, to reduce morbidity, and to prevent complications, including premature death. Lifestyle modification is the preferred first-step treatment of the metabolic syndrome. There is no single effective drug treatment affecting all components of the syndrome equally known yet. However, each component of metabolic syndrome has independent goals to be achieved, so miscellaneous types of drugs are used in the treatment of this syndrome, including weight losing drugs, antidiabetics, antihypertensives, antilipemic and anticlothing drugs etc. This article provides a brief insight into contemporary drug treatment of components the metabolic syndrome.

  17. Impact of metabolism and growth phase on the hydrogen isotopic composition of microbial fatty acids

    Science.gov (United States)

    Heinzelmann, Sandra M.; Villanueva, Laura; Sinke-Schoen, Danielle; Sinninghe Damsté, Jaap S.; Schouten, Stefan; van der Meer, Marcel T. J.

    2015-01-01

    Microorganisms are involved in all elemental cycles and therefore it is important to study their metabolism in the natural environment. A recent technique to investigate this is the hydrogen isotopic composition of microbial fatty acids, i.e., heterotrophic microorganisms produce fatty acids enriched in deuterium (D) while photoautotrophic and chemoautotrophic microorganisms produce fatty acids depleted in D compared to the water in the culture medium (growth water). However, the impact of factors other than metabolism have not been investigated. Here, we evaluate the impact of growth phase compared to metabolism on the hydrogen isotopic composition of fatty acids of different environmentally relevant microorganisms with heterotrophic, photoautotrophic and chemoautotrophic metabolisms. Fatty acids produced by heterotrophs are enriched in D compared to growth water with εlipid/water between 82 and 359‰ when grown on glucose or acetate, respectively. Photoautotrophs (εlipid/water between −149 and −264‰) and chemoautotrophs (εlipid/water between −217 and −275‰) produce fatty acids depleted in D. Fatty acids become, in general, enriched by between 4 and 46‰ with growth phase which is minor compared to the influence of metabolisms. Therefore, the D/H ratio of fatty acids is a promising tool to investigate community metabolisms in nature. PMID:26005437

  18. Metabolic Interaction of Helicobacter pylori Infection and Gut Microbiota

    Directory of Open Access Journals (Sweden)

    Yao-Jong Yang

    2016-02-01

    Full Text Available As a barrier, gut commensal microbiota can protect against potential pathogenic microbes in the gastrointestinal tract. Crosstalk between gut microbes and immune cells promotes human intestinal homeostasis. Dysbiosis of gut microbiota has been implicated in the development of many human metabolic disorders like obesity, hepatic steatohepatitis, and insulin resistance in type 2 diabetes (T2D. Certain microbes, such as butyrate-producing bacteria, are lower in T2D patients. The transfer of intestinal microbiota from lean donors increases insulin sensitivity in individuals with metabolic syndrome, but the exact pathogenesis remains unclear. H. pylori in the human stomach cause chronic gastritis, peptic ulcers, and gastric cancers. H. pylori infection also induces insulin resistance and has been defined as a predisposing factor to T2D development. Gastric and fecal microbiota may have been changed in H. pylori-infected persons and mice to promote gastric inflammation and specific diseases. However, the interaction of H. pylori and gut microbiota in regulating host metabolism also remains unknown. Further studies aim to identify the H. pylori-microbiota-host metabolism axis and to test if H. pylori eradication or modification of gut microbiota can improve the control of human metabolic disorders.

  19. Regional cerebral glucose metabolism in frontotemporal lobar degeneration

    International Nuclear Information System (INIS)

    Park, J.M.; Cho, S.S.; Lee, K.-H.; Choi, Y.; Choe, Y.S.; Kim, B.-T.; Kim, S.E.; Kwon, J.C.; Na, D.L.

    2002-01-01

    Purpose: Frontotemporal lobar degeneration (FTLD) is the third most common cause of dementia, following Alzheimer's disease and Lewy body disease. Four prototypic neuro behavioral syndromes can be produced by FTLD: frontotemporal dementia (FTD), frontotemporal dementia with motor neuron disease (MND), semantic dementia (SD), and progressive aphasia (PA). We investigated patterns of metabolic impairment in patients with FTLD presented with four different clinical syndromes. Methods: We analyzed glucose metabolic patterns on FDG PET images obtained from 34 patients with a clinical diagnosis of FTLD (19 FTD, 6 MND, 6 SD, and 3 PA, according to a consensus criteria for clinical syndromes associated with FTLD) and 7 age-matched healthy controls using SPM99. Results: Patients with FTD had metabolic deficit in the left frontal cortex and bilateral anterior temporal cortex. Hypometabolism in the bilateral pre-motor area was shown in patients with MND. Patients with SD had metabolic deficit in the left posterior temporal cortex including Wernicke's area, while hypometabolism in the bilateral inferior frontal gyrus including Broca's area and left angular gyrus was seen in patients with PA. These metabolic patterns were well correlated with clinical and neuropsychological features of FTLD syndromes. Conclusion: These data provide a biochemical basis of clinical classification of FTLD. FDG PET may help evaluate and classify patients with FTLD

  20. Metabolic flux analysis of heterotrophic growth in Chlamydomonas reinhardtii.

    Directory of Open Access Journals (Sweden)

    Nanette R Boyle

    Full Text Available Despite the wealth of knowledge available for C. reinhardtii, the central metabolic fluxes of growth on acetate have not yet been determined. In this study, 13C-metabolic flux analysis (13C-MFA was used to determine and quantify the metabolic pathways of primary metabolism in C. reinhardtii cells grown under heterotrophic conditions with acetate as the sole carbon source. Isotopic labeling patterns of compartment specific biomass derived metabolites were used to calculate the fluxes. It was found that acetate is ligated with coenzyme A in the three subcellular compartments (cytosol, mitochondria and plastid included in the model. Two citrate synthases were found to potentially be involved in acetyl-coA metabolism; one localized in the mitochondria and the other acting outside the mitochondria. Labeling patterns demonstrate that Acetyl-coA synthesized in the plastid is directly incorporated in synthesis of fatty acids. Despite having a complete TCA cycle in the mitochondria, it was also found that a majority of the malate flux is shuttled to the cytosol and plastid where it is converted to oxaloacetate providing reducing equivalents to these compartments. When compared to predictions by flux balance analysis, fluxes measured with 13C-MFA were found to be suboptimal with respect to biomass yield; C. reinhardtii sacrifices biomass yield to produce ATP and reducing equivalents.

  1. Metabolic Profiling in Patients with Pneumonia on Intensive Care.

    Science.gov (United States)

    Antcliffe, David; Jiménez, Beatriz; Veselkov, Kirill; Holmes, Elaine; Gordon, Anthony C

    2017-04-01

    Clinical features and investigations lack predictive value when diagnosing pneumonia, especially when patients are ventilated and when patients develop ventilator associated pneumonia (VAP). New tools to aid diagnosis are important to improve outcomes. This pilot study examines the potential for metabolic profiling to aid the diagnosis in critical care. In this prospective observational study ventilated patients with brain injuries or pneumonia were recruited in the intensive care unit and serum samples were collected soon after the start of ventilation. Metabolic profiles were produced using 1D 1 H NMR spectra. Metabolic data were compared using multivariate statistical techniques including Principal Component Analysis (PCA) and Orthogonal Partial Least Squares Discriminant Analysis (OPLS-DA). We recruited 15 patients with pneumonia and 26 with brain injuries, seven of whom went on to develop VAP. Comparison of metabolic profiles using OPLS-DA differentiated those with pneumonia from those with brain injuries (R 2 Y=0.91, Q 2 Y=0.28, p=0.02) and those with VAP from those without (R 2 Y=0.94, Q 2 Y=0.27, p=0.05). Metabolites that differentiated patients with pneumonia included lipid species, amino acids and glycoproteins. Metabolic profiling shows promise to aid in the diagnosis of pneumonia in ventilated patients and may allow a more timely diagnosis and better use of antibiotics. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

  2. Research Opportunities in Nutrition and Metabolism in Space

    Science.gov (United States)

    Altman, Philip L. (Editor); Fisher, Kenneth D. (Editor)

    1986-01-01

    The objectives of the Life Sciences Research Office (LSRO) study on nutrient requirements for meeting metabolic needs in manned space flights are as follows: review extant knowledge on the subject; identify significant gaps in knowledge; formulate suggestions for possible research; and produce a documented report of the foregoing items that can be used for program planning. In accordance with NASA's request for this study, the report focuses on issues of nutrition and metabolism that relate primarily to the contemplated United States Space Station, secondarily to the Shuttle Program as an orbital test bed for operational studies, and incidentally to scenarios for future long-term space flights. Members of the LSRO ad hoc Working Group on Nutrition and Metabolism were provided with pertinent articles and summaries on the subject. At the meeting of the Working Group, presentations were made by NASA Headquarters program staff on past experiences relative to space-flight nutrition and metabolism, as well as scenarios for future flights. The discussions of the ad hoc Working Group focused on the following: (1) metabolic needs related to work and exercise; (2) nutrients required to meet such needs; (3) food types, management, and records; and (4) nutritional amelioration or prevention of space-related physiological and behavioral changes.

  3. Role of peripheral serotonin in glucose and lipid metabolism.

    Science.gov (United States)

    Watanabe, Hitoshi; Rose, Michael T; Aso, Hisashi

    2011-06-01

    Two independent serotonin systems exist, one in the brain and the other in the periphery. Serotonin is a well known monoaminergic neurotransmitter in the central nervous system and it is known to regulate feeding behavior, meal size, and body weight. On the other hand, there is much less evidence for the role of serotonin as a gastrointestinal hormone, particularly with respect to its effects on glucose and lipid metabolism. This review summarizes our current understanding of the role of peripheral serotonin on glucose and lipid metabolism and the implications of this for further research. The enterochromaffin cells of the gastrointestinal tract produce peripheral serotonin postprandially. In mice, it induces a decrease in the concentration of circulating lipids as well as hyperglycemia and hyperinsulinemia through its action on several serotonin receptors. Further, serotonin metabolites act as endogenous agonists for peroxisome proliferator-activated receptor γ and serotonin accelerates adipocyte differentiation via serotonin receptor 2A and 2C. Studies of serotonin are likely to provide new insights into the field of lipid accumulation and metabolism. Recent studies show new physiological functions of peripheral serotonin, linked to glucose and lipid metabolism. Peripheral serotonin may serve as an attractive new therapeutic target for the treatment of metabolic disorders in the near future.

  4. Intermittent hypoxic resistance training: is metabolic stress the key moderator?

    Science.gov (United States)

    Scott, Brendan R; Slattery, Katie M; Dascombe, Ben J

    2015-02-01

    Traditionally, researchers and practitioners have manipulated acute resistance exercise variables to elicit the desired responses to training. However, recent research indicates that altering the muscular environment during resistance training, namely by implementing a hypoxic stimulus, can augment muscle hypertrophy and strength. Intermittent hypoxic resistance training (IHRT), whereby participants inspire hypoxic air during resistance training, has been previously demonstrated to increase muscle cross-sectional area and maximum strength by significantly greater amounts than the equivalent training in normoxia. However, some recent evidence has provided conflicting results, reporting that the use of systemic hypoxia during resistance training provided no added benefit. While the definitive mechanisms that may augment muscular responses to IHRT are not yet fully understood, an increased metabolic stress is thought to be important for moderating many downstream processes related to hypertrophy. It is likely that methodological differences between conflicting IHRT studies have resulted in different degrees of metabolic stress during training, particularly when considering the inter-set recovery intervals used. Given that the most fundamental physiological stresses resulting from hypoxia are disturbances to oxidative metabolism, it becomes apparent that resistance training may only benefit from additional hypoxia if the exercise is structured to elicit a strong metabolic response. We hypothesize that for IHRT to be more effective in producing muscular hypertrophy and increasing strength than the equivalent normoxic training, exercise should be performed with relatively brief inter-set recovery periods, with the aim of providing a potent metabolic stimulus to enhance anabolic responses. Copyright © 2014 Elsevier Ltd. All rights reserved.

  5. FGF21-based pharmacotherapy--potential utility for metabolic disorders.

    Science.gov (United States)

    Gimeno, Ruth E; Moller, David E

    2014-06-01

    Currently available therapies for diabetes or obesity produce modest efficacy and are usually used in combination with agents targeting cardiovascular risk factors. Fibroblast growth factor 21 (FGF21) is a circulating protein with pleiotropic metabolic actions; pharmacological doses of FGF21 produce anti-diabetic, lipid-lowering, and weight-reducing effects in rodents. Several potential benefits have translated to non-human primates and obese humans with type 2 diabetes (T2D). Accumulating results point to a specific receptor complex and actions in adipose tissue, liver, and brain; several pathways lead to enhanced fatty acid oxidation, increased insulin sensitivity, and augmented energy expenditure. A range of strategies are being explored to derive potent, safe, and convenient therapies which could potentially represent novel approaches to prevent and treat a variety of metabolic disorders. Copyright © 2014 Elsevier Ltd. All rights reserved.

  6. Why mammalian lineages respond differently to sexual selection: metabolic rate constrains the evolution of sperm size.

    Science.gov (United States)

    Gomendio, Montserrat; Tourmente, Maximiliano; Roldan, Eduardo R S

    2011-10-22

    The hypothesis that sperm competition should favour increases in sperm size, because it results in faster swimming speeds, has received support from studies on many taxa, but remains contentious for mammals. We suggest that this may be because mammalian lineages respond differently to sexual selection, owing to major differences in body size, which are associated with differences in mass-specific metabolic rate. Recent evidence suggests that cellular metabolic rate also scales with body size, so that small mammals have cells that process energy and resources from the environment at a faster rate. We develop the 'metabolic rate constraint hypothesis' which proposes that low mass-specific metabolic rate among large mammals may limit their ability to respond to sexual selection by increasing sperm size, while this constraint does not exist among small mammals. Here we show that among rodents, which have high mass-specific metabolic rates, sperm size increases under sperm competition, reaching the longest sperm sizes found in eutherian mammals. By contrast, mammalian lineages with large body sizes have small sperm, and while metabolic rate (corrected for body size) influences sperm size, sperm competition levels do not. When all eutherian mammals are analysed jointly, our results suggest that as mass-specific metabolic rate increases, so does maximum sperm size. In addition, species with low mass-specific metabolic rates produce uniformly small sperm, while species with high mass-specific metabolic rates produce a wide range of sperm sizes. These findings support the hypothesis that mass-specific metabolic rates determine the budget available for sperm production: at high levels, sperm size increases in response to sexual selection, while low levels constrain the ability to respond to sexual selection by increasing sperm size. Thus, adaptive and costly traits, such as sperm size, may only evolve under sexual selection when metabolic rate does not constrain cellular

  7. Metabolic syndrome: clinical concept and molecular basis.

    Science.gov (United States)

    Funahashi, Tohru; Matsuzawa, Yuji

    2007-01-01

    The metabolic syndrome is a cluster of insulin resistance, elevated blood pressure, and atherogenic dyslipidemia and is a common basis of cardiovascular diseases (CVD). Although the precise mechanism remains to be elucidated, a practical definition is needed. A worldwide definition that considers increased waist circumference as an essential component has been settled. Visceral fat locates upstream of the liver. Free fatty acids and glycerol derived from visceral fat reach the liver and stimulate lipoprotein synthesis and gluconeogenesis, respectively. The adipose tissue produces a variety of bioactive substances conceptualized as 'adipocytokines'. Overproduction of plasminogen activator inhibitor-1 and tumor necrosis factor- seems to relate to the thrombotic and inflammatory tendency. On the other hand, adiponectin, which has antiatherogenic and antidiabetic activities, is reduced in subjects with metabolic syndrome. In Japan, the waist circumference criterion based on visceral fat accumulation has been adopted. The concept of this syndrome has been widely publicized, and health promotion programs based on the concept have commenced in various areas of the country. Such 'Adipo-Do-It' movement is an incentive to encourage physical exercise to reduce visceral fat and is a big challenge to prevent life-style-related diseases and CVD.

  8. Extracellular DNA metabolism in Haloferax volcanii

    Directory of Open Access Journals (Sweden)

    Scott eChimileski

    2014-02-01

    Full Text Available Extracellular DNA is found in all environments and is a dynamic component of the micro-bial ecosystem. Microbial cells produce and interact with extracellular DNA through many endogenous mechanisms. Extracellular DNA is processed and internalized for use as genetic information and as a major source of macronutrients, and plays several key roles within prokaryotic biofilms. Hypersaline sites contain some of the highest extracellular DNA con-centrations measured in nature–a potential rich source of carbon, nitrogen and phosphorus for halophilic microorganisms. We conducted DNA growth studies for the halophilic archaeon Haloferax volcanii DS2 and show that this model Halobacteriales strain is capable of using exogenous double-stranded DNA as a nutrient. Further experiments with varying medium composition, DNA concentration and DNA types revealed that DNA is utilized primarily as a phosphorus source, that growth on DNA is concentration-dependent and that DNA isolated from different sources is metabolized selectively, with a bias against highly divergent methylated DNA sources. Additionally, fluorescence microscopy experiments showed that labeled DNA colocalized with Haloferax volcanii cells. The gene Hvo_1477 was also identified using a comparative genomic approach as a factor likely to be involved in extracellular DNA processing at the cell surface, and deletion of Hvo_1477 created an H. volcanii strain deficient in its ability to grow on extracellular DNA. Widespread distribution of Hvo_1477 homologs in archaea suggests metabolism of extracellular DNA may be of broad ecological and physiological relevance in this domain of life.

  9. Analyzing clonal variation of monoclonal antibody-producing CHO cell lines using an in silico metabolomic platform.

    Directory of Open Access Journals (Sweden)

    Atefeh Ghorbaniaghdam

    Full Text Available Monoclonal antibody producing Chinese hamster ovary (CHO cells have been shown to undergo metabolic changes when engineered to produce high titers of recombinant proteins. In this work, we have studied the distinct metabolism of CHO cell clones harboring an efficient inducible expression system, based on the cumate gene switch, and displaying different expression levels, high and low productivities, compared to that of the parental cells from which they were derived. A kinetic model for CHO cell metabolism was further developed to include metabolic regulation. Model calibration was performed using intracellular and extracellular metabolite profiles obtained from shake flask batch cultures. Model simulations of intracellular fluxes and ratios known as biomarkers revealed significant changes correlated with clonal variation but not to the recombinant protein expression level. Metabolic flux distribution mostly differs in the reactions involving pyruvate metabolism, with an increased net flux of pyruvate into the tricarboxylic acid (TCA cycle in the high-producer clone, either being induced or non-induced with cumate. More specifically, CHO cell metabolism in this clone was characterized by an efficient utilization of glucose and a high pyruvate dehydrogenase flux. Moreover, the high-producer clone shows a high rate of anaplerosis from pyruvate to oxaloacetate, through pyruvate carboxylase and from glutamate to α-ketoglutarate, through glutamate dehydrogenase, and a reduced rate of cataplerosis from malate to pyruvate, through malic enzyme. Indeed, the increase of flux through pyruvate carboxylase was not driven by an increased anabolic demand. It is in fact linked to an increase of the TCA cycle global flux, which allows better regulation of higher redox and more efficient metabolic states. To the best of our knowledge, this is the first time a dynamic in silico platform is proposed to analyze and compare the metabolomic behavior of different CHO

  10. Optimization of lysine metabolism in Corynebacterium glutamicum

    DEFF Research Database (Denmark)

    Rytter, Jakob Vang

    Commercial pig and poultry production use the essential amino acid lysine as a feed additive with the purpose of optimizing the feed utilization. Lysine is produced by a fermentation process involving either Corynebacterium glutamicum or Escherichia coli. The global annual production is around 1......,000,000 tons. The aim of this project is to optimize the yield of lysine in C. glutamicum using metabolic engineering strategies. According to a genome scale model of C. glutamicum, theoretically there is much room for increasing the lysine yield (Kjeldsen and Nielsen 2009). Lysine synthesis requires NADPH...... the PPP, increasing the NADPH synthesis and enabling increased lysine production. Synthetic promoter libraries (SPL) enable fine tuning of the expression of genes. To test the feasibility of SPL in C. glutamicum four constitutive SPLs and one inducible SPL were constructed. The libraries were placed...

  11. Anaerobic metabolism of pentachloronitrobenzene (PCNB) in soils

    International Nuclear Information System (INIS)

    Murthy, N.B.K.

    1980-01-01

    A manifold assembly system was used to study the metabolism of 14 C labelled PCNB in flooded and moist anaerobic soils. Soil respiration was generally enhanced by PCNB. More CO 2 was produced in moist anaerobic than in flooded anaerobic soil. Flooding reduced the volatilization of pesticide. The extractable radioactivity from the soil was same (70%) in the treatments. Nevertheless, differences were observed in distribution of PCNB and its degradation products. Pentachloroaniline (PCA) was the principal degradation product. Pentachlorothioanisole (PCTA) was more abundant in moist anaerobic than in flooded anaerobic soil. Pentachlorophenol (PCP) was formed from PCNB in anaerobic soil. Degradation of PCA, PCTA and PCP were further studied in soil and a possible pathway for anaerobic degradation of PCNB was proposed. (author)

  12. Metabolic modeling of a mutualistic microbial community

    Energy Technology Data Exchange (ETDEWEB)

    Stolyar, Sergey; Van Dien, Steve; Hillesland, Kristina Linnea; Pinel, Nicolas; Lie, Thomas J.; Leigh, John A.; Stahl, David A.

    2007-03-13

    The rate of production of methane in many environmentsdepends upon mutualistic interactions between sulfate-reducing bacteriaand methanogens. To enhance our understanding of these relationships, wetook advantage of the fully sequenced genomes of Desulfovibrio vulgarisand Methanococcus maripaludis to produce and analyze the firstmultispecies stoichiometric metabolic model. Model results were comparedto data on growth of the co-culture on lactate in the absence of sulfate.The model accurately predicted several ecologically relevantcharacteristics, including the flux of metabolites and the ratio of D.vulgaris to M. maripaludis cells during growth. In addition, the modeland our data suggested that it was possible to eliminate formate as aninterspecies electron shuttle, but hydrogen transfer was essential forsyntrophic growth. Our work demonstrated that reconstructed metabolicnetworks and stoichiometric models can serve not only to predictmetabolic fluxes and growth phenotypes of single organisms, but also tocapture growth parameters and community composition of simple bacterialcommunities.

  13. Ketone ester effects on metabolism and transcription.

    Science.gov (United States)

    Veech, Richard L

    2014-10-01

    Ketosis induced by starvation or feeding a ketogenic diet has widespread and often contradictory effects due to the simultaneous elevation of both ketone bodies and free fatty acids. The elevation of ketone bodies increases the energy of ATP hydrolysis by reducing the mitochondrial NAD couple and oxidizing the coenzyme Q couple, thus increasing the redox span between site I and site II. In contrast, metabolism of fatty acids leads to a reduction of both mitochondrial NAD and mitochondrial coenzyme Q causing a decrease in the ΔG of ATP hydrolysis. In contrast, feeding ketone body esters leads to pure ketosis, unaccompanied by elevation of free fatty acids, producing a physiological state not previously seen in nature. The effects of pure ketosis on transcription and upon certain neurodegenerative diseases make approach not only interesting, but of potential therapeutic value.

  14. Modelling of FDG metabolism in liver voxels.

    Science.gov (United States)

    Baker, C; Dowson, N; Thomas, P; Rose, S

    2015-01-21

    Kinetic analysis is a tool used to glean additional information from positron emission tomography (PET) data by exploiting the dynamics of tissue metabolism. The standard irreversible and reversible two compartment models used in kinetic analysis were initially developed to analyse brain PET data. The application of kinetic analysis to PET of the liver presents the opportunity to move beyond the generic standard models and develop physiologically informed pharmacokinetic models that incorporate structural and functional features in particular to the liver. In this paper, we develop a new compartment model, called the tubes model, which is informed by the liver׳s sinusoidal architecture, high fractional blood volume, high perfusion rate, and large hepatocyte surface area facing the space of Disse. The tubes model distributes tracer between the blood and intracellular compartments in more physiologically faithful proportions than the standard model, producing parametric images with improved contrast between healthy and neoplastic tissue. Crown Copyright © 2014. Published by Elsevier Ltd. All rights reserved.

  15. The Role of Underlying Type 2 Diabetes Mellitus and Obesity in Ozone-Induced Pulmonary Injury and Metabolic Impairment

    Science.gov (United States)

    RATIONALE: A growing body of evidence indicates an association between air pollution exposure and metabolic disorders such as obesity and type 2 diabetes mellitus (T2DM). We have recently demonstrated that an acute exposure to ozone in metabolically normal rat strains produces h...

  16. Symptoms and Diagnosis of Metabolic Syndrome

    Science.gov (United States)

    ... Thromboembolism Aortic Aneurysm More Symptoms and Diagnosis of Metabolic Syndrome Updated:Apr 13,2017 What are the symptoms ... Syndrome? This content was last reviewed August 2016. Metabolic Syndrome • Home • About Metabolic Syndrome • Why Metabolic Syndrome Matters • ...

  17. [Metabolic syndrome after kidney transplantation].

    Science.gov (United States)

    Nedbálková, Marta; Svojanovský, Jan; Trnavský, Karel; Kuman, Milan; Jarkovský, Jiří; Karpíšek, Michal; Souček, Miroslav

    2014-03-01

    Metabolic syndrome is a risk factor for cardiovascular diseases. Higher risk of the metabolic syndrome and its components in patients after kidney transplantation is caused by immunosuppressive therapy. THE AIM OF OUR STUDY was to evaluate the prevalence of the metabolic syndrome and its components in kidney transplant recipients and to analyse their influence on allograft function and albuminuria. In the study we monitored 69 patients after cadaveric kidney transplantation. The prevalence of the meta-bolic syndrome was 61.3 % 3 years after kidney transplantation. The prevalence of new onset diabetes mellitus after transplantation was 27 % and that of abdominal obesity 59.7 % of patients. The age of kidney transplant recipients with the metabolic syndrome was higher than of these without it, but not statistically significant. The age of kidney transplant recipients with new onset diabetes mellitus after transplantation was significantly higher, 54.0 (35.0; 69.0) years, than in patients without it, 45.5 (27.0; 60.0) years, OR (95% IS) 1.116 (1.031; 1.207), p = 0.006.The number of components of the metabolic syndrome was negatively correlated with the graft function (rs -0,275, p = 0,031). In patients with impaired renal function with estimated glomerular filtration (using MDRD equation) metabolic syndrome and hypertriglyceridaemia was significantly higher. Chronic allograft dysfunction was predicted by donor age, delayed allograft function, rejection, low level of HDL-cholesterol, hypertriglyceridaemia and hyperuricaemia. Hyperuricaemia was the only significant predictor of allograft dysfunction independently of the presence of delayed allograft function, rejection episodes and donor age. The metabolic syndrome, elevation of apolipoprotein B and nonHDL-cholesterol and increased systolic blood pressure were associated with albuminuria. Higher levels of apolipoprotein B and total cholesterol were independent predictors of increased albumin-creatinine ratio. Obesity

  18. Favourable metabolic profile sustains mitophagy and prevents metabolic abnormalities in metabolically healthy obese individuals.

    Science.gov (United States)

    Bhansali, Shipra; Bhansali, Anil; Dhawan, Veena

    2017-01-01

    Obesity-mediated oxidative stress results in mitochondrial dysfunction, which has been implicated in the pathogenesis of metabolic syndrome and T2DM. Recently, mitophagy, a cell-reparative process has emerged as a key facet in maintaining the mitochondrial health, which may contribute to contain the metabolic abnormalities in obese individuals. However, the status of mitophagy in metabolically healthy obese (MHO) and metabolically abnormal diabetic obese (MADO) subjects remains to be elucidated. Hence, the present study aims to unravel the alterations in mitochondrial oxidative stress (MOS) and mitophagy in these subjects. 60 subjects including MHNO (metabolically healthy non-obese), MHO and MADO were enrolled as per the Asian criteria for obesity (n = 20 each). Biochemical parameters, MOS indices, transcriptional and translational expression of mitophagy markers ( PINK1 , PARKIN , MFN2 , NIX , LC3 - II , and LAMP - 2 ), and transmission electron microscopic (TEM) studies were performed in peripheral blood mononuclear cells. The MHO subjects displayed a favorable metabolic profile, despite accompanied by an increased adiposity as compared to the MHNO group; while MADO group exhibited several metabolic abnormalities, inspite of similar body composition as MHO subjects. A progressive rise in the MOS was observed in MHO and MADO subjects as compared to the MHNO group, and it showed a positive and significant correlation with the body composition in these groups. Further, mitophagy remained unaltered in the MHO group, while it was significantly downregulated in the MADO group. In addition, TEM studies revealed a significant increase in the percentage of damaged mitochondria in MADO patients as compared to other groups, while MHO and MHNO groups did not show any significant alterations for the same. A favorable metabolic profile and moderate levels of MOS in the MHO group may play a crucial role in the sustenance of mitophagy, which may further limit the aggravation

  19. The Metabolic Cost of Click Production in Bottlenose Dolphins

    Science.gov (United States)

    2014-09-30

    of the previous work was on communicative sound production in bottlenose dolphins (Holt et al. 2011 a, b; Noren et al. 2011, 2013). There is... dolphin per day. Dissimilar to the previous study to determine the metabolic cost of communicative sound in which sound production occurred at the...rates from oxygen consumption values is similar to those used previously on bottlenose dolphins producing communicative sounds (Noren et al. 2011

  20. Metabolic theory predicts whole-ecosystem properties.

    Science.gov (United States)

    Schramski, John R; Dell, Anthony I; Grady, John M; Sibly, Richard M; Brown, James H

    2015-02-24

    Understanding the effects of individual organisms on material cycles and energy fluxes within ecosystems is central to predicting the impacts of human-caused changes on climate, land use, and biodiversity. Here we present a theory that integrates metabolic (organism-based bottom-up) and systems (ecosystem-based top-down) approaches to characterize how the metabolism of individuals affects the flows and stores of materials and energy in ecosystems. The theory predicts how the average residence time of carbon molecules, total system throughflow (TST), and amount of recycling vary with the body size and temperature of the organisms and with trophic organization. We evaluate the theory by comparing theoretical predictions with outputs of numerical models designed to simulate diverse ecosystem types and with empirical data for real ecosystems. Although residence times within different ecosystems vary by orders of magnitude-from weeks in warm pelagic oceans with minute phytoplankton producers to centuries in cold forests with large tree producers-as predicted, all ecosystems fall along a single line: residence time increases linearly with slope = 1.0 with the ratio of whole-ecosystem biomass to primary productivity (B/P). TST was affected predominantly by primary productivity and recycling by the transfer of energy from microbial decomposers to animal consumers. The theory provides a robust basis for estimating the flux and storage of energy, carbon, and other materials in terrestrial, marine, and freshwater ecosystems and for quantifying the roles of different kinds of organisms and environments at scales from local ecosystems to the biosphere.