WorldWideScience

Sample records for metabolic control analysis

  1. Metabolic control analysis of xylose catabolism in Aspergillus

    NARCIS (Netherlands)

    Prathumpai, W.; Gabelgaard, J.B.; Wanchanthuek, P.; Vondervoort, van de P.J.I.; Groot, de M.J.L.; McIntyre, M.; Nielsen, J.

    2003-01-01

    A kinetic model for xylose catabolism in Aspergillus is proposed. From a thermodynamic analysis it was found that the intermediate xylitol will accumulate during xylose catabolism. Use of the kinetic model allowed metabolic control analysis (MCA) of the xylose catabolic pathway to be carried out,

  2. Metabolic control analysis of xylose catabolism in Aspergillus

    DEFF Research Database (Denmark)

    Prathumpai, Wai; Gabelgaard, J.B.; Wanchanthuek, P.

    2003-01-01

    A kinetic model for xylose catabolism in Aspergillus is proposed. From a thermodynamic analysis it was found that the intermediate xylitol will accumulate during xylose catabolism. Use of the kinetic model allowed metabolic control analysis (MCA) of the xylose catabolic pathway to be carried out......, and flux control was shown to be dependent on the metabolite levels. Due to thermodynamic constraints, flux control may reside at the first step in the pathway, i.e., at the xylose reductase, even when the intracellular xylitol concentration is high. On the basis of the kinetic analysis, the general dogma...... specifying that flux control often resides at the step following an intermediate present at high concentrations was, therefore, shown not to hold. The intracellular xylitol concentration was measured in batch cultivations of two different strains of Aspergillus niger and two different strains of Aspergillus...

  3. (Im) Perfect robustness and adaptation of metabolic networks subject to metabolic and gene-expression regulation: marrying control engineering with metabolic control analysis

    NARCIS (Netherlands)

    He, F.; Fromion, V.; Westerhoff, H.V.

    2013-01-01

    Background: Metabolic control analysis (MCA) and supply-demand theory have led to appreciable understanding of the systems properties of metabolic networks that are subject exclusively to metabolic regulation. Supply-demand theory has not yet considered gene-expression regulation explicitly whilst a

  4. Metabolic control analysis of xylose catabolism in Aspergillus

    DEFF Research Database (Denmark)

    Prathumpai, Wai; Gabelgaard, J.B.; Wanchanthuek, P.

    2003-01-01

    A kinetic model for xylose catabolism in Aspergillus is proposed. From a thermodynamic analysis it was found that the intermediate xylitol will accumulate during xylose catabolism. Use of the kinetic model allowed metabolic control analysis (MCA) of the xylose catabolic pathway to be carried out...... specifying that flux control often resides at the step following an intermediate present at high concentrations was, therefore, shown not to hold. The intracellular xylitol concentration was measured in batch cultivations of two different strains of Aspergillus niger and two different strains of Aspergillus...... nidulans grown on media containing xylose, and a concentration up to 30 mM was found. Applying MCA showed that the first polyol dehydrogenase (XDH) in the catabolic pathway of xylose exerted the main flux control in the two strains of A. nidulans and A. niger NW324, but the flux control was exerted mainly...

  5. Metabolic control analysis of Aspergillus niger L-arabinose catabolism

    DEFF Research Database (Denmark)

    de Groot, M.J.L.; Prathumpai, Wai; Visser, J.

    2005-01-01

    A mathematical model of the L-arabinose/D-xylose catabolic pathway of Aspergillus niger was constructed based on the kinetic properties of the enzymes. For this purpose L-arabinose reductase, L-arabitol dehydrogenase and D-xylose reductase were purified using dye-affinity chromatography, and thei......A mathematical model of the L-arabinose/D-xylose catabolic pathway of Aspergillus niger was constructed based on the kinetic properties of the enzymes. For this purpose L-arabinose reductase, L-arabitol dehydrogenase and D-xylose reductase were purified using dye-affinity chromatography......-arabinose, a level that resulted in realistic intermediate concentrations in the model, flux control coefficients for L-arabinose reductase, L-arabitol dehydrogenase and L-xylulose reductase were 0.68, 0.17 and 0.14, respectively. The analysis can be used as a guide to identify targets for metabolic engineering...

  6. (Im)Perfect robustness and adaptation of metabolic networks subject to metabolic and gene-expression regulation: marrying control engineering with metabolic control analysis.

    Science.gov (United States)

    He, Fei; Fromion, Vincent; Westerhoff, Hans V

    2013-11-21

    Metabolic control analysis (MCA) and supply-demand theory have led to appreciable understanding of the systems properties of metabolic networks that are subject exclusively to metabolic regulation. Supply-demand theory has not yet considered gene-expression regulation explicitly whilst a variant of MCA, i.e. Hierarchical Control Analysis (HCA), has done so. Existing analyses based on control engineering approaches have not been very explicit about whether metabolic or gene-expression regulation would be involved, but designed different ways in which regulation could be organized, with the potential of causing adaptation to be perfect. This study integrates control engineering and classical MCA augmented with supply-demand theory and HCA. Because gene-expression regulation involves time integration, it is identified as a natural instantiation of the 'integral control' (or near integral control) known in control engineering. This study then focuses on robustness against and adaptation to perturbations of process activities in the network, which could result from environmental perturbations, mutations or slow noise. It is shown however that this type of 'integral control' should rarely be expected to lead to the 'perfect adaptation': although the gene-expression regulation increases the robustness of important metabolite concentrations, it rarely makes them infinitely robust. For perfect adaptation to occur, the protein degradation reactions should be zero order in the concentration of the protein, which may be rare biologically for cells growing steadily. A proposed new framework integrating the methodologies of control engineering and metabolic and hierarchical control analysis, improves the understanding of biological systems that are regulated both metabolically and by gene expression. In particular, the new approach enables one to address the issue whether the intracellular biochemical networks that have been and are being identified by genomics and systems

  7. A computer program for the algebraic determination of control coefficients in Metabolic Control Analysis.

    Science.gov (United States)

    Thomas, S; Fell, D A

    1993-06-01

    A computer program (MetaCon) is described for the evaluation of flux control, concentration control and branch-point distribution control coefficients of a metabolic pathway. Requiring only the reaction scheme as input, the program produces algebraic expressions for the control coefficients in terms of elasticity coefficients, metabolite concentrations and pathway fluxes. Any of these variables can be substituted by numeric or simple algebraic expressions; the expressions will then be automatically rearranged in terms of the remaining unknown variables. When all variables have been substituted, numeric values will be obtained for the control coefficients. The program is a computerized implementation of the matrix method for the determination of control coefficients. The features of MetaCon are compared with those of other programs available to workers in Metabolic Control Analysis. Potential benefits of, and methods of using, MetaCon are discussed. The mathematical background and validity of the matrix method rules are discussed, and the algorithm used by MetaCon is described. The matrix method is shown to be a specific case of a previously described general formalism for calculating control coefficients.

  8. Detection of driver metabolites in the human liver metabolic network using structural controllability analysis

    Science.gov (United States)

    2014-01-01

    Background Abnormal states in human liver metabolism are major causes of human liver diseases ranging from hepatitis to hepatic tumor. The accumulation in relevant data makes it feasible to derive a large-scale human liver metabolic network (HLMN) and to discover important biological principles or drug-targets based on network analysis. Some studies have shown that interesting biological phenomenon and drug-targets could be discovered by applying structural controllability analysis (which is a newly prevailed concept in networks) to biological networks. The exploration on the connections between structural controllability theory and the HLMN could be used to uncover valuable information on the human liver metabolism from a fresh perspective. Results We applied structural controllability analysis to the HLMN and detected driver metabolites. The driver metabolites tend to have strong ability to influence the states of other metabolites and weak susceptibility to be influenced by the states of others. In addition, the metabolites were classified into three classes: critical, high-frequency and low-frequency driver metabolites. Among the identified 36 critical driver metabolites, 27 metabolites were found to be essential; the high-frequency driver metabolites tend to participate in different metabolic pathways, which are important in regulating the whole metabolic systems. Moreover, we explored some other possible connections between the structural controllability theory and the HLMN, and find that transport reactions and the environment play important roles in the human liver metabolism. Conclusion There are interesting connections between the structural controllability theory and the human liver metabolism: driver metabolites have essential biological functions; the crucial role of extracellular metabolites and transport reactions in controlling the HLMN highlights the importance of the environment in the health of human liver metabolism. PMID:24885538

  9. Synergizing metabolic flux analysis and nucleotide sugar metabolism to understand the control of glycosylation of recombinant protein in CHO cells

    LENUS (Irish Health Repository)

    Burleigh, Susan C

    2011-10-18

    Abstract Background The glycosylation of recombinant proteins can be altered by a range of parameters including cellular metabolism, metabolic flux and the efficiency of the glycosylation process. We present an experimental set-up that allows determination of these key processes associated with the control of N-linked glycosylation of recombinant proteins. Results Chinese hamster ovary cells (CHO) were cultivated in shake flasks at 0 mM glutamine and displayed a reduced growth rate, glucose metabolism and a slower decrease in pH, when compared to other glutamine-supplemented cultures. The N-linked glycosylation of recombinant human chorionic gonadotrophin (HCG) was also altered under these conditions; the sialylation, fucosylation and antennarity decreased, while the proportion of neutral structures increased. A continuous culture set-up was subsequently used to understand the control of HCG glycosylation in the presence of varied glutamine concentrations; when glycolytic flux was reduced in the absence of glutamine, the glycosylation changes that were observed in shake flask culture were similarly detected. The intracellular content of UDP-GlcNAc was also reduced, which correlated with a decrease in sialylation and antennarity of the N-linked glycans attached to HCG. Conclusions The use of metabolic flux analysis illustrated a case of steady state multiplicity, where use of the same operating conditions at each steady state resulted in altered flux through glycolysis and the TCA cycle. This study clearly demonstrated that the control of glycoprotein microheterogeneity may be examined by use of a continuous culture system, metabolic flux analysis and assay of intracellular nucleotides. This system advances our knowledge of the relationship between metabolic flux and the glycosylation of biotherapeutics in CHO cells and will be of benefit to the bioprocessing industry.

  10. How to determine control of growth rate in a chemostat. Using metabolic control analysis to resolve the paradox

    DEFF Research Database (Denmark)

    Snoep, Jacky L.; Jensen, Peter Ruhdal; Groeneveld, Philip

    1994-01-01

    how, paradoxically, one can determine control of growth rate, of growth yield and of other fluxes in a chemostat. We develop metabolic control analysis for the chemostat. this analysis does not depend on the particular way in which specific growth rate varies with the concentration of the growth...

  11. A computer program for the algebraic determination of control coefficients in Metabolic Control Analysis.

    OpenAIRE

    Thomas, S; Fell, D A

    1993-01-01

    A computer program (MetaCon) is described for the evaluation of flux control, concentration control and branch-point distribution control coefficients of a metabolic pathway. Requiring only the reaction scheme as input, the program produces algebraic expressions for the control coefficients in terms of elasticity coefficients, metabolite concentrations and pathway fluxes. Any of these variables can be substituted by numeric or simple algebraic expressions; the expressions will then be automat...

  12. Metabolic control analysis of Aspergillus niger L-arabinose catabolism

    DEFF Research Database (Denmark)

    de Groot, M.J.L.; Prathumpai, Wai; Visser, J.

    2005-01-01

    A mathematical model of the L-arabinose/D-xylose catabolic pathway of Aspergillus niger was constructed based on the kinetic properties of the enzymes. For this purpose L-arabinose reductase, L-arabitol dehydrogenase and D-xylose reductase were purified using dye-affinity chromatography, and thei......A mathematical model of the L-arabinose/D-xylose catabolic pathway of Aspergillus niger was constructed based on the kinetic properties of the enzymes. For this purpose L-arabinose reductase, L-arabitol dehydrogenase and D-xylose reductase were purified using dye-affinity chromatography...... at the enzyme following the intermediate with the highest concentration, L-arabitol, but is distributed over the first three steps in the pathway, preceding and following L-arabitol. Flux control appeared to be strongly dependent on the intracellular L-arabinose concentration. At 5 mM intracellular L...

  13. Metabolic control analysis of biochemical pathways based on a thermokinetic description of reaction rates

    DEFF Research Database (Denmark)

    Nielsen, Jens Bredal

    1997-01-01

    of the thermokinetic description of reaction rates to include the influence of effecters. Here the reaction rate is written as a linear function of the logarithm of the metabolite concentrations. With this type of rate function it is shown that the approach of Delgado and Liao [Biochem. J. (1992) 282, 919-927] can......Metabolic control analysis is a powerful technique for the evaluation of flux control within biochemical pathways. Its foundation is the elasticity coefficients and the flux control coefficients (FCCs). On the basis of a thermokinetic description of reaction rates it is here shown...... that the elasticity coefficients can be calculated directly from the pool levels of metabolites at steady state. The only requirement is that one thermodynamic parameter be known, namely the reaction affinity at the intercept of the tangent in the inflection point of the curve of reaction rate against reaction...

  14. Metabolic control analysis of biochemical pathways based on a thermokinetic description of reaction rates

    DEFF Research Database (Denmark)

    Nielsen, Jens Bredal

    1997-01-01

    Metabolic control analysis is a powerful technique for the evaluation of flux control within biochemical pathways. Its foundation is the elasticity coefficients and the flux control coefficients (FCCs). On the basis of a thermokinetic description of reaction rates it is here shown...... that the elasticity coefficients can be calculated directly from the pool levels of metabolites at steady state. The only requirement is that one thermodynamic parameter be known, namely the reaction affinity at the intercept of the tangent in the inflection point of the curve of reaction rate against reaction...... of the thermokinetic description of reaction rates to include the influence of effecters. Here the reaction rate is written as a linear function of the logarithm of the metabolite concentrations. With this type of rate function it is shown that the approach of Delgado and Liao [Biochem. J. (1992) 282, 919-927] can...

  15. Thermodynamic and Probabilistic Metabolic Control Analysis of Riboflavin (Vitamin B₂) Biosynthesis in Bacteria.

    Science.gov (United States)

    Birkenmeier, Markus; Mack, Matthias; Röder, Thorsten

    2015-10-01

    In this study, we applied a coupled in silico thermodynamic and probabilistic metabolic control analysis methodology to investigate the control mechanisms of the commercially relevant riboflavin biosynthetic pathway in bacteria. Under the investigated steady-state conditions, we found that several enzyme reactions of the pathway operate far from thermodynamic equilibrium (transformed Gibbs energies of reaction below about -17 kJ mol(-1)). Using the obtained thermodynamic information and applying enzyme elasticity sampling, we calculated the distributions of the scaled concentration control coefficients (CCCs) and scaled flux control coefficients (FCCs). From the statistical analysis of the calculated distributions, we inferred that the control over the riboflavin producing flux is shared among several enzyme activities and mostly resides in the initial reactions of the pathway. More precisely, the guanosine triphosphate (GTP) cyclohydrolase II activity, and therefore the bifunctional RibA protein of Bacillus subtilis because it catalyzes this activity, appears to mainly control the riboflavin producing flux (mean FCCs = 0.45 and 0.55, respectively). The GTP cyclohydrolase II activity and RibA also exert a high positive control over the riboflavin concentration (mean CCCs = 2.43 and 2.91, respectively). This prediction is consistent with previous findings for microbial riboflavin overproducing strains.

  16. Metabolic control analysis of L-lactate synthesis pathway in Rhizopus oryzae As 3.2686.

    Science.gov (United States)

    Ke, Wei; Chang, Shu; Chen, Xiaoju; Luo, Shuizhong; Jiang, Shaotong; Yang, Peizhou; Wu, Xuefeng; Zheng, Zhi

    2015-11-01

    The relationship between the metabolic flux and the activities of the pyruvate branching enzymes of Rhizopus oryzae As 3.2686 during L-lactate fermentation was investigated using the perturbation method of aeration. The control coefficients for five enzymes, pyruvate dehydrogenase (PDH), pyruvate carboxylase (PC), pyruvate decarboxylase (PDC), lactate dehydrogenase (LDH), and alcohol dehydrogenase (ADH), were calculated. Our results indicated significant correlations between PDH and PC, PDC and LDH, PDC and ADH, LDH and ADH, and PDC and PC. It also appeared that PDH, PC, and LDH strongly controlled the L-lactate flux; PDH and ADH strongly controlled the ethanol flux; while PDH and PC strongly controlled the acetyl coenzyme A flux and the oxaloacetate flux. Further, the flux control coefficient curves indicated that the control of the system gradually transferred from PDC to PC during the steady state. Therefore, PC was the key rate-limiting enzyme that controls the flux distribution.

  17. Analysis of clock-regulated genes in Neurospora reveals widespread posttranscriptional control of metabolic potential

    Science.gov (United States)

    Hurley, Jennifer M.; Dasgupta, Arko; Emerson, Jillian M.; Zhou, Xiaoying; Ringelberg, Carol S.; Knabe, Nicole; Lipzen, Anna M.; Lindquist, Erika A.; Daum, Christopher G.; Barry, Kerrie W.; Grigoriev, Igor V.; Smith, Kristina M.; Galagan, James E.; Bell-Pedersen, Deborah; Freitag, Michael; Cheng, Chao; Loros, Jennifer J.; Dunlap, Jay C.

    2014-01-01

    Neurospora crassa has been for decades a principal model for filamentous fungal genetics and physiology as well as for understanding the mechanism of circadian clocks. Eukaryotic fungal and animal clocks comprise transcription-translation–based feedback loops that control rhythmic transcription of a substantial fraction of these transcriptomes, yielding the changes in protein abundance that mediate circadian regulation of physiology and metabolism: Understanding circadian control of gene expression is key to understanding eukaryotic, including fungal, physiology. Indeed, the isolation of clock-controlled genes (ccgs) was pioneered in Neurospora where circadian output begins with binding of the core circadian transcription factor WCC to a subset of ccg promoters, including those of many transcription factors. High temporal resolution (2-h) sampling over 48 h using RNA sequencing (RNA-Seq) identified circadianly expressed genes in Neurospora, revealing that from ∼10% to as much 40% of the transcriptome can be expressed under circadian control. Functional classifications of these genes revealed strong enrichment in pathways involving metabolism, protein synthesis, and stress responses; in broad terms, daytime metabolic potential favors catabolism, energy production, and precursor assembly, whereas night activities favor biosynthesis of cellular components and growth. Discriminative regular expression motif elicitation (DREME) identified key promoter motifs highly correlated with the temporal regulation of ccgs. Correlations between ccg abundance from RNA-Seq, the degree of ccg-promoter activation as reported by ccg-promoter–luciferase fusions, and binding of WCC as measured by ChIP-Seq, are not strong. Therefore, although circadian activation is critical to ccg rhythmicity, posttranscriptional regulation plays a major role in determining rhythmicity at the mRNA level. PMID:25362047

  18. Melatonin for Atypical Antipsychotic-Induced Metabolic Adverse Effects: A Meta-Analysis of Randomized Controlled Trials

    Directory of Open Access Journals (Sweden)

    Ashwin Kamath

    2018-01-01

    Full Text Available The objective of our study was to determine the effect of melatonin administration on atypical antipsychotic-induced metabolic adverse effects in patients with psychiatric disorders. A systematic search was performed in PUBMED, Cochrane Library, Scopus, Web of Science, and EBSCOhost electronic databases. Randomized controlled trials studying the effect of melatonin on antipsychotic-induced metabolic adverse effects were identified and subjected to meta-analysis. Four studies were included in the meta-analysis, including 57 patients on melatonin and 61 patients on placebo. Melatonin produced a significant decrease in the diastolic blood pressure compared with placebo (mean difference = −4.44 [95% CI, −7.00 to −1.88]; p=0.0007; I2 = 13%, but not the systolic blood pressure (mean difference = −4.23 [95% CI, −8.11 to −0.36]; p=0.03; I2 = 0%. Although a decrease in the body mass index was seen in the melatonin group, the difference was not significant in the random-effects analysis model. To conclude, in patients on atypical antipsychotics, melatonin at a dose of up to 5 mg/day for a treatment duration of up to 12 weeks attenuated the rise in diastolic blood pressure compared with placebo but had no significant effects on other metabolic parameters.

  19. Melatonin for Atypical Antipsychotic-Induced Metabolic Adverse Effects: A Meta-Analysis of Randomized Controlled Trials.

    Science.gov (United States)

    Kamath, Ashwin; Rather, Zahoor Ahmad

    2018-01-01

    The objective of our study was to determine the effect of melatonin administration on atypical antipsychotic-induced metabolic adverse effects in patients with psychiatric disorders. A systematic search was performed in PUBMED, Cochrane Library, Scopus, Web of Science, and EBSCOhost electronic databases. Randomized controlled trials studying the effect of melatonin on antipsychotic-induced metabolic adverse effects were identified and subjected to meta-analysis. Four studies were included in the meta-analysis, including 57 patients on melatonin and 61 patients on placebo. Melatonin produced a significant decrease in the diastolic blood pressure compared with placebo (mean difference = -4.44 [95% CI, -7.00 to -1.88]; p = 0.0007; I 2 = 13%), but not the systolic blood pressure (mean difference = -4.23 [95% CI, -8.11 to -0.36]; p = 0.03; I 2 = 0%). Although a decrease in the body mass index was seen in the melatonin group, the difference was not significant in the random-effects analysis model. To conclude, in patients on atypical antipsychotics, melatonin at a dose of up to 5 mg/day for a treatment duration of up to 12 weeks attenuated the rise in diastolic blood pressure compared with placebo but had no significant effects on other metabolic parameters.

  20. Thermodynamics of the control of metabolism

    NARCIS (Netherlands)

    Westerhoff, H. V.; Plomp, P. J.; Groen, A. K.; Wanders, R. J.

    1987-01-01

    A theory is presented, describing the control analysis of metabolic systems in terms of Gibbs free energies, extending earlier work of Kacser and Burns (25), and Heinrich and Rapoport (29). It is shown that relationships exist between flux control coefficients (the degree to which enzymes control

  1. In-depth proteomic analysis of Glycine max seeds during controlled deterioration treatment reveals a shift in seed metabolism.

    Science.gov (United States)

    Min, Cheol Woo; Lee, Seo Hyun; Cheon, Ye Eun; Han, Won Young; Ko, Jong Min; Kang, Hang Won; Kim, Yong Chul; Agrawal, Ganesh Kumar; Rakwal, Randeep; Gupta, Ravi; Kim, Sun Tae

    2017-10-03

    Seed aging is one of the major events, affecting the overall quality of agricultural seeds. To analyze the effect of seed aging, soybean seeds were exposed to controlled deterioration treatment (CDT) for 3 and 7days, followed by their physiological, biochemical, and proteomic analyses. Seed proteins were subjected to protamine sulfate precipitation for the enrichment of low-abundance proteins and utilized for proteome analysis. A total of 14 differential proteins were identified on 2-DE, whereas label-free quantification resulted in the identification of 1626 non-redundant proteins. Of these identified proteins, 146 showed significant changes in protein abundance, where 5 and 141 had increased and decreased abundances, respectively while 352 proteins were completely degraded during CDT. Gene ontology and KEGG analyses suggested the association of differential proteins with primary metabolism, ROS detoxification, translation elongation and initiation, protein folding, and proteolysis, where most, if not all, had decreased abundance during CDT. Western blotting confirmed reduced level of antioxidant enzymes (DHAR, APx1, MDAR, and SOD) upon CDT. This in-depth integrated study reveals a major downshift in seed metabolism upon CDT. Reported data here serve as a resource for its exploitation to metabolic engineering of seeds for multiple purposes, including increased seed viability, vigor, and quality. Controlled deterioration treatment (CDT) is one of the major events that negatively affects the quality and nutrient composition of agricultural seeds. However, the molecular mechanism of CDT is largely unknown. A combination of gel-based and gel-free proteomic approach was utilized to investigate the effects of CDT in soybean seeds. Moreover, we utilized protamine sulfate precipitation method for enrichment of low-abundance proteins, which are generally masked due to the presence of high-abundance seed storage proteins. Reported data here serve as resource for its

  2. 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.

  3. Artificial neural network analysis of factors controlling ecosystem metabolism in coastal systems

    NARCIS (Netherlands)

    Rochelle-Newall, E.J.; Winter, C.; Barrón, C.; Borges, A.V.; Duarte, C.M.; Elliott, M.; Frankignoulle, M.; Gazeau, F.P.H.; Middelburg, J.J.; Pizay, M-D.; Thioulouse, J.; Gattuso, J.P.

    2007-01-01

    Knowing the metabolic balance of an ecosystem is of utmost importance in determining whether the system is a net source or net sink of carbon dioxide to the atmosphere. However, obtaining these estimates often demands significant amounts of time and manpower. Here we present a simplified way to

  4. Spatially resolved metabolic analysis reveals a central role for transcriptional control in carbon allocation to wood.

    Science.gov (United States)

    Roach, Melissa; Arrivault, Stéphanie; Mahboubi, Amir; Krohn, Nicole; Sulpice, Ronan; Stitt, Mark; Niittylä, Totte

    2017-06-15

    The contribution of transcriptional and post-transcriptional regulation to modifying carbon allocation to developing wood of trees is not well defined. To clarify the role of transcriptional regulation, the enzyme activity patterns of eight central primary metabolism enzymes across phloem, cambium, and developing wood of aspen (Populus tremula L.) were compared with transcript levels obtained by RNA sequencing of sequential stem sections from the same trees. Enzymes were selected on the basis of their importance in sugar metabolism and in linking primary metabolism to lignin biosynthesis. Existing enzyme assays were adapted to allow measurements from ~1 mm3 sections of dissected stem tissue. These experiments provided high spatial resolution of enzyme activity changes across different stages of wood development, and identified the gene transcripts probably responsible for these changes. In most cases, there was a clear positive relationship between transcripts and enzyme activity. During secondary cell wall formation, the increases in transcript levels and enzyme activities also matched with increased levels of glucose, fructose, hexose phosphates, and UDP-glucose, emphasizing an important role for transcriptional regulation in carbon allocation to developing aspen wood. These observations corroborate the efforts to increase carbon allocation to wood by engineering gene regulatory networks. © The Author 2017. Published by Oxford University Press on behalf of the Society for Experimental Biology.

  5. Integrative analysis of transgenic alfalfa (Medicago sativa L. suggests new metabolic control mechanisms for monolignol biosynthesis.

    Directory of Open Access Journals (Sweden)

    Yun Lee

    2011-05-01

    Full Text Available The entanglement of lignin polymers with cellulose and hemicellulose in plant cell walls is a major biological barrier to the economically viable production of biofuels from woody biomass. Recent efforts of reducing this recalcitrance with transgenic techniques have been showing promise for ameliorating or even obviating the need for costly pretreatments that are otherwise required to remove lignin from cellulose and hemicelluloses. At the same time, genetic manipulations of lignin biosynthetic enzymes have sometimes yielded unforeseen consequences on lignin composition, thus raising the question of whether the current understanding of the pathway is indeed correct. To address this question systemically, we developed and applied a novel modeling approach that, instead of analyzing the pathway within a single target context, permits a comprehensive, simultaneous investigation of different datasets in wild type and transgenic plants. Specifically, the proposed approach combines static flux-based analysis with a Monte Carlo simulation in which very many randomly chosen sets of parameter values are evaluated against kinetic models of lignin biosynthesis in different stem internodes of wild type and lignin-modified alfalfa plants. In addition to four new postulates that address the reversibility of some key reactions, the modeling effort led to two novel postulates regarding the control of the lignin biosynthetic pathway. The first posits functionally independent pathways toward the synthesis of different lignin monomers, while the second postulate proposes a novel feedforward regulatory mechanism. Subsequent laboratory experiments have identified the signaling molecule salicylic acid as a potential mediator of the postulated control mechanism. Overall, the results demonstrate that mathematical modeling can be a valuable complement to conventional transgenic approaches and that it can provide biological insights that are otherwise difficult to obtain.

  6. A systems biological analysis links ROS metabolism to mitochondrial protein quality control.

    Science.gov (United States)

    Kowald, Axel; Hamann, Andrea; Zintel, Sandra; Ullrich, Sebastian; Klipp, Edda; Osiewacz, Heinz D

    2012-05-01

    The analyses of previously generated Podospora anserina strains in which the mitochondrial superoxide dismutase, PaSOD3, is increased in abundance, revealed unexpected results, which, at first glance, are contradictory to the 'free radical theory of aging' (FRTA). To re-analyze these results, we performed additional experiments and developed a mathematical model consisting of a set of differential equations describing the time course of various ROS (reactive oxygen species), components of the cellular antioxidant system (PaSOD3 and mitochondrial peroxiredoxin, PaPRX1), and PaCLPP, a mitochondrial matrix protease involved in protein quality control. Incorporating these components we could identify a positive feed-back loop and demonstrate that the role of superoxide as the primary ROS responsible for age-related molecular damage is more complicated than originally stated by the FRTA. Our study is a first step towards the integration of the various pathways known to be involved in the control of biological aging. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  7. Glycaemic Control, Dyslipidaemia and Metabolic Syndrome among ...

    African Journals Online (AJOL)

    BACKGROUND: Poor glycaemic control, dyslipidaemia and metabolic syndrome are all risk factors for cardiovascular disease. OBJECTIVE: To determine the association between glycaemic control, dyslipidaemia and metabolic syndrome and their relative incidence among recently diagnosed diabetic patients in Tamale ...

  8. Glycaemic Control, Dyslipidaemia and Metabolic Syndrome among ...

    African Journals Online (AJOL)

    Glycaemic Control, Dyslipidaemia and Metabolic Syndrome among Recently Diagnosed Diabetes Mellitus Patients in Tamale Teaching Hospital, Ghana. ... West African Journal of Medicine ... BACKGROUND: Poor glycaemic control, dyslipidaemia and metabolic syndrome are all risk factors for cardiovascular disease.

  9. Clinical study on the prevalence and comparative analysis of metabolic syndrome and its components among Chinese breast cancer women and control population.

    Science.gov (United States)

    Wu, Yu-Tuan; Luo, Qing-Qing; Li, Xin; Arshad, Bilal; Xu, Zhou; Ran, Liang; Zhao, Chun-Xia; Wu, He; Shi, Yan-Ling; Chen, Hao-Ran; Li, Hao; Li, Hong-Yuan; Wu, Kai-Nan; Kong, Ling-Quan

    2018-01-01

    Metabolic syndrome has been previously identified as a risk factor for breast cancer and is increasingly a public health concern. This study aims to investigate the prevalence of metabolic syndrome and its components among primary breast cancer and control population. The clinical data of metabolic syndrome and its components in the breast cancer (605 cases) and control population (3212 cases), from Breast Cancer Center and Physical Examination Center of Chongqing, China, from July 2015 to February 2017, were collected for comparative analysis. This study was prospectively registered in Chinese Clinical Trial Registry (http://www.chictr.org.cn/, number: ChiCTR-OOB-15007543). The prevalence of metabolic syndrome in breast cancer (32.6%) was obviously higher than that in control population (18.2%) (pmetabolic syndrome in breast cancer group aged below 60 years (24.9%, pmetabolic syndrome and its components in Chinese breast cancer women, and metabolic syndrome is closely related with breast cancer. Therefore, screening and prevention strategy of metabolic syndrome should be carried out in the management of breast cancer.

  10. 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...

  11. Principal Metabolic Flux Mode Analysis.

    Science.gov (United States)

    Bhadra, Sahely; Blomberg, Peter; Castillo, Sandra; Rousu, Juho; Wren, Jonathan

    2018-02-06

    In the analysis of metabolism, two distinct and complementary approaches are frequently used: Principal component analysis (PCA) and stoichiometric flux analysis. PCA is able to capture the main modes of variability in a set of experiments and does not make many prior assumptions about the data, but does not inherently take into account the flux mode structure of metabolism. Stoichiometric flux analysis methods, such as Flux Balance Analysis (FBA) and Elementary Mode Analysis, on the other hand, are able to capture the metabolic flux modes, however, they are primarily designed for the analysis of single samples at a time, and not best suited for exploratory analysis on a large sets of samples. We propose a new methodology for the analysis of metabolism, called Principal Metabolic Flux Mode Analysis (PMFA), which marries the PCA and stoichiometric flux analysis approaches in an elegant regularized optimization framework. In short, the method incorporates a variance maximization objective form PCA coupled with a stoichiometric regularizer, which penalizes projections that are far from any flux modes of the network. For interpretability, we also introduce a sparse variant of PMFA that favours flux modes that contain a small number of reactions. Our experiments demonstrate the versatility and capabilities of our methodology. The proposed method can be applied to genome-scale metabolic network in efficient way as PMFA does not enumerate elementary modes. In addition, the method is more robust on out-of-steady steady-state experimental data than competing flux mode analysis approaches. Matlab software for PMFA and SPMFA and data set used for experiments are available in https://github.com/aalto-ics-kepaco/PMFA. sahely@iitpkd.ac.in, juho.rousu@aalto.fi, Peter.Blomberg@vtt.fi, Sandra.Castillo@vtt.fi. Detailed results are in Supplementary files. Supplementary data are available at https://github.com/aalto-ics-kepaco/PMFA/blob/master/Results.zip.

  12. Effects of testosterone treatment on glucose metabolism and symptoms in men with type 2 diabetes and the metabolic syndrome: a systematic review and meta-analysis of randomized controlled clinical trials.

    Science.gov (United States)

    Grossmann, Mathis; Hoermann, Rudolf; Wittert, Gary; Yeap, Bu B

    2015-09-01

    The effects of testosterone treatment on glucose metabolism and other outcomes in men with type 2 diabetes (T2D) and/or the metabolic syndrome are controversial. To perform a systematic review and meta-analysis of placebo-controlled double-blind randomized controlled clinical trials (RCT) of testosterone treatment in men with T2D and/or the metabolic syndrome. A systematic search of RCTs was conducted using Medline, Embase and the Cochrane Register of controlled trials from inception to July 2014 followed by a manual review of the literature. Eligible studies were published placebo-controlled double-blind RCTs published in English. Two reviewers independently selected studies, determined study quality and extracted outcome and descriptive data. Of the 112 identified studies, seven RCTs including 833 men were eligible for the meta-analysis. In studies using a simple linear equation to calculate the homeostatic model assessment of insulin resistance (HOMA1), testosterone treatment modestly improved insulin resistance, compared to placebo, pooled mean difference (MD) -1·58 [-2·25, -0·91], P treatment effect was nonsignificant for RCTs using a more stringent computer-based equation (HOMA2), MD -0·19 [-0·86, 0·49], P = 0·58). Testosterone treatment did not improve glycaemic (HbA1c) control, MD -0·15 [-0·39, 0·10], P = 0·25, or constitutional symptoms, Aging Male Symptom score, MD -2·49 [-5·81, 0·83], P = 0·14). This meta-analysis does not support the routine use of testosterone treatment in men with T2D and/or the metabolic syndrome without classical hypogonadism. Additional studies are needed to determine whether hormonal interventions are warranted in selected men with T2D and/or the metabolic syndrome. © 2014 John Wiley & Sons Ltd.

  13. Metabolic control analysis of the penicillin biosynthetic pathway: the influence of the LLD-ACV:bisACV ratio on the flux control.

    Science.gov (United States)

    Theilgaard, H A; Nielsen, J

    1999-01-01

    An extended kinetic model for the first two steps of the penicillin biosynthetic pathway in Penicillium chrysogenum is set up. It includes the formation and reduction of the dimer bis-delta-(L-alpha-aminoadipyl)-L-cysteinyl-D-valine (bisACV) from the first pathway intermediate LLD-ACV and their parallel inhibition of the enzyme ACV synthetase (ACVS). The kinetic model is based on Michaelis-Menten type kinetics, with non-competitive inhibition of the ACVS by both LLD-ACV and bisACV, and competitive inhibition of the isopenicillin N synthetase (IPNS) by glutathione. The inhibition constant of LLD-ACV, KACV is determined to be 0.54 mm. With the kinetic model metabolic control analysis is performed to identify the distribution of rate-control in the pathway at all ratios of LLD-ACV:bisACV. It is concluded that the flux control totally resides at the IPNS. This is a result of the regulation of the ACVS by both the LLD-ACV and bisACV demanding a higher flux through the IPNS enzyme to alleviate their inhibition. The measurement of an intracellular ratio of LLD-ACV:bisACV to be in the range of 1-2 moles per moles emphasises the importance of a fast conversion of LLD-ACV to IPN, and accumulation of LLD-ACV above the K(m)-value of the IPNS should therefore be avoided.

  14. Effect of probiotics on metabolic profiles in type 2 diabetes mellitus: A meta-analysis of randomized, controlled trials.

    Science.gov (United States)

    Li, Caifeng; Li, Xin; Han, Hongqiu; Cui, Hailong; Peng, Min; Wang, Guolin; Wang, Zhiqiang

    2016-06-01

    Type 2 diabetes mellitus (T2DM) is a prevalent metabolic disease which is imposing heavy burden on global health and economy. Recent studies indicate gut microbiota play important role on the pathogenesis and metabolic disturbance of T2DM. As an effective mean of regulating gut microbiota, probiotics are live micro-organisms that are believed to provide a specific health benefit on the host. Whether probiotic supplementation could improve metabolic profiles by modifying gut microbiota in T2DM or not is still in controversy.The aim of the study is to assess the effect of probiotic supplementation on metabolic profiles in T2DM.We searched PubMed, EMBASE, and Cochrane Library up to 12 April 2016. Two review authors independently assessed study eligibility, extracted data, and evaluated risk of bias of included studies. Data were pooled by using the random-effect model and expressed as standardized mean difference (SMD) with 95% confidence interval (CI). Heterogeneity was assessed and quantified (I).A total of 12 randomized controlled trials (RCTs) were included. Lipid profiles (n = 508) and fasting blood glucose (FBG) (n = 520) were reported in 9 trials; the homeostasis model of assessment for insulin resistance index (HOMA-IR) (n = 368) and glycosylated hemoglobin (HbA1c) (n = 380) were reported in 6 trials. Probiotics could alleviate FBG (SMD -0.61 mmol/L, 95% CI [-0.92, -0.30], P = 0.0001). Probiotics could increase high-density lipoprotein-cholesterol (HDL-C) (SMD 0.42 mmol/L, 95% CI [0.08, 0.76], P = 0.01). There were no significant differences in low-density lipoprotein-cholesterol (LDL-C), total cholesterol (TC), triglyceride (TG), HbA1c and HOMA-IR between the treatment group and the control group.Probiotics may improve glycemic control and lipid metabolism in T2DM. Application of probiotic agents might become a new method for glucose management in T2DM.

  15. Effects of periodontal therapy on metabolic control in patients with type 2 diabetes mellitus and periodontal disease: a meta-analysis.

    Science.gov (United States)

    Wang, Tze-Fang; Jen, I-An; Chou, Chyuan; Lei, Yen-Ping

    2014-12-01

    Epidemiologic studies have reported increased incidence, prevalence and acuity of periodontitis in adults with diabetes and some have also suggested that treating periodontal disease may improve glycemic control in diabetic patients. This meta-analysis was conducted to evaluate the effects of different periodontal therapies on metabolic control in patients with type 2 diabetes mellitus (T2DM) and periodontal disease. We searched the Medline, EMBASE and Cochrane Library (Central) databases up to January 2014 for relevant studies pertaining to periodontal treatments and glycemic control in adults with T2DM. The search terms were periodontal treatment/periodontal therapy, diabetes/diabetes mellitus, periodontitis/periodontal and glycemic control. The primary outcome measure taken from the included studies was glycated hemoglobin (HbA1c). We compared differences in patients' pre- and post-intervention HbA1c results between a treatment group receiving scaling and root planing (SRP) combined with administration of oral doxycycline (n=71) and controls receiving SRP alone or SRP plus placebo (n=72). Meta-analysis was performed using Comprehensive Meta Analysis software. Nineteen randomized controlled trials (RCTs) were identified. Four trials involving a total of 143 patients with T2DM and periodontal disease were determined to be eligible for analysis. Data of 1 study were not retained for meta-analysis because HbA1c results were recorded as median with IQR. Meta-analysis of the included 3 studies revealed no significant differences in HbA1c results between the periodontal treatment group (n=71) and control group (n=72) (HbA1c SMD=-0.238, 95% CI=-0.616 to 0.140; P=0.217). Systemic doxycycline added to SRP does not significantly improve metabolic control in patients with T2DM and chronic periodontitis. Current evidence is insufficient to support a significant association between periodontal therapy and metabolic control in this patient population. However, evidence

  16. Effect of Probiotics on Glucose and Lipid Metabolism in Type 2 Diabetes Mellitus: A Meta-Analysis of 12 Randomized Controlled Trials

    OpenAIRE

    Yao, Kecheng; Zeng, Linghai; He, Qian; Wang, Wei; Lei, Jiao; Zou, Xiulan

    2017-01-01

    Background It has been unclear whether supplemental probiotics therapy improves clinical outcomes in type 2 diabetic patients. This meta-analysis aimed to summarize the effect of probiotics on glucose and lipid metabolism and C-reactive protein (CRP) from 12 randomized controlled trials (RCTs). Material/Methods An up-to-date search was performed for all relevant RCTs up to April 2016 from PubMed, Embase, and Cochrane Library. Standardized mean difference (SMD) and weighted mean difference (WM...

  17. Effect of probiotics on glucose metabolism in patients with type 2 diabetes mellitus: A meta-analysis of randomized controlled trials

    OpenAIRE

    Qingqing Zhang; Yucheng Wu; Xiaoqiang Fei

    2016-01-01

    Objective: Our aim was to investigate the effects of probiotics on glucose metabolism in patients with type 2 diabetes mellitus using a meta-analysis of randomized, controlled trials. Materials and methods: Online databases Embase, Web of Science, and PubMed were searched until August 2014 to identify eligible articles. Finally, 7 trials were included. Results: Probiotic consumption significantly changed fasting plasma glucose (FPG) by −15.92 mg/dL (95% confidence interval [CI], −29.75 ...

  18. Clinical study on the prevalence and comparative analysis of metabolic syndrome and its components among Chinese breast cancer women and control population

    Science.gov (United States)

    Wu, Yu-tuan; Luo, Qing-qing; Li, Xin; Arshad, Bilal; Xu, Zhou; Ran, Liang; Zhao, Chun-xia; Wu, He; Shi, Yan-ling; Chen, Hao-ran; Li, Hao; Li, Hong-yuan; Wu, Kai-nan; Kong, Ling-quan

    2018-01-01

    Metabolic syndrome has been previously identified as a risk factor for breast cancer and is increasingly a public health concern. This study aims to investigate the prevalence of metabolic syndrome and its components among primary breast cancer and control population. The clinical data of metabolic syndrome and its components in the breast cancer (605 cases) and control population (3212 cases), from Breast Cancer Center and Physical Examination Center of Chongqing, China, from July 2015 to February 2017, were collected for comparative analysis. This study was prospectively registered in Chinese Clinical Trial Registry (http://www.chictr.org.cn/, number: ChiCTR-OOB-15007543). The prevalence of metabolic syndrome in breast cancer (32.6%) was obviously higher than that in control population (18.2%) (p<0.001; OR: 2.173, 95%CI: 1.793 to 2.633). With age stratification, the prevalence of metabolic syndrome in breast cancer group aged below 60 years (24.9%, p<0.001; OR: 2.216, 95%CI: 1.744 to 2.816) and equal/above 60 years (58.3%, p<0.001; OR: 2.291, 95%CI: 1.580 to 3.322) were also statistically higher than those (13.0% & 37.9%) in control population, respectively. Breast cancer women were more likely to have preobese (BMI 25.0-29.9) or obesity (BMI ≥30.0), broader waist circumference, lower HDL-C level, higher systolic and/or diastolic blood pressure and higher fasting blood glucose level compared to the control population, corresponding prevalence were 31.7%vs.19.4%, 76.0%vs.29.6%, 37.4%vs.30.4%, 34.2%/27.3%vs.27.6%/14.2% and 25.0%vs.20.1%, respectively (p<0.01). In summary, there is high prevalence of metabolic syndrome and its components in Chinese breast cancer women, and metabolic syndrome is closely related with breast cancer. Therefore, screening and prevention strategy of metabolic syndrome should be carried out in the management of breast cancer. PMID:29483960

  19. [An analysis of the diabetic population in a Spanish rural are: morbidity profile, use of resources, complications and metabolic control].

    Science.gov (United States)

    Inoriza, José M; Pérez, Marc; Cols, Montse; Sánchez, Inma; Carreras, Marc; Coderch, Jordi

    2013-11-01

    To describe the characteristics of a diabetic population, morbidity profile, resource consumption, complications and degree of metabolic control. Cross-sectional study during 2010. Four Health Areas (91.301 people) where the integrated management organization Serveis de Salut integrated Baix Empordà completely provide healthcare assistance. 4.985 diabetic individuals, identified through clinical codes using the ICD-9-MC classification and the 3M? Clinical Risk Groups software. Morbidity profile, related complications and degree of metabolic control were obtained for the target diabetic population. We analyzed the consumption of healthcare resources, pharmaceutical and blood glucose reagent strips. All measurements obtained at individual level. 99.3% of the diabetic population were attended at least once at a primary care center (14.9% of visits). 39.5% of primary care visits and less than 10% of the other scanned resources were related to the management of diabetes. The pharmaceutical expenditure was 25.4% of the population consumption (average cost ?1.014,57). 36.5% of diabetics consumed reagents strips (average cost ?120,65). The more frequent CRG are 5424-Diabetes (27%); 6144-Diabetes and Hypertension (25,5%) and 6143-Diabetes and Other Moderate Chronic Disease (17,2%). The degree of disease control is better in patients not consumers of antidiabetic drugs or treated with oral antidiabetic agents not secretagogues. Comorbidity is decisive in the consumption of resources. Just a few part of this consumption is specifically related to the management of diabetes. Results obtained provide a whole population approach to the main existing studies in our national and regional context. Copyright © 2012 Elsevier España, S.L. All rights reserved.

  20. RNA-Seq Analysis of Abdominal Fat in Genetically Fat and Lean Chickens Highlights a Divergence in Expression of Genes Controlling Adiposity, Hemostasis, and Lipid Metabolism.

    Directory of Open Access Journals (Sweden)

    Christopher W Resnyk

    Full Text Available Genetic selection for enhanced growth rate in meat-type chickens (Gallus domesticus is usually accompanied by excessive adiposity, which has negative impacts on both feed efficiency and carcass quality. Enhanced visceral fatness and several unique features of avian metabolism (i.e., fasting hyperglycemia and insulin insensitivity mimic overt symptoms of obesity and related metabolic disorders in humans. Elucidation of the genetic and endocrine factors that contribute to excessive visceral fatness in chickens could also advance our understanding of human metabolic diseases. Here, RNA sequencing was used to examine differential gene expression in abdominal fat of genetically fat and lean chickens, which exhibit a 2.8-fold divergence in visceral fatness at 7 wk. Ingenuity Pathway Analysis revealed that many of 1687 differentially expressed genes are associated with hemostasis, endocrine function and metabolic syndrome in mammals. Among the highest expressed genes in abdominal fat, across both genotypes, were 25 differentially expressed genes associated with de novo synthesis and metabolism of lipids. Over-expression of numerous adipogenic and lipogenic genes in the FL chickens suggests that in situ lipogenesis in chickens could make a more substantial contribution to expansion of visceral fat mass than previously recognized. Distinguishing features of the abdominal fat transcriptome in lean chickens were high abundance of multiple hemostatic and vasoactive factors, transporters, and ectopic expression of several hormones/receptors, which could control local vasomotor tone and proteolytic processing of adipokines, hemostatic factors and novel endocrine factors. Over-expression of several thrombogenic genes in abdominal fat of lean chickens is quite opposite to the pro-thrombotic state found in obese humans. Clearly, divergent genetic selection for an extreme (2.5-2.8-fold difference in visceral fatness provokes a number of novel regulatory responses

  1. Controlling fluxes for microbial metabolic engineering

    OpenAIRE

    Sachdeva, Gairik

    2014-01-01

    This thesis presents novel synthetic biology tools and design principles usable for microbial metabolic engineering. Controlling metabolic fluxes is essential for biological manufacturing of fuels, materials, and high value chemicals. Insulating the flow of metabolites is a successful natural strategy for metabolic flux regulation. Recently, approaches using scaffolds, both in vitro and in vivo, to spatially co-localize enzymes have reported significant gains in product yields. RNA is suitabl...

  2. Metabolic effects of testosterone replacement therapy on hypogonadal men with type 2 diabetes mellitus: a systematic review and meta-analysis of randomized controlled trials

    Directory of Open Access Journals (Sweden)

    Xiang Cai

    2014-02-01

    Full Text Available This systematic review was aimed at assessing the metabolic effects of testosterone replacement therapy (TRT on hypogonadal men with type 2 diabetes mellitus (T2DM. A literature search was performed using the Cochrane Library, EMBASE and PubMed. Only randomized controlled trials (RCTs were included in the meta-analysis. Two reviewers retrieved articles and evaluated the study quality using an appropriate scoring method. Outcomes including glucose metabolism, lipid parameters, body fat and blood pressure were pooled using a random effects model and tested for heterogeneity. We used the Cochrane Collaboration's Review Manager 5.2 software for statistical analysis. Five RCTs including 351 participants with a mean follow-up time of 6.5-months were identified that strictly met our eligibility criteria. A meta-analysis of the extractable data showed that testosterone reduced fasting plasma glucose levels (mean difference (MD: −1.10; 95% confidence interval (CI (−1.88, −0.31, fasting serum insulin levels (MD: −2.73; 95% CI (−3.62, −1.84, HbA1c % (MD: −0.87; 95% CI (−1.32, −0.42 and triglyceride levels (MD: −0.35; 95% CI (−0.62, −0.07. The testosterone and control groups demonstrated no significant difference for other outcomes. In conclusion, we found that TRT can improve glycemic control and decrease triglyceride levels of hypogonadal men with T2DM. Considering the limited number of participants and the confounding factors in our systematic review; additional large, well-designed RCTs are needed to address the metabolic effects of TRT and its long-term influence on hypogonadal men with T2DM.

  3. Effect of probiotics on glucose metabolism in patients with type 2 diabetes mellitus: A meta-analysis of randomized controlled trials.

    Science.gov (United States)

    Zhang, Qingqing; Wu, Yucheng; Fei, Xiaoqiang

    2016-01-01

    Our aim was to investigate the effects of probiotics on glucose metabolism in patients with type 2 diabetes mellitus using a meta-analysis of randomized, controlled trials. Online databases Embase, Web of Science, and PubMed were searched until August 2014 to identify eligible articles. Finally, 7 trials were included. Probiotic consumption significantly changed fasting plasma glucose (FPG) by -15.92mg/dL (95% confidence interval [CI], -29.75 to -2.09) and glycosylated hemoglobin (HbA1c) by -0.54% (95% CI, -0.82 to -0.25) compared with control groups. Subgroup analysis was conducted to trials with non-yogurts control. Meta-analysis of trials with multiple species of probiotics found a significant reduction in FPG (weighted mean difference [WMD]: -35.41mg/dL, 95% CI: -51.98 to -18.89). The duration of intervention for ≥8 weeks resulted in a significant reduction in FPG (WMD: -20.34mg/dL, 95% CI: -35.92 to -4.76). Subgroup analysis of trials with species of probiotics did not result in a significant meta-analysis effect. Furthermore, the duration of intervention probiotic therapy significantly decreased homeostasis model assessment of insulin resistance (HOMA-IR) and insulin concentration (WMD: -1.08, 95% CI: -1.88 to -0.28; and WMD: -1.35mIU/L, 95% CI: -2.38 to -0.31, respectively). The present meta-analysis suggests that consuming probiotics may improve glucose metabolism by a modest degree, with a potentially greater effect when the duration of intervention is ≥8 weeks, or multiple species of probiotics are consumed. Copyright © 2016 The Lithuanian University of Health Sciences. Production and hosting by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

  4. Temporal Control of Metabolic Amplitude by Nocturnin

    Directory of Open Access Journals (Sweden)

    Jeremy J. Stubblefield

    2018-01-01

    Full Text Available The timing of food intake and nutrient utilization is critical to health and regulated partly by the circadian clock. Increased amplitude of circadian oscillations and metabolic output has been found to improve health in diabetic and obesity mouse models. Here, we report a function for the circadian deadenylase Nocturnin as a regulator of metabolic amplitude across the day/night cycle and in response to nutrient challenge. We show that mice lacking Nocturnin (Noct−/− display significantly increased amplitudes of mRNA expression of hepatic genes encoding key metabolic enzymes regulating lipid and cholesterol synthesis, both over the daily circadian cycle and in response to fasting and refeeding. Noct−/− mice have increased plasma triglyceride throughout the night and increased amplitude of hepatic cholesterol levels. Therefore, posttranscriptional control by Nocturnin regulates the amplitude of these critical metabolic pathways, and loss of this activity results in increased metabolic flux and reduced obesity.

  5. Effect of probiotics on glucose metabolism in patients with type 2 diabetes mellitus: A meta-analysis of randomized controlled trials

    Directory of Open Access Journals (Sweden)

    Qingqing Zhang

    2016-01-01

    Conclusions: The present meta-analysis suggests that consuming probiotics may improve glucose metabolism by a modest degree, with a potentially greater effect when the duration of intervention is ≥8 weeks, or multiple species of probiotics are consumed.

  6. Metabolic and neurological complications of second-generation antipsychotic use in children: a systematic review and meta-analysis of randomized controlled trials.

    Science.gov (United States)

    Pringsheim, Tamara; Lam, Darren; Ching, Heidi; Patten, Scott

    2011-08-01

    Available evidence indicates that the use of antipsychotics, especially second-generation antipsychotics (SGAs), for children with mental health disorders has increased dramatically. Given the demonstrated metabolic and neurological adverse effects seen in adult patients on these medications, detailed evaluation of the risk for these adverse effects in children is appropriate. The aim of the study was to assess the evidence for specific metabolic and neurological adverse effects associated with the use of SGAs in children. MEDLINE (1996-May 2010) and EMBASE (1996-May 2010) databases were searched using highly sensitive search strategies for clinical trials in a paediatric population (children up to age 18 years). We included any double-blind, randomized controlled trial (RCT) of SGA medications conducted specifically in a paediatric population for the treatment of a mental health disorder. This included the medications risperidone, olanzapine, quetiapine, aripiprazole, clozapine, ziprasidone and paliperidone. The primary outcomes assessed for this review were metabolic and neurological adverse effects, as measured using physical examination manoeuvres, rating scales or laboratory tests. A total of 35 RCTs were included in the analysis, but not all studies had data that could be used in the meta-analysis. Abstracts retrieved from the searches were reviewed independently by two different reviewers for potential relevant articles. Full-text articles were then read in detail independently by two different reviewers to see if inclusion criteria were fulfilled. Data were extracted independently by two review authors from included studies and entered onto pre-designed summary forms. Clinical trials were evaluated for methodological quality using quality criteria developed by the US Preventive Services Task Force. Based on the fulfilment of quality criteria, studies were rated as good, fair or poor. Meta-analysis was performed on the data for synthesis, and was carried out

  7. Metabolic control by S6 kinases depends on dietary lipids.

    Directory of Open Access Journals (Sweden)

    Tamara R Castañeda

    Full Text Available Targeted deletion of S6 kinase (S6K 1 in mice leads to higher energy expenditure and improved glucose metabolism. However, the molecular mechanisms controlling these effects remain to be fully elucidated. Here, we analyze the potential role of dietary lipids in regulating the mTORC1/S6K system. Analysis of S6K phosphorylation in vivo and in vitro showed that dietary lipids activate S6K, and this effect is not dependent upon amino acids. Comparison of male mice lacking S6K1 and 2 (S6K-dko with wt controls showed that S6K-dko mice are protected against obesity and glucose intolerance induced by a high-fat diet. S6K-dko mice fed a high-fat diet had increased energy expenditure, improved glucose tolerance, lower fat mass gain, and changes in markers of lipid metabolism. Importantly, however, these metabolic phenotypes were dependent upon dietary lipids, with no such effects observed in S6K-dko mice fed a fat-free diet. These changes appear to be mediated via modulation of cellular metabolism in skeletal muscle, as shown by the expression of genes involved in energy metabolism. Taken together, our results suggest that the metabolic functions of S6K in vivo play a key role as a molecular interface connecting dietary lipids to the endogenous control of energy metabolism.

  8. Metabolic effects of fluoxetine in adults with type 2 diabetes mellitus: a meta-analysis of randomized placebo-controlled trials.

    Directory of Open Access Journals (Sweden)

    Zi Ye

    Full Text Available BACKGROUND: The prevalence of obesity and diabetes is increasing dramatically throughout the world. Studies have shown that excess adiposity is a critical predictor of new onset T2DM. This meta-analysis is aimed to assess the metabolic effects of fluoxetine in T2DM. METHODS AND FINDINGS: Electronic search was conducted in the database Medline, PubMed, EMBASE, and the Cochrane library, from inception through to March 2011. A systematic review of the studies on the metabolic effects of fluoxetine in T2DM was performed. The weighted mean difference (WMD and its 95% CI were calculated from the raw data extracted from the original literature. The software Review Manager (version 4.3.1 and Stata (version 11.0 were applied for meta-analysis. Five randomized, placebo-controlled trials were included in the meta-analysis. According to WMD calculation, fluoxetine therapy led to 4.27 Kg of weight loss (95%CI 2.58-5.97, P<0.000 01, 1.41 mmol/L of fasting plasma glucose (FPG decrement (95%CI 0.19-2.64, P = 0.02 and 0.54 mmol/L of triglyceride (TG reduction (95%CI 0.35-0.73, P<0.000 01 compared with placebo. Moreover, fluoxetine therapy produced 0.78% of HbA1c decrement (95%CI -0.23-1.78. However, this effect was not statistically significant (P = 0.13. CONCLUSIONS: Short period of fluoxetine therapy can lead to weight loss as well as reduction of FPG, HbA1c and TG in T2DM.

  9. Metabolic gene polymorphism frequencies in control populations

    DEFF Research Database (Denmark)

    Garte, Seymour; Gaspari, Laura; Alexandrie, Anna-Karin

    2001-01-01

    Using the International Project on Genetic Susceptibility to Environmental Carcinogens (GSEC) database containing information on over 15,000 control (noncancer) subjects, the allele and genotype frequencies for many of the more commonly studied metabolic genes (CYP1A1, CYP2E1, CYP2D6, GSTM1, GSTT1...

  10. Metabolic gene polymorphism frequencies in control populations.

    NARCIS (Netherlands)

    Garte, S.; Gaspari, L.; Alexandrie, A.K.; Ambrosone, C.; Autrup, H.; Autrup, J.L.; Baranova, H.; Bathum, L.; Benhamou, S.; Boffetta, P.; Bouchardy, C.; Breskvar, K.; Brockmoller, J.; Cascorbi, I.; Clapper, M.L.; Coutelle, C.; Daly, A.; Dell'Omo, M.; Dolzan, V.; Dresler, C.M.; Fryer, A.; Haugen, A.; Hein, D.W.; Hildesheim, A.; Hirvonen, A.; Hsieh, L.L.; Ingelman-Sundberg, M.; Kalina, I.; Kang, D.; Kihara, M.; Kiyohara, C.; Kremers, P.; Lazarus, P.; Marchand, L. le; Lechner, M.C.; Lieshout, E.M.M. van; London, S.; Manni, J.J.; Maugard, C.M.; Morita, S.; Nazar-Stewart, V.; Noda, K.; Oda, Y.; Parl, F.F.; Pastorelli, R.; Persson, I.; Peters, W.H.M.; Rannug, A.; Rebbeck, T.R.; Risch, A.; Roelandt, L.; Romkes, M.; Ryberg, D.; Salagovic, J.; Schoket, B.; Seidegard, J.; Shields, P.G.; Sim, E.; Sinnet, D.; Strange, R.C.; Stucker, I.; Sugimura, H.; To-Figueras, J.; Vineis, P.; Yu, M.C.; Taioli, E.

    2001-01-01

    Using the International Project on Genetic Susceptibility to Environmental Carcinogens (GSEC) database containing information on over 15,000 control (noncancer) subjects, the allele and genotype frequencies for many of the more commonly studied metabolic genes (CYP1A1, CYP2E1, CYP2D6, GSTM1, GSTT1,

  11. Analysis of the impact of environmental and social factors, with a particular emphasis on education, on the level of metabolic control in type 1 diabetes in children.

    Science.gov (United States)

    Stefanowicz, Anna; Birkholz, Dorota; Myśliwiec, Małgorzata; Niedźwiecki, Maciej; Owczuk, Radosław; Balcerska, Anna

    2012-01-01

    Type 1 diabetes is a chronic, incurable childhood disease. Chronically uncontrolled diabetes is associated with eye, kidney, nerve, heart and blood vessel damage and function impairment. The aim of this study was to evaluate the impact of various social and environmental factors, with a particular emphasis on education, on the level of metabolic control in diabetes. The survey research was conducted in 102 children aged 0-18 years, diagnosed with type 1 diabetes. Based on the HbA(1c ) level, patients were divided into: group A (63 patients with fairly well and moderately controlled type 1 diabetes mellitus) and group B (39 patients with metabolically uncontrolled type 1 diabetes mellitus). The impact of various environmental and social factors on the degree of metabolic control of type 1 diabetes was analysed. No effect of typical environmental and social factors, such as: place of residence, gender, parents' education and their professional activity, on the level of metabolic control of type 1 diabetes was found. However, groups A and B significantly differed in the level of knowledge about diabetes and its treatment, in the regularity of meals, in possessing a nutrition scale and in the self-assessed preparation for taking care and custody of a child with type 1 diabetes. 1. Children with type 1 diabetes and their parents require ongoing education about the disease and its treatment. 2. The regularity of meals and the use of a nutrition scale have considerable impact on the level of metabolic control of the disease.

  12. The Effect of a Breakfast Rich in Slowly Digestible Starch on Glucose Metabolism: A Statistical Meta-Analysis of Randomized Controlled Trials.

    Science.gov (United States)

    Vinoy, Sophie; Meynier, Alexandra; Goux, Aurélie; Jourdan-Salloum, Nathalie; Normand, Sylvie; Rabasa-Lhoret, Rémi; Brack, Olivier; Nazare, Julie-Anne; Péronnet, François; Laville, Martine

    2017-03-23

    Starch digestibility may have an effect on the postprandial blood glucose profile. The aim of this meta-analysis was to analyze the relationship between Slowly Digestible Starch (SDS) levels and plasma glucose appearance and disappearance rates, as well as other parameters of glucose metabolism, after healthy subjects consumed cereal products that differed in SDS content. Three randomized controlled clinical trials that included a total of 79 subjects were identified. Using binary classification for the variables (high versus low levels, more than 12 g of SDS per portion, and less than 1 g of SDS per portion, respectively), we found that there was a 15-fold higher chance of having a low rate of appearance of exogenous glucose (RaE) after consumption of a high-SDS product. A high SDS content was also associated with a 12-fold and 4-fold higher chance of having a low rate of disappearance of exogenous glucose (RdE) and rate of disappearance of total plasma glucose (RdT), respectively. The RaE kinetics were further analyzed by modeling the contribution of SDS content to the different phases of the RaE response. We show that the higher the SDS content per portion of cereal product, the higher its contribution to the incremental area under the curve (iAUC) of the RaE response after 165 min. Using the association rule technique, we found that glycemic iAUC and insulinemic iAUC values vary in the same direction. In conclusion, this meta-analysis confirms the effect of the SDS level in cereal products on the metabolic response, and shows for the first time that the degree to which SDS affects the RaE response differs depending on the SDS content of the food product, as well as the phase of the postprandial period.

  13. Effect of Probiotics on Glucose and Lipid Metabolism in Type 2 Diabetes Mellitus: A Meta-Analysis of 12 Randomized Controlled Trials.

    Science.gov (United States)

    Yao, Kecheng; Zeng, Linghai; He, Qian; Wang, Wei; Lei, Jiao; Zou, Xiulan

    2017-06-22

    BACKGROUND It has been unclear whether supplemental probiotics therapy improves clinical outcomes in type 2 diabetic patients. This meta-analysis aimed to summarize the effect of probiotics on glucose and lipid metabolism and C-reactive protein (CRP) from 12 randomized controlled trials (RCTs). MATERIAL AND METHODS An up-to-date search was performed for all relevant RCTs up to April 2016 from PubMed, Embase, and Cochrane Library. Standardized mean difference (SMD) and weighted mean difference (WMD) were calculated for a fixed-effect and random-effect meta-analysis to assess the impact of supplemental probiotics on fasting plasma glucose (FPG), glycated hemoglobin (HbA1c), fasting insulin, homeostasis model assessment of insulin resistance (HOMA-IR), lipid profile, and CRP level. RESULTS A total of 12 studies (684 patients) were entered into the final analysis. The effect of probiotics was significant on reducing HbA1c level (standardized mean difference [SMD], -0.38; confidence interval [CI], -0.62 to -0.14, P=0.002; I²=0%, P=0.72 for heterogeneity), fasting insulin level (SMD, -0.38; CI -0.59 to -0.18, P=0.0003; I²=0%, P=0.81 for heterogeneity), and HOMA-IR (SMD, -0.99; CI -1.52 to -0.47, P=0.0002; I²=86%, Pprobiotics on FPG, CRP, or lipid profile were either non-significant or highly heterogeneous. CONCLUSIONS This meta-analysis demonstrated that probiotics supplementation was associated with significant improvement in HbA1c and fasting insulin in type 2 diabetes patients. More randomized placebo-controlled trials with large sample sizes are warranted to confirm our conclusions.

  14. Pathway kinetics and metabolic control analysis of a high-yielding strain of Penicillium chrysogenum during fed-batch cultivations

    DEFF Research Database (Denmark)

    Pissarra, Pedro de N.; Nielsen, Jens Bredal; Bazin, M. J.

    1996-01-01

    , the flux is controlled by IPNS as this enzyme becomes saturated with tripeptide delta-(L-alpha-amino-adipyl)-L-cysteinyl-D-valine (LLD-ACV). In the simulations, oxygen was shown to be a bottleneck alleviator by stimulating the rate of IPNS which prevents the accumulation of LLD-ACV. As a consequence...

  15. A Systematic Review and Meta-Analysis of the Effect of Lifestyle Modification on Metabolic Control in Overweight Children

    Directory of Open Access Journals (Sweden)

    Angela Shin-Yu Lien

    2017-01-01

    Full Text Available Childhood obesity is associated with type 2 diabetes mellitus. We aimed to determine the effects of lifestyle modification programs on fasting plasma glucose (FPG levels in overweight children. We queried six relevant electronic databases and manually searched for studies published before December 2016. Overweight/obese children who underwent a lifestyle modification for more than 6 months were included. A total of 3923 children from eight randomized controlled trials (RCTs were included. Compared with the control group, the lifestyle modification group had significantly lower FPG levels by 1.3 mg/dL. The mean differences were significantly decreased for both secondary outcomes; BMI z-score decreased by 0.16 units and insulin levels decreased by 2.4 mU/L. The metaregression showed that the follow-up duration was associated with FPG levels and BMI and insulin levels and half year is a suitable follow-up duration for this population. This study showed that lifestyle modification programs may be effective in reducing the FPG levels of overweight/obese children. Further high-quality RCTs with longer follow-up periods are needed to evaluate the long-term effect of this complementary approach for diabetes mellitus prevention on overweight/obese children.

  16. Identification of a previously undetected metabolic defect in the Complex II Caenorhabditis elegans mev-1 mutant strain using respiratory control analysis.

    Science.gov (United States)

    Fong, Sheng; Ng, Li Fang; Ng, Li Theng; Moore, Philip K; Halliwell, Barry; Gruber, Jan

    2017-04-01

    Hypometabolism may play an important role in the pathogenesis of ageing and ageing-related diseases. The nematode Caenorhabditis elegans offers the opportunity to study "living mitochondria" in a small (~1 mm) animal replete with a highly stereotypical, yet complex, anatomy and physiology. Basal oxygen consumption rate is often employed as a proxy for energy metabolism in this context. This parameter is traditionally measured using single-chamber Clark electrodes without the addition of metabolic modulators. Recently, multi-well oxygen electrodes, facilitating addition of metabolic modulators and hence study of respiratory control during different mitochondrial respiration states, have been developed. However, only limited official protocols exist for C. elegans, and key limitations of these techniques are therefore unclear. Following modification and testing of some of the existing protocols, we used these methods to explore mitochondrial bioenergetics in live nematodes of an electron transfer chain Complex II mutant strain, mev-1, and identified a previously undetected metabolic defect. We find that mev-1 mutants cannot respond adequately to increased energy demands, suggesting that oxidative phosphorylation is more severely impaired in these animals than has previously been appreciated.

  17. Pareto optimality in organelle energy metabolism analysis.

    Science.gov (United States)

    Angione, Claudio; Carapezza, Giovanni; Costanza, Jole; Lió, Pietro; Nicosia, Giuseppe

    2013-01-01

    In low and high eukaryotes, energy is collected or transformed in compartments, the organelles. The rich variety of size, characteristics, and density of the organelles makes it difficult to build a general picture. In this paper, we make use of the Pareto-front analysis to investigate the optimization of energy metabolism in mitochondria and chloroplasts. Using the Pareto optimality principle, we compare models of organelle metabolism on the basis of single- and multiobjective optimization, approximation techniques (the Bayesian Automatic Relevance Determination), robustness, and pathway sensitivity analysis. Finally, we report the first analysis of the metabolic model for the hydrogenosome of Trichomonas vaginalis, which is found in several protozoan parasites. Our analysis has shown the importance of the Pareto optimality for such comparison and for insights into the evolution of the metabolism from cytoplasmic to organelle bound, involving a model order reduction. We report that Pareto fronts represent an asymptotic analysis useful to describe the metabolism of an organism aimed at maximizing concurrently two or more metabolite concentrations.

  18. Bilateral Diabetic Papillopathy and Metabolic Control

    DEFF Research Database (Denmark)

    Ostri, Christoffer; Lund-Andersen, Henrik; Sander, Birgit

    2010-01-01

    -six patients with type 1 diabetes. METHODS: Review of clinical, photographic, and clinical chemistry records from a large diabetology and ophthalmology unit between 2001 and 2008. MAIN OUTCOME MEASURES: Simultaneous, bilateral diabetic papillopathy. RESULTS: The mean follow-up was 4.9 years. During 10 020...... patient-years of observation, bilateral diabetic papillopathy developed in 5 patients. During the year preceding this incident, all 5 patients had experienced a decrease in glycosylated hemoglobin A(1c) (HbA(1C)) at a maximum rate of -2.5 (mean) percentage points per quarter year, which was significantly......OBJECTIVE: The pathogenesis of diabetic papillopathy largely is unknown, but case reports suggest that it may follow rapidly improved metabolic control. The present study was designed to investigate this hypothesis. DESIGN: Retrospective case-control study. PARTICIPANTS: Two thousand sixty...

  19. Computational Functional Analysis of Lipid Metabolic Enzymes.

    Science.gov (United States)

    Bagnato, Carolina; Have, Arjen Ten; Prados, María B; Beligni, María V

    2017-01-01

    The computational analysis of enzymes that participate in lipid metabolism has both common and unique challenges when compared to the whole protein universe. Some of the hurdles that interfere with the functional annotation of lipid metabolic enzymes that are common to other pathways include the definition of proper starting datasets, the construction of reliable multiple sequence alignments, the definition of appropriate evolutionary models, and the reconstruction of phylogenetic trees with high statistical support, particularly for large datasets. Most enzymes that take part in lipid metabolism belong to complex superfamilies with many members that are not involved in lipid metabolism. In addition, some enzymes that do not have sequence similarity catalyze similar or even identical reactions. Some of the challenges that, albeit not unique, are more specific to lipid metabolism refer to the high compartmentalization of the routes, the catalysis in hydrophobic environments and, related to this, the function near or in biological membranes.In this work, we provide guidelines intended to assist in the proper functional annotation of lipid metabolic enzymes, based on previous experiences related to the phospholipase D superfamily and the annotation of the triglyceride synthesis pathway in algae. We describe a pipeline that starts with the definition of an initial set of sequences to be used in similarity-based searches and ends in the reconstruction of phylogenies. We also mention the main issues that have to be taken into consideration when using tools to analyze subcellular localization, hydrophobicity patterns, or presence of transmembrane domains in lipid metabolic enzymes.

  20. Noise propagation in synthetic gene circuits for metabolic control.

    Science.gov (United States)

    Oyarzún, Diego A; Lugagne, Jean-Baptiste; Stan, Guy-Bart V

    2015-02-20

    Dynamic control of enzyme expression can be an effective strategy to engineer robust metabolic pathways. It allows a synthetic pathway to self-regulate in response to changes in bioreactor conditions or the metabolic state of the host. The implementation of this regulatory strategy requires gene circuits that couple metabolic signals with the genetic machinery, which is known to be noisy and one of the main sources of cell-to-cell variability. One of the unexplored design aspects of these circuits is the propagation of biochemical noise between enzyme expression and pathway activity. In this article, we quantify the impact of a synthetic feedback circuit on the noise in a metabolic product in order to propose design criteria to reduce cell-to-cell variability. We consider a stochastic model of a catalytic reaction under negative feedback from the product to enzyme expression. On the basis of stochastic simulations and analysis, we show that, depending on the repression strength and promoter strength, transcriptional repression of enzyme expression can amplify or attenuate the noise in the number of product molecules. We obtain analytic estimates for the metabolic noise as a function of the model parameters and show that noise amplification/attenuation is a structural property of the model. We derive an analytic condition on the parameters that lead to attenuation of metabolic noise, suggesting that a higher promoter sensitivity enlarges the parameter design space. In the theoretical case of a switch-like promoter, our analysis reveals that the ability of the circuit to attenuate noise is subject to a trade-off between the repression strength and promoter strength.

  1. Automated metabolic gas analysis systems: a review.

    Science.gov (United States)

    Macfarlane, D J

    2001-01-01

    The use of automated metabolic gas analysis systems or metabolic measurement carts (MMC) in exercise studies is common throughout the industrialised world. They have become essential tools for diagnosing many hospital patients, especially those with cardiorespiratory disease. Moreover, the measurement of maximal oxygen uptake (VO2max) is routine for many athletes in fitness laboratories and has become a defacto standard in spite of its limitations. The development of metabolic carts has also facilitated the noninvasive determination of the lactate threshold and cardiac output, respiratory gas exchange kinetics, as well as studies of outdoor activities via small portable systems that often use telemetry. Although the fundamental principles behind the measurement of oxygen uptake (VO2) and carbon dioxide production (VCO2) have not changed, the techniques used have, and indeed, some have almost turned through a full circle. Early scientists often employed a manual Douglas bag method together with separate chemical analyses, but the need for faster and more efficient techniques fuelled the development of semi- and full-automated systems by private and commercial institutions. Yet, recently some scientists are returning back to the traditional Douglas bag or Tissot-spirometer methods, or are using less complex automated systems to not only save capital costs, but also to have greater control over the measurement process. Over the last 40 years, a considerable number of automated systems have been developed, with over a dozen commercial manufacturers producing in excess of 20 different automated systems. The validity and reliability of all these different systems is not well known, with relatively few independent studies having been published in this area. For comparative studies to be possible and to facilitate greater consistency of measurements in test-retest or longitudinal studies of individuals, further knowledge about the performance characteristics of these

  2. 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

  3. Pathway analysis and optimization in metabolic engineering

    National Research Council Canada - National Science Library

    Torres, Néstor V; Voit, Eberhard O

    2002-01-01

    ... Engineering introduces researchers and advanced students in biology and engineering to methods of optimizing biochemical systems of biotechnological relevance. It examines the development of strategies for manipulating metabolic pathways, demonstrates the need for effective systems models, and discusses their design and analysis, while placing special emp...

  4. Autonomous mathematical models: constructing theories of metabolic control.

    Science.gov (United States)

    Donaghy, Josephine

    2013-01-01

    This paper considers how the relationship between mathematical models and theories in biology may change over time, on the basis of a historical analysis of the development of a mathematical model of metabolism, metabolic control analysis, and its relationship to theories of metabolic control. I argue that one can distinguish two ways of characterising the relationship between models and theories, depending on the stage of model and/or theory development that one is considering: partial independence and autonomy. Partial independence describes a model's relationship with existing theory, thus referring to relationships that have already been established between model and theory during model construction. By contrast, autonomy is a feature of relationships which may become established between model and theory in the future, and is expressed by a model's open ended role in constructing emerging theory. These characteristics have often been conflated by existing philosophical accounts, partly because they can only be identified and analysed when adopting a historical perspective on scientific research. Adopting a clear distinction between partial independence and autonomy improves philosophical insight into the changing relationship between models and theories.

  5. Effects of Avena nuda L. on metabolic control and cardiovascular disease risk among Chinese patients with diabetes and meeting metabolic syndrome criteria: secondary analysis of a randomized clinical trial.

    Science.gov (United States)

    Ma, X; Gu, J; Zhang, Z; Jing, L; Xu, M; Dai, X; Jiang, Y; Li, Y; Bao, L; Cai, X; Ding, Y; Wang, J; Li, Y; Li, Y

    2013-12-01

    Most patients with Type 2 diabetes mellitus(DM) also have metabolic syndrome (MetS), which is associated with an increased risk of coronary heart disease prevalence. Limited information is available on the effect and effective doses of oat intake with a structured dietary intervention in metabolic control and cardiovascular disease (CVD) risk prevention with the population who has Type 2 DM and meets the MetS criteria. A total of 260 Type 2 DM patients meeting MetS National Cholesterol Education Program Adult Treatment Panel III criteria were selected from 445 patients between 50 and 65 years of age, and they participated in a single-blinded, 30-day centralized management of a dietary program in China. Participants in the program were randomly assigned into one of the four groups: usual care group (control group, only basic health advice), diet group (systematic diet plans and intensive education), 50 g-organic naked oat with whole germ group (ONOG) and 100 g-organic naked oat with whole germ group (daily ONOG replacement boiled into porridge based on diet group). The primary outcomes were the relative changes in glycosylated hemoglobin (HbA1c) and insulin resistance after a 30-day intervention among the four groups. HbA1c decreased significantly with the increase in interventions (Ptrend<0.05). Similar results were also obtained in plasma glucose, serum lipid and hypersensitive C-reactive protein (hs-CRP). For the 100 g-ONOG group but not 50 g-ONOG group, HbA1c and hs-CRP reduced significantly by 0.51% and 1.29 mg/l (P<0.05, vs diet group), respectively. The 100 g-ONOG group showed a reduction by 0.22 U*mol/l(2) in insulin resistance, compared with the 50 g-ONOG group (P=0.039). Compared with diet alone or no diet, 50-100 g/day ONOG supplement to structured dietary intervention, at a dose of 100 g/day especially, contributes to the Type 2 DM patients meeting MetS criteria in their metabolic control and CVD risk prevention, with external factors

  6. Effect of Probiotics on Metabolic Outcomes in Pregnant Women with Gestational Diabetes: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

    Science.gov (United States)

    Taylor, Bonnie L; Woodfall, Georgia E; Sheedy, Katherine E; O'Riley, Meggan L; Rainbow, Kelsie A; Bramwell, Elsa L; Kellow, Nicole J

    2017-05-05

    The metabolic effects of probiotic administration in women with gestational diabetes mellitus (GDM) is unknown. The objective of this review was to investigate the effect of probiotics on fasting plasma glucose (FPG), insulin resistance (HOMA-IR) and LDL-cholesterol levels in pregnant women diagnosed with GDM. Seven electronic databases were searched for RCTs published in English between 2001 and 2017 investigating the metabolic effects of a 6-8 week dietary probiotic intervention in pregnant women following diagnosis with GDM. Eligible studies were assessed for risk of bias and subjected to qualitative and quantitative synthesis using a random effects model meta-analyses. Four high quality RCTs involving 288 participants were included in the review. Probiotic supplementation was not effective in decreasing FBG (Mean Difference = -0.13; 95% CI -0.32, 0.06, p = 0.18) or LDL-cholesterol (-0.16; 95% CI -0.45, 0.13, p = 0.67) in women with GDM. However, a significant reduction in HOMA-IR was observed following probiotic supplementation (-0.69; 95% CI -1.24, -0.14, p = 0.01). There were no significant differences in gestational weight gain, delivery method or neonatal outcomes between experimental and control groups, and no adverse effects of the probiotics were reported. Probiotic supplementation for 6-8 weeks resulted in a significant reduction in insulin resistance in pregnant women diagnosed with GDM. The use of probiotic supplementation is promising as a potential therapy to assist in the metabolic management of GDM. Further high quality studies of longer duration are required to determine the safety, optimal dose and ideal bacterial composition of probiotics before their routine use can be recommended in this patient group.

  7. Central nervous system control of triglyceride metabolism

    NARCIS (Netherlands)

    Geerling, Johanna Janetta (Janine)

    2013-01-01

    This thesis describes the role of the brain in the regulation of peripheral triglyceride metabolism, in the context of the metabolic syndrome. Based on various pharmacological studies we described the role of two hormones, insulin and glucagon-like peptide-1, in the production and clearance of

  8. 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.

  9. 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.

  10. Sleep Control, GPCRs, and Glucose Metabolism.

    Science.gov (United States)

    Tsuneki, Hiroshi; Sasaoka, Toshiyasu; Sakurai, Takeshi

    2016-09-01

    Modern lifestyles prolong daily activities into the nighttime, disrupting circadian rhythms, which may cause sleep disturbances. Sleep disturbances have been implicated in the dysregulation of blood glucose levels and reported to increase the risk of type 2 diabetes (T2D) and diabetic complications. Sleep disorders are treated using anti-insomnia drugs that target ionotropic and G protein-coupled receptors (GPCRs), including γ-aminobutyric acid (GABA) agonists, melatonin agonists, and orexin receptor antagonists. A deeper understanding of the effects of these medications on glucose metabolism and their underlying mechanisms of action is crucial for the treatment of diabetic patients with sleep disorders. In this review we focus on the beneficial impact of sleep on glucose metabolism and suggest a possible strategy for therapeutic intervention against sleep-related metabolic disorders. Copyright © 2016. Published by Elsevier Ltd.

  11. Association of metabolic gene polymorphisms with alcohol consumption in controls.

    NARCIS (Netherlands)

    Raimondi, S.C.; Benhamou, S.; Coutelle, C.; Garte, S.; Hayes, R.; Kiemeney, L.A.L.M.; Lazarus, P.; Marchand, L.L.; Morita, S.; Povey, A.; Romkes, M.; Zijno, A.; Taioli, E.

    2004-01-01

    The objectives were to study the association between metabolic genes involved in alcohol metabolism (CYP2E1 RsaI, CYP2E1 DraI, ADH1C, NQO1) and alcohol consumption in a large sample of healthy controls. Healthy subjects were selected from the International Collaborative Study on Genetic

  12. Bile salts in control of lipid metabolism

    NARCIS (Netherlands)

    Schonewille, Marleen; de Boer, Jan Freark; Groen, Albert K.

    Purpose of review The view on bile salts has evolved over the years from being regarded as simple detergents that aid intestinal absorption of fat-soluble nutrients to being important hormone-like integrators of metabolism. This review provides an update on the rapidly developing field of

  13. Bile salts in control of lipid metabolism

    NARCIS (Netherlands)

    Schonewille, Marleen; de Boer, Jan Freark; Groen, Albert K.

    2016-01-01

    The view on bile salts has evolved over the years from being regarded as simple detergents that aid intestinal absorption of fat-soluble nutrients to being important hormone-like integrators of metabolism. This review provides an update on the rapidly developing field of interactions between bile

  14. Bone metabolism in healthy ambulatory control premonopausal ...

    African Journals Online (AJOL)

    Long-term anti-epileptic drug use significantly affects biochemical parameters of bone metabolism. These effects on bone biochemistry markers were not reflected in lumbar spine BMD in this study. The mean duration of treatment for epilepsy was eight years (±6.3). Majority of the patients were on enzyme inducing drugs ...

  15. Metabolic Control of Glia-Mediated Neuroinflammation.

    Science.gov (United States)

    Jha, Mithilesh Kumar; Park, Dong Ho; Kook, Hyun; Lee, In-Kyu; Lee, Won-Ha; Suk, Kyoungho

    2016-01-01

    The central nervous system (CNS) shows dynamic immune and inflammatory responses to a variety of insults having crucial implications for reactive gliosis. Glial cells in the CNS serve not only as the source, but also as targets of proinflammatory mediators. Undoubtedly, these cells efficiently work towards the disposal of tissue debris and promotion of wound healing as well as tissue repair. However, these non-neuronal glial cells synthesize and release numerous inflammatory mediators, which can be detrimental to neurons, axons, myelin, and the glia themselves. While an acute insult is typically transient and unlikely to be detrimental to neuronal survival, chronic neuroinflammation is a long-standing and often self-perpetuating response, which persists even long after the initial injury or insult. It can serve as a point of origin for diverse neurological disorders including Alzheimer's disease. Accumulating evidence demonstrates the contribution of metabolic dysfunction and mitochondrial failure to the pathogenesis of neuroinflammatory and neurodegenerative diseases. Neurodegenerative conditions are also characterized by increased oxidative and endoplasmic reticulum stresses and autophagy defects. Furthermore, neuroinflammatory conditions are accompanied by an alteration in glial energy metabolism. Here, we comprehensively review the metabolic hallmarks of glia-mediated neuroinflammation and how the glial metabolic shift orchestrates the neuroinflammatory response and pathophysiology of diverse neurological disorders.

  16. High precision isotope measurements reveal poor control of copper metabolism in parkinsonism.

    Science.gov (United States)

    Larner, F; Sampson, B; Rehkämper, M; Weiss, D J; Dainty, J R; O'Riordan, S; Panetta, T; Bain, P G

    2013-02-01

    Disordered copper metabolism may be important in the aetiology of Parkinsonism, as caeruloplasmin is a key enzyme in handling oxidative stress and is involved in the synthesis pathway of dopamine. The human Cu metabolism of ten Parkinsonism patients was compared to ten healthy controls with the aid of a stable (65)Cu isotope tracer. The analyses of blood serum (65)Cu/(63)Cu ratios yielded individual isotopic profiles, which indicate that the Cu metabolism is less controlled in patients with Parkinsonism. Modelling based on both isotope tracer and total Cu concentrations suggests that 30% of the subjects affected by Parkinsonism have abnormally large Cu stores in tissues. To detect the small differences in Cu metabolism between Parkinsonism and controls, the analysis of stable isotope composition must be performed using multiple-collector inductively coupled plasma mass spectrometry and the associated sample preparation techniques. This pilot investigation supports full-scale medical studies into the Cu metabolism of those with Parkinsonism.

  17. Mitochondrial quality control pathways as determinants of metabolic health

    NARCIS (Netherlands)

    Held, Ntsiki M.; Houtkooper, Riekelt H.

    2015-01-01

    Mitochondrial function is key for maintaining cellular health, while mitochondrial failure is associated with various pathologies, including inherited metabolic disorders and age-related diseases. In order to maintain mitochondrial quality, several pathways of mitochondrial quality control have

  18. Effect of Probiotics on Metabolic Outcomes in Pregnant Women with Gestational Diabetes: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

    OpenAIRE

    Taylor, Bonnie L.; Woodfall, Georgia E.; Sheedy, Katherine E.; O?Riley, Meggan L.; Rainbow, Kelsie A.; Bramwell, Elsa L.; Kellow, Nicole J.

    2017-01-01

    The metabolic effects of probiotic administration in women with gestational diabetes mellitus (GDM) is unknown. The objective of this review was to investigate the effect of probiotics on fasting plasma glucose (FPG), insulin resistance (HOMA-IR) and LDL-cholesterol levels in pregnant women diagnosed with GDM. Seven electronic databases were searched for RCTs published in English between 2001 and 2017 investigating the metabolic effects of a 6?8 week dietary probiotic intervention in pregnant...

  19. Hormonal and metabolic effects of polyunsaturated fatty acids in young women with polycystic ovary syndrome: results from a cross-sectional analysis and a randomized, placebo-controlled, crossover trial.

    LENUS (Irish Health Repository)

    Phelan, Niamh

    2012-02-01

    BACKGROUND: Polycystic ovary syndrome (PCOS) is characterized by an adverse metabolic profile. Although dietary changes are advocated, optimal nutritional management remains uncertain. Polyunsaturated fatty acids (PUFAs), particularly long-chain (LC) n-3 (omega-3) PUFAs, improve metabolic health, but their therapeutic potential in PCOS is unknown. OBJECTIVES: We aimed to determine the associations between plasma PUFAs and metabolic and hormonal aspects of PCOS to investigate the efficacy of LC n-3 PUFA supplementation and to support the findings with mechanistic cellular studies. DESIGN: We selected a cross-sectional PCOS cohort (n = 104) and conducted a principal component analysis on plasma fatty acid profiles. Effects of LC n-3 PUFA supplementation on fasting and postprandial metabolic and hormonal markers were determined in PCOS subjects (n = 22) by a randomized, crossover, placebo-controlled intervention. Direct effects of n-6 (omega-6) compared with n-3 PUFAs on steroidogenesis were investigated in primary bovine theca cells. RESULTS: Cross-sectional data showed that a greater plasma n-6 PUFA concentration and n-6:n-3 PUFA ratio were associated with higher circulating androgens and that plasma LC n-3 PUFA status was associated with a less atherogenic lipid profile. LC n-3 PUFA supplementation reduced plasma bioavailable testosterone concentrations (P < 0.05), with the greatest reductions in subjects who exhibited greater reductions in plasma n-6:n-3 PUFA ratios. The treatment of bovine theca cells with n-6 rather than with n-3 PUFAs up-regulated androstenedione secretion (P < 0.05). CONCLUSIONS: Cross-sectional data suggest that PUFAs modulated hormonal and lipid profiles and that supplementation with LC n-3 PUFAs improves androgenic profiles in PCOS. In bovine theca cells, arachidonic acid modulated androstenedione secretion, which suggests an indirect effect of n-3 PUFAs through the displacement of or increased competition with n-6 PUFAs. This trial was

  20. Analysis of Subclinical Hyperthyroidism Influence on Parameters of Bone Metabolism

    Directory of Open Access Journals (Sweden)

    I.V. Pankiv

    2016-03-01

    Full Text Available State of subclinical hypothyroidism can be considered as the optimal model for assessing the significance of thyroid stimulating hormone (TSH for bone tissue in clinical practice. Objective: to make a comparative analysis of the impact of subclinical hyperthyroidism of various origins on the performance of bone mineral density (BMD and bone metabolism parameters. Materials and methods. The study in an outpatient setting included 112 women with a diagnosis of subclinical hyperthyroidism and duration of menopause for at least 5 years. Among the examinees, endogenous subclinical hyperthyroidism has been detected in 78 women (group I, exogenous subclinical hyperthyroidism on the background of suppressive levothyroxine therapy (group II — in 34. The control group (group III included 20 women without thyroid dysfunction. Results. The study first conducted a comparative analysis of bone metabolism, BMD indicators, as well as parameters of phosphorus and calcium, blood lipids in women with subclinical hyperthyroidism of various origins. A positive correlation between markers of bone metabolism and free triiodothyronine (fT3 as hormones necessary for the development of the skeleton and to maintain its homeostasis indicates a physiological effect of parathyroid hormone and fT3 on bone tissue. It is shown that the bone metabolism and BMD depend not only on the content of TSH, but also on the causes of subclinical hyperthyroidism.Conclusions. In postmenopausal women with endogenous subclinical hyperthyroidism, there is a significant decline in BMD indices, more pronounced in the bones with the cortical structure. A negative correlation between markers of bone metabolism and TSH has been observed among all patients included in the study.

  1. Slave nodes and the controllability of metabolic networks

    International Nuclear Information System (INIS)

    Kim, Dong-Hee; Motter, Adilson E

    2009-01-01

    Recent work on synthetic rescues has shown that the targeted deletion of specific metabolic genes can often be used to rescue otherwise non-viable mutants. This raises a fundamental biophysical question: to what extent can the whole-cell behavior of a large metabolic network be controlled by constraining the flux of one or more reactions in the network? This touches upon the issue of the number of degrees of freedom contained by one such network. Using the metabolic network of Escherichia coli as a model system, here we address this question theoretically by exploring not only reaction deletions, but also a continuum of all possible reaction expression levels. We show that the behavior of the metabolic network can be largely manipulated by the pinned expression of a single reaction. In particular, a relevant fraction of the metabolic reactions exhibits canalizing interactions, in that the specification of one reaction flux determines cellular growth as well as the fluxes of most other reactions in optimal steady states. The activity of individual reactions can thus be used as surrogates to monitor and possibly control cellular growth and other whole-cell behaviors. In addition to its implications for the study of control processes, our methodology provides a new approach to study how the integrated dynamics of the entire metabolic network emerges from the coordinated behavior of its component parts.

  2. Hypothalamic control of energy metabolism via the autonomic nervous system

    NARCIS (Netherlands)

    Kalsbeek, A.; Bruinstroop, E.; Yi, C. X.; Klieverik, L. P.; La Fleur, S. E.; Fliers, E.

    2010-01-01

    The hypothalamic control of hepatic glucose production is an evident aspect of energy homeostasis. In addition to the control of glucose metabolism by the circadian timing system, the hypothalamus also serves as a key relay center for (humoral) feedback information from the periphery, with the

  3. Framework for network modularization and Bayesian network analysis to investigate the perturbed metabolic network.

    Science.gov (United States)

    Kim, Hyun Uk; Kim, Tae Yong; Lee, Sang Yup

    2011-01-01

    Genome-scale metabolic network models have contributed to elucidating biological phenomena, and predicting gene targets to engineer for biotechnological applications. With their increasing importance, their precise network characterization has also been crucial for better understanding of the cellular physiology. We herein introduce a framework for network modularization and Bayesian network analysis (FMB) to investigate organism's metabolism under perturbation. FMB reveals direction of influences among metabolic modules, in which reactions with similar or positively correlated flux variation patterns are clustered, in response to specific perturbation using metabolic flux data. With metabolic flux data calculated by constraints-based flux analysis under both control and perturbation conditions, FMB, in essence, reveals the effects of specific perturbations on the biological system through network modularization and Bayesian network analysis at metabolic modular level. As a demonstration, this framework was applied to the genetically perturbed Escherichia coli metabolism, which is a lpdA gene knockout mutant, using its genome-scale metabolic network model. After all, it provides alternative scenarios of metabolic flux distributions in response to the perturbation, which are complementary to the data obtained from conventionally available genome-wide high-throughput techniques or metabolic flux analysis.

  4. Serum uric acid level as a determinant of the metabolic syndrome: A case control study.

    Science.gov (United States)

    Khichar, Satyendra; Choudhary, Shyama; Singh, Veer Bahadur; Tater, Priyanka; Arvinda, R V; Ujjawal, Vivek

    To determine whether elevations of uric acid levels are associated with the cluster of disorders described in metabolic syndrome and to evaluate whether hyperuricemia may be considered a component of this syndrome. One year case-control study was conducted in Bikaner, Rajasthan, India from January to December 2013. The study population consisted of 200 subjects, 100 with metabolic syndrome (case) and 100 without metabolic syndrome (control) aged between 18 and 80 years, attending OPD at PBM Hospital were studied. Controls were age and sex matched to the cases. Blood tests and all physical variables were examined using standard methods. Subjects were divided into 6 groups according to their possession of 0, 1, 2, 3, 4 or 5 components of the metabolic syndrome. Statistical analysis was done using ANOVA, linear regression analysis and multivariate linear regression model. Mean serum UA level was significantly associated with all components of metabolic syndrome (pmetabolic factors increased showing a highly significant trend (pmetabolic syndrome. The current multivariate regression analysis clearly infers that uric acid can be considered as a marker and potential modifier of metabolic syndrome. Copyright © 2016 Diabetes India. Published by Elsevier Ltd. All rights reserved.

  5. Controllability in cancer metabolic networks according to drug targets as driver nodes.

    Science.gov (United States)

    Asgari, Yazdan; Salehzadeh-Yazdi, Ali; Schreiber, Falk; Masoudi-Nejad, Ali

    2013-01-01

    Networks are employed to represent many nonlinear complex systems in the real world. The topological aspects and relationships between the structure and function of biological networks have been widely studied in the past few decades. However dynamic and control features of complex networks have not been widely researched, in comparison to topological network features. In this study, we explore the relationship between network controllability, topological parameters, and network medicine (metabolic drug targets). Considering the assumption that targets of approved anticancer metabolic drugs are driver nodes (which control cancer metabolic networks), we have applied topological analysis to genome-scale metabolic models of 15 normal and corresponding cancer cell types. The results show that besides primary network parameters, more complex network metrics such as motifs and clusters may also be appropriate for controlling the systems providing the controllability relationship between topological parameters and drug targets. Consequently, this study reveals the possibilities of following a set of driver nodes in network clusters instead of considering them individually according to their centralities. This outcome suggests considering distributed control systems instead of nodal control for cancer metabolic networks, leading to a new strategy in the field of network medicine.

  6. Constraining genome-scale models to represent the bow tie structure of metabolism for 13C metabolic flux analysis

    DEFF Research Database (Denmark)

    Backman, Tyler W.H.; Ando, David; Singh, Jahnavi

    2018-01-01

    Determination of internal metabolic fluxes is crucial for fundamental and applied biology because they map how carbon and electrons flow through metabolism to enable cell function. 13C Metabolic Flux Analysis (13C MFA) and Two-Scale 13C Metabolic Flux Analysis (2S-13C MFA) are two techniques used...

  7. 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.

  8. Computational systems analysis of dopamine metabolism.

    Directory of Open Access Journals (Sweden)

    Zhen Qi

    2008-06-01

    Full Text Available A prominent feature of Parkinson's disease (PD is the loss of dopamine in the striatum, and many therapeutic interventions for the disease are aimed at restoring dopamine signaling. Dopamine signaling includes the synthesis, storage, release, and recycling of dopamine in the presynaptic terminal and activation of pre- and post-synaptic receptors and various downstream signaling cascades. As an aid that might facilitate our understanding of dopamine dynamics in the pathogenesis and treatment in PD, we have begun to merge currently available information and expert knowledge regarding presynaptic dopamine homeostasis into a computational model, following the guidelines of biochemical systems theory. After subjecting our model to mathematical diagnosis and analysis, we made direct comparisons between model predictions and experimental observations and found that the model exhibited a high degree of predictive capacity with respect to genetic and pharmacological changes in gene expression or function. Our results suggest potential approaches to restoring the dopamine imbalance and the associated generation of oxidative stress. While the proposed model of dopamine metabolism is preliminary, future extensions and refinements may eventually serve as an in silico platform for prescreening potential therapeutics, identifying immediate side effects, screening for biomarkers, and assessing the impact of risk factors of the disease.

  9. Physiology and genetics of metabolic flux control in Zymomonas mobilis

    Energy Technology Data Exchange (ETDEWEB)

    Conway, T.

    1992-01-01

    This work seeks to understand the role of gene expression in regulating glycolytic enzyme synthesis in a balance that allows proper glycoltic flux control. The seven genes targeted for study in this laboratory have been cloned and sequenced, and molecular details of regulation have been investigated. Clear that glycolytic enzyme synthesis is coordinated to prevent the build up of toxic metabolic intermediates. The genetic mechanisms responsible for regulating balanced expression of the EntnerDoudoroff and glycolytic genes in Z. mobilis are beginning to be understood. Several layers of genetic control, perhaps in a hierarchal arrangement act in concert to determine the relative abundance of the glycolytic enzymes. These genetic controls involve differential translational efficiency, highly conserved promoter sequences, transcription factors, differential mRNA stabilities, and nucleolytic mRNA processing. The serendipitous cloning of the glucose facilitator, glf, as a result of linkage to several other genes of interest will have a significant impact on the study of Z. mobilis metabolism. The glucose facilitator is being characterized in a genetically reconstituted system in E. coli. Molecular genetic studies indicate that the ratio of glf expression to that of glk, zmf, and edd is carefully regulated, and suggests a critical role in metabolic control. Regulation of glycolytic gene expression is now sufficiently well understood to allow use of the glycolytic genes as tools to manipulate specified enzyme levels for the purpose of analyzing metabolic flux control. The critical genes have been subcloned for stable expression in Z. mobilis and placed under control of a regulated promoter system involving the tac promoter, the lacI repressor, and gene induction in by IPTG. HPLC methods have been developed that allow quantitation of virtually all of the metabolic intermediates in the cell pool.

  10. Adherence to two methods of education and metabolic control in ...

    African Journals Online (AJOL)

    . VRG Herrera, HM Zerón, MRM Alcántara. Abstract. BACKGROUND: Education in diabetes optimizes metabolic control, prevents acute and chronic complications, and improves quality of life. Our main objective was to evaluate if a better ...

  11. metabolic control of type 2 diabetic patients commonly treated

    African Journals Online (AJOL)

    Kateee

    2003-04-01

    Apr 1, 2003 ... Objective: To assess metabolic control in type 2 diabetic patients predominantly treated with sulphonylurea drugs at ... method. Results: Of the 179 patients studied, 87% of male and 92% of female patients were treated ... patients of East Indian ethnic group had significantly higher prevalence rates of insulin.

  12. IDENTIFICATION AND ANALYSIS OF BACTERIAL GENOMIC METABOLIC SIGNATURES.

    Science.gov (United States)

    Bowerman, Nathaniel; Tintle, Nathan; Dejongh, Matthew; Best, Aaron A

    2017-01-01

    With continued rapid growth in the number and quality of fully sequenced and accurately annotated bacterial genomes, we have unprecedented opportunities to understand metabolic diversity. We selected 101 diverse and representative completely sequenced bacteria and implemented a manual curation effort to identify 846 unique metabolic variants present in these bacteria. The presence or absence of these variants act as a metabolic signature for each of the bacteria, which can then be used to understand similarities and differences between and across bacterial groups. We propose a novel and robust method of summarizing metabolic diversity using metabolic signatures and use this method to generate a metabolic tree, clustering metabolically similar organisms. Resulting analysis of the metabolic tree confirms strong associations with well-established biological results along with direct insight into particular metabolic variants which are most predictive of metabolic diversity. The positive results of this manual curation effort and novel method development suggest that future work is needed to further expand the set of bacteria to which this approach is applied and use the resulting tree to test broad questions about metabolic diversity and complexity across the bacterial tree of life.

  13. The reconstruction and analysis of tissue specific human metabolic networks.

    Science.gov (United States)

    Hao, Tong; Ma, Hong-Wu; Zhao, Xue-Ming; Goryanin, Igor

    2012-02-01

    Human tissues have distinct biological functions. Many proteins/enzymes are known to be expressed only in specific tissues and therefore the metabolic networks in various tissues are different. Though high quality global human metabolic networks and metabolic networks for certain tissues such as liver have already been studied, a systematic study of tissue specific metabolic networks for all main tissues is still missing. In this work, we reconstruct the tissue specific metabolic networks for 15 main tissues in human based on the previously reconstructed Edinburgh Human Metabolic Network (EHMN). The tissue information is firstly obtained for enzymes from Human Protein Reference Database (HPRD) and UniprotKB databases and transfers to reactions through the enzyme-reaction relationships in EHMN. As our knowledge of tissue distribution of proteins is still very limited, we replenish the tissue information of the metabolic network based on network connectivity analysis and thorough examination of the literature. Finally, about 80% of proteins and reactions in EHMN are determined to be in at least one of the 15 tissues. To validate the quality of the tissue specific network, the brain specific metabolic network is taken as an example for functional module analysis and the results reveal that the function of the brain metabolic network is closely related with its function as the centre of the human nervous system. The tissue specific human metabolic networks are available at .

  14. Large-scale transcriptome analysis reveals arabidopsis metabolic pathways are frequently influenced by different pathogens.

    Science.gov (United States)

    Jiang, Zhenhong; He, Fei; Zhang, Ziding

    2017-07-01

    Through large-scale transcriptional data analyses, we highlighted the importance of plant metabolism in plant immunity and identified 26 metabolic pathways that were frequently influenced by the infection of 14 different pathogens. Reprogramming of plant metabolism is a common phenomenon in plant defense responses. Currently, a large number of transcriptional profiles of infected tissues in Arabidopsis (Arabidopsis thaliana) have been deposited in public databases, which provides a great opportunity to understand the expression patterns of metabolic pathways during plant defense responses at the systems level. Here, we performed a large-scale transcriptome analysis based on 135 previously published expression samples, including 14 different pathogens, to explore the expression pattern of Arabidopsis metabolic pathways. Overall, metabolic genes are significantly changed in expression during plant defense responses. Upregulated metabolic genes are enriched on defense responses, and downregulated genes are enriched on photosynthesis, fatty acid and lipid metabolic processes. Gene set enrichment analysis (GSEA) identifies 26 frequently differentially expressed metabolic pathways (FreDE_Paths) that are differentially expressed in more than 60% of infected samples. These pathways are involved in the generation of energy, fatty acid and lipid metabolism as well as secondary metabolite biosynthesis. Clustering analysis based on the expression levels of these 26 metabolic pathways clearly distinguishes infected and control samples, further suggesting the importance of these metabolic pathways in plant defense responses. By comparing with FreDE_Paths from abiotic stresses, we find that the expression patterns of 26 FreDE_Paths from biotic stresses are more consistent across different infected samples. By investigating the expression correlation between transcriptional factors (TFs) and FreDE_Paths, we identify several notable relationships. Collectively, the current study

  15. Spectroscopic analysis and control

    Energy Technology Data Exchange (ETDEWEB)

    Tate; , James D.; Reed, Christopher J.; Domke, Christopher H.; Le, Linh; Seasholtz, Mary Beth; Weber, Andy; Lipp, Charles

    2017-04-18

    Apparatus for spectroscopic analysis which includes a tunable diode laser spectrometer having a digital output signal and a digital computer for receiving the digital output signal from the spectrometer, the digital computer programmed to process the digital output signal using a multivariate regression algorithm. In addition, a spectroscopic method of analysis using such apparatus. Finally, a method for controlling an ethylene cracker hydrogenator.

  16. Interactive Controls Analysis (INCA)

    Science.gov (United States)

    Bauer, Frank H.

    1989-01-01

    Version 3.12 of INCA provides user-friendly environment for design and analysis of linear control systems. System configuration and parameters easily adjusted, enabling INCA user to create compensation networks and perform sensitivity analysis in convenient manner. Full complement of graphical routines makes output easy to understand. Written in Pascal and FORTRAN.

  17. Hierarchical analysis of dependency in metabolic networks.

    Science.gov (United States)

    Gagneur, Julien; Jackson, David B; Casari, Georg

    2003-05-22

    Elucidation of metabolic networks for an increasing number of organisms reveals that even small networks can contain thousands of reactions and chemical species. The intimate connectivity between components complicates their decomposition into biologically meaningful sub-networks. Moreover, traditional higher-order representations of metabolic networks as metabolic pathways, suffers from the lack of rigorous definition, yielding pathways of disparate content and size. We introduce a hierarchical representation that emphasizes the gross organization of metabolic networks in largely independent pathways and sub-systems at several levels of independence. The approach highlights the coupling of different pathways and the shared compounds responsible for those couplings. By assessing our results on Escherichia coli (E.coli metabolic reactions, Genetic Circuits Research Group, University of California, San Diego, http://gcrg.ucsd.edu/organisms/ecoli.html, 'model v 1.01. reactions') against accepted biochemical annotations, we provide the first systematic synopsis of an organism's metabolism. Comparison with operons of E.coli shows that low-level clusters are reflected in genome organization and gene regulation. Source code, data sets and supplementary information are available at http://www.mas.ecp.fr/labo/equipe/gagneur/hierarchy/hierarchy.html

  18. The impact of cognitive distortions, stress, and adherence on metabolic control in youths with type 1 diabetes.

    Science.gov (United States)

    Farrell, Stephanie P; Hains, Anthony A; Davies, W Hobart; Smith, Philip; Parton, Elaine

    2004-06-01

    To investigate the role of cognitive distortions in the relationship between adherence behavior, diabetes-specific stress, general stress, and metabolic control. Obtained questionnaire data, glucometer readings, and glycosylated hemoglobin (HbgA(1c)) assays from 143 youths (11-18 years old) with type 1 diabetes. Examined path model of relationships between cognitive distortions, stress, adherence behavior, and metabolic control. Data were analyzed using path analysis. Higher levels of negative cognitive distortions were associated with more stress (both diabetes-specific and general). Higher levels of general stress then led to less adherent behavior and subsequently poorer metabolic control (higher HbgA(1c)). More diabetes-specific stress also led to poorer metabolic control, as well as general stress. The findings indicate an indirect role of negative cognitive distortions in metabolic control. The current findings suggest that instead of the proposed direct link between cognitive distortions and adherence behavior, an indirect relationship may exist through stress.

  19. Cardiorespiratory Fitness and Adiposity as Determinants of Metabolic Health-Pooled Analysis of Two Twin Cohorts

    DEFF Research Database (Denmark)

    Jukarainen, Sakari; Holst, René; Dalgård, Christine

    2017-01-01

    Context: The joint effects of cardiorespiratory fitness (CRF) and body composition on metabolic health are not well known. Objective: To examine the associations of CRF, fat-free mass index (FFMI), and fat mass index (FMI) with metabolic health in individual twins and controlling for genetic...... their associations with CRF and FFMI were at most weak (|β| 0.02 to 0.15). The results of the monozygotic intrapair differences analysis showed the same pattern. Conclusions: Although FMI is strongly associated with worsening of metabolic health traits, even after controlling for genetic and shared environmental...... factors, there was little evidence for the effects of CRF or FFMI on metabolic health. This suggests that changing FMI rather than CRF or FFMI may affect metabolic health irrespective of genetic or early environmental determinants....

  20. Model-driven multi-omic data analysis elucidates metabolic immunomodulators of macrophage activation

    Energy Technology Data Exchange (ETDEWEB)

    Bordbar, Aarash; Mo, Monica L.; Nakayasu, Ernesto S.; Rutledge, Alexandra C.; Kim, Young-Mo; Metz, Thomas O.; Jones, Marcus B.; Frank, Bryan C.; Smith, Richard D.; Peterson, Scott N.; Hyduke, Daniel R.; Adkins, Joshua N.; Palsson, Bernhard O.

    2012-06-26

    Macrophages are central players in the immune response, manifesting divergent phenotypes to control inflammation and innate immunity through the release of cytokines and other regulatory factor-dependent signaling pathways. In recent years, the focus on metabolism has been reemphasized as critical signaling and regulatory pathways of human pathophysiology, ranging from cancer to aging, often converge on metabolic responses. Here, we used genome-scale modeling and multi-omics (transcriptomics, proteomics, and metabolomics) analysis to assess metabolic features critical for macrophage functions. We constructed a genome-scale metabolic network for the RAW 264.7 cell line to determine metabolic modulators of macrophage activation. Metabolites well-known to be associated with immunoactivation (e.g., glucose and arginine) and immunosuppression (e.g., tryptophan and vitamin D3) were amongst the most critical effectors. Intracellular metabolic mechanisms linked to critical suppressive effectors were then assessed, identifying a suppressive role for de novo nucleotide synthesis. Finally, the underlying metabolic mechanisms of macrophage activation are identified by analyzing multi-omic data obtained from LPS-stimulated RAW cells in the context of our flux-based predictions. Our study demonstrates metabolism's role in regulating activation may be greater than previously anticipated and elucidates underlying metabolic connections between activation and metabolic effectors.

  1. Controlling cell-free metabolism through physiochemical perturbations.

    Science.gov (United States)

    Karim, Ashty S; Heggestad, Jacob T; Crowe, Samantha A; Jewett, Michael C

    2018-01-01

    Building biosynthetic pathways and engineering metabolic reactions in cells can be time-consuming due to complexities in cellular metabolism. These complexities often convolute the combinatorial testing of biosynthetic pathway designs needed to define an optimal biosynthetic system. To simplify the optimization of biosynthetic systems, we recently reported a new cell-free framework for pathway construction and testing. In this framework, multiple crude-cell extracts are selectively enriched with individual pathway enzymes, which are then mixed to construct full biosynthetic pathways on the time scale of a day. This rapid approach to building pathways aids in the study of metabolic pathway performance by providing a unique freedom of design to modify and control biological systems for both fundamental and applied biotechnology. The goal of this work was to demonstrate the ability to probe biosynthetic pathway performance in our cell-free framework by perturbing physiochemical conditions, using n-butanol synthesis as a model. We carried out three unique case studies. First, we demonstrated the power of our cell-free approach to maximize biosynthesis yields by mapping physiochemical landscapes using a robotic liquid-handler. This allowed us to determine that NAD and CoA are the most important factors that govern cell-free n-butanol metabolism. Second, we compared metabolic profile differences between two different approaches for building pathways from enriched lysates, heterologous expression and cell-free protein synthesis. We discover that phosphate from PEP utilization, along with other physiochemical reagents, during cell-free protein synthesis-coupled, crude-lysate metabolic system operation inhibits optimal cell-free n-butanol metabolism. Third, we show that non-phosphorylated secondary energy substrates can be used to fuel cell-free protein synthesis and n-butanol biosynthesis. Taken together, our work highlights the ease of using cell-free systems to explore

  2. Comprehensive Metabolomic Analysis in Blood, Urine, Fat, and Muscle in Men with Metabolic Syndrome: A Randomized, Placebo-Controlled Clinical Trial on the Effects of Resveratrol after Four Months' Treatment.

    Science.gov (United States)

    Korsholm, Anne Sofie; Kjær, Thomas Nordstrøm; Ornstrup, Marie Juul; Pedersen, Steen Bønløkke

    2017-03-04

    Resveratrol possesses several beneficial metabolic effects in rodents, while the effects of resveratrol in humans remain unclear. Therefore, we performed a non-targeted comprehensive metabolomic analysis on blood, urine, adipose tissue, and skeletal muscle tissue in middle-aged men with metabolic syndrome randomized to either resveratrol or placebo treatment for four months. Changes in steroid hormones across all four matrices were the most pronounced changes observed. Resveratrol treatment reduced sulfated androgen precursors in blood, adipose tissue, and muscle tissue, and increased these metabolites in urine. Furthermore, markers of muscle turnover were increased and lipid metabolism was affected, with increased intracellular glycerol and accumulation of long-chain saturated, monounsaturated, and polyunsaturated (n3 and n6) free fatty acids in resveratrol-treated men. Finally, urinary derivatives of aromatic amino acids, which mainly reflect the composition of the gut microbiota, were altered upon resveratrol treatment. In conclusion, the non-targeted metabolomics approach applied to four different matrices provided evidence of subtle but robust effects on several metabolic pathways following resveratrol treatment for four months in men with metabolic syndrome-effects that, for the most part, would not have been detected by routine analyses. The affected pathways should be the focus of future clinical trials on resveratrol's effects, and perhaps particularly the areas of steroid metabolism and the gut microbiome.

  3. Two-Scale 13C Metabolic Flux Analysis for Metabolic Engineering.

    Science.gov (United States)

    Ando, David; Garcia Martin, Hector

    2018-01-01

    Accelerating the Design-Build-Test-Learn (DBTL) cycle in synthetic biology is critical to achieving rapid and facile bioengineering of organisms for the production of, e.g., biofuels and other chemicals. The Learn phase involves using data obtained from the Test phase to inform the next Design phase. As part of the Learn phase, mathematical models of metabolic fluxes give a mechanistic level of comprehension to cellular metabolism, isolating the principle drivers of metabolic behavior from the peripheral ones, and directing future experimental designs and engineering methodologies. Furthermore, the measurement of intracellular metabolic fluxes is specifically noteworthy as providing a rapid and easy-to-understand picture of how carbon and energy flow throughout the cell. Here, we present a detailed guide to performing metabolic flux analysis in the Learn phase of the DBTL cycle, where we show how one can take the isotope labeling data from a 13 C labeling experiment and immediately turn it into a determination of cellular fluxes that points in the direction of genetic engineering strategies that will advance the metabolic engineering process.For our modeling purposes we use the Joint BioEnergy Institute (JBEI) Quantitative Metabolic Modeling (jQMM) library, which provides an open-source, python-based framework for modeling internal metabolic fluxes and making actionable predictions on how to modify cellular metabolism for specific bioengineering goals. It presents a complete toolbox for performing different types of flux analysis such as Flux Balance Analysis, 13 C Metabolic Flux Analysis, and it introduces the capability to use 13 C labeling experimental data to constrain comprehensive genome-scale models through a technique called two-scale 13 C Metabolic Flux Analysis (2S- 13 C MFA) [1]. In addition to several other capabilities, the jQMM is also able to predict the effects of knockouts using the MoMA and ROOM methodologies. The use of the jQMM library is

  4. Application of a controllable degron strategy for metabolic engineering

    DEFF Research Database (Denmark)

    Knuf, Christoph; Maury, Jerome; Jacobsen, Simo Abdessamad

    2014-01-01

    In numerous cases of metabolic engineering, metabolite pools have to be increased in order to obtain flux into heterologous pathways. A simple tool for this would be the deletion of genes that would practically lead to a block of the natural pathway, so that the carbon can flow into the heterolog......In numerous cases of metabolic engineering, metabolite pools have to be increased in order to obtain flux into heterologous pathways. A simple tool for this would be the deletion of genes that would practically lead to a block of the natural pathway, so that the carbon can flow......, as the existing enzyme will still be active. We present a strategy for down-regulation that acts on the protein level and which can therefore be controlled in a more precise manner than the hitherto reported strategies. As a case study we show the action of the degron strategy for controlling the pools...

  5. SELF-PERCEIVED HEALTH AND METABOLIC CONTROL IN ...

    African Journals Online (AJOL)

    hi-tech

    2000-12-12

    Dec 12, 2000 ... their self-perceived health in social and emotional functioning and they had an improved metabolic control over the ... mean age at diagnosis was 40.3±12.5 years and mean diabetes duration was 5.3±6.0 years .... When calculating the self- perceived health over the two-year period the effect size was used.

  6. BioMet Toolbox: genome-wide analysis of metabolism

    DEFF Research Database (Denmark)

    Cvijovic, M.; Olivares Hernandez, Roberto; Agren, R.

    2010-01-01

    standardized simulations. Model files for various model organisms (fungi and bacteria) are included. Overall, the BioMet Toolbox serves as a valuable resource for exploring the capabilities of these metabolic networks. BioMet Toolbox is freely available at www.sysbio.se/BioMet/....... models. Systematic analysis of biological processes by means of modelling and simulations has made the identification of metabolic networks and prediction of metabolic capabilities under different conditions possible. For facilitating such systemic analysis, we have developed the BioMet Toolbox, a web......-based resource for stoichiometric analysis and for integration of transcriptome and interactome data, thereby exploiting the capabilities of genome-scale metabolic models. The BioMet Toolbox provides an effective user-friendly way to perform linear programming simulations towards maximized or minimized growth...

  7. [Review on periodontal disease and metabolic control of diabetes mellitus].

    Science.gov (United States)

    Steffens, João Paulo; Glaci Reinke, Stella Maria; Angel Muñoz, Miguel; Santos, Fábio André dos; Luiz Pilatti, Gibson

    2010-09-01

    There may be an interaction between periodontal disease and some systemic diseases such as diabetes mellitus. The objective of this review was to verify, by means of a review of clinical trials, if there is a positive association between periodontal disease and the glycemic control of type 2 diabetes mellitus (DM-2) patients. Eleven articles that fi t the study criteria were revised. It was concluded that periodontal disease may influence the metabolic control of DM-2. Additional studies with larger sample sizes and longer follow up are necessary for a better clarification of this issue.

  8. Lansoprazole Is Associated with Worsening Asthma Control in Children with the CYP2C19 Poor Metabolizer Phenotype.

    Science.gov (United States)

    Lang, Jason E; Holbrook, Janet T; Mougey, Edward B; Wei, Christine Y; Wise, Robert A; Teague, W Gerald; Lima, John J

    2015-06-01

    Gastric acid blockade in children with asymptomatic acid reflux has not improved asthma control in published studies. There is substantial population variability regarding metabolism of and response to proton pump inhibitors based on metabolizer phenotype. How metabolizer phenotype affects asthma responses to acid blockage is not known. To determine how metabolizer phenotype based on genetic analysis of CYP2C19 affects asthma control among children treated with a proton pump inhibitor. Asthma control as measured by the Asthma Control Questionnaire (ACQ) and other questionnaires from a 6-month clinical trial of lansoprazole in children with asthma was analyzed for associations with surrogates of lansoprazole exposure (based on treatment assignment and metabolizer phenotype). Groups included placebo-treated children; lansoprazole-treated extensive metabolizers (EMs); and lansoprazole-treated poor metabolizers (PMs). Metabolizer phenotypes were based on CYP2C19 haplotypes. Carriers of the CYP2C19*2, *3, *8, *9, or *10 allele were PMs; carriers of two wild-type alleles were extensive metabolizers (EMs). Asthma control through most of the treatment period was unaffected by lansoprazole exposure or metabolizer phenotype. At 6 months, PMs displayed significantly worsened asthma control compared with EMs (+0.16 vs. -0.13; P = 0.02) and placebo-treated children (+0.16 vs. -0.23; P lansoprazole-treated PMs. Children with the PM phenotype developed worse asthma control after 6 months of lansoprazole treatment for poorly controlled asthma. Increased exposure to proton pump inhibitor may worsen asthma control by altering responses to respiratory infections. Clinical trial registered with www.clinicaltrials.gov (NCT00604851).

  9. Sense and Nonsense in Metabolic Control of Reproduction

    Directory of Open Access Journals (Sweden)

    Jill eSchneider

    2012-03-01

    Full Text Available An exciting synergistic interaction occurs among researchers working at the interface of reproductive biology and energy homeostasis. Reproductive biologists benefit from the theories, experimental designs, and methodologies used by experts on energy homeostasis, and bring context and meaning to the study of energy homeostasis. There is a growing recognition that identification of candidate genes for obesity is little more than meaningless reductionism unless those genes and their expression are placed in a developmental, environmental, and evolutionary context. Reproductive biology provides this context because 1 metabolic energy is the most important factor that controls reproductive success, 2 gonadal hormones affect energy intake, storage and expenditure, 3 reproductive hormone secretion changes during development, and 4 reproductive success is key to evolutionary adaptation, the process that most likely molded the mechanisms that control energy balance. It is likely that by viewing energy intake, storage, and expenditure in the context of reproductive success, we will gain insight into human obesity, eating disorders, diabetes, and other pathologies related to fuel homeostasis.This review emphasizes the metabolic hypothesis: A sensory system monitors the availability of oxidizable metabolic fuels and orchestrates behavioral motivation to optimize reproductive success in environments where energy availability fluctuates or is unpredictable.

  10. Control of lipid metabolism by tachykinin in Drosophila.

    Science.gov (United States)

    Song, Wei; Veenstra, Jan A; Perrimon, Norbert

    2014-10-09

    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. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

  11. In silico analysis of human metabolism: Reconstruction, contextualization and application of genome-scale models

    DEFF Research Database (Denmark)

    Geng, Jun; Nielsen, Jens

    2017-01-01

    The arising prevalence of metabolic diseases calls for a holistic approach for analysis of the underlying nature of abnormalities in cellular functions. Through mathematic representation and topological analysis of cellular metabolism, GEnome scale metabolic Models (GEMs) provide a promising fram...

  12. Machine Learning Methods for Analysis of Metabolic Data and Metabolic Pathway Modeling.

    Science.gov (United States)

    Cuperlovic-Culf, Miroslava

    2018-01-11

    Machine learning uses experimental data to optimize clustering or classification of samples or features, or to develop, augment or verify models that can be used to predict behavior or properties of systems. It is expected that machine learning will help provide actionable knowledge from a variety of big data including metabolomics data, as well as results of metabolism models. A variety of machine learning methods has been applied in bioinformatics and metabolism analyses including self-organizing maps, support vector machines, the kernel machine, Bayesian networks or fuzzy logic. To a lesser extent, machine learning has also been utilized to take advantage of the increasing availability of genomics and metabolomics data for the optimization of metabolic network models and their analysis. In this context, machine learning has aided the development of metabolic networks, the calculation of parameters for stoichiometric and kinetic models, as well as the analysis of major features in the model for the optimal application of bioreactors. Examples of this very interesting, albeit highly complex, application of machine learning for metabolism modeling will be the primary focus of this review presenting several different types of applications for model optimization, parameter determination or system analysis using models, as well as the utilization of several different types of machine learning technologies.

  13. Machine Learning Methods for Analysis of Metabolic Data and Metabolic Pathway Modeling

    Science.gov (United States)

    Cuperlovic-Culf, Miroslava

    2018-01-01

    Machine learning uses experimental data to optimize clustering or classification of samples or features, or to develop, augment or verify models that can be used to predict behavior or properties of systems. It is expected that machine learning will help provide actionable knowledge from a variety of big data including metabolomics data, as well as results of metabolism models. A variety of machine learning methods has been applied in bioinformatics and metabolism analyses including self-organizing maps, support vector machines, the kernel machine, Bayesian networks or fuzzy logic. To a lesser extent, machine learning has also been utilized to take advantage of the increasing availability of genomics and metabolomics data for the optimization of metabolic network models and their analysis. In this context, machine learning has aided the development of metabolic networks, the calculation of parameters for stoichiometric and kinetic models, as well as the analysis of major features in the model for the optimal application of bioreactors. Examples of this very interesting, albeit highly complex, application of machine learning for metabolism modeling will be the primary focus of this review presenting several different types of applications for model optimization, parameter determination or system analysis using models, as well as the utilization of several different types of machine learning technologies. PMID:29324649

  14. Perturbations in amino acids and metabolic pathways in osteoarthritis patients determined by targeted metabolomics analysis.

    Science.gov (United States)

    Chen, Rui; Han, Su; Liu, Xuefeng; Wang, Kunpeng; Zhou, Yong; Yang, Chundong; Zhang, Xi

    2018-05-15

    Osteoarthritis (OA) is a degenerative synovial joint disease affecting people worldwide. However, the exact pathogenesis of OA remains unclear. Metabolomics analysis was performed to obtain insight into possible pathogenic mechanisms and diagnostic biomarkers of OA. Ultra-high performance liquid chromatography-triple quadrupole mass spectrometry (UPLC-TQ-MS), followed by multivariate statistical analysis, was used to determine the serum amino acid profiles of 32 OA patients and 35 healthy controls. Variable importance for project values and Student's t-test were used to determine the metabolic abnormalities in OA. Another 30 OA patients were used as independent samples to validate the alterations in amino acids. MetaboAnalyst was used to identify the key amino acid pathways and construct metabolic networks describing their relationships. A total of 25 amino acids and four biogenic amines were detected by UPLC-TQ-MS. Differences in amino acid profiles were found between the healthy controls and OA patients. Alanine, γ-aminobutyric acid and 4-hydroxy-l-proline were important biomarkers distinguishing OA patients from healthy controls. The metabolic pathways with the most significant effects were involved in metabolism of alanine, aspartate, glutamate, arginine and proline. The results of this study improve understanding of the amino acid metabolic abnormalities and pathogenic mechanisms of OA at the molecular level. The metabolic perturbations may be important for the diagnosis and prevention of OA. Copyright © 2018 Elsevier B.V. All rights reserved.

  15. Using PSAMM for the Curation and Analysis of Genome-Scale Metabolic Models.

    Science.gov (United States)

    Dufault-Thompson, Keith; Steffensen, Jon Lund; Zhang, Ying

    2018-01-01

    PSAMM is an open source software package that supports the iterative curation and analysis of genome-scale models (GEMs). It aims to integrate the annotation and consistency checking of metabolic models with the simulation of metabolic fluxes. The model representation in PSAMM is compatible with version tracking systems like Git, which allows for full documentation of model file changes and enables collaborative curations of large, complex models. This chapter provides a protocol for using PSAMM functions and a detailed description of the various aspects in setting up and using PSAMM for the simulation and analysis of metabolic models. The overall PSAMM workflow outlined in this chapter includes the import and export of model files, the documentation of model modifications using the Git version control system, the application of consistency checking functions for model curations, and the numerical simulation of metabolic models.

  16. Metabolic control of muscle blood flow during exercise in humans

    DEFF Research Database (Denmark)

    Boushel, Robert Christopher

    2003-01-01

    that combined blockade of NOS and PGI2, and NOS and cytochrome P450, both attenuate exercise-induced hyperemia in humans. Combined vasodilator blockade studies offer the potential to uncover important interactions and compensatory vasodilator responses. The signaling pathways that link metabolic events evoked...... to exert control of muscle vasodilation. Adenosine, nitric oxide (NO), prostacyclin (PGI2), and endothelial-derived hyperpolarization factor (EDHF) are possible mediators of muscle vasodilation during exercise. In humans, adenosine has been shown to contribute to functional hyperemia as blood flow...... by muscle contraction to vasodilatory signals in the local vascular bed remains an important area of study....

  17. Integrated proteomic and metabolic analysis of breast cancer progression.

    Directory of Open Access Journals (Sweden)

    Patrick G Shaw

    Full Text Available One of the most persistent hallmarks of cancer biology is the preference of tumor cells to derive energy through glycolysis as opposed to the more efficient process of oxidative phosphorylation (OXPHOS. However, little is known about the molecular cascades by which oncogenic pathways bring about this metabolic switch. We carried out a quantitative proteomic and metabolic analysis of the MCF10A derived cell line model of breast cancer progression that includes parental cells and derivatives representing three different tumor grades of Ras-driven cancer with a common genetic background. A SILAC (Stable Isotope Labeling by Amino acids in Cell culture labeling strategy was used to quantify protein expression in conjunction with subcellular fractionation to measure dynamic subcellular localization in the nucleus, cytosol and mitochondria. Protein expression and localization across cell lines were compared to cellular metabolic rates as a measure of oxidative phosphorylation (OXPHOS, glycolysis and cellular ATP. Investigation of the metabolic capacity of the four cell lines revealed that cellular OXPHOS decreased with breast cancer progression independently of mitochondrial copy number or electron transport chain protein expression. Furthermore, glycolytic lactate secretion did not increase in accordance with cancer progression and decreasing OXPHOS capacity. However, the relative expression and subcellular enrichment of enzymes critical to lactate and pyruvate metabolism supported the observed extracellular acidification profiles. This analysis of metabolic dysfunction in cancer progression integrated with global protein expression and subcellular localization is a novel and useful technique for determining organelle-specific roles of proteins in disease.

  18. Thermodynamics-based Metabolite Sensitivity Analysis in metabolic networks.

    Science.gov (United States)

    Kiparissides, A; Hatzimanikatis, V

    2017-01-01

    The increasing availability of large metabolomics datasets enhances the need for computational methodologies that can organize the data in a way that can lead to the inference of meaningful relationships. Knowledge of the metabolic state of a cell and how it responds to various stimuli and extracellular conditions can offer significant insight in the regulatory functions and how to manipulate them. Constraint based methods, such as Flux Balance Analysis (FBA) and Thermodynamics-based flux analysis (TFA), are commonly used to estimate the flow of metabolites through genome-wide metabolic networks, making it possible to identify the ranges of flux values that are consistent with the studied physiological and thermodynamic conditions. However, unless key intracellular fluxes and metabolite concentrations are known, constraint-based models lead to underdetermined problem formulations. This lack of information propagates as uncertainty in the estimation of fluxes and basic reaction properties such as the determination of reaction directionalities. Therefore, knowledge of which metabolites, if measured, would contribute the most to reducing this uncertainty can significantly improve our ability to define the internal state of the cell. In the present work we combine constraint based modeling, Design of Experiments (DoE) and Global Sensitivity Analysis (GSA) into the Thermodynamics-based Metabolite Sensitivity Analysis (TMSA) method. TMSA ranks metabolites comprising a metabolic network based on their ability to constrain the gamut of possible solutions to a limited, thermodynamically consistent set of internal states. TMSA is modular and can be applied to a single reaction, a metabolic pathway or an entire metabolic network. This is, to our knowledge, the first attempt to use metabolic modeling in order to provide a significance ranking of metabolites to guide experimental measurements. Copyright © 2016 International Metabolic Engineering Society. Published by Elsevier

  19. Both the frequency of HbA1c testing and the frequency of self-monitoring of blood glucose predict metabolic control: A multicentre analysis of 15 199 adult type 1 diabetes patients from Germany and Austria.

    Science.gov (United States)

    Schwandt, A; Best, F; Biester, T; Grünerbel, A; Kopp, F; Krakow, D; Laimer, M; Wagner, C; Holl, R W

    2017-10-01

    The objective of this study was to examine the association between metabolic control and frequency of haemoglobin A 1c (HbA 1c ) measurements and of self-monitoring of blood glucose, as well as the interaction of both. Data of 15 199 adult type 1 diabetes patients registered in a standardized electronic health record (DPV) were included. To model the association between metabolic control and frequency of HbA 1c testing or of self-monitoring of blood glucose, multiple hierarchic regression models with adjustment for confounders were fitted. Tukey-Kramer test was used to adjust P values for multiple comparisons. Vuong test was used to compare non-nested models. The baseline variables of the study population were median age 19.9 [Q1; Q3: 18.4; 32.2] years and diabetes duration 10.4 [6.8; 15.7] years. Haemoglobin A 1c was 60.4 [51.5; 72.5] mmol/mol. Frequency of HbA 1c testing was 8.0 [5.0; 9.0] within 2 years, and daily self-monitoring of blood glucose frequency was 5.0 [4.0; 6.0]. After adjustment, a U-shaped association between metabolic control and frequency of HbA 1c testing was observed with lowest HbA 1c levels in the 3-monthly HbA 1c testing group. There was an inverse relationship between self-monitoring of blood glucose and HbA 1c with lower HbA 1c associated with highest frequency of testing (>6 daily measurements). Quarterly HbA 1c testing and frequent self-monitoring of blood glucose were associated with best metabolic control. The adjusted Vuong Z statistic suggests that metabolic control might be better explained by HbA 1c testing compared to self-monitoring of blood glucose (P monitoring together with frequent self-monitoring of blood glucose in diabetes management to reach and maintain target HbA 1c . Copyright © 2017 John Wiley & Sons, Ltd.

  20. First-year metabolic control guidelines and their impact on future metabolic control and neurocognitive functioning in children with PKU.

    Science.gov (United States)

    de la Parra, Alicia; García, María Ignacia; Hamilton, Valerie; Arias, Carolina; Cabello, Juan Francisco; Cornejo, Verónica

    2017-12-01

    There is a consensus on the importance of early and life-long treatment for PKU patients. Still, differences exist on target blood phenylalanine (Phe) concentrations for children with PKU in different countries and treatment centers. For the first time, long-term metabolic control and child development and cognitive functioning is compared between children with mean phenylalanine concentrations under 240 μmol/L (group A), between 240 and 360 μmol/L (group B) or over 360 μmol/L (group C) during their first year of life. 70 patients diagnosed with PKU through neonatal screening with Phe > 900 μmol/L, were divided into 3 groups: A, B and C, according to mean Phe concentrations and standard deviation (SD). Metabolic control during childhood, psychomotor development and IQ were compared. In group A, Phe was maintained within the recommended range until 6 years of age, in Group B, until 3 years of age, and in group C, Phe was always over the recommended range. No significant differences were found between the three groups in mental development index (MDI) and motor development index (PDI) scores at 12, 24, and 30 months of age, but group C had the lowest scores on MDI at all age periods. At preschool and school age, IQ was higher in group A compared to group C. Results show that mean blood Phe concentrations between 120 and 240 μmol/L during first year of life have a positive impact in metabolic control and cognitive functioning during childhood.

  1. Synergy between 13C-metabolic flux analysis and flux balance analysis for understanding metabolic adaption to anaerobiosis in e. coli

    Science.gov (United States)

    Genome-based Flux Balance Analysis (FBA, constraints based flux analysis) and steady state isotopic-labeling-based Metabolic Flux Analysis (MFA) are complimentary approaches to predicting and measuring the operation and regulation of metabolic networks. Here a genome-derived model of E. coli metabol...

  2. Determination of key enzymes for threonine synthesis through in vitro metabolic pathway analysis.

    Science.gov (United States)

    Zhang, Yanfei; Meng, Qinglong; Ma, Hongwu; Liu, Yongfei; Cao, Guoqiang; Zhang, Xiaoran; Zheng, Ping; Sun, Jibin; Zhang, Dawei; Jiang, Wenxia; Ma, Yanhe

    2015-06-13

    The overexpression of key enzymes in a metabolic pathway is a frequently used genetic engineering strategy for strain improvement. Metabolic control analysis has been proposed to quantitatively determine key enzymes. However, the lack of quality data often makes it difficult to correctly identify key enzymes through control analysis. Here, we proposed a method combining in vitro metabolic pathway analysis and proteomics measurement to find the key enzymes in threonine synthesis pathway. All enzymes in the threonine synthesis pathway were purified for the reconstruction and perturbation of the in vitro pathway. Label-free proteomics technology combined with APEX (absolute protein expression measurements) data analysis method were employed to determine the absolute enzyme concentrations in the crude enzyme extract obtained from a threonine production strain during the fastest threonine production period. The flux control coefficient of each enzyme in the pathway was then calculated by measuring the flux changes after titration of the corresponding enzyme. The isoenzyme LysC catalyzing the first step in the pathway has the largest flux control coefficient, and thus its concentration change has the biggest impact on pathway flux. To verify that the key enzyme identified through in vitro pathway analysis is also the key enzyme in vivo, we overexpressed LysC in the original threonine production strain. Fermentation results showed that the threonine concentration was increased 30% and the yield was increased 20%. In vitro metabolic pathways simulating in vivo cells can be built based on precise measurement of enzyme concentrations through proteomics technology and used for the determination of key enzymes through metabolic control analysis. This provides a new way to find gene overexpression targets for industrial strain improvement.

  3. Combining mechanistic and data-driven approaches to gain process knowledge on the control of the metabolic shift to lactate uptake in a fed-batch CHO process.

    Science.gov (United States)

    Zalai, Dénes; Koczka, Krisztina; Párta, László; Wechselberger, Patrick; Klein, Tobias; Herwig, Christoph

    2015-01-01

    A growing body of knowledge is available on the cellular regulation of overflow metabolism in mammalian hosts of recombinant protein production. However, to develop strategies to control the regulation of overflow metabolism in cell culture processes, the effect of process parameters on metabolism has to be well understood. In this study, we investigated the effect of pH and temperature shift timing on lactate metabolism in a fed-batch Chinese hamster ovary (CHO) process by using a Design of Experiments (DoE) approach. The metabolic switch to lactate consumption was controlled in a broad range by the proper timing of pH and temperature shifts. To extract process knowledge from the large experimental dataset, we proposed a novel methodological concept and demonstrated its usefulness with the analysis of lactate metabolism. Time-resolved metabolic flux analysis and PLS-R VIP were combined to assess the correlation of lactate metabolism and the activity of the major intracellular pathways. Whereas the switch to lactate uptake was mainly triggered by the decrease in the glycolytic flux, lactate uptake was correlated to TCA activity in the last days of the cultivation. These metabolic interactions were visualized on simple mechanistic plots to facilitate the interpretation of the results. Taken together, the combination of knowledge-based mechanistic modeling and data-driven multivariate analysis delivered valuable insights into the metabolic control of lactate production and has proven to be a powerful tool for the analysis of large metabolic datasets. © 2015 American Institute of Chemical Engineers.

  4. Analysis of Piscirickettsia salmonis Metabolism Using Genome-Scale Reconstruction, Modeling, and Testing

    Directory of Open Access Journals (Sweden)

    María P. Cortés

    2017-12-01

    Full Text Available Piscirickettsia salmonis is an intracellular bacterial fish pathogen that causes piscirickettsiosis, a disease with highly adverse impact in the Chilean salmon farming industry. The development of effective treatment and control methods for piscireckttsiosis is still a challenge. To meet it the number of studies on P. salmonis has grown in the last couple of years but many aspects of the pathogen’s biology are still poorly understood. Studies on its metabolism are scarce and only recently a metabolic model for reference strain LF-89 was developed. We present a new genome-scale model for P. salmonis LF-89 with more than twice as many genes as in the previous model and incorporating specific elements of the fish pathogen metabolism. Comparative analysis with models of different bacterial pathogens revealed a lower flexibility in P. salmonis metabolic network. Through constraint-based analysis, we determined essential metabolites required for its growth and showed that it can benefit from different carbon sources tested experimentally in new defined media. We also built an additional model for strain A1-15972, and together with an analysis of P. salmonis pangenome, we identified metabolic features that differentiate two main species clades. Both models constitute a knowledge-base for P. salmonis metabolism and can be used to guide the efficient culture of the pathogen and the identification of specific drug targets.

  5. Stoichiometric Correlation Analysis: Principles of Metabolic Functionality from Metabolomics Data

    Directory of Open Access Journals (Sweden)

    Kevin Schwahn

    2017-12-01

    Full Text Available Recent advances in metabolomics technologies have resulted in high-quality (time-resolved metabolic profiles with an increasing coverage of metabolic pathways. These data profiles represent read-outs from often non-linear dynamics of metabolic networks. Yet, metabolic profiles have largely been explored with regression-based approaches that only capture linear relationships, rendering it difficult to determine the extent to which the data reflect the underlying reaction rates and their couplings. Here we propose an approach termed Stoichiometric Correlation Analysis (SCA based on correlation between positive linear combinations of log-transformed metabolic profiles. The log-transformation is due to the evidence that metabolic networks can be modeled by mass action law and kinetics derived from it. Unlike the existing approaches which establish a relation between pairs of metabolites, SCA facilitates the discovery of higher-order dependence between more than two metabolites. By using a paradigmatic model of the tricarboxylic acid cycle we show that the higher-order dependence reflects the coupling of concentration of reactant complexes, capturing the subtle difference between the employed enzyme kinetics. Using time-resolved metabolic profiles from Arabidopsis thaliana and Escherichia coli, we show that SCA can be used to quantify the difference in coupling of reactant complexes, and hence, reaction rates, underlying the stringent response in these model organisms. By using SCA with data from natural variation of wild and domesticated wheat and tomato accession, we demonstrate that the domestication is accompanied by loss of such couplings, in these species. Therefore, application of SCA to metabolomics data from natural variation in wild and domesticated populations provides a mechanistic way to understanding domestication and its relation to metabolic networks.

  6. Subclinical peripheral neuropathy in type 1 diabetic adolescents and its relationship with metabolic control

    Directory of Open Access Journals (Sweden)

    Sajić Silvija

    2005-01-01

    Full Text Available Professional management of paediatric diabetology, according to consensus guidelines, involves the screening of micro-vascular complications at puberty. The subclinical form of peripheral neural dysfunction in diabetic teenagers is reported with a frequency of 50-88%, by different authors. The purpose of this study was to evaluate the frequency of subclinical distal neuropathy (DSMN in type 1 diabetic pediatric patients during the second decade of life, and its relationship with metabolic control. The Endocrinology Department and the Neurology-Physiology Laboratory of the Pediatric Clinic in Belgrade carried out a longitudinal follow-up study (lasting 18 months, beginning in November 2000 on a selection of patients with poor metabolic control. During routine clinical treatment, patients were evaluated using the electrophysiological diagnostic method on peripheral neural dysfunction, a subclinical form of neuropathy. Metabolic control was manifested through HbA1c levels, measured every 3 months, using ion-exchange chromatography. Finally, here is the data collected from the clinical follow-up investigation of 60 children, aged 13-19 (median 1S.S±2.2, with duration of diabetes from 2-16 years (median b.3±3.b, and on the following therapies: 43 CT-conventional and 17 IIT-intensive, and insulin dose/day, median 1.02 (0.6-2.1 U/kg. Detected DSMN parameters at the beginning and at the end of the study were also noted. DSMN frequency was positive, at 64% for HbA1c of 9.44; DSMN dysfunction was reversed in 5% of the patients, for HbA1c of 10.17; the worst result was the progression of DSMN at 6.7% for HbA1c of 10.52; 6.7% had negative DSMN, with improved metabolic control, for HbA1c of 8.4; 15% of the examinations were unfinished (+/*. ANOVA statistical analysis showed a significant statistical relationship between metabolic control (HbA1c levels and DSMN neuropathy (sig. 0.043, p<0.05. There was no significant relationship between the reversion of

  7. PSAMM: A Portable System for the Analysis of Metabolic Models.

    Directory of Open Access Journals (Sweden)

    Jon Lund Steffensen

    2016-02-01

    Full Text Available The genome-scale models of metabolic networks have been broadly applied in phenotype prediction, evolutionary reconstruction, community functional analysis, and metabolic engineering. Despite the development of tools that support individual steps along the modeling procedure, it is still difficult to associate mathematical simulation results with the annotation and biological interpretation of metabolic models. In order to solve this problem, here we developed a Portable System for the Analysis of Metabolic Models (PSAMM, a new open-source software package that supports the integration of heterogeneous metadata in model annotations and provides a user-friendly interface for the analysis of metabolic models. PSAMM is independent of paid software environments like MATLAB, and all its dependencies are freely available for academic users. Compared to existing tools, PSAMM significantly reduced the running time of constraint-based analysis and enabled flexible settings of simulation parameters using simple one-line commands. The integration of heterogeneous, model-specific annotation information in PSAMM is achieved with a novel format of YAML-based model representation, which has several advantages, such as providing a modular organization of model components and simulation settings, enabling model version tracking, and permitting the integration of multiple simulation problems. PSAMM also includes a number of quality checking procedures to examine stoichiometric balance and to identify blocked reactions. Applying PSAMM to 57 models collected from current literature, we demonstrated how the software can be used for managing and simulating metabolic models. We identified a number of common inconsistencies in existing models and constructed an updated model repository to document the resolution of these inconsistencies.

  8. Pyruvate Kinase Triggers a Metabolic Feedback Loop that Controls Redox Metabolism in Respiring Cells

    NARCIS (Netherlands)

    Grüning, N.M.; Rinnerthaler, M.; Bluemlein, K.; Mulleder, M.; Wamelink, M.M.C.; Lehrach, H.; Jakobs, C.A.J.M.; Breitenbach, M.; Ralser, M.

    2011-01-01

    In proliferating cells, a transition from aerobic to anaerobic metabolism is known as the Warburg effect, whose reversal inhibits cancer cell proliferation. Studying its regulator pyruvate kinase (PYK) in yeast, we discovered that central metabolism is self-adapting to synchronize redox metabolism

  9. Astroculture™ Root Metabolism and Cytochemical Analysis

    Science.gov (United States)

    Porterfield, D. M.; Barta, D. J.; Ming, D. W.; Morrow, R. C.; Musgrave, M. E.

    Physiology of the root system is dependent upon oxygen availability and tissue respiration. During hypoxia nutrient and water acquisition may be inhibited, thus affecting the overall biochemical and physiological status of the plant. For the Astroculture™ plant growth hardware, the availability of oxygen in the root zone was measured by examining the changes in alcohol dehydrogenase (ADH) activity within the root tissue. ADH activity is a sensitive biochemical indicator of hypoxic conditions in plants and was measured in both spaceflight and control roots. In addition to the biochemical enzyme assays, localization of ADH in the root tissue was examined cytochemically. The results of these analyses showed that ADH activity increased significantly as a result of spaceflight exposure. Enzyme activity increased 248% to 304% in dwarf wheat when compared with the ground controls and Brassica showed increases between 334% and 579% when compared with day zero controls. Cytochemical staining revealed no differences in ADH tissue localization in any of the dwarf wheat treatments. These results show the importance of considering root system oxygenation in designing and building nutrient delivery hardware for spaceflight plant cultivation and confirm previous reports of an ADH response associated with spaceflight exposure

  10. ASTROCULTURE (TM) root metabolism and cytochemical analysis

    Science.gov (United States)

    Porterfield, D. M.; Barta, D. J.; Ming, D. W.; Morrow, R. C.; Musgrave, M. E.

    2000-01-01

    Physiology of the root system is dependent upon oxygen availability and tissue respiration. During hypoxia nutrient and water acquisition may be inhibited, thus affecting the overall biochemical and physiological status of the plant. For the Astroculture (TM) plant growth hardware, the availability of oxygen in the root zone was measured by examining the changes in alcohol dehydrogenase (ADH) activity within the root tissue. ADH activity is a sensitive biochemical indicator of hypoxic conditions in plants and was measured in both spaceflight and control roots. In addition to the biochemical enzyme assays, localization of ADH in the root tissue was examined cytochemically. The results of these analyses showed that ADH activity increased significantly as a result of spaceflight exposure. Enzyme activity increased 248% to 304% in dwarf wheat when compared with the ground controls and Brassica showed increases between 334% and 579% when compared with day zero controls. Cytochemical staining revealed no differences in ADH tissue localization in any of the dwarf wheat treatments. These results show the importance of considering root system oxygenation in designing and building nutrient delivery hardware for spaceflight plant cultivation and confirm previous reports of an ADH response associated with spaceflight exposure.

  11. 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.

  12. Metabolic pathway analysis using a nash equilibrium approach

    NARCIS (Netherlands)

    Lucia, Angelo; DiMaggio, Peter A.; Alonso-Martinez, Diego

    2018-01-01

    A novel approach to metabolic network analysis using a Nash Equilibrium (NE) formulation is proposed in which enzymes are considered players in a multi-player game. Each player has its own payoff function with the objective of minimizing the Gibbs free energy associated with the biochemical

  13. Dynamic metabolic flux analysis using B-splines to study the effects of temperature shift on CHO cell metabolism

    Directory of Open Access Journals (Sweden)

    Verónica S. Martínez

    2015-12-01

    Full Text Available Metabolic flux analysis (MFA is widely used to estimate intracellular fluxes. Conventional MFA, however, is limited to continuous cultures and the mid-exponential growth phase of batch cultures. Dynamic MFA (DMFA has emerged to characterize time-resolved metabolic fluxes for the entire culture period. Here, the linear DMFA approach was extended using B-spline fitting (B-DMFA to estimate mass balanced fluxes. Smoother fits were achieved using reduced number of knots and parameters. Additionally, computation time was greatly reduced using a new heuristic algorithm for knot placement. B-DMFA revealed that Chinese hamster ovary cells shifted from 37 °C to 32 °C maintained a constant IgG volume-specific productivity, whereas the productivity for the controls peaked during mid-exponential growth phase and declined afterward. The observed 42% increase in product titer at 32 °C was explained by a prolonged cell growth with high cell viability, a larger cell volume and a more stable volume-specific productivity. Keywords: Dynamic, Metabolism, Flux analysis, CHO cells, Temperature shift, B-spline curve fitting

  14. WUFlux: an open-source platform for 13C metabolic flux analysis of bacterial metabolism.

    Science.gov (United States)

    He, Lian; Wu, Stephen G; Zhang, Muhan; Chen, Yixin; Tang, Yinjie J

    2016-11-04

    Flux analyses, including flux balance analysis (FBA) and 13 C-metabolic flux analysis ( 13 C-MFA), offer direct insights into cell metabolism, and have been widely used to characterize model and non-model microbial species. Nonetheless, constructing the 13 C-MFA model and performing flux calculation are demanding for new learners, because they require knowledge of metabolic networks, carbon transitions, and computer programming. To facilitate and standardize the 13 C-MFA modeling work, we set out to publish a user-friendly and programming-free platform (WUFlux) for flux calculations in MATLAB ® . We constructed an open-source platform for steady-state 13 C-MFA. Using GUIDE (graphical user interface design environment) in MATLAB, we built a user interface that allows users to modify models based on their own experimental conditions. WUFlux is capable of directly correcting mass spectrum data of TBDMS (N-tert-butyldimethylsilyl-N-methyltrifluoroacetamide)-derivatized proteinogenic amino acids by removing background noise. To simplify 13 C-MFA of different prokaryotic species, the software provides several metabolic network templates, including those for chemoheterotrophic bacteria and mixotrophic cyanobacteria. Users can modify the network and constraints, and then analyze the microbial carbon and energy metabolisms of various carbon substrates (e.g., glucose, pyruvate/lactate, acetate, xylose, and glycerol). WUFlux also offers several ways of visualizing the flux results with respect to the constructed network. To validate our model's applicability, we have compared and discussed the flux results obtained from WUFlux and other MFA software. We have also illustrated how model constraints of cofactor and ATP balances influence fluxome results. Open-source software for 13 C-MFA, WUFlux, with a user-friendly interface and easy-to-modify templates, is now available at http://www.13cmfa.org /or ( http://tang.eece.wustl.edu/ToolDevelopment.htm ). We will continue

  15. INCA- INTERACTIVE CONTROLS ANALYSIS

    Science.gov (United States)

    Bauer, F. H.

    1994-01-01

    The Interactive Controls Analysis (INCA) program was developed to provide a user friendly environment for the design and analysis of linear control systems, primarily feedback control systems. INCA is designed for use with both small and large order systems. Using the interactive graphics capability, the INCA user can quickly plot a root locus, frequency response, or time response of either a continuous time system or a sampled data system. The system configuration and parameters can be easily changed, allowing the INCA user to design compensation networks and perform sensitivity analysis in a very convenient manner. A journal file capability is included. This stores an entire sequence of commands, generated during an INCA session into a file which can be accessed later. Also included in INCA are a context-sensitive help library, a screen editor, and plot windows. INCA is robust to VAX-specific overflow problems. The transfer function is the basic unit of INCA. Transfer functions are automatically saved and are available to the INCA user at any time. A powerful, user friendly transfer function manipulation and editing capability is built into the INCA program. The user can do all transfer function manipulations and plotting without leaving INCA, although provisions are made to input transfer functions from data files. By using a small set of commands, the user may compute and edit transfer functions, and then examine these functions by using the ROOT_LOCUS, FREQUENCY_RESPONSE, and TIME_RESPONSE capabilities. Basic input data, including gains, are handled as single-input single-output transfer functions. These functions can be developed using the function editor or by using FORTRAN- like arithmetic expressions. In addition to the arithmetic functions, special functions are available to 1) compute step, ramp, and sinusoid functions, 2) compute closed loop transfer functions, 3) convert from S plane to Z plane with optional advanced Z transform, and 4) convert from Z

  16. Adipocyte Metabolic Pathways Regulated by Diet Control the Female Germline Stem Cell Lineage inDrosophila melanogaster.

    Science.gov (United States)

    Matsuoka, Shinya; Armstrong, Alissa R; Sampson, Leesa L; Laws, Kaitlin M; Drummond-Barbosa, Daniela

    2017-06-01

    Nutrients affect adult stem cells through complex mechanisms involving multiple organs. Adipocytes are highly sensitive to diet and have key metabolic roles, and obesity increases the risk for many cancers. How diet-regulated adipocyte metabolic pathways influence normal stem cell lineages, however, remains unclear. Drosophila melanogaster has highly conserved adipocyte metabolism and a well-characterized female germline stem cell (GSC) lineage response to diet. Here, we conducted an isobaric tags for relative and absolute quantification (iTRAQ) proteomic analysis to identify diet-regulated adipocyte metabolic pathways that control the female GSC lineage. On a rich (relative to poor) diet, adipocyte Hexokinase-C and metabolic enzymes involved in pyruvate/acetyl-CoA production are upregulated, promoting a shift of glucose metabolism toward macromolecule biosynthesis. Adipocyte-specific knockdown shows that these enzymes support early GSC progeny survival. Further, enzymes catalyzing fatty acid oxidation and phosphatidylethanolamine synthesis in adipocytes promote GSC maintenance, whereas lipid and iron transport from adipocytes controls vitellogenesis and GSC number, respectively. These results show a functional relationship between specific metabolic pathways in adipocytes and distinct processes in the GSC lineage, suggesting the adipocyte metabolism-stem cell link as an important area of investigation in other stem cell systems. Copyright © 2017 by the Genetics Society of America.

  17. Molecular network analysis of phosphotyrosine and lipid metabolism in hepatic PTP1b deletion mice.

    Science.gov (United States)

    Miraldi, Emily R; Sharfi, Hadar; Friedline, Randall H; Johnson, Hannah; Zhang, Tejia; Lau, Ken S; Ko, Hwi Jin; Curran, Timothy G; Haigis, Kevin M; Yaffe, Michael B; Bonneau, Richard; Lauffenburger, Douglas A; Kahn, Barbara B; Kim, Jason K; Neel, Benjamin G; Saghatelian, Alan; White, Forest M

    2013-07-24

    Metabolic syndrome describes a set of obesity-related disorders that increase diabetes, cardiovascular, and mortality risk. Studies of liver-specific protein-tyrosine phosphatase 1b (PTP1b) deletion mice (L-PTP1b(-/-)) suggest that hepatic PTP1b inhibition would mitigate metabolic-syndrome through amelioration of hepatic insulin resistance, endoplasmic-reticulum stress, and whole-body lipid metabolism. However, the altered molecular-network states underlying these phenotypes are poorly understood. We used mass spectrometry to quantify protein-phosphotyrosine network changes in L-PTP1b(-/-) mouse livers relative to control mice on normal and high-fat diets. We applied a phosphosite-set-enrichment analysis to identify known and novel pathways exhibiting PTP1b- and diet-dependent phosphotyrosine regulation. Detection of a PTP1b-dependent, but functionally uncharacterized, set of phosphosites on lipid-metabolic proteins motivated global lipidomic analyses that revealed altered polyunsaturated-fatty-acid (PUFA) and triglyceride metabolism in L-PTP1b(-/-) mice. To connect phosphosites and lipid measurements in a unified model, we developed a multivariate-regression framework, which accounts for measurement noise and systematically missing proteomics data. This analysis resulted in quantitative models that predict roles for phosphoproteins involved in oxidation-reduction in altered PUFA and triglyceride metabolism.

  18. Exhaustive Analysis of a Genotype Space Comprising 10(15 Central Carbon Metabolisms Reveals an Organization Conducive to Metabolic Innovation.

    Directory of Open Access Journals (Sweden)

    Sayed-Rzgar Hosseini

    2015-08-01

    Full Text Available All biological evolution takes place in a space of possible genotypes and their phenotypes. The structure of this space defines the evolutionary potential and limitations of an evolving system. Metabolism is one of the most ancient and fundamental evolving systems, sustaining life by extracting energy from extracellular nutrients. Here we study metabolism's potential for innovation by analyzing an exhaustive genotype-phenotype map for a space of 10(15 metabolisms that encodes all possible subsets of 51 reactions in central carbon metabolism. Using flux balance analysis, we predict the viability of these metabolisms on 10 different carbon sources which give rise to 1024 potential metabolic phenotypes. Although viable metabolisms with any one phenotype comprise a tiny fraction of genotype space, their absolute numbers exceed 10(9 for some phenotypes. Metabolisms with any one phenotype typically form a single network of genotypes that extends far or all the way through metabolic genotype space, where any two genotypes can be reached from each other through a series of single reaction changes. The minimal distance of genotype networks associated with different phenotypes is small, such that one can reach metabolisms with novel phenotypes--viable on new carbon sources--through one or few genotypic changes. Exceptions to these principles exist for those metabolisms whose complexity (number of reactions is close to the minimum needed for viability. Increasing metabolic complexity enhances the potential for both evolutionary conservation and evolutionary innovation.

  19. Metabolic syndrome risk factors and dry eye syndrome: a Meta-analysis.

    Science.gov (United States)

    Tang, Ye-Lei; Cheng, Ya-Lan; Ren, Yu-Ping; Yu, Xiao-Ning; Shentu, Xing-Chao

    2016-01-01

    To explore the relationship between metabolic risk factors and dry eye syndrome (DES). Retrieved studies on the association of metabolic syndrome risk factors (hypertension, hyperglycemia, obesity, and hyperlipidemia) and DES were collected from PubMed, Web of Science, and the Cochrane Library in December 2015. Odds ratio (OR) with 95% confidence interval (CI) were pooled to evaluate the final relationship. Subgroup analyses were conducted according to diagnostic criteria of DES. Nine cross-sectional studies and three case-control studies were included in this Meta-analysis. The pooled results showed that people with hypertension, hyperglycemia, and hyperlipidemia had a higher risk of suffering from DES (PDES symptoms. On the other hand, obesity did not increase the risk of DES. The present Meta-analysis suggests that all metabolic risk factors except obesity were risk factors for DES.

  20. Basal metabolic rate in women with PCOS compared to eumenorrheic controls.

    Science.gov (United States)

    Churchill, Sara J; Wang, Erica T; Bhasin, Gaisu; Alexander, Carolyn; Bresee, Catherine; Pall, Marita; Azziz, Ricardo; Mathur, Ruchi; Pisarska, Margareta D

    2015-09-01

    PCOS is associated with obesity and insulin resistance. Efforts have focused on whether an abnormal energy homeostasis contributes to the development of obesity in these patients. There are conflicting results in the literature regarding whether women with PCOS have an altered basal metabolic rate (BMR), thereby leading to difficulties in weight loss. The objective of this study is to compare basal metabolic rate (BMR) in women with PCOS and controls. Cross-sectional study. One hundred and twenty-eight PCOS patients diagnosed by original NIH consensus criteria and 72 eumenorrheic, non-hirsute controls were recruited from an academic medical centre. Assessment of BMR using the InBody portable bioelectrical impedance analysis (BIA) device and insulin resistance by HOMA-IR indices. PCOS women were younger than controls. As expected, PCOS subjects had higher body mass index (BMI), serum androgens and estimated insulin resistance. After adjusting for age and BMI, there was no significant difference in BMR between PCOS subjects (adjusted mean 5807 kJ/day, 95% CI 5715-5899) and controls (adjusted mean 5916 kJ/day, 95% CI 5786-6046) (P = 0·193). BMR was also comparable in a secondary analysis comparing PCOS women with and without insulin resistance. After adjusting for age and BMI, there was no difference in BMR between PCOS women and controls. © 2015 John Wiley & Sons Ltd.

  1. Evolution of amino acid metabolism inferred through cladistic analysis.

    Science.gov (United States)

    Cunchillos, Chomin; Lecointre, Guillaume

    2003-11-28

    Because free amino acids were most probably available in primitive abiotic environments, their metabolism is likely to have provided some of the very first metabolic pathways of life. What were the first enzymatic reactions to emerge? A cladistic analysis of metabolic pathways of the 16 aliphatic amino acids and 2 portions of the Krebs cycle was performed using four criteria of homology. The analysis is not based on sequence comparisons but, rather, on coding similarities in enzyme properties. The properties used are shared specific enzymatic activity, shared enzymatic function without substrate specificity, shared coenzymes, and shared functional family. The tree shows that the earliest pathways to emerge are not portions of the Krebs cycle but metabolisms of aspartate, asparagine, glutamate, and glutamine. The views of Horowitz (Horowitz, N. H. (1945) Proc. Natl. Acad. Sci. U. S. A. 31, 153-157) and Cordón (Cordón, F. (1990) Tratado Evolucionista de Biologia, Aguilar, Madrid, Spain), according to which the upstream reactions in the catabolic pathways and the downstream reactions in the anabolic pathways are the earliest in evolution, are globally corroborated; however, with some exceptions. These are due to later opportunistic connections of pathways (actually already suggested by these authors). Earliest enzymatic functions are mostly catabolic; they were deaminations, transaminations, and decarboxylations. From the consensus tree we extracted four time spans for amino acid metabolism development. For some amino acids catabolism and biosynthesis occurred at the same time (Asp, Glu, Lys, Leu, Ala, Val, Ile, Pro, Arg). For others ultimate reactions that use amino acids as a substrate or as a product are distinct in time, with catabolism preceding anabolism for Asn, Gln, and Cys and anabolism preceding catabolism for Ser, Met, and Thr. Cladistic analysis of the structure of biochemical pathways makes hypotheses in biochemical evolution explicit and parsimonious.

  2. Eat, breathe, ROS: controlling stem cell fate through metabolism.

    Science.gov (United States)

    Kubli, Dieter A; Sussman, Mark A

    2017-05-01

    Research reveals cardiac regeneration exists at levels previously deemed unattainable. Clinical trials using stem cells demonstrate promising cardiomyogenic and regenerative potential but insufficient contractile recovery. Incomplete understanding of the biology of administered cells likely contributes to inconsistent patient outcomes. Metabolism is a core component of many well-characterized stem cell types, and metabolic changes fundamentally alter stem cell fate from self-renewal to lineage commitment, and vice versa. However, the metabolism of stem cells currently studied for cardiac regeneration remains incompletely understood. Areas covered: Key metabolic features of stem cells are reviewed and unique stem cell metabolic characteristics are discussed. Metabolic changes altering stem cell fate are considered from quiescence and self-renewal to lineage commitment. Key metabolic concepts are applied toward examining cardiac regeneration through stem cell-based approaches, and clinical implications of current cell therapies are evaluated to identify potential areas of improvement. Expert commentary: The metabolism and biology of stem cells used for cardiac therapy remain poorly characterized. A growing appreciation for the fundamental relationship between stem cell functionality and metabolic phenotype is developing. Future studies unraveling links between cardiac stem cell metabolism and regenerative potential may considerably improve treatment strategies and therapeutic outcomes.

  3. Synthetic biology and regulatory networks: where metabolic systems biology meets control engineering.

    Science.gov (United States)

    He, Fei; Murabito, Ettore; Westerhoff, Hans V

    2016-04-01

    Metabolic pathways can be engineered to maximize the synthesis of various products of interest. With the advent of computational systems biology, this endeavour is usually carried out through in silico theoretical studies with the aim to guide and complement further in vitro and in vivo experimental efforts. Clearly, what counts is the result in vivo, not only in terms of maximal productivity but also robustness against environmental perturbations. Engineering an organism towards an increased production flux, however, often compromises that robustness. In this contribution, we review and investigate how various analytical approaches used in metabolic engineering and synthetic biology are related to concepts developed by systems and control engineering. While trade-offs between production optimality and cellular robustness have already been studied diagnostically and statically, the dynamics also matter. Integration of the dynamic design aspects of control engineering with the more diagnostic aspects of metabolic, hierarchical control and regulation analysis is leading to the new, conceptual and operational framework required for the design of robust and productive dynamic pathways. © 2016 The Author(s).

  4. Proton NMR metabolic profiling of CSF reveals distinct differentiation of meningitis from negative controls.

    Science.gov (United States)

    Chatterji, Tanushri; Singh, Suruchi; Sen, Manodeep; Singh, Ajai Kumar; Agarwal, Gaurav Raj; Singh, Deepak Kumar; Srivastava, Janmejai Kumar; Singh, Alka; Srivastava, Rajeshwar Nath; Roy, Raja

    2017-06-01

    Cerebrospinal fluid (CSF) is an essential bio-fluid of the central nervous system (CNS), playing a vital role in the protection of CNS and performing neuronal function regulation. The chemical composition of CSF varies during onset of meningitis, neurodegenerative disorders (positive controls) and in traumatic cases (negative controls). The study design was broadly categorized into meningitis cases, negative controls and positive controls. Further differentiation among the three groups was carried out using Principal Component Analysis (PCA) followed by supervised Partial Least Square Discriminant Analysis (PLS-DA). The statistical analysis of meningitis vs. negative controls using PLS-DA model resulted in R 2 of 0.97 and Q 2 of 0.85. There was elevation in the levels of ketone bodies, total free amino acids, glutamine, creatine, citrate and choline containing compounds (choline and GPC) in meningitis cases. Similarly, meningitis vs. positive controls resulted in R 2 of 0.80 and Q 2 of 0.60 and showed elevation in the levels of total free amino acids, glutamine, creatine/creatinine and citrate in the meningitis group. Four cases of HIV were identified by PLS-DA model as well as by clinical investigations. On the basis of metabolic profile it was found that negative control CSF samples are more appropriate for differentiation of meningitis than positive control CSF samples. Copyright © 2017 Elsevier B.V. All rights reserved.

  5. PFA toolbox: a MATLAB tool for Metabolic Flux Analysis.

    Science.gov (United States)

    Morales, Yeimy; Bosque, Gabriel; Vehí, Josep; Picó, Jesús; Llaneras, Francisco

    2016-07-11

    Metabolic Flux Analysis (MFA) is a methodology that has been successfully applied to estimate metabolic fluxes in living cells. However, traditional frameworks based on this approach have some limitations, particularly when measurements are scarce and imprecise. This is very common in industrial environments. The PFA Toolbox can be used to face those scenarios. Here we present the PFA (Possibilistic Flux Analysis) Toolbox for MATLAB, which simplifies the use of Interval and Possibilistic Metabolic Flux Analysis. The main features of the PFA Toolbox are the following: (a) It provides reliable MFA estimations in scenarios where only a few fluxes can be measured or those available are imprecise. (b) It provides tools to easily plot the results as interval estimates or flux distributions. (c) It is composed of simple functions that MATLAB users can apply in flexible ways. (d) It includes a Graphical User Interface (GUI), which provides a visual representation of the measurements and their uncertainty. (e) It can use stoichiometric models in COBRA format. In addition, the PFA Toolbox includes a User's Guide with a thorough description of its functions and several examples. The PFA Toolbox for MATLAB is a freely available Toolbox that is able to perform Interval and Possibilistic MFA estimations.

  6. Constraining Genome-Scale Models to Represent the Bow Tie Structure of Metabolism for 13C Metabolic Flux Analysis

    Directory of Open Access Journals (Sweden)

    Tyler W. H. Backman

    2018-01-01

    Full Text Available Determination of internal metabolic fluxes is crucial for fundamental and applied biology because they map how carbon and electrons flow through metabolism to enable cell function. 13 C Metabolic Flux Analysis ( 13 C MFA and Two-Scale 13 C Metabolic Flux Analysis (2S- 13 C MFA are two techniques used to determine such fluxes. Both operate on the simplifying approximation that metabolic flux from peripheral metabolism into central “core” carbon metabolism is minimal, and can be omitted when modeling isotopic labeling in core metabolism. The validity of this “two-scale” or “bow tie” approximation is supported both by the ability to accurately model experimental isotopic labeling data, and by experimentally verified metabolic engineering predictions using these methods. However, the boundaries of core metabolism that satisfy this approximation can vary across species, and across cell culture conditions. Here, we present a set of algorithms that (1 systematically calculate flux bounds for any specified “core” of a genome-scale model so as to satisfy the bow tie approximation and (2 automatically identify an updated set of core reactions that can satisfy this approximation more efficiently. First, we leverage linear programming to simultaneously identify the lowest fluxes from peripheral metabolism into core metabolism compatible with the observed growth rate and extracellular metabolite exchange fluxes. Second, we use Simulated Annealing to identify an updated set of core reactions that allow for a minimum of fluxes into core metabolism to satisfy these experimental constraints. Together, these methods accelerate and automate the identification of a biologically reasonable set of core reactions for use with 13 C MFA or 2S- 13 C MFA, as well as provide for a substantially lower set of flux bounds for fluxes into the core as compared with previous methods. We provide an open source Python implementation of these algorithms at https://github.com/JBEI/limitfluxtocore.

  7. Infection homeostasis: implications for therapeutic and immune programming of metabolism in controlling infection.

    Science.gov (United States)

    Kotzamanis, Konstantinos; Angulo, Ana; Ghazal, Peter

    2015-06-01

    Homeostasis underpins at a systems level the regulatory control of immunity and metabolism. While physiologically these systems are often viewed as independent, there is increasing evidence showing a tight coupling between immune and metabolic functions. Critically upon infection, the homeostatic regulation for both immune and metabolic pathways is altered yet these changes are often investigated in isolation. Here, we summarise our current understanding of these processes in the context of a clinically relevant pathogen, cytomegalovirus. We synthesise from the literature an integrative view of a coupled immune-metabolic infection process, centred on sugar and lipid metabolism. We put forward the notion that understanding immune control of key metabolic enzymatic steps in infection will promote the future development of novel therapeutic modalities based on metabolic modifiers that either enhance protection or inhibit infection.

  8. Presumptive binge eating disorder in type 2 diabetes mellitus patients and its effect in metabolic control

    OpenAIRE

    Sandra Soares Melo; Cíntia Milene Comelli Odorizzi

    2009-01-01

    Objective: This study sought to determine the presence of diagnosis suggestive of binge eating disorder in individuals with type 2 diabetes mellitus, and to evaluate the influence of such disorder on the metabolic control. Methods: sixty-three patients with type 2 diabetes mellitus and registered  at the Diabetes and Hypertension Program of a Health Unit in the town of Balneário Camboriú, Santa Catarina, Brazil, were evaluated. The diagnosis of binge eating disorder was made by analysis of th...

  9. 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 ...

  10. 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 ...

  11. CONCEPT ANALYSIS OF PERCEIVED CONTROL

    Directory of Open Access Journals (Sweden)

    Mardiyono Mardiyono

    2011-07-01

    Full Text Available Background. Perceived control is a personality characteristic that contributes psychological adjustment. It was derived from various theories, so that definitions of perceived control were ambiguous meaning. Disclosing concept of perceived control is required.Objective. The analysis aims to identify definition and use of perceived control, examine the basic attributes of perceived control, and the measurements of perceived control.Method. Databases searched for electronic journals and books that were published from 1994 to 2010 were analyzed.Result. Perceived control is personal belief that refers to controllability on behalf of one’s self and ability to control threats or events. The use of perceived control includes maternal, pediatric, medical, surgical, psychiatric, community nursing, and pain management. Perceived control was composed of two dimensions: belief about controllability and belief about ability to control to threats.Conclusion. Instrument of Anxiety Control Questionnaire most closely corresponds to two dimensions: belief about controllability and ability to control. Defining attributes and dimensions of perceived control are useful for developing tool.Keywords: perceived control, controllability, ability to control, and agency

  12. Finding elementary flux modes in metabolic networks based on flux balance analysis and flux coupling analysis: application to the analysis of Escherichia coli metabolism.

    Science.gov (United States)

    Tabe-Bordbar, Shayan; Marashi, Sayed-Amir

    2013-12-01

    Elementary modes (EMs) are steady-state metabolic flux vectors with minimal set of active reactions. Each EM corresponds to a metabolic pathway. Therefore, studying EMs is helpful for analyzing the production of biotechnologically important metabolites. However, memory requirements for computing EMs may hamper their applicability as, in most genome-scale metabolic models, no EM can be computed due to running out of memory. In this study, we present a method for computing randomly sampled EMs. In this approach, a network reduction algorithm is used for EM computation, which is based on flux balance-based methods. We show that this approach can be used to recover the EMs in the medium- and genome-scale metabolic network models, while the EMs are sampled in an unbiased way. The applicability of such results is shown by computing “estimated” control-effective flux values in Escherichia coli metabolic network.

  13. FluxFix: automatic isotopologue normalization for metabolic tracer analysis.

    Science.gov (United States)

    Trefely, Sophie; Ashwell, Peter; Snyder, Nathaniel W

    2016-11-25

    Isotopic tracer analysis by mass spectrometry is a core technique for the study of metabolism. Isotopically labeled atoms from substrates, such as [ 13 C]-labeled glucose, can be traced by their incorporation over time into specific metabolic products. Mass spectrometry is often used for the detection and differentiation of the isotopologues of each metabolite of interest. For meaningful interpretation, mass spectrometry data from metabolic tracer experiments must be corrected to account for the naturally occurring isotopologue distribution. The calculations required for this correction are time consuming and error prone and existing programs are often platform specific, non-intuitive, commercially licensed and/or limited in accuracy by using theoretical isotopologue distributions, which are prone to artifacts from noise or unresolved interfering signals. Here we present FluxFix ( http://fluxfix.science ), an application freely available on the internet that quickly and reliably transforms signal intensity values into percent mole enrichment for each isotopologue measured. 'Unlabeled' data, representing the measured natural isotopologue distribution for a chosen analyte, is entered by the user. This data is used to generate a correction matrix according to a well-established algorithm. The correction matrix is applied to labeled data, also entered by the user, thus generating the corrected output data. FluxFix is compatible with direct copy and paste from spreadsheet applications including Excel (Microsoft) and Google sheets and automatically adjusts to account for input data dimensions. The program is simple, easy to use, agnostic to the mass spectrometry platform, generalizable to known or unknown metabolites, and can take input data from either a theoretical natural isotopologue distribution or an experimentally measured one. Our freely available web-based calculator, FluxFix ( http://fluxfix.science ), quickly and reliably corrects metabolic tracer data for

  14. Thermodynamic principles governing metabolic operation : inference, analysis, and prediction

    NARCIS (Netherlands)

    Niebel, Bastian

    2015-01-01

    The principles governing metabolic flux are poorly understood. Because diverse organisms show similar metabolic flux patterns, we hypothesized that fundamental thermodynamic constraints might shape cellular metabolism. We developed a constraint-based model for Saccharomyces cerevisiae that included

  15. A structured approach to the study of metabolic control principles in intact and impaired mitochondria.

    Science.gov (United States)

    Huber, Heinrich J; Connolly, Niamh M C; Dussmann, Heiko; Prehn, Jochen H M

    2012-03-01

    We devised an approach to extract control principles of cellular bioenergetics for intact and impaired mitochondria from ODE-based models and applied it to a recently established bioenergetic model of cancer cells. The approach used two methods for varying ODE model parameters to determine those model components that, either alone or in combination with other components, most decisively regulated bioenergetic state variables. We found that, while polarisation of the mitochondrial membrane potential (ΔΨ(m)) and, therefore, the protomotive force were critically determined by respiratory complex I activity in healthy mitochondria, complex III activity was dominant for ΔΨ(m) during conditions of cytochrome-c deficiency. As a further important result, cellular bioenergetics in healthy, ATP-producing mitochondria was regulated by three parameter clusters that describe (1) mitochondrial respiration, (2) ATP production and consumption and (3) coupling of ATP-production and respiration. These parameter clusters resembled metabolic blocks and their intermediaries from top-down control analyses. However, parameter clusters changed significantly when cells changed from low to high ATP levels or when mitochondria were considered to be impaired by loss of cytochrome-c. This change suggests that the assumption of static metabolic blocks by conventional top-down control analyses is not valid under these conditions. Our approach is complementary to both ODE and top-down control analysis approaches and allows a better insight into cellular bioenergetics and its pathological alterations.

  16. Metabolic flux balance analysis and the in silico analysis of Escherichia coli K-12 gene deletions

    Directory of Open Access Journals (Sweden)

    Edwards Jeremy S

    2000-07-01

    Full Text Available Abstract Background Genome sequencing and bioinformatics are producing detailed lists of the molecular components contained in many prokaryotic organisms. From this 'parts catalogue' of a microbial cell, in silico representations of integrated metabolic functions can be constructed and analyzed using flux balance analysis (FBA. FBA is particularly well-suited to study metabolic networks based on genomic, biochemical, and strain specific information. Results Herein, we have utilized FBA to interpret and analyze the metabolic capabilities of Escherichia coli. We have computationally mapped the metabolic capabilities of E. coli using FBA and examined the optimal utilization of the E. coli metabolic pathways as a function of environmental variables. We have used an in silico analysis to identify seven gene products of central metabolism (glycolysis, pentose phosphate pathway, TCA cycle, electron transport system essential for aerobic growth of E. coli on glucose minimal media, and 15 gene products essential for anaerobic growth on glucose minimal media. The in silico tpi-, zwf, and pta- mutant strains were examined in more detail by mapping the capabilities of these in silico isogenic strains. Conclusions We found that computational models of E. coli metabolism based on physicochemical constraints can be used to interpret mutant behavior. These in silica results lead to a further understanding of the complex genotype-phenotype relation. Supplementary information: http://gcrg.ucsd.edu/supplementary_data/DeletionAnalysis/main.htm

  17. Tetrahydrobiopterin (BH4) in PKU: effect on dietary treatment, metabolic control, and quality of life.

    Science.gov (United States)

    Ziesch, B; Weigel, J; Thiele, A; Mütze, U; Rohde, C; Ceglarek, U; Thiery, J; Kiess, W; Beblo, S

    2012-11-01

    Tetrahydrobiopterin (BH(4))-sensitive phenylketonuria (PKU) can be treated with sapropterin dihydrochloride. We studied metabolic control and health-related quality of life (HRQoL) in PKU patients treated with BH(4). Based on the review of neonatal BH(4) test results and mutation analysis in 41 PKU patients, 19 were identified as potentially BH(4)-sensitive (9 females, 10 males, age 4-18 years). We analyzed phenylalanine (phe) concentrations in dried blood samples, nutrition protocols, and HRQoL questionnaires (KINDL(®)) beginning from 1 year before, during the first 42 days, and after 3 months of BH(4) therapy. Eight BH(4)-sensitive patients increased their phe tolerance (629 ± 476 vs. 2131 ± 1084 mg, p = 0.006) while maintaining good metabolic control (phe concentration in dried blood 283 ± 145 vs. 304 ± 136 μM, p = 1.0). Six of them were able to stop dietary protein restriction entirely. BH(4)-sensitive patients had average HRQoL scores that were comparable to age-matched healthy children. There was no improvement in HRQoL scores after replacing classic dietary treatment with BH(4) supply, although personal reports given by the patients and their parents suggest that available questionnaires are inappropriate to detect aspects relevant to inborn metabolic disorders. BH(4) can allow PKU patients to increase their phe consumption significantly or even stop dietary protein restrictions. Unexpectedly, this does not improve HRQoL as assessed with KINDL(®), partly due to high scores even before BH(4) therapy. Specific questionnaires should be developed for inborn metabolic disorders.

  18. Identification of regulatory network hubs that control lipid metabolism in Chlamydomonas reinhardtii.

    Science.gov (United States)

    Gargouri, Mahmoud; Park, Jeong-Jin; Holguin, F Omar; Kim, Min-Jeong; Wang, Hongxia; Deshpande, Rahul R; Shachar-Hill, Yair; Hicks, Leslie M; Gang, David R

    2015-08-01

    Microalgae-based biofuels are promising sources of alternative energy, but improvements throughout the production process are required to establish them as economically feasible. One of the most influential improvements would be a significant increase in lipid yields, which could be achieved by altering the regulation of lipid biosynthesis and accumulation. Chlamydomonas reinhardtii accumulates oil (triacylglycerols, TAG) in response to nitrogen (N) deprivation. Although a few important regulatory genes have been identified that are involved in controlling this process, a global understanding of the larger regulatory network has not been developed. In order to uncover this network in this species, a combined omics (transcriptomic, proteomic and metabolomic) analysis was applied to cells grown in a time course experiment after a shift from N-replete to N-depleted conditions. Changes in transcript and protein levels of 414 predicted transcription factors (TFs) and transcriptional regulators (TRs) were monitored relative to other genes. The TF and TR genes were thus classified by two separate measures: up-regulated versus down-regulated and early response versus late response relative to two phases of polar lipid synthesis (before and after TAG biosynthesis initiation). Lipidomic and primary metabolite profiling generated compound accumulation levels that were integrated with the transcript dataset and TF profiling to produce a transcriptional regulatory network. Evaluation of this proposed regulatory network led to the identification of several regulatory hubs that control many aspects of cellular metabolism, from N assimilation and metabolism, to central metabolism, photosynthesis and lipid metabolism. © The Author 2015. Published by Oxford University Press on behalf of the Society for Experimental Biology.

  19. Comparative genomic reconstruction of transcriptional networks controlling central metabolism in the Shewanella genus

    Directory of Open Access Journals (Sweden)

    Kovaleva Galina

    2011-06-01

    Full Text Available Abstract Background Genome-scale prediction of gene regulation and reconstruction of transcriptional regulatory networks in bacteria is one of the critical tasks of modern genomics. The Shewanella genus is comprised of metabolically versatile gamma-proteobacteria, whose lifestyles and natural environments are substantially different from Escherichia coli and other model bacterial species. The comparative genomics approaches and computational identification of regulatory sites are useful for the in silico reconstruction of transcriptional regulatory networks in bacteria. Results To explore conservation and variations in the Shewanella transcriptional networks we analyzed the repertoire of transcription factors and performed genomics-based reconstruction and comparative analysis of regulons in 16 Shewanella genomes. The inferred regulatory network includes 82 transcription factors and their DNA binding sites, 8 riboswitches and 6 translational attenuators. Forty five regulons were newly inferred from the genome context analysis, whereas others were propagated from previously characterized regulons in the Enterobacteria and Pseudomonas spp.. Multiple variations in regulatory strategies between the Shewanella spp. and E. coli include regulon contraction and expansion (as in the case of PdhR, HexR, FadR, numerous cases of recruiting non-orthologous regulators to control equivalent pathways (e.g. PsrA for fatty acid degradation and, conversely, orthologous regulators to control distinct pathways (e.g. TyrR, ArgR, Crp. Conclusions We tentatively defined the first reference collection of ~100 transcriptional regulons in 16 Shewanella genomes. The resulting regulatory network contains ~600 regulated genes per genome that are mostly involved in metabolism of carbohydrates, amino acids, fatty acids, vitamins, metals, and stress responses. Several reconstructed regulons including NagR for N-acetylglucosamine catabolism were experimentally validated in S

  20. Significance of family and peer support for metabolic control of type 1 diabetes in adolescents

    Directory of Open Access Journals (Sweden)

    Đurović Dušanka

    2009-01-01

    Full Text Available The aim of the paper was to explore the significance of family and peer support for metabolic control of Type 1 diabetes in adolescents. Metabolic control refers to maintenance of acceptable blood glucose level thus diminishing risk for chronic complications. It involves regular insulin shots, measuring blood glucose and keeping diary, as the daily based self-control. Regular visits to endocrinologist and screening for chronic complications are compulsory. The sample comprised 79 adolescents age 10-17 years with diagnose of Type 1 diabetes and properly treated at the institute. The sample was divided in two groups - with good (N=40 and poor (N=39 metabolic control. A criterium for good metabolic control was glycosilated hemoglobin less than 7,6%. Social support was measured by Social Support Scale consisting of two parts - the first for estimation of registered family support (based upon modified Perceived Social Support Family Scale and the second for estimation of registered friends' support (modified Perceived Social Support Friend Scale. Adolescents with good metabolic control referred statistically more significant social support in the family, unlike the group with poor metabolic control. Considering peer social support, there was no statistically significant difference. Positive family history for diabetes also appeared to be directly linked to good metabolic control.

  1. Primary metabolism in Lactobacillus sakei food isolates by proteomic analysis

    Directory of Open Access Journals (Sweden)

    Champomier-Vergès Marie-Christine

    2010-04-01

    Full Text Available Abstract Background Lactobacillus sakei is an important food-associated lactic acid bacterium commonly used as starter culture for industrial meat fermentation, and with great potential as a biopreservative in meat and fish products. Understanding the metabolic mechanisms underlying the growth performance of a strain to be used for food fermentations is important for obtaining high-quality and safe products. Proteomic analysis was used to study the primary metabolism in ten food isolates after growth on glucose and ribose, the main sugars available for L. sakei in meat and fish. Results Proteins, the expression of which varied depending on the carbon source were identified, such as a ribokinase and a D-ribose pyranase directly involved in ribose catabolism, and enzymes involved in the phosphoketolase and glycolytic pathways. Expression of enzymes involved in pyruvate and glycerol/glycerolipid metabolism were also affected by the change of carbon source. Interestingly, a commercial starter culture and a protective culture strain down-regulated the glycolytic pathway more efficiently than the rest of the strains when grown on ribose. The overall two-dimensional gel electrophoresis (2-DE protein expression pattern was similar for the different strains, though distinct differences were seen between the two subspecies (sakei and carnosus, and a variation of about 20% in the number of spots in the 2-DE gels was observed between strains. A strain isolated from fermented fish showed a higher expression of stress related proteins growing on both carbon sources. Conclusions It is obvious from the data obtained in this study that the proteomic approach efficiently identifies differentially expressed proteins caused by the change of carbon source. Despite the basic similarity in the strains metabolic routes when they ferment glucose and ribose, there were also interesting differences. From the application point of view, an understanding of regulatory

  2. Effects of short- and long-term Mediterranean-based dietary treatment on plasma LC-QTOF/MS metabolic profiling of subjects with metabolic syndrome features: The Metabolic Syndrome Reduction in Navarra (RESMENA) randomized controlled trial.

    Science.gov (United States)

    Bondia-Pons, Isabel; Martinez, José Alfredo; de la Iglesia, Rocio; Lopez-Legarrea, Patricia; Poutanen, Kaisa; Hanhineva, Kati; Zulet, Maria de los Ángeles

    2015-04-01

    Adherence to the Mediterranean diet has been associated with a reduced risk of metabolic syndrome (MetS). Metabolomics approach may contribute to identify beneficial associations of metabolic changes affected by Mediterranean diet-based interventions with inflammatory and oxidative-stress markers related to the etiology and development of the MetS. Liquid chromatography coupled to quadrupole-time of flight-MS metabolic profiling was applied to plasma from a 6-month randomized intervention with two sequential periods, a 2-month nutritional-learning intervention period, and a 4-month self-control period, with two energy-restricted diets; the RESMENA diet (based on the Mediterranean dietary pattern) and the Control diet (based on the American Heart Association guidelines), in 72 subjects with a high BMI and at least two features of MetS. The major contributing biomarkers of each sequential period were lipids, mainly phospholipids and lysophospholipids. Dependency network analysis showed a different pattern of associations between metabolic changes and clinical variables after 2 and 6 month of intervention, with a highly interconnected network during the nutritional-learning intervention period of the study. The 2-month RESMENA diet produced significant changes in the plasma metabolic profile of subjects with MetS features. However, at the end of the 6-month study, most of the associations between metabolic and clinical variables disappeared; suggesting that adherence to healthy dietary habits had declined during the self-control period. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  3. Nucleotide Metabolism and its Control in Lactic Acid Bacteria

    DEFF Research Database (Denmark)

    Kilstrup, Mogens; Hammer, Karin; Jensen, Peter Ruhdal

    2005-01-01

    Most metabolic reactions are connected through either their utilization of nucleotides or their utilization of nucleotides or their regulation by these metabolites. In this review the biosynthetic pathways for pyrimidine and purine metabolism in lactic acid bacteria are described including...... the interconversion pathways, the formation of deoxyribonucleotides and the salvage pathways for use of exogenous precursors. The data for the enzymatic and the genetic regulation of these pathways are reviewed, as well as the gene organizations in different lactic acid bacteria. Mutant phenotypes and methods...... for manipulation of nucleotide pools are also discussed. Our aim is to provide an overview of the physiology and genetics of nucleotide metabolism and its regulation that will facilitate the interpretation of data arising from genetics, metabolomics, proteomics, and transcriptomics in lactic acid bacteria....

  4. Cerebral vascular control and metabolism in heat stress

    DEFF Research Database (Denmark)

    Bain, Anthony R; Nybo, Lars; Ainslie, Philip N

    2015-01-01

    This review provides an in-depth update on the impact of heat stress on cerebrovascular functioning. The regulation of cerebral temperature, blood flow, and metabolism are discussed. We further provide an overview of vascular permeability, the neurocognitive changes, and the key clinical implicat......This review provides an in-depth update on the impact of heat stress on cerebrovascular functioning. The regulation of cerebral temperature, blood flow, and metabolism are discussed. We further provide an overview of vascular permeability, the neurocognitive changes, and the key clinical...

  5. 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...

  6. Presumptive binge eating disorder in type 2 diabetes mellitus patients and its effect in metabolic control

    Directory of Open Access Journals (Sweden)

    Sandra Soares Melo

    2009-09-01

    Full Text Available Objective: This study sought to determine the presence of diagnosis suggestive of binge eating disorder in individuals with type 2 diabetes mellitus, and to evaluate the influence of such disorder on the metabolic control. Methods: sixty-three patients with type 2 diabetes mellitus and registered  at the Diabetes and Hypertension Program of a Health Unit in the town of Balneário Camboriú, Santa Catarina, Brazil, were evaluated. The diagnosis of binge eating disorder was made by analysis of the Questionnaire on Eating and Weight Patterms – Revised. For the evaluation of metabolic control, 10 ml of blood was collected, and the serum glucose, glycated hemoglobin, tryglicerides, cholestrol and fractions were determined. Weight and height were determined for evaluation of national nutritional state, according to the body mass index. Rresults: Among the evaluated individuals, 29% presented a diagnosis suggestive of binge eating disorder, with higher prevalence among females. The individuals with diagnosis suggestive of binge eating disorder presented a higher average body mass index value than the group without diagnosis. The serum concentrations of glycated hemoglobin (p = 0.02 and triglicerides (p = 0.03 were statistically higher in the group with diagnosis suggestive of binge eating disorder. Cconclusions: Based on the results of this study, it is possible to conclude that the presence of binge eating disorder in individuals with type 2 diabetes mellitus favors an increase in body weight and has a negative influence on metabolic control, contributing to the early emergence of complications related to the disease.

  7. GAM: a web-service for integrated transcriptional and metabolic network analysis.

    Science.gov (United States)

    Sergushichev, Alexey A; Loboda, Alexander A; Jha, Abhishek K; Vincent, Emma E; Driggers, Edward M; Jones, Russell G; Pearce, Edward J; Artyomov, Maxim N

    2016-07-08

    Novel techniques for high-throughput steady-state metabolomic profiling yield information about changes of nearly thousands of metabolites. Such metabolomic profiles, when analyzed together with transcriptional profiles, can reveal novel insights about underlying biological processes. While a number of conceptual approaches have been developed for data integration, easily accessible tools for integrated analysis of mammalian steady-state metabolomic and transcriptional data are lacking. Here we present GAM ('genes and metabolites'): a web-service for integrated network analysis of transcriptional and steady-state metabolomic data focused on identification of the most changing metabolic subnetworks between two conditions of interest. In the web-service, we have pre-assembled metabolic networks for humans, mice, Arabidopsis and yeast and adapted exact solvers for an optimal subgraph search to work in the context of these metabolic networks. The output is the most regulated metabolic subnetwork of size controlled by false discovery rate parameters. The subnetworks are then visualized online and also can be downloaded in Cytoscape format for subsequent processing. The web-service is available at: https://artyomovlab.wustl.edu/shiny/gam/. © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.

  8. Locomotor Adaptation Improves Balance Control, Multitasking Ability and Reduces the Metabolic Cost of Postural Instability

    Science.gov (United States)

    Bloomberg, J. J.; Peters, B. T.; Mulavara, A. P.; Brady, R. A.; Batson, C. D.; Miller, C. A.; Ploutz-Snyder, R. J.; Guined, J. R.; Buxton, R. E.; Cohen, H. S.

    2011-01-01

    During exploration-class missions, sensorimotor disturbances may lead to disruption in the ability to ambulate and perform functional tasks during the initial introduction to a novel gravitational environment following a landing on a planetary surface. The overall goal of our current project is to develop a sensorimotor adaptability training program to facilitate rapid adaptation to these environments. We have developed a unique training system comprised of a treadmill placed on a motion-base facing a virtual visual scene. It provides an unstable walking surface combined with incongruent visual flow designed to enhance sensorimotor adaptability. Greater metabolic cost incurred during balance instability means more physical work is required during adaptation to new environments possibly affecting crewmembers? ability to perform mission critical tasks during early surface operations on planetary expeditions. The goal of this study was to characterize adaptation to a discordant sensory challenge across a number of performance modalities including locomotor stability, multi-tasking ability and metabolic cost. METHODS: Subjects (n=15) walked (4.0 km/h) on a treadmill for an 8 -minute baseline walking period followed by 20-minutes of walking (4.0 km/h) with support surface motion (0.3 Hz, sinusoidal lateral motion, peak amplitude 25.4 cm) provided by the treadmill/motion-base system. Stride frequency and auditory reaction time were collected as measures of locomotor stability and multi-tasking ability, respectively. Metabolic data (VO2) were collected via a portable metabolic gas analysis system. RESULTS: At the onset of lateral support surface motion, subj ects walking on our treadmill showed an increase in stride frequency and auditory reaction time indicating initial balance and multi-tasking disturbances. During the 20-minute adaptation period, balance control and multi-tasking performance improved. Similarly, throughout the 20-minute adaptation period, VO2 gradually

  9. Bibliometric analysis of Indian Journal of Endocrinology and Metabolism

    Directory of Open Access Journals (Sweden)

    Garima Bhutani

    2013-01-01

    Full Text Available Background: Bibliometric analysis of the journal is a method to assess the research impact or research influence of that journal. This information can also be used to evaluate the influence/performance of a researcher and to provide a comparison between researchers. This work was aimed at performing bibliometric analysis of Indian Journal of Endocrinology and Metabolism (IJEM. Materials and Methods: The publications of year 2011-12 of IJEM were analyzed. Total number of articles published, type of articles, their authorship, and the coverage of various subspecialties was studied. The publications were also classified as Indian or foreign, from endocrine or nonendocrine departments and from academic or nonacademic institutions according to the institution of first author. Results and Conclusions: A total of 10 main issues and 7 supplementary issues were published in IJEM in year 2011 and 2012. These included a total of 605 publications, which depict a dramatic increase in the number of publications in last 2 years as compared to the previous years. Taking collectively, review articles were published in majority. Maximum number of articles was dealing with pancreas and metabolic disorders followed by thyroid. Other endocrine organs were given almost similar importance. Publications were largely originating from endocrine departments and from academic institutions. Although maximum number of articles were from India, but the publications from other countries are also on an increase. Thus, the widespread coverage of this journal suggests that IJEM has begun to represent global face of Indian endocrinology.

  10. Feedback control of polyketide metabolism during tylosin production.

    Science.gov (United States)

    Butler, A R; Flint, S A; Cundliffe, E

    2001-04-01

    Tylosin is produced by Streptomyces fradiae via a combination of polyketide metabolism and synthesis of three deoxyhexose sugars, of which mycaminose is the first to be added to the polyketide aglycone, tylactone (protylonolide). Previously, disruption of the gene (tylMII) encoding attachment of mycaminose to the aglycone unexpectedly abolished accumulation of the latter, raising the possibility of a link between polyketide metabolism and deoxyhexose biosynthesis in S. fradiae. However, at that time, it was not possible to eliminate an alternative explanation, namely, that downstream effects on the expression of other genes, not involved in mycaminose metabolism, might have contributed to this phenomenon. Here, it is shown that disruption of any of the four genes (tylMI--III and tylB) specifically involved in mycaminose biosynthesis elicits a similar response, confirming that production of mycaminosyl-tylactone directly influences polyketide metabolism in S. fradiae. Under similar conditions, when mycaminose biosynthesis was specifically blocked by gene disruption, accumulation of tylactone could be restored by exogenous addition of glycosylated tylosin precursors. Moreover, certain other macrolides, not of the tylosin pathway, were also found to elicit qualitatively similar effects. Comparison of the structures of stimulatory macrolides will facilitate studies of the stimulatory mechanism.

  11. Self-Efficacy, Self-Care, and Metabolic Control in Persons with Type 2, Diet and Exercised Controlled Diabetes

    National Research Council Canada - National Science Library

    Randall, Lisa

    1998-01-01

    .... psychological determinants of self-care and metabolic control must be explored. Self-efficacy (Bandura, 1977) has demonstrated its importance in behavioral modification but has been minimally investigated in diabetes...

  12. Control of alanine metabolism in rat liver by transport processes or cellular metabolism.

    OpenAIRE

    Fafournoux, P; Rémésy, C; Demigné, C

    1983-01-01

    1. Factors governing hepatic utilization of alanine were studied in vivo and in vitro in rats adapted to increasing dietary protein. 2. Hepatic alanine utilization was enhanced 5-fold with a 90%-casein diet, compared with a 13%-casein diet. The increased uptake resulted from enhanced fractional extraction in the presence of high concentrations of alanine in the portal vein. 3. The increase in alanine metabolism on high-protein diets was associated with an increase in alanine aminotransferase ...

  13. Prevalence of metabolic syndrome and metabolic syndrome components in young adults: A pooled analysis

    Directory of Open Access Journals (Sweden)

    Paul B. Nolan

    2017-09-01

    Full Text Available Metabolic syndrome (MetSyn represents a clustering of different metabolic abnormalities. MetSyn prevalence is present in approximately 25% of all adults with increased prevalence in advanced ages. The presence of one component of MetSyn increases the risk of developing MetSyn later in life and likely represents a high lifetime burden of cardiovascular disease risk. Therefore we pooled data from multiple studies to establish the prevalence of MetSyn and MetSyn component prevalence across a broad range of ethnicities. PubMed, SCOPUS and Medline databases were searched to find papers presenting MetSyn and MetSyn component data for 18–30 year olds who were apparently healthy, free of disease, and MetSyn was assessed using either the harmonized, National Cholesterol Education Program Adult Treatment Panel III (NCEP-ATPIII, American Heart Association/National Heart, Blood and Lung Institute (AHA/NHBLI, or International Diabetes Federation (IDF definitions of MetSyn. After reviewing returned articles, 26,609 participants' data from 34 studies were included in the analysis and the data were pooled. MetSyn was present in 4.8–7% of young adults. Atherogenic dyslipidaemia defined as low high density lipoprotein (HDL cholesterol was the most prevalent MetSyn component (26.9–41.2%, followed by elevated blood pressure (16.6–26.6%, abdominal obesity (6.8–23.6%, atherogenic dyslipidaemia defined as raised triglycerides (8.6–15.6%, and raised fasting glucose (2.8–15.4%. These findings highlight that MetSyn is prevalent in young adults. Establishing the reason why low HDL is the most prevalent component may represent an important step in promoting primary prevention of MetSyn and reducing the incidence of subsequent clinical disease.

  14. Hypoglycemia in pregnant women with type 1 diabetes: predictors and role of metabolic control

    DEFF Research Database (Denmark)

    Nielsen, Lene Ringholm; Pedersen-Bjergaard, Ulrik; Thorsteinsson, Birger

    2008-01-01

    In pregnancy with type 1 diabetes, we evaluated occurrence of mild and severe hypoglycemia and analyzed the influence of strict metabolic control, nausea, vomiting, and other potential predictors of occurrence of severe hypoglycemia....

  15. Protocol for quality control in metabolic profiling of biological fluids by U(H)PLC-MS.

    Science.gov (United States)

    Gika, Helen G; Zisi, Chrysostomi; Theodoridis, Georgios; Wilson, Ian D

    2016-01-01

    The process of untargeted metabolic profiling/phenotyping of complex biological matrices, i.e., biological fluids such as blood plasma/serum, saliva, bile, and tissue extracts, provides the analyst with a wide range of challenges. Not the least of these challenges is demonstrating that the acquired data are of "good" quality and provide the basis for more detailed multivariate, and other, statistical analysis necessary to detect, and identify, potential biomarkers that might provide insight into the process under study. Here straightforward and pragmatic "quality control (QC)" procedures are described that allow investigators to monitor the analytical processes employed for global, untargeted, metabolic profiling. The use of this methodology is illustrated with an example from the analysis of human urine where an excel spreadsheet of the preprocessed LC-MS output is provided with embedded macros, calculations and visualization plots that can be used to explore the data. Whilst the use of these procedures is exemplified on human urine samples, this protocol is generally applicable to metabonomic/metabolomic profiling of biofluids, tissue and cell extracts from many sources. Copyright © 2015 Elsevier B.V. All rights reserved.

  16. Analysis of metabolic and gene expression changes after hydrodynamic DNA injection into mouse liver.

    Science.gov (United States)

    Herrero, Maria Jose; Monleon, Daniel; Morales, Jose Manuel; Mata, Manuel; Serna, Eva; Aliño, Salvador Francisco

    2011-01-01

    The hydrodynamic injection in mice tail vein of a plasmid (40 µg DNA) bearing the human α1-antitrypsin gene mediates: a) good liver gene transfer resulting in therapeutic plasma levels of human protein (1 mg/ml, approximately) from days 1-10 after injection; b) low liver injury as demonstrated by a poor and transient increase of aspartate aminotransferase (AST) and alanine transaminase (ALT) in mouse plasma; 3) limited expression and metabolic changes in host liver genes and metabolites as evaluated on days 2 and 10 after injection. Groups of three mice were uninjected (control) or hydrodynamically injected with saline or plasmid DNA and then sacrificed on days 2 and 10 after injection. The results of principal component analysis (PCA) show, both in expression microarray and metabolomic analysis, that changes between control and hydrodynamically injected groups are not dramatic and tend to normalize after 10 d. The differences are even smaller between DNA and saline hydrodynamically injected mice. Hydrodynamic injection induces a complex but limited gene expression and metabolic change which includes variations in molecules related to energy metabolism and stress response. The results contribute to support that hydrodynamic method is a safe procedure of liver gene transfer but the long-term effect of hydrodynamic gene transfer procedure, remains to be studied.

  17. Subcubic Control Flow Analysis Algorithms

    DEFF Research Database (Denmark)

    Midtgaard, Jan; Van Horn, David

    We give the first direct subcubic algorithm for performing control flow analysis of higher-order functional programs. Despite the long held belief that inclusion-based flow analysis could not surpass the ``cubic bottleneck, '' we apply known set compression techniques to obtain an algorithm...... that runs in time O(n^3/log n) on a unit cost random-access memory model machine. Moreover, we refine the initial flow analysis into two more precise analyses incorporating notions of reachability. We give subcubic algorithms for these more precise analyses and relate them to an existing analysis from...

  18. Control of Hepatic Glucose Metabolism by the Oral Hypoglycemic Sulfonylureas

    Science.gov (United States)

    1984-05-11

    observed were specific for the hypo- glycemic sulfonylureas and could not be extended to Include other para-substltuted sulfonamides. The inhibition...tolbutamide in glucose-free medium (Kaldor and Pogasta, 1960). In vivo measurements in dogs (Shambye and Tarding, 1957) and man (Recant and Fischer, 1957) of...accepted as the most appropriate model for the study of hepatic carbohydrate metabolism. 2) The evaluation of ̂ vitro potencies of the sulfonylureas in

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

    Indian Academy of Sciences (India)

    Here, we analyse a genome-scale metabolic model of rice leaf using Flux Balance Analysis to investigate whether it has potential metabolic flexibility to increase the biosynthesis of any of the biomass components. We initially simulate the metabolic responses under an objective to maximize the biomass components.

  20. Metabolic syndrome and atypical antipsychotics: Possibility of prediction and control.

    Science.gov (United States)

    Franch Pato, Clara M; Molina Rodríguez, Vicente; Franch Valverde, Juan I

    Schizophrenia and other psychotic disorders are associated with high morbidity and mortality, due to inherent health factors, genetic factors, and factors related to psychopharmacological treatment. Antipsychotics, like other drugs, have side-effects that can substantially affect the physical health of patients, with substantive differences in the side-effect profile and in the patients in which these side-effects occur. To understand and identify these risk groups could help to prevent the occurrence of the undesired effects. A prospective study, with 24 months follow-up, was conducted in order to analyse the physical health of severe mental patients under maintenance treatment with atypical antipsychotics, as well as to determine any predictive parameters at anthropometric and/or analytical level for good/bad outcome of metabolic syndrome in these patients. There were no significant changes in the physical and biochemical parameters individually analysed throughout the different visits. The baseline abdominal circumference (lambda Wilks P=.013) and baseline HDL-cholesterol levels (lambda Wilks P=.000) were the parameters that seem to be more relevant above the rest of the metabolic syndrome constituents diagnosis criteria as predictors in the long-term. In the search for predictive factors of metabolic syndrome, HDL-cholesterol and abdominal circumference at the time of inclusion were selected, as such that the worst the baseline results were, the higher probability of long-term improvement. Copyright © 2016 SEP y SEPB. Publicado por Elsevier España, S.L.U. All rights reserved.

  1. Metabolic control of circulation. Effects of iodoacetate and fluoroacetate.

    Science.gov (United States)

    Liang, C S

    1977-01-01

    The circulatory effects of selective metabolic inhibition of glycolysis and of the tricarboxylic acid cycle by iodoacetate and fluoroacetate were studied in intact chloralose-anesthetized dogs. Pulmonary arterial blood pressure and vascular resistance increased after administration of both inhibitors, but neither systemic hemodynamics nor myocardial contractility changed significantly. Coronary blood flow did not change after iodoacetate administration but increased four- to five-fold after fluoroacetate. Administration of normal saline had no effect on any of the parameters. The changes in pulmonary arterial blood pressure and coronary blood flow after fluoroacetate were not mediated via the autonomic nerves or adrenergic neurohumors because they still occurred after autonomic nervous system inhibition. Neither myocardial oxygen consumption nor left ventricular work changed. A selective increase in myocardial blood flow also occurred in conscious dogs after fluoroacetate administration; hepatic artery flow was reduced, but other organ flows did not change significantly. These results indicate that pulmonary pressor and coronary dilator effects may be produced in intact dogs by selective metabolic blockade, in the absence of reduced oxygen supply or impairment in the electron transport system. These results also suggest that the increases in pulmonary arterial blood pressure, coronary blood flow, and cardiac output that occur during hypoxia probably are related to separate metabolic events in the tissue. PMID:874090

  2. Metabolic Control and Academic Achievement over Time among Adolescents with Type 1 Diabetes

    Science.gov (United States)

    Winnick, Joel B.; Berg, Cynthia A.; Wiebe, Deborah J.; Schaefer, Barbara A.; Lei, Pui-Wa; Butner, Jonathan E.

    2017-01-01

    The relation between metabolic control (HbA1c) and achievement (grade point average [GPA]) was examined over a period of 2.5 years (every 6 months) employing a dynamical systems approach that allowed for the examination of whether HbA1c was associated with change in subsequent GPA and vice versa. Metabolic control tends to deteriorate (i.e., with…

  3. Small RNA-dependent expression of secondary metabolism is controlled by Krebs cycle function in Pseudomonas fluorescens.

    Science.gov (United States)

    Takeuchi, Kasumi; Kiefer, Patrick; Reimmann, Cornelia; Keel, Christoph; Dubuis, Christophe; Rolli, Joëlle; Vorholt, Julia A; Haas, Dieter

    2009-12-11

    Pseudomonas fluorescens CHA0, an antagonist of phytopathogenic fungi in the rhizosphere of crop plants, elaborates and excretes several secondary metabolites with antibiotic properties. Their synthesis depends on three small RNAs (RsmX, RsmY, and RsmZ), whose expression is positively controlled by the GacS-GacA two-component system at high cell population densities. To find regulatory links between primary and secondary metabolism in P. fluorescens and in the related species Pseudomonas aeruginosa, we searched for null mutations that affected central carbon metabolism as well as the expression of rsmY-gfp and rsmZ-gfp reporter constructs but without slowing down the growth rate in rich media. Mutation in the pycAB genes (for pyruvate carboxylase) led to down-regulation of rsmXYZ and secondary metabolism, whereas mutation in fumA (for a fumarase isoenzyme) resulted in up-regulation of the three small RNAs and secondary metabolism in the absence of detectable nutrient limitation. These effects required the GacS sensor kinase but not the accessory sensors RetS and LadS. An analysis of intracellular metabolites in P. fluorescens revealed a strong positive correlation between small RNA expression and the pools of 2-oxoglutarate, succinate, and fumarate. We conclude that Krebs cycle intermediates (already known to control GacA-dependent virulence factors in P. aeruginosa) exert a critical trigger function in secondary metabolism via the expression of GacA-dependent small RNAs.

  4. Metagenomic analysis revealed highly diverse microbial arsenic metabolism genes in paddy soils with low-arsenic contents

    International Nuclear Information System (INIS)

    Xiao, Ke-Qing; Li, Li-Guan; Ma, Li-Ping; Zhang, Si-Yu; Bao, Peng; Zhang, Tong; Zhu, Yong-Guan

    2016-01-01

    Microbe-mediated arsenic (As) metabolism plays a critical role in global As cycle, and As metabolism involves different types of genes encoding proteins facilitating its biotransformation and transportation processes. Here, we used metagenomic analysis based on high-throughput sequencing and constructed As metabolism protein databases to analyze As metabolism genes in five paddy soils with low-As contents. The results showed that highly diverse As metabolism genes were present in these paddy soils, with varied abundances and distribution for different types and subtypes of these genes. Arsenate reduction genes (ars) dominated in all soil samples, and significant correlation existed between the abundance of arr (arsenate respiration), aio (arsenite oxidation), and arsM (arsenite methylation) genes, indicating the co-existence and close-relation of different As resistance systems of microbes in wetland environments similar to these paddy soils after long-term evolution. Among all soil parameters, pH was an important factor controlling the distribution of As metabolism gene in five paddy soils (p = 0.018). To the best of our knowledge, this is the first study using high-throughput sequencing and metagenomics approach in characterizing As metabolism genes in the five paddy soil, showing their great potential in As biotransformation, and therefore in mitigating arsenic risk to humans. - Highlights: • Use metagenomics to analyze As metabolism genes in paddy soils with low-As content. • These genes were ubiquitous, abundant, and associated with diverse microbes. • pH as an important factor controlling their distribution in paddy soil. • Imply combinational effect of evolution and selection on As metabolism genes. - Metagenomics was used to analyze As metabolism genes in paddy soils with low-As contents. These genes were ubiquitous, abundant, and associated with diverse microbes.

  5. "Slave" metabolites and enzymes. A rapid way of delineating metabolic control.

    NARCIS (Netherlands)

    Teusink, B.; Westerhoff, H.V.

    2000-01-01

    Although control of fluxes and concentrations tends to be distributed rather than confined to a single rate-limiting enzyme, the extent of control can differ widely between enzymes in a metabolic network. In some cases, there are enzymes that lack control completely. This paper identifies one

  6. Metabolic flux analysis of the halophilic archaeon Haladaptatus paucihalophilus

    International Nuclear Information System (INIS)

    Liu, Guangxiu; Zhang, Manxiao; Mo, Tianlu; He, Lian; Zhang, Wei; Yu, Yi; Zhang, Qi; Ding, Wei

    2015-01-01

    This work reports the 13 C-assisted metabolic flux analysis of Haladaptatus paucihalophilus, a halophilic archaeon possessing an intriguing osmoadaption mechanism. We showed that the carbon flow is through the oxidative tricarboxylic acid (TCA) cycle whereas the reductive TCA cycle is not operative in H. paucihalophilus. In addition, both threonine and the citramalate pathways contribute to isoleucine biosynthesis, whereas lysine is synthesized through the diaminopimelate pathway and not through the α-aminoadipate pathway. Unexpected, the labeling patterns of glycine from the cells grown on [1- 13 C]pyruvate and [2- 13 C]pyruvate suggest that, unlike all the organisms investigated so far, in which glycine is produced exclusively from the serine hydroxymethyltransferase (SHMT) pathway, glycine biosynthesis in H. paucihalophilus involves different pathways including SHMT, threonine aldolase (TA) and the reverse reaction of glycine cleavage system (GCS), demonstrating for the first time that other pathways instead of SHMT can also make a significant contribution to the cellular glycine pool. Transcriptional analysis confirmed that both TA and GCS genes were transcribed in H. paucihalophilus, and the transcriptional level is independent of salt concentrations in the culture media. This study expands our understanding of amino acid biosynthesis and provides valuable insights into the metabolism of halophilic archaea. - Highlights: • Serine hydroxymethyltransferase, threonine aldolase, and glycine cleavage system all contribute to the glycine pool of H. paucihalophilus. • Threonine and the citramalate pathways contribute equally to the isoleucine biosynthesis in H. paucihalophilus. • Lysine in H. paucihalophilus is synthesized through the diaminopimelate pathway and not through the α-aminoadipate pathway. • Glycine biosynthesis is likely unrelated to the cell osmoadaption mechanism.

  7. Metabolic flux analysis of the halophilic archaeon Haladaptatus paucihalophilus

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Guangxiu; Zhang, Manxiao [Key Laboratory of Desert and Desertification, Cold and Arid Regions Environmental and Engineering Research Institute, Chinese Academy of Sciences, Lanzhou, 730000 (China); Key Laboratory of Extreme Environmental Microbial Resources and Engineering, Gansu Province, Lanzhou, 730000 (China); Mo, Tianlu [Department of Chemistry, Fudan University, Shanghai, 200433 (China); He, Lian [Key Laboratory of Combinatory Biosynthesis and Drug Discovery (Ministry of Education), School of Pharmaceutical Sciences, Wuhan University, Wuhan, 430071 (China); Zhang, Wei [Key Laboratory of Desert and Desertification, Cold and Arid Regions Environmental and Engineering Research Institute, Chinese Academy of Sciences, Lanzhou, 730000 (China); Key Laboratory of Extreme Environmental Microbial Resources and Engineering, Gansu Province, Lanzhou, 730000 (China); Yu, Yi, E-mail: yu_yi@whu.edu.cn [Key Laboratory of Combinatory Biosynthesis and Drug Discovery (Ministry of Education), School of Pharmaceutical Sciences, Wuhan University, Wuhan, 430071 (China); Zhang, Qi, E-mail: qizhang@sioc.ac.cn [Department of Chemistry, Fudan University, Shanghai, 200433 (China); Ding, Wei, E-mail: dingw@lzu.edu.cn [Key Laboratory of Desert and Desertification, Cold and Arid Regions Environmental and Engineering Research Institute, Chinese Academy of Sciences, Lanzhou, 730000 (China); Key Laboratory of Extreme Environmental Microbial Resources and Engineering, Gansu Province, Lanzhou, 730000 (China); Department of Chemistry, Fudan University, Shanghai, 200433 (China)

    2015-11-27

    This work reports the {sup 13}C-assisted metabolic flux analysis of Haladaptatus paucihalophilus, a halophilic archaeon possessing an intriguing osmoadaption mechanism. We showed that the carbon flow is through the oxidative tricarboxylic acid (TCA) cycle whereas the reductive TCA cycle is not operative in H. paucihalophilus. In addition, both threonine and the citramalate pathways contribute to isoleucine biosynthesis, whereas lysine is synthesized through the diaminopimelate pathway and not through the α-aminoadipate pathway. Unexpected, the labeling patterns of glycine from the cells grown on [1-{sup 13}C]pyruvate and [2-{sup 13}C]pyruvate suggest that, unlike all the organisms investigated so far, in which glycine is produced exclusively from the serine hydroxymethyltransferase (SHMT) pathway, glycine biosynthesis in H. paucihalophilus involves different pathways including SHMT, threonine aldolase (TA) and the reverse reaction of glycine cleavage system (GCS), demonstrating for the first time that other pathways instead of SHMT can also make a significant contribution to the cellular glycine pool. Transcriptional analysis confirmed that both TA and GCS genes were transcribed in H. paucihalophilus, and the transcriptional level is independent of salt concentrations in the culture media. This study expands our understanding of amino acid biosynthesis and provides valuable insights into the metabolism of halophilic archaea. - Highlights: • Serine hydroxymethyltransferase, threonine aldolase, and glycine cleavage system all contribute to the glycine pool of H. paucihalophilus. • Threonine and the citramalate pathways contribute equally to the isoleucine biosynthesis in H. paucihalophilus. • Lysine in H. paucihalophilus is synthesized through the diaminopimelate pathway and not through the α-aminoadipate pathway. • Glycine biosynthesis is likely unrelated to the cell osmoadaption mechanism.

  8. Systematic identification and analysis of frequent gene fusion events in metabolic pathways.

    Science.gov (United States)

    Henry, Christopher S; Lerma-Ortiz, Claudia; Gerdes, Svetlana Y; Mullen, Jeffrey D; Colasanti, Ric; Zhukov, Aleksey; Frelin, Océane; Thiaville, Jennifer J; Zallot, Rémi; Niehaus, Thomas D; Hasnain, Ghulam; Conrad, Neal; Hanson, Andrew D; de Crécy-Lagard, Valérie

    2016-06-24

    Gene fusions are the most powerful type of in silico-derived functional associations. However, many fusion compilations were made when fusions need updating to handle the current avalanche of sequenced genomes. The availability of a large fusion dataset would help probe functional associations and enable systematic analysis of where and why fusion events occur. Here we present a systematic analysis of fusions in prokaryotes. We manually generated two training sets: (i) 121 fusions in the model organism Escherichia coli; (ii) 131 fusions found in B vitamin metabolism. These sets were used to develop a fusion prediction algorithm that captured the training set fusions with only 7 % false negatives and 50 % false positives, a substantial improvement over existing approaches. This algorithm was then applied to identify 3.8 million potential fusions across 11,473 genomes. The results of the analysis are available in a searchable database at http://modelseed.org/projects/fusions/ . A functional analysis identified 3,000 reactions associated with frequent fusion events and revealed areas of metabolism where fusions are particularly prevalent. Customary definitions of fusions were shown to be ambiguous, and a stricter one was proposed. Exploring the genes participating in fusion events showed that they most commonly encode transporters, regulators, and metabolic enzymes. The major rationales for fusions between metabolic genes appear to be overcoming pathway bottlenecks, avoiding toxicity, controlling competing pathways, and facilitating expression and assembly of protein complexes. Finally, our fusion dataset provides powerful clues to decipher the biological activities of domains of unknown function.

  9. Improving fatty acids production by engineering dynamic pathway regulation and metabolic control

    Science.gov (United States)

    Xu, Peng; Li, Lingyun; Zhang, Fuming; Stephanopoulos, Gregory; Koffas, Mattheos

    2014-01-01

    Global energy demand and environmental concerns have stimulated increasing efforts to produce carbon-neutral fuels directly from renewable resources. Microbially derived aliphatic hydrocarbons, the petroleum-replica fuels, have emerged as promising alternatives to meet this goal. However, engineering metabolic pathways with high productivity and yield requires dynamic redistribution of cellular resources and optimal control of pathway expression. Here we report a genetically encoded metabolic switch that enables dynamic regulation of fatty acids (FA) biosynthesis in Escherichia coli. The engineered strains were able to dynamically compensate the critical enzymes involved in the supply and consumption of malonyl-CoA and efficiently redirect carbon flux toward FA biosynthesis. Implementation of this metabolic control resulted in an oscillatory malonyl-CoA pattern and a balanced metabolism between cell growth and product formation, yielding 15.7- and 2.1-fold improvement in FA titer compared with the wild-type strain and the strain carrying the uncontrolled metabolic pathway. This study provides a new paradigm in metabolic engineering to control and optimize metabolic pathways facilitating the high-yield production of other malonyl-CoA–derived compounds. PMID:25049420

  10. Impact of probiotics in women with gestational diabetes mellitus on metabolic health: a randomized controlled trial.

    Science.gov (United States)

    Lindsay, Karen L; Brennan, Lorraine; Kennelly, Maria A; Maguire, Orla C; Smith, Thomas; Curran, Sinead; Coffey, Mary; Foley, Michael E; Hatunic, Mensud; Shanahan, Fergus; McAuliffe, Fionnuala M

    2015-04-01

    Probiotics are live microorganisms that may confer health benefits on the host. Recent trials of probiotic use among healthy pregnant women demonstrate potential for improved glycemic control. The aim of this study was to investigate the effects of a probiotic capsule intervention on maternal metabolic parameters and pregnancy outcome among women with gestational diabetes. This double-blind placebo-controlled randomized trial recruited pregnant women with a new diagnosis of gestational diabetes or impaired glucose tolerance following a 3-hour 100-g glucose tolerance test. Women were randomized to a daily probiotic (Lactobacillus salivarius UCC118) or placebo capsule from diagnosis until delivery. Fasting blood samples were collected at baseline and 4-6 weeks after capsule commencement for analysis of glucose, insulin, c-peptide, and lipids. The primary outcome was difference in fasting glucose postintervention, first analyzed on an intention-to-treat basis and followed by per-protocol analysis that excluded women commenced on pharmacological therapy (insulin or metformin). Secondary outcomes were changes in insulin, c-peptide, homeostasis model assessment and lipids, requirement for pharmacological therapy, and neonatal anthropometry. Of 149 women recruited and randomized, there were no differences between the probiotic and placebo groups in postintervention fasting glucose (4.65 ± 0.49 vs 4.65 ± 0.53 mmol/L; P = 373), requirement for pharmacological therapy (17% vs 14%; P = .643), or birthweight (3.57 ± 0.64 vs 3.60 ± 0.57 kg; P = .845). Among 100 women managed with diet and exercise alone, fasting plasma glucose decreased significantly within both the probiotic (4.76 ± 0.45 to 4.57 ± 0.42 mmol/L; P probiotic vs the placebo group (+0.27 ± 0.48 vs +0.50 ± 0.52 mmol/L total cholesterol, P = .031; +0.08 ± 0.51 vs +0.31 ± 0.45 mmol/L LDL cholesterol, P = .011). No differences were noted between groups in other metabolic parameters or pregnancy

  11. APOE-by-sex interactions on brain structure and metabolism in healthy elderly controls.

    Science.gov (United States)

    Sampedro, Frederic; Vilaplana, Eduard; de Leon, Mony J; Alcolea, Daniel; Pegueroles, Jordi; Montal, Victor; Carmona-Iragui, María; Sala, Isabel; Sánchez-Saudinos, María-Belén; Antón-Aguirre, Sofía; Morenas-Rodríguez, Estrella; Camacho, Valle; Falcón, Carles; Pavía, Javier; Ros, Domènec; Clarimón, Jordi; Blesa, Rafael; Lleó, Alberto; Fortea, Juan

    2015-09-29

    The APOE effect on Alzheimer Disease (AD) risk is stronger in women than in men but its mechanisms have not been established. We assessed the APOE-by-sex interaction on core CSF biomarkers, brain metabolism and structure in healthy elderly control individuals (HC). Cross-sectional study. HC from the Alzheimer's Disease Neuroimaging Initiative with available CSF (n = 274) and/or 3T-MRI (n = 168) and/or a FDG-PET analyses (n = 328) were selected. CSF amyloid-β1-42 (Aβ1-42), total-tau (t-tau) and phospho-tau (p-tau181p) levels were measured by Luminex assays. We analyzed the APOE-by-sex interaction on the CSF biomarkers in an analysis of covariance (ANCOVA). FDG uptake was analyzed by SPM8 and cortical thickness (CTh) was measured by FreeSurfer. FDG and CTh difference maps were derived from interaction and group analyses. APOE4 carriers had lower CSF Aβ1-42 and higher CSF p-tau181p values than non-carriers, but there was no APOE-by-sex interaction on CSF biomarkers. The APOE-by-sex interaction on brain metabolism and brain structure was significant. Sex stratification showed that female APOE4 carriers presented widespread brain hypometabolism and cortical thinning compared to female non-carriers whereas male APOE4 carriers showed only a small cluster of hypometabolism and regions of cortical thickening compared to male non-carriers. The impact of APOE4 on brain metabolism and structure is modified by sex. Female APOE4 carriers show greater hypometabolism and atrophy than male carriers. This APOE-by-sex interaction should be considered in clinical trials in preclinical AD where APOE4 status is a selection criterion.

  12. Reduced Metabolism in Brain 'Control Networks' Following Cocaine-Cues Exposure in Female Cocaine Abusers

    International Nuclear Information System (INIS)

    Volkow, N.D.; Tomasi, D.; Wang, G.-J.; Fowler, J.S.; Telang, F.; Goldstein, R.Z.; Alia-Klein, N.; Wong, C.T.

    2011-01-01

    Gender differences in vulnerability for cocaine addiction have been reported. Though the mechanisms are not understood, here we hypothesize that gender differences in reactivity to conditioned-cues, which contributes to relapse, are involved. To test this we compared brain metabolism (using PET and 18 FDG) between female (n = 10) and male (n = 16) active cocaine abusers when they watched a neutral video (nature scenes) versus a cocaine-cues video. Self-reports of craving increased with the cocaine-cue video but responses did not differ between genders. In contrast, changes in whole brain metabolism with cocaine-cues differed by gender (p<0.05); females significantly decreased metabolism (-8.6% ± 10) whereas males tended to increase it (+5.5% ± 18). SPM analysis (Cocaine-cues vs Neutral) in females revealed decreases in frontal, cingulate and parietal cortices, thalamus and midbrain (p<0.001) whereas males showed increases in right inferior frontal gyrus (BA 44/45) (only at p<0.005). The gender-cue interaction showed greater decrements with Cocaine-cues in females than males (p<0.001) in frontal (BA 8, 9, 10), anterior cingulate (BA 24, 32), posterior cingulate (BA 23, 31), inferior parietal (BA 40) and thalamus (dorsomedial nucleus). Females showed greater brain reactivity to cocaine-cues than males but no differences in craving, suggesting that there may be gender differences in response to cues that are not linked with craving but could affect subsequent drug use. Specifically deactivation of brain regions from 'control networks' (prefrontal, cingulate, inferior parietal, thalamus) in females could increase their vulnerability to relapse since it would interfere with executive function (cognitive inhibition). This highlights the importance of gender tailored interventions for cocaine addiction.

  13. Reduced metabolism in brain "control networks" following cocaine-cues exposure in female cocaine abusers.

    Directory of Open Access Journals (Sweden)

    Nora D Volkow

    2011-02-01

    Full Text Available Gender differences in vulnerability for cocaine addiction have been reported. Though the mechanisms are not understood, here we hypothesize that gender differences in reactivity to conditioned-cues, which contributes to relapse, are involved.To test this we compared brain metabolism (using PET and ¹⁸FDG between female (n = 10 and male (n = 16 active cocaine abusers when they watched a neutral video (nature scenes versus a cocaine-cues video.Self-reports of craving increased with the cocaine-cue video but responses did not differ between genders. In contrast, changes in whole brain metabolism with cocaine-cues differed by gender (p<0.05; females significantly decreased metabolism (-8.6%±10 whereas males tended to increase it (+5.5%±18. SPM analysis (Cocaine-cues vs Neutral in females revealed decreases in frontal, cingulate and parietal cortices, thalamus and midbrain (p<0.001 whereas males showed increases in right inferior frontal gyrus (BA 44/45 (only at p<0.005. The gender-cue interaction showed greater decrements with Cocaine-cues in females than males (p<0.001 in frontal (BA 8, 9, 10, anterior cingulate (BA 24, 32, posterior cingulate (BA 23, 31, inferior parietal (BA 40 and thalamus (dorsomedial nucleus.Females showed greater brain reactivity to cocaine-cues than males but no differences in craving, suggesting that there may be gender differences in response to cues that are not linked with craving but could affect subsequent drug use. Specifically deactivation of brain regions from "control networks" (prefrontal, cingulate, inferior parietal, thalamus in females could increase their vulnerability to relapse since it would interfere with executive function (cognitive inhibition. This highlights the importance of gender tailored interventions for cocaine addiction.

  14. Pseudotemporal Ordering of Single Cells Reveals Metabolic Control of Postnatal β Cell Proliferation.

    Science.gov (United States)

    Zeng, Chun; Mulas, Francesca; Sui, Yinghui; Guan, Tiffany; Miller, Nathanael; Tan, Yuliang; Liu, Fenfen; Jin, Wen; Carrano, Andrea C; Huising, Mark O; Shirihai, Orian S; Yeo, Gene W; Sander, Maike

    2017-05-02

    Pancreatic β cell mass for appropriate blood glucose control is established during early postnatal life. β cell proliferative capacity declines postnatally, but the extrinsic cues and intracellular signals that cause this decline remain unknown. To obtain a high-resolution map of β cell transcriptome dynamics after birth, we generated single-cell RNA-seq data of β cells from multiple postnatal time points and ordered cells based on transcriptional similarity using a new analytical tool. This analysis captured signatures of immature, proliferative β cells and established high expression of amino acid metabolic, mitochondrial, and Srf/Jun/Fos transcription factor genes as their hallmark feature. Experimental validation revealed high metabolic activity in immature β cells and a role for reactive oxygen species and Srf/Jun/Fos transcription factors in driving postnatal β cell proliferation and mass expansion. Our work provides the first high-resolution molecular characterization of state changes in postnatal β cells and paves the way for the identification of novel therapeutic targets to stimulate β cell regeneration. Copyright © 2017 Elsevier Inc. All rights reserved.

  15. Proteomic analysis of the metabolic adaptation of the biocontrol agent Pseudozyma flocculosa leading to glycolipid production

    Directory of Open Access Journals (Sweden)

    Bélanger Richard R

    2010-02-01

    Full Text Available Abstract The yeast-like epiphytic fungus Pseudozyma flocculosa is known to antagonize powdery mildew fungi through proliferation on colonies presumably preceded by the release of an antifungal glycolipid (flocculosin. In culture conditions, P. flocculosa can be induced to produce or not flocculosin through manipulation of the culture medium nutrients. In order to characterize and understand the metabolic changes in P. flocculosa linked to glycolipid production, we conducted a 2-DE proteomic analysis and compared the proteomic profile of P. flocculosa growing under conditions favoring the development of the fungus (control or conducive to flocculosin synthesis (stress. A large number of protein spots (771 were detected in protein extracts of the control treatment compared to only 435 matched protein spots in extracts of the stress cultures, which clearly suggests an important metabolic reorganization in slow-growing cells producing flocculosin. From the latter treatment, we were able to identify 21 protein spots that were either specific to the treatment or up-regulated significantly (2-fold increase. All of them were identified based on similarity between predicted ORF of the newly sequenced genome of P. flocculosa with Ustilago maydis' available annotated sequences. These proteins were associated with the carbon and fatty acid metabolism, and also with the filamentous change of the fungus leading to flocculosin production. This first look into the proteome of P. flocculosa suggests that flocculosin synthesis is elicited in response to specific stress or limiting conditions.

  16. The post-transcriptional regulatory system CSR controls the balance of metabolic pools in upper glycolysis of Escherichia coli.

    Science.gov (United States)

    Morin, Manon; Ropers, Delphine; Letisse, Fabien; Laguerre, Sandrine; Portais, Jean-Charles; Cocaign-Bousquet, Muriel; Enjalbert, Brice

    2016-05-01

    Metabolic control in Escherichia coli is a complex process involving multilevel regulatory systems but the involvement of post-transcriptional regulation is uncertain. The post-transcriptional factor CsrA is stated as being the only regulator essential for the use of glycolytic substrates. A dozen enzymes in the central carbon metabolism (CCM) have been reported as potentially controlled by CsrA, but its impact on the CCM functioning has not been demonstrated. Here, a multiscale analysis was performed in a wild-type strain and its isogenic mutant attenuated for CsrA (including growth parameters, gene expression levels, metabolite pools, abundance of enzymes and fluxes). Data integration and regulation analysis showed a coordinated control of the expression of glycolytic enzymes. This also revealed the imbalance of metabolite pools in the csrA mutant upper glycolysis, before the phosphofructokinase PfkA step. This imbalance is associated with a glucose-phosphate stress. Restoring PfkA activity in the csrA mutant strain suppressed this stress and increased the mutant growth rate on glucose. Thus, the carbon storage regulator system is essential for the effective functioning of the upper glycolysis mainly through its control of PfkA. This work demonstrates the pivotal role of post-transcriptional regulation to shape the carbon metabolism. © 2016 John Wiley & Sons Ltd.

  17. NF-κB controls energy homeostasis and metabolic adaptation by upregulating mitochondrial respiration.

    Science.gov (United States)

    Mauro, Claudio; Leow, Shi Chi; Anso, Elena; Rocha, Sonia; Thotakura, Anil K; Tornatore, Laura; Moretti, Marta; De Smaele, Enrico; Beg, Amer A; Tergaonkar, Vinay; Chandel, Navdeep S; Franzoso, Guido

    2011-08-28

    Cell proliferation is a metabolically demanding process. It requires active reprogramming of cellular bioenergetic pathways towards glucose metabolism to support anabolic growth. NF-κB/Rel transcription factors coordinate many of the signals that drive proliferation during immunity, inflammation and oncogenesis, but whether NF-κB regulates the metabolic reprogramming required for cell division during these processes is unknown. Here, we report that NF-κB organizes energy metabolism networks by controlling the balance between the utilization of glycolysis and mitochondrial respiration. NF-κB inhibition causes cellular reprogramming to aerobic glycolysis under basal conditions and induces necrosis on glucose starvation. The metabolic reorganization that results from NF-κB inhibition overcomes the requirement for tumour suppressor mutation in oncogenic transformation and impairs metabolic adaptation in cancer in vivo. This NF-κB-dependent metabolic pathway involves stimulation of oxidative phosphorylation through upregulation of mitochondrial synthesis of cytochrome c oxidase 2 (SCO2; ref. ). Our findings identify NF-κB as a physiological regulator of mitochondrial respiration and establish a role for NF-κB in metabolic adaptation in normal cells and cancer.

  18. 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.

  19. Review of metabolic pathways activated in cancer cells as determined through isotopic labeling and network analysis.

    Science.gov (United States)

    Dong, Wentao; Keibler, Mark A; Stephanopoulos, Gregory

    2017-09-01

    Cancer metabolism has emerged as an indispensable part of contemporary cancer research. During the past 10 years, the use of stable isotopic tracers and network analysis have unveiled a number of metabolic pathways activated in cancer cells. Here, we review such pathways along with the particular tracers and labeling observations that led to the discovery of their rewiring in cancer cells. The list of such pathways comprises the reductive metabolism of glutamine, altered glycolysis, serine and glycine metabolism, mutant isocitrate dehydrogenase (IDH) induced reprogramming and the onset of acetate metabolism. Additionally, we demonstrate the critical role of isotopic labeling and network analysis in identifying these pathways. The alterations described in this review do not constitute a complete list, and future research using these powerful tools is likely to discover other cancer-related pathways and new metabolic targets for cancer therapy. Copyright © 2017 International Metabolic Engineering Society. Published by Elsevier Inc. All rights reserved.

  20. Mammalian iron metabolism and its control by iron regulatory proteins☆

    Science.gov (United States)

    Anderson, Cole P.; Shen, Lacy; Eisenstein, Richard S.; Leibold, Elizabeth A.

    2013-01-01

    Cellular iron homeostasis is maintained by iron regulatory proteins 1 and 2 (IRP1 and IRP2). IRPs bind to iron-responsive elements (IREs) located in the untranslated regions of mRNAs encoding protein involved in iron uptake, storage, utilization and export. Over the past decade, significant progress has been made in understanding how IRPs are regulated by iron-dependent and iron-independent mechanisms and the pathological consequences of IRP2 deficiency in mice. The identification of novel IREs involved in diverse cellular pathways has revealed that the IRP–IRE network extends to processes other than iron homeostasis. A mechanistic understanding of IRP regulation will likely yield important insights into the basis of disorders of iron metabolism. This article is part of a Special Issue entitled: Cell Biology of Metals. PMID:22610083

  1. Metabolic Control of Tobacco Pollination by Sugars and Invertases1

    Science.gov (United States)

    Goetz, Marc; Hirsche, Jörg; Bauerfeind, Martin Andreas; González, María-Cruz; Hyun, Tae Kyung; Eom, Seung Hee; Chriqui, Dominique; Engelke, Thomas; Großkinsky, Dominik K.; Roitsch, Thomas

    2017-01-01

    Pollination in flowering plants is initiated by germination of pollen grains on stigmas followed by fast growth of pollen tubes representing highly energy-consuming processes. The symplastic isolation of pollen grains and tubes requires import of Suc available in the apoplast. We show that the functional coupling of Suc cleavage by invertases and uptake of the released hexoses by monosaccharide transporters are critical for pollination in tobacco (Nicotiana tabacum). Transcript profiling, in situ hybridization, and immunolocalization of extracellular invertases and two monosaccharide transporters in vitro and in vivo support the functional coupling in supplying carbohydrates for pollen germination and tube growth evidenced by spatiotemporally coordinated expression. Detection of vacuolar invertases in maternal tissues by these approaches revealed metabolic cross talk between male and female tissues and supported the requirement for carbohydrate supply in transmitting tissue during pollination. Tissue-specific expression of an invertase inhibitor and addition of the chemical invertase inhibitor miglitol strongly reduced extracellular invertase activity and impaired pollen germination. Measurements of (competitive) uptake of labeled sugars identified two import pathways for exogenously available Suc into the germinating pollen operating in parallel: direct Suc uptake and via the hexoses after cleavage by extracellular invertase. Reduction of extracellular invertase activity in pollen decreases Suc uptake and severely compromises pollen germination. We further demonstrate that Glc as sole carbon source is sufficient for pollen germination, whereas Suc is supporting tube growth, revealing an important regulatory role of both the invertase substrate and products contributing to a potential metabolic and signaling-based multilayer regulation of pollination by carbohydrates. PMID:27923989

  2. Metabolic Control of Tobacco Pollination by Sugars and Invertases.

    Science.gov (United States)

    Goetz, Marc; Guivarćh, Anne; Hirsche, Jörg; Bauerfeind, Martin Andreas; González, María-Cruz; Hyun, Tae Kyung; Eom, Seung Hee; Chriqui, Dominique; Engelke, Thomas; Großkinsky, Dominik K; Roitsch, Thomas

    2017-02-01

    Pollination in flowering plants is initiated by germination of pollen grains on stigmas followed by fast growth of pollen tubes representing highly energy-consuming processes. The symplastic isolation of pollen grains and tubes requires import of Suc available in the apoplast. We show that the functional coupling of Suc cleavage by invertases and uptake of the released hexoses by monosaccharide transporters are critical for pollination in tobacco (Nicotiana tabacum). Transcript profiling, in situ hybridization, and immunolocalization of extracellular invertases and two monosaccharide transporters in vitro and in vivo support the functional coupling in supplying carbohydrates for pollen germination and tube growth evidenced by spatiotemporally coordinated expression. Detection of vacuolar invertases in maternal tissues by these approaches revealed metabolic cross talk between male and female tissues and supported the requirement for carbohydrate supply in transmitting tissue during pollination. Tissue-specific expression of an invertase inhibitor and addition of the chemical invertase inhibitor miglitol strongly reduced extracellular invertase activity and impaired pollen germination. Measurements of (competitive) uptake of labeled sugars identified two import pathways for exogenously available Suc into the germinating pollen operating in parallel: direct Suc uptake and via the hexoses after cleavage by extracellular invertase. Reduction of extracellular invertase activity in pollen decreases Suc uptake and severely compromises pollen germination. We further demonstrate that Glc as sole carbon source is sufficient for pollen germination, whereas Suc is supporting tube growth, revealing an important regulatory role of both the invertase substrate and products contributing to a potential metabolic and signaling-based multilayer regulation of pollination by carbohydrates. © 2017 American Society of Plant Biologists. All Rights Reserved.

  3. Integrated analysis of transcript-level regulation of metabolism reveals disease-relevant nodes of the human metabolic network.

    Science.gov (United States)

    Galhardo, Mafalda; Sinkkonen, Lasse; Berninger, Philipp; Lin, Jake; Sauter, Thomas; Heinäniemi, Merja

    2014-02-01

    Metabolic diseases and comorbidities represent an ever-growing epidemic where multiple cell types impact tissue homeostasis. Here, the link between the metabolic and gene regulatory networks was studied through experimental and computational analysis. Integrating gene regulation data with a human metabolic network prompted the establishment of an open-sourced web portal, IDARE (Integrated Data Nodes of Regulation), for visualizing various gene-related data in context of metabolic pathways. Motivated by increasing availability of deep sequencing studies, we obtained ChIP-seq data from widely studied human umbilical vein endothelial cells. Interestingly, we found that association of metabolic genes with multiple transcription factors (TFs) enriched disease-associated genes. To demonstrate further extensions enabled by examining these networks together, constraint-based modeling was applied to data from human preadipocyte differentiation. In parallel, data on gene expression, genome-wide ChIP-seq profiles for peroxisome proliferator-activated receptor (PPAR) γ, CCAAT/enhancer binding protein (CEBP) α, liver X receptor (LXR) and H3K4me3 and microRNA target identification for miR-27a, miR-29a and miR-222 were collected. Disease-relevant key nodes, including mitochondrial glycerol-3-phosphate acyltransferase (GPAM), were exposed from metabolic pathways predicted to change activity by focusing on association with multiple regulators. In both cell types, our analysis reveals the convergence of microRNAs and TFs within the branched chain amino acid (BCAA) metabolic pathway, possibly providing an explanation for its downregulation in obese and diabetic conditions.

  4. Metabolic cancer biology: structural-based analysis of cancer as a metabolic disease, new sights and opportunities for disease treatment.

    Science.gov (United States)

    Masoudi-Nejad, Ali; Asgari, Yazdan

    2015-02-01

    The cancer cell metabolism or the Warburg effect discovery goes back to 1924 when, for the first time Otto Warburg observed, in contrast to the normal cells, cancer cells have different metabolism. With the initiation of high throughput technologies and computational systems biology, cancer cell metabolism renaissances and many attempts were performed to revise the Warburg effect. The development of experimental and analytical tools which generate high-throughput biological data including lots of information could lead to application of computational models in biological discovery and clinical medicine especially for cancer. Due to the recent availability of tissue-specific reconstructed models, new opportunities in studying metabolic alteration in various kinds of cancers open up. Structural approaches at genome-scale levels seem to be suitable for developing diagnostic and prognostic molecular signatures, as well as in identifying new drug targets. In this review, we have considered these recent advances in structural-based analysis of cancer as a metabolic disease view. Two different structural approaches have been described here: topological and constraint-based methods. The ultimate goal of this type of systems analysis is not only the discovery of novel drug targets but also the development of new systems-based therapy strategies. Copyright © 2014 Elsevier Ltd. All rights reserved.

  5. Metagenomic analysis revealed highly diverse microbial arsenic metabolism genes in paddy soils with low-arsenic contents.

    Science.gov (United States)

    Xiao, Ke-Qing; Li, Li-Guan; Ma, Li-Ping; Zhang, Si-Yu; Bao, Peng; Zhang, Tong; Zhu, Yong-Guan

    2016-04-01

    Microbe-mediated arsenic (As) metabolism plays a critical role in global As cycle, and As metabolism involves different types of genes encoding proteins facilitating its biotransformation and transportation processes. Here, we used metagenomic analysis based on high-throughput sequencing and constructed As metabolism protein databases to analyze As metabolism genes in five paddy soils with low-As contents. The results showed that highly diverse As metabolism genes were present in these paddy soils, with varied abundances and distribution for different types and subtypes of these genes. Arsenate reduction genes (ars) dominated in all soil samples, and significant correlation existed between the abundance of arr (arsenate respiration), aio (arsenite oxidation), and arsM (arsenite methylation) genes, indicating the co-existence and close-relation of different As resistance systems of microbes in wetland environments similar to these paddy soils after long-term evolution. Among all soil parameters, pH was an important factor controlling the distribution of As metabolism gene in five paddy soils (p = 0.018). To the best of our knowledge, this is the first study using high-throughput sequencing and metagenomics approach in characterizing As metabolism genes in the five paddy soil, showing their great potential in As biotransformation, and therefore in mitigating arsenic risk to humans. Copyright © 2015 Elsevier Ltd. All rights reserved.

  6. Comparative Analysis of Yeast Metabolic Network Models Highlights Progress, Opportunities for Metabolic Reconstruction.

    Directory of Open Access Journals (Sweden)

    Benjamin D Heavner

    2015-11-01

    Full Text Available We have compared 12 genome-scale models of the Saccharomyces cerevisiae metabolic network published since 2003 to evaluate progress in reconstruction of the yeast metabolic network. We compared the genomic coverage, overlap of annotated metabolites, predictive ability for single gene essentiality with a selection of model parameters, and biomass production predictions in simulated nutrient-limited conditions. We have also compared pairwise gene knockout essentiality predictions for 10 of these models. We found that varying approaches to model scope and annotation reflected the involvement of multiple research groups in model development; that single-gene essentiality predictions were affected by simulated medium, objective function, and the reference list of essential genes; and that predictive ability for single-gene essentiality did not correlate well with predictive ability for our reference list of synthetic lethal gene interactions (R = 0.159. We conclude that the reconstruction of the yeast metabolic network is indeed gradually improving through the iterative process of model development, and there remains great opportunity for advancing our understanding of biology through continued efforts to reconstruct the full biochemical reaction network that constitutes yeast metabolism. Additionally, we suggest that there is opportunity for refining the process of deriving a metabolic model from a metabolic network reconstruction to facilitate mechanistic investigation and discovery. This comparative study lays the groundwork for developing improved tools and formalized methods to quantitatively assess metabolic network reconstructions independently of any particular model application, which will facilitate ongoing efforts to advance our understanding of the relationship between genotype and cellular phenotype.

  7. Expression analysis in response to drought stress in soybean: Shedding light on the regulation of metabolic pathway genes.

    Science.gov (United States)

    Guimarães-Dias, Fábia; Neves-Borges, Anna Cristina; Viana, Antonio Americo Barbosa; Mesquita, Rosilene Oliveira; Romano, Eduardo; de Fátima Grossi-de-Sá, Maria; Nepomuceno, Alexandre Lima; Loureiro, Marcelo Ehlers; Alves-Ferreira, Márcio

    2012-06-01

    Metabolomics analysis of wild type Arabidopsis thaliana plants, under control and drought stress conditions revealed several metabolic pathways that are induced under water deficit. The metabolic response to drought stress is also associated with ABA dependent and independent pathways, allowing a better understanding of the molecular mechanisms in this model plant. Through combining an in silico approach and gene expression analysis by quantitative real-time PCR, the present work aims at identifying genes of soybean metabolic pathways potentially associated with water deficit. Digital expression patterns of Arabidopsis genes, which were selected based on the basis of literature reports, were evaluated under drought stress condition by Genevestigator. Genes that showed strong induction under drought stress were selected and used as bait to identify orthologs in the soybean genome. This allowed us to select 354 genes of putative soybean orthologs of 79 Arabidopsis genes belonging to 38 distinct metabolic pathways. The expression pattern of the selected genes was verified in the subtractive libraries available in the GENOSOJA project. Subsequently, 13 genes from different metabolic pathways were selected for validation by qPCR experiments. The expression of six genes was validated in plants undergoing drought stress in both pot-based and hydroponic cultivation systems. The results suggest that the metabolic response to drought stress is conserved in Arabidopsis and soybean plants.

  8. Hormone regulation of rhizome development in tall fescue (Festuca arundinacea) associated with proteomic changes controlling respiratory and amino acid metabolism.

    Science.gov (United States)

    Ma, Xiqing; Xu, Qian; Meyer, William A; Huang, Bingru

    2016-09-01

    Rhizomes are underground stems with meristematic tissues capable of generating shoots and roots. However, mechanisms controlling rhizome formation and growth are yet to be completely understood. The objectives of this study were to investigate whether rhizome development could be regulated by cytokinins (CKs) and gibberellic acids (GAs), and determine underlying mechanisms of regulation of rhizome formation and growth of tall fescue (Festuca arundinacea) by a CK or GA through proteomic and transcript analysis. A rhizomatous genotype of tall fescue ('BR') plants were treated with 6-benzylaminopurine (BAP, a synthetic cytokinin) or GA3 in hydroponic culture in growth chambers. Furthermore, comparative proteomic analysis of two-dimensional electrophoresis and mass spectrometry were performed to investigate proteins and associated metabolic pathways imparting increased rhizome number by BAP and rhizome elongation by GA3 KEY RESULTS: BAP stimulated rhizome formation while GA3 promoted rhizome elongation. Proteomic analysis identified 76 differentially expressed proteins (DEPs) due to BAP treatment and 37 DEPs due to GA3 treatment. Cytokinin-related genes and cell division-related genes were upregulated in the rhizome node by BAP and gibberellin-related and cell growth-related genes in the rhizome by GA3 CONCLUSIONS: Most of the BAP- or GA-responsive DEPs were involved in respiratory metabolism and amino acid metabolism. Transcription analysis demonstrated that genes involved in hormone metabolism, signalling pathways, cell division and cell-wall loosening were upregulated by BAP or GA3 The CK and GA promoted rhizome formation and growth, respectively, by activating metabolic pathways that supply energy and amino acids to support cell division and expansion during rhizome initiation and elongation in tall fescue. © The Author 2016. Published by Oxford University Press on behalf of the Annals of Botany Company. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  9. Analysis of requirements for teaching materials based on the course bioinformatics for plant metabolism

    Science.gov (United States)

    Balqis, Widodo, Lukiati, Betty; Amin, Mohamad

    2017-05-01

    A way to improve the quality of learning in the course of Plant Metabolism in the Department of Biology, State University of Malang, is to develop teaching materials. This research evaluates the needs of bioinformatics-based teaching material in the course Plant Metabolism by the Analyze, Design, Develop, Implement, and Evaluate (ADDIE) development model. Data were collected through questionnaires distributed to the students in the Plant Metabolism course of the Department of Biology, University of Malang, and analysis of the plan of lectures semester (RPS). Learning gains of this course show that it is not yet integrated into the field of bioinformatics. All respondents stated that plant metabolism books do not include bioinformatics and fail to explain the metabolism of a chemical compound of a local plant in Indonesia. Respondents thought that bioinformatics can explain examples and metabolism of a secondary metabolite analysis techniques and discuss potential medicinal compounds from local plants. As many as 65% of the respondents said that the existing metabolism book could not be used to understand secondary metabolism in lectures of plant metabolism. Therefore, the development of teaching materials including plant metabolism-based bioinformatics is important to improve the understanding of the lecture material in plant metabolism.

  10. 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.

  11. Dietary iron controls circadian hepatic glucose metabolism through heme synthesis.

    Science.gov (United States)

    Simcox, Judith A; Mitchell, Thomas Creighton; Gao, Yan; Just, Steven F; Cooksey, Robert; Cox, James; Ajioka, Richard; Jones, Deborah; Lee, Soh-Hyun; King, Daniel; Huang, Jingyu; McClain, Donald A

    2015-04-01

    The circadian rhythm of the liver maintains glucose homeostasis, and disruption of this rhythm is associated with type 2 diabetes. Feeding is one factor that sets the circadian clock in peripheral tissues, but relatively little is known about the role of specific dietary components in that regard. We assessed the effects of dietary iron on circadian gluconeogenesis. Dietary iron affects circadian glucose metabolism through heme-mediated regulation of the interaction of nuclear receptor subfamily 1 group d member 1 (Rev-Erbα) with its cosuppressor nuclear receptor corepressor 1 (NCOR). Loss of regulated heme synthesis was achieved by aminolevulinic acid (ALA) treatment of mice or cultured cells to bypass the rate-limiting enzyme in hepatic heme synthesis, ALA synthase 1 (ALAS1). ALA treatment abolishes differences in hepatic glucose production and in the expression of gluconeogenic enzymes seen with variation of dietary iron. The differences among diets are also lost with inhibition of heme synthesis with isonicotinylhydrazine. Dietary iron modulates levels of peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α), a transcriptional activator of ALAS1, to affect hepatic heme. Treatment of mice with the antioxidant N-acetylcysteine diminishes PGC-1α variation observed among the iron diets, suggesting that iron is acting through reactive oxygen species signaling. © 2015 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

  12. Metabolic reconstruction of sulfur assimilation in the extremophile Acidithiobacillus ferrooxidans based on genome analysis

    Directory of Open Access Journals (Sweden)

    Jedlicki Eugenia

    2003-12-01

    Full Text Available Abstract Background Acidithiobacillus ferrooxidans is a gamma-proteobacterium that lives at pH2 and obtains energy by the oxidation of sulfur and iron. It is used in the biomining industry for the recovery of metals and is one of the causative agents of acid mine drainage. Effective tools for the study of its genetics and physiology are not in widespread use and, despite considerable effort, an understanding of its unusual physiology remains at a rudimentary level. Nearly complete genome sequences of A. ferrooxidans are available from two public sources and we have exploited this information to reconstruct aspects of its sulfur metabolism. Results Two candidate mechanisms for sulfate uptake from the environment were detected but both belong to large paralogous families of membrane transporters and their identification remains tentative. Prospective genes, pathways and regulatory mechanisms were identified that are likely to be involved in the assimilation of sulfate into cysteine and in the formation of Fe-S centers. Genes and regulatory networks were also uncovered that may link sulfur assimilation with nitrogen fixation, hydrogen utilization and sulfur reduction. Potential pathways were identified for sulfation of extracellular metabolites that may possibly be involved in cellular attachment to pyrite, sulfur and other solid substrates. Conclusions A bioinformatic analysis of the genome sequence of A. ferrooxidans has revealed candidate genes, metabolic process and control mechanisms potentially involved in aspects of sulfur metabolism. Metabolic modeling provides an important preliminary step in understanding the unusual physiology of this extremophile especially given the severe difficulties involved in its genetic manipulation and biochemical analysis.

  13. Metabolic reconstruction of sulfur assimilation in the extremophile Acidithiobacillus ferrooxidans based on genome analysis

    Science.gov (United States)

    Valdés, Jorge; Veloso, Felipe; Jedlicki, Eugenia; Holmes, David

    2003-01-01

    Background Acidithiobacillus ferrooxidans is a gamma-proteobacterium that lives at pH2 and obtains energy by the oxidation of sulfur and iron. It is used in the biomining industry for the recovery of metals and is one of the causative agents of acid mine drainage. Effective tools for the study of its genetics and physiology are not in widespread use and, despite considerable effort, an understanding of its unusual physiology remains at a rudimentary level. Nearly complete genome sequences of A. ferrooxidans are available from two public sources and we have exploited this information to reconstruct aspects of its sulfur metabolism. Results Two candidate mechanisms for sulfate uptake from the environment were detected but both belong to large paralogous families of membrane transporters and their identification remains tentative. Prospective genes, pathways and regulatory mechanisms were identified that are likely to be involved in the assimilation of sulfate into cysteine and in the formation of Fe-S centers. Genes and regulatory networks were also uncovered that may link sulfur assimilation with nitrogen fixation, hydrogen utilization and sulfur reduction. Potential pathways were identified for sulfation of extracellular metabolites that may possibly be involved in cellular attachment to pyrite, sulfur and other solid substrates. Conclusions A bioinformatic analysis of the genome sequence of A. ferrooxidans has revealed candidate genes, metabolic process and control mechanisms potentially involved in aspects of sulfur metabolism. Metabolic modeling provides an important preliminary step in understanding the unusual physiology of this extremophile especially given the severe difficulties involved in its genetic manipulation and biochemical analysis. PMID:14675496

  14. 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...

  15. [The effect of initial periodontal therapy on metabolic control in type 2 diabetes mellitus].

    Science.gov (United States)

    Shen, Chi-Jing; Yin, Yuan-Zheng; Shu, Rong

    2008-02-01

    To investigate the effect of periodontal initial therapy on metabolic control in type 2 diabetes mellitus patients with chronic periodontitis. Thirty type 2 diabetic patients with chronic periodontitis were selected as experimental group, 30 patients with chronic periodontitis were selected as control group. Their gingival index(GI), probing depth(PD), clinical attachment level(CAL), fasting plasma glucose(FPG), glycated hemoglobin A1c(HbA1c), total cholesterol(TC) and triglyceride(TG) were evaluated using SAS 6.12 software package for multiple linear regression analysis before treatment(as base) and 1, 3 month(s) after periodontal initial therapy. In both two groups, a significant improvement of periodontal index was found after periodontal initial therapy (P0.05), and FPG, HbA1c in fairly-controlled diabetic patients were reduced significantly(P0.05). The result of periodontal initial therapy in the type 2 diabetic patients with chronic periodontitis is significant in short time. It can reduce the level of FPG and HbA1c. Supported by National Key Science and Technology Project from "Tenth Five Year Plan" (Grant No.2004BA720A26).

  16. Integrated omics analysis of specialized metabolism in medicinal plants.

    Science.gov (United States)

    Rai, Amit; Saito, Kazuki; Yamazaki, Mami

    2017-05-01

    Medicinal plants are a rich source of highly diverse specialized metabolites with important pharmacological properties. Until recently, plant biologists were limited in their ability to explore the biosynthetic pathways of these metabolites, mainly due to the scarcity of plant genomics resources. However, recent advances in high-throughput large-scale analytical methods have enabled plant biologists to discover biosynthetic pathways for important plant-based medicinal metabolites. The reduced cost of generating omics datasets and the development of computational tools for their analysis and integration have led to the elucidation of biosynthetic pathways of several bioactive metabolites of plant origin. These discoveries have inspired synthetic biology approaches to develop microbial systems to produce bioactive metabolites originating from plants, an alternative sustainable source of medicinally important chemicals. Since the demand for medicinal compounds are increasing with the world's population, understanding the complete biosynthesis of specialized metabolites becomes important to identify or develop reliable sources in the future. Here, we review the contributions of major omics approaches and their integration to our understanding of the biosynthetic pathways of bioactive metabolites. We briefly discuss different approaches for integrating omics datasets to extract biologically relevant knowledge and the application of omics datasets in the construction and reconstruction of metabolic models. © 2017 The Authors The Plant Journal © 2017 John Wiley & Sons Ltd.

  17. Investigation of Biological Soil Crusts Metabolic Webs Using Exometabolomic Analysis

    Science.gov (United States)

    Northen, T.; Karaoz, U.; Jenkins, S.; Lau, R.; Bowen, B.; Cadillo-Quiroz, H.; Garcia-Pichel, F.; Brodie, E.; Richard, B.

    2014-12-01

    Desert biological soil crusts are simple cyanobacteria-dominated surface soil microbial communities found in areas with infrequent wetting, often extreme temperatures, low coverage of vascular plants and constitute the world's largest biofilm. They exist for extended periods in a desiccated dormant state, yet rapidly re-boot metabolism within minutes of wetting. These soil microbial communities are highly dependent on filamentous cyanobacteria such as Microcoleus vaginatusto stabilize the soil and to act as primary producers for the community through the release carbon sources to feed a diversity of heterotrophs. Exometabolomic analysis was performed using liquid chromatography coupled to tandem mass spectrometry on biological soil crust pore water and spent media of key soil bacterial isolates. Comparison of spent vs. fresh media was used to determine uptake or release of metabolites by specific microbes. To link pore water experiments with isolate studies, metabolite extracts of authentic soil were used as supplements for isolate exometabolomic profiling. Our soil metabolomics methods detected hundreds of metabolites from soils including may novel compounds. Only a small set of which being targeted by all isolates. Beyond these few metabolites, the individual bacteria examined showed specialization towards specific metabolites. Surprisingly, many of the most abundant oligosaccharides and other metabolites were ignored by these isolates. The observed specialization of biological soil crust bacteria may play a significant role in determining community structure.

  18. Community health orientation of Indian Journal of Endocrinology and Metabolism: A bibliometric analysis of Indian Journal of Endocrinology and Metabolism

    Directory of Open Access Journals (Sweden)

    Kanica Kaushal

    2015-01-01

    Full Text Available Background: Endocrine and metabolic diseases especially diabetes have become focus areas for public health professionals. Indian Journal of Endocrinology and Metabolism (IJEM, a publication of Endocrine Society of India, is a peer-reviewed online journal, which covers technical and clinical studies related to health, ethical and social issues in field of diabetes, endocrinology and metabolism. This bibliometric analysis assesses the journal from a community health perspective. Materials and Methods: Every article published in IJEM over a period of 4 years (2011-2014 was accessed to review coverage of community health in the field of endocrinology. Results: Seven editorials, 30 review articles, 41 original articles, 12 brief communications, 20 letter to editors, 4 articles on guidelines and 2 in the section "endocrinology and gender" directly or indirectly dealt with community health aspects of endocrinology. Together these amounted to 17% of all articles published through these 4 years. There were 14 articles on general, 60 pertaining to pancreas and diabetes, 10 on thyroid, 7 on pituitary/adrenal/gonads, 21 on obesity and metabolism and 4 on parathyroid and bone; all community medicine related. Conclusion: Community health is an integral part of the modern endocrinology diabetology and metabolism practice and it received adequate journal space during the last 4 years. The coverage is broad based involving all the major endocrine disorders.

  19. Diabetes in children and adolescents from ethnic minorities: barriers to education, treatment and good metabolic control

    DEFF Research Database (Denmark)

    Povlsen, Lene; Olsen, Birthe; Ladelund, Steen

    2005-01-01

    AIM: This paper reports an investigation to establish whether metabolic control is different in children and adolescents from ethnic minorities with type 1 diabetes compared with young Danish patients, and to learn about factors affecting their opportunities to achieve good metabolic control....... BACKGROUND: The prevalence of diabetes in children and adolescents from ethnic minorities in Denmark is increasing. Having a different ethnic background has frequently been described as a risk factor for poor metabolic control, but whether the risk is represented by the ethnicity and immigration itself...... or in combination with other factors is unclear. METHODS: The study included data (gender, age, diabetes duration HbA(1c), number of incidents of severe hypoglycaemia and ketoacidosis) from a national register including 919 Danish and 58 children and adolescents from ethnic minorities, questionnaires to all 20...

  20. Metabolic Control and Illness Perceptions in Adolescents with Type 1 Diabetes.

    Science.gov (United States)

    Wisting, Line; Bang, Lasse; Natvig, Henrik; Skrivarhaug, Torild; Dahl-Jørgensen, Knut; Lask, Bryan; Rø, Øyvind

    2016-01-01

    Disturbed eating behavior and psychosocial variables have been found to influence metabolic control, but little is known about how these variables interact or how they influence metabolic control, separately and combined. To explore associations between metabolic control (measured by HbA1c) and eating disorder psychopathology, coping strategies, illness perceptions, and insulin beliefs in adolescents with type 1 diabetes. A total of 105 patients (41.9% males) with type 1 diabetes (12-20 years) were interviewed with the Child Eating Disorder Examination. In addition, self-report psychosocial questionnaires were completed. Clinical data, including HbA1c, was obtained from the Norwegian Childhood Diabetes Registry. Significant gender differences were demonstrated. Among females, HbA1c correlated significantly with eating restriction (.29, p diabetes.

  1. [Path analysis of lifestyle habits to the metabolic syndrome].

    Science.gov (United States)

    Zhu, Zhen-xin; Zhang, Cheng-qi; Tang, Fang; Song, Xin-hong; Xue, Fu-zhong

    2013-04-01

    To evaluate the relationship between lifestyle habits and the components of metabolic syndrome (MS). Based on the routine health check-up system in a certain Center for Health Management of Shandong Province, a longitudinal surveillance health check-up cohort from 2005 to 2010 was set up. There were 13 225 urban workers in Jinan included in the analysis. The content of the survey included demographic information, medical history, lifestyle habits, body mass index (BMI) and the level of blood pressure, fasting blood-glucose, and blood lipid, etc. The distribution of BMI, blood pressure, fasting blood-glucose, blood lipid and lifestyle habits between MS patients and non-MS population was compared, latent variables were extracted by exploratory factor analysis to determine the structure model, and then a partial least squares path model was constructed between lifestyle habits and the components of MS. Participants'age was (46.62 ± 12.16) years old. The overall prevalence of the MS was 22.43% (2967/13 225), 26.49% (2535/9570) in males and 11.82% (432/3655) in females. The prevalence of the MS was statistically different between males and females (χ(2) = 327.08, P vegetarian, mixed and animal food was 23.39% (694/2967), 42.50% (1261/2967) and 34.11% (1012/2967) respectively, while in non-MS population was 30.80% (3159/10 258), 46.37% (4757/10 258), 22.83% (2342/10 258) respectively. Their alcohol consumption has statistical difference (χ(2) = 374.22, P Unhealthy lifestyle habits are closely related to MS. Meat diet, excessive drinking and smoking are risk factors for MS.

  2. Relative Quantitative Proteomic Analysis of Brucella abortus Reveals Metabolic Adaptation to Multiple Environmental Stresses

    Science.gov (United States)

    Zai, Xiaodong; Yang, Qiaoling; Yin, Ying; Li, Ruihua; Qian, Mengying; Zhao, Taoran; Li, Yaohui; Zhang, Jun; Fu, Ling; Xu, Junjie; Chen, Wei

    2017-01-01

    Brucella spp. are facultative intracellular pathogens that cause chronic brucellosis in humans and animals. The virulence of Brucella primarily depends on its successful survival and replication in host cells. During invasion of the host tissue, Brucella is simultaneously subjected to a variety of harsh conditions, including nutrient limitation, low pH, antimicrobial defenses, and extreme levels of reactive oxygen species (ROS) via the host immune response. This suggests that Brucella may be able to regulate its metabolic adaptation in response to the distinct stresses encountered during its intracellular infection of the host. An investigation into the differential proteome expression patterns of Brucella grown under the relevant stress conditions may contribute toward a better understanding of its pathogenesis and adaptive response. Here, we utilized a mass spectrometry-based label-free relative quantitative proteomics approach to investigate and compare global proteomic changes in B. abortus in response to eight different stress treatments. The 3 h short-term in vitro single-stress and multi-stress conditions mimicked the in vivo conditions of B. abortus under intracellular infection, with survival rates ranging from 3.17 to 73.17%. The proteomic analysis identified and quantified a total of 2,272 proteins and 74% of the theoretical proteome, thereby providing wide coverage of the B. abortus proteome. By including eight distinct growth conditions and comparing these with a control condition, we identified a total of 1,221 differentially expressed proteins (DEPs) that were significantly changed under the stress treatments. Pathway analysis revealed that most of the proteins were involved in oxidative phosphorylation, ABC transporters, two-component systems, biosynthesis of secondary metabolites, the citrate cycle, thiamine metabolism, and nitrogen metabolism; constituting major response mechanisms toward the reconstruction of cellular homeostasis and metabolic

  3. Relative Quantitative Proteomic Analysis of Brucella abortus Reveals Metabolic Adaptation to Multiple Environmental Stresses.

    Science.gov (United States)

    Zai, Xiaodong; Yang, Qiaoling; Yin, Ying; Li, Ruihua; Qian, Mengying; Zhao, Taoran; Li, Yaohui; Zhang, Jun; Fu, Ling; Xu, Junjie; Chen, Wei

    2017-01-01

    Brucella spp. are facultative intracellular pathogens that cause chronic brucellosis in humans and animals. The virulence of Brucella primarily depends on its successful survival and replication in host cells. During invasion of the host tissue, Brucella is simultaneously subjected to a variety of harsh conditions, including nutrient limitation, low pH, antimicrobial defenses, and extreme levels of reactive oxygen species (ROS) via the host immune response. This suggests that Brucella may be able to regulate its metabolic adaptation in response to the distinct stresses encountered during its intracellular infection of the host. An investigation into the differential proteome expression patterns of Brucella grown under the relevant stress conditions may contribute toward a better understanding of its pathogenesis and adaptive response. Here, we utilized a mass spectrometry-based label-free relative quantitative proteomics approach to investigate and compare global proteomic changes in B. abortus in response to eight different stress treatments. The 3 h short-term in vitro single-stress and multi-stress conditions mimicked the in vivo conditions of B. abortus under intracellular infection, with survival rates ranging from 3.17 to 73.17%. The proteomic analysis identified and quantified a total of 2,272 proteins and 74% of the theoretical proteome, thereby providing wide coverage of the B. abortus proteome. By including eight distinct growth conditions and comparing these with a control condition, we identified a total of 1,221 differentially expressed proteins (DEPs) that were significantly changed under the stress treatments. Pathway analysis revealed that most of the proteins were involved in oxidative phosphorylation, ABC transporters, two-component systems, biosynthesis of secondary metabolites, the citrate cycle, thiamine metabolism, and nitrogen metabolism; constituting major response mechanisms toward the reconstruction of cellular homeostasis and metabolic

  4. Depression, disturbed eating behavior, and metabolic control in teenage girls with type 1 diabetes.

    Science.gov (United States)

    Colton, Patricia A; Olmsted, Marion P; Daneman, Denis; Rodin, Gary M

    2013-08-01

    Depression and disturbed eating behavior (DEB) are more common in girls with type 1 diabetes (T1D) than in the general population, and may negatively affect metabolic control. To examine the relationship among depression, DEB, and metabolic control in teenage girls with T1D. Metabolic control, body mass index and interview-ascertained symptoms of depression, and DEB were assessed twice in 98 girls with T1D, 9-14 y at baseline and 5 yr later at 14-18 yr. At year 5, 12.2% of girls reported current depressive symptoms, 49.0% reported current DEB, and 13.3% had a full or subthreshold eating disorder (ED). Eating Disorder Examination score was higher in girls with depression (1.4 ± 1.3 vs. 0.5 ± 0.7; p = 0.03), and 75.0% of girls with depression also endorsed DEB vs. 45.3% of girls without depression (p = 0.05). Girls with an ED were at high risk for depressive symptoms; 69.2% reported depressive symptoms vs. 22.0% of girls with no DEB (p = 0.004). Metabolic control was not significantly associated with either depression or DEB in this cohort. A regression model using baseline and year 5 depression and DEB to predict year 5 hemoglobin A1c was not significant overall. Depression and DEB were common and frequently concurrent in this cohort. It was encouraging that poor metabolic control was not yet strongly associated with either depression or DEB. Early detection and treatment may help to prevent the development of entrenched difficulties in this triad of mood, eating behavior, and metabolic control in a vulnerable population. © 2013 John Wiley & Sons A/S.

  5. Ecological relationship analysis of the urban metabolic system of Beijing, China

    International Nuclear Information System (INIS)

    Li Shengsheng; Zhang Yan; Yang Zhifeng; Liu Hong; Zhang Jinyun

    2012-01-01

    Cities can be modelled as giant organisms, with their own metabolic processes, and can therefore be studied using the same tools used for biological metabolic systems. The complicated distribution of compartments within these systems and the functional relationships among them define the system's network structure. Taking Beijing as an example, we divided the city's internal system into metabolic compartments, then used ecological network analysis to calculate a comprehensive utility matrix for the flows between compartments within Beijing's metabolic system from 1998 to 2007 and to identify the corresponding functional relationships among the system's compartments. Our results show how ecological network analysis, utility analysis, and relationship analysis can be used to discover the implied ecological relationships within a metabolic system, thereby providing insights into the system's internal metabolic processes. Such analyses provide scientific support for urban ecological management. - Highlights: ► Urban metabolic processes can be analyzed by treating cities as superorganisms. ► We developed an ecological network model for an urban system. ► We studied the system's network relationships using ecological network analysis. ► We developed indices for judging the system's synergism and degree of stability. - Using Beijing as an example of an urban superorganism, we used ecological network analysis to describe the ecological relationships among the urban metabolic system's compartments.

  6. [Clinical analysis of metabolic syndrome in vertiginous diseases].

    Science.gov (United States)

    Yamanaka, Toshiaki; Fukuda, Takehiko; Sawai, Yachiyo; Shirota, Shiho; Shimizu, Naoki; Murai, Takayuki; Okamoto, Hideyuki; Fujita, Nobuya; Hosoi, Hiroshi

    2011-01-01

    To explore the relationship between metabolic syndrome and vertigo, we measured waist circumference, plasma glucose, triglycerides and blood pressure in 333 subjects aged 20-79 years with vertigo. We found overall metabolic syndrome prevalence defined by Japanese diagnostic criteria to be 13.2%, similar to that in other national surveys by the Japanese Ministry of Health, Labour and Welfare. The 6-fold higher prevalence in men over women exceeded that of other reports, however. The highest frequency was in vertebrobasilar insufficiency (VBI) disorders, suggesting that conditions such as VBI in men with vertigo could involve metabolic syndrome as a risk factor for vertigo incidence.

  7. Emerging roles of the intestine in control of cholesterol metabolism

    NARCIS (Netherlands)

    Kruit, Janine-K.; Groen, Albert K.; van Berkel, Theo J.; Kuipers, Folkert

    2006-01-01

    The liver is considered the major "control center" for maintenance of whole body cholesterol homeostasis. This organ is the main site for de novo cholesterol synthesis, clears cholesterol-containing chylomicron remnants and low density lipoprotein particles from plasma and is the major contributor

  8. Metabolic Control with Insulin Pump Therapy: Preliminary Experience

    Directory of Open Access Journals (Sweden)

    Shang-Ren Hsu

    2008-07-01

    Conclusion: Our preliminary experience demonstrated the effectiveness of insulin pump therapy for both type 1 and type 2 diabetic patients. The reduction in their HbA1C values was both statistically and clinically significant. This treatment should be considered for patients poorly controlled by subcutaneous insulin injection therapy.

  9. Flux Balance Analysis of Cyanobacterial Metabolism.The Metabolic Network of Synechocystis sp. PCC 6803

    Czech Academy of Sciences Publication Activity Database

    Knoop, H.; Gründel, M.; Zilliges, Y.; Lehmann, R.; Hoffmann, S.; Lockau, W.; Steuer, Ralf

    2013-01-01

    Roč. 9, č. 6 (2013), e1003081-e1003081 ISSN 1553-7358 R&D Projects: GA MŠk(CZ) EE2.3.20.0256 Institutional support: RVO:67179843 Keywords : SP STRAIN PCC-6803 * SP ATCC 51142 * photoautotrophic metabolism * anacystis-nidulans * reconstructions * pathway * plants * models * growth Subject RIV: EI - Biotechnology ; Bionics Impact factor: 4.829, year: 2013

  10. Metabolic Control and Illness Perceptions in Adolescents with Type 1 Diabetes

    Directory of Open Access Journals (Sweden)

    Line Wisting

    2016-01-01

    Full Text Available Background. Disturbed eating behavior and psychosocial variables have been found to influence metabolic control, but little is known about how these variables interact or how they influence metabolic control, separately and combined. Objective. To explore associations between metabolic control (measured by HbA1c and eating disorder psychopathology, coping strategies, illness perceptions, and insulin beliefs in adolescents with type 1 diabetes. Methods. A total of 105 patients (41.9% males with type 1 diabetes (12–20 years were interviewed with the Child Eating Disorder Examination. In addition, self-report psychosocial questionnaires were completed. Clinical data, including HbA1c, was obtained from the Norwegian Childhood Diabetes Registry. Results. Significant gender differences were demonstrated. Among females, HbA1c correlated significantly with eating restriction (.29, p < .05, the illness perception dimensions consequences, personal control, coherence, and concern (ranging from .33 to .48, and the coping strategy ventilating negative feelings (−.26, p < .05. Illness perception personal control contributed significantly to HbA1c in a regression model, explaining 23% of the variance among females (β .48, p < .001. None of the variables were significantly associated with HbA1c among males. Conclusions. Illness perceptions appear to be important contributors to metabolic control in females, but not males, with type 1 diabetes.

  11. Roles for Orexin/Hypocretin in the Control of Energy Balance and Metabolism.

    Science.gov (United States)

    Goforth, Paulette B; Myers, Martin G

    The neuropeptide hypocretin is also commonly referred to as orexin, since its orexigenic action was recognized early. Orexin/hypocretin (OX) neurons project widely throughout the brain and the physiologic and behavioral functions of OX are much more complex than initially conceived based upon the stimulation of feeding. OX most notably controls functions relevant to attention, alertness, and motivation. OX also plays multiple crucial roles in the control of food intake, metabolism, and overall energy balance in mammals. OX signaling not only promotes food-seeking behavior upon short-term fasting to increase food intake and defend body weight, but, conversely, OX signaling also supports energy expenditure to protect against obesity. Furthermore, OX modulates the autonomic nervous system to control glucose metabolism, including during the response to hypoglycemia. Consistently, a variety of nutritional cues (including the hormones leptin and ghrelin) and metabolites (e.g., glucose, amino acids) control OX neurons. In this chapter, we review the control of OX neurons by nutritional/metabolic cues, along with our current understanding of the mechanisms by which OX and OX neurons contribute to the control of energy balance and metabolism.

  12. Periodontitis deteriorates metabolic control in type 2 diabetic Goto-Kakizaki rats

    DEFF Research Database (Denmark)

    Pontes Andersen, Carla C; Buschard, Karsten; Flyvbjerg, Allan

    2006-01-01

    BACKGROUND: Epidemiologic and clinical studies have indicated that periodontal disease (PD) may cause disturbances in general health and even affect diabetes. The aim of this study was to gain knowledge on the effect of PD on diabetes metabolic control in a new model for type 2 diabetes-associate......BACKGROUND: Epidemiologic and clinical studies have indicated that periodontal disease (PD) may cause disturbances in general health and even affect diabetes. The aim of this study was to gain knowledge on the effect of PD on diabetes metabolic control in a new model for type 2 diabetes...

  13. Diabetes in children and adolescents from ethnic minorities: barriers to education, treatment and good metabolic control

    DEFF Research Database (Denmark)

    Povlsen, Lene; Olsen, Birthe; Ladelund, Steen

    2005-01-01

    AIM: This paper reports an investigation to establish whether metabolic control is different in children and adolescents from ethnic minorities with type 1 diabetes compared with young Danish patients, and to learn about factors affecting their opportunities to achieve good metabolic control. BAC...... to improve methods, quality and knowledge should be encouraged in order to provide tailored support to members of individual ethnic groups. We recommend that the use of professional interpreters should become the gold standard in health care provision to all immigrant families....

  14. Prevention of complications in glycogen storage disease type Ia with optimization of metabolic control.

    Science.gov (United States)

    Dambska, M; Labrador, E B; Kuo, C L; Weinstein, D A

    2017-08-01

    Prior to 1971, type Ia glycogen storage disease was marked by life-threatening hypoglycemia, lactic acidosis, severe failure to thrive, and developmental delay. With the introduction of continuous feeds in the 1970s and cornstarch in the 1980s, the prognosis improved, but complications almost universally developed. Changes in the management of type Ia glycogen storage disease have resulted in improved metabolic control, and this manuscript reviews the increasing evidence that complications can be delayed or prevented with optimal metabolic control as previously was seen in diabetes. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  15. Role of Parenting Style in Achieving Metabolic Control in Adolescents With Type 1 Diabetes

    OpenAIRE

    Shorer, Maayan; David, Ravit; Schoenberg-Taz, Michal; Levavi-Lavi, Ifat; Phillip, Moshe; Meyerovitch, Joseph

    2011-01-01

    OBJECTIVE To examine the role of parenting style in achieving metabolic control and treatment adherence in adolescents with type 1 diabetes. RESEARCH DESIGN AND METHODS Parents of 100 adolescents with type 1 diabetes completed assessments of their parenting style and sense of helplessness. Parents and patients rated patient adherence to the treatment regimen. Glycemic control was evaluated by HbA1c values. RESULTS An authoritative paternal parenting style predicted better glycemic control and...

  16. Comprehensive analysis of glucose and xylose metabolism in Escherichia coli under aerobic and anaerobic conditions by13C metabolic flux analysis.

    Science.gov (United States)

    Gonzalez, Jacqueline E; Long, Christopher P; Antoniewicz, Maciek R

    2017-01-01

    Glucose and xylose are the two most abundant sugars derived from the breakdown of lignocellulosic biomass. While aerobic glucose metabolism is relatively well understood in E. coli, until now there have been only a handful of studies focused on anaerobic glucose metabolism and no 13 C-flux studies on xylose metabolism. In the absence of experimentally validated flux maps, constraint-based approaches such as MOMA and RELATCH cannot be used to guide new metabolic engineering designs. In this work, we have addressed this critical gap in current understanding by performing comprehensive characterizations of glucose and xylose metabolism under aerobic and anaerobic conditions, using recent state-of-the-art techniques in 13 C metabolic flux analysis ( 13 C-MFA). Specifically, we quantified precise metabolic fluxes for each condition by performing parallel labeling experiments and analyzing the data through integrated 13 C-MFA using the optimal tracers [1,2- 13 C]glucose, [1,6- 13 C]glucose, [1,2- 13 C]xylose and [5- 13 C]xylose. We also quantified changes in biomass composition and confirmed turnover of macromolecules by applying [U- 13 C]glucose and [U- 13 C]xylose tracers. We demonstrated that under anaerobic growth conditions there is significant turnover of lipids and that a significant portion of CO 2 originates from biomass turnover. Using knockout strains, we also demonstrated that β-oxidation is critical for anaerobic growth on xylose. Quantitative analysis of co-factor balances (NADH/FADH 2 , NADPH, and ATP) for different growth conditions provided new insights regarding the interplay of energy and redox metabolism and the impact on E. coli cell physiology. Copyright © 2016 International Metabolic Engineering Society. Published by Elsevier Inc. All rights reserved.

  17. A Nested Case-Control Study of Metabolically Defined Body Size Phenotypes and Risk of Colorectal Cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC.

    Directory of Open Access Journals (Sweden)

    Neil Murphy

    2016-04-01

    Full Text Available Obesity is positively associated with colorectal cancer. Recently, body size subtypes categorised by the prevalence of hyperinsulinaemia have been defined, and metabolically healthy overweight/obese individuals (without hyperinsulinaemia have been suggested to be at lower risk of cardiovascular disease than their metabolically unhealthy (hyperinsulinaemic overweight/obese counterparts. Whether similarly variable relationships exist for metabolically defined body size phenotypes and colorectal cancer risk is unknown.The association of metabolically defined body size phenotypes with colorectal cancer was investigated in a case-control study nested within the European Prospective Investigation into Cancer and Nutrition (EPIC study. Metabolic health/body size phenotypes were defined according to hyperinsulinaemia status using serum concentrations of C-peptide, a marker of insulin secretion. A total of 737 incident colorectal cancer cases and 737 matched controls were divided into tertiles based on the distribution of C-peptide concentration amongst the control population, and participants were classified as metabolically healthy if below the first tertile of C-peptide and metabolically unhealthy if above the first tertile. These metabolic health definitions were then combined with body mass index (BMI measurements to create four metabolic health/body size phenotype categories: (1 metabolically healthy/normal weight (BMI < 25 kg/m2, (2 metabolically healthy/overweight (BMI ≥ 25 kg/m2, (3 metabolically unhealthy/normal weight (BMI < 25 kg/m2, and (4 metabolically unhealthy/overweight (BMI ≥ 25 kg/m2. Additionally, in separate models, waist circumference measurements (using the International Diabetes Federation cut-points [≥80 cm for women and ≥94 cm for men] were used (instead of BMI to create the four metabolic health/body size phenotype categories. Statistical tests used in the analysis were all two-sided, and a p-value of <0.05 was

  18. Control of Hepatic Glucose Metabolism by Islet and Brain

    Science.gov (United States)

    Rojas, Jennifer M.; Schwartz, Michael W.

    2014-01-01

    Dysregulation of hepatic glucose uptake (HGU) and inability of insulin to suppress hepatic glucose production (HGP), both contribute to hyperglycemia in patients with type 2 diabetes (T2D). Growing evidence suggests that insulin can inhibit HGP not only through a direct effect on the liver, but also via a mechanism involving the brain. Yet the notion that insulin action in the brain plays a physiological role in the control of HGP continues to be controversial. Although studies in dogs suggest that the direct hepatic effect of insulin is sufficient to explain day-to-day control of HGP, a surprising outcome has been revealed by recent studies in mice investigating whether the direct hepatic action of insulin is necessary for normal HGP: when hepatic insulin signaling pathway was genetically disrupted, HGP was maintained normally even in the absence of direct input from insulin. Here we present evidence that points to a potentially important role of the brain in the physiological control of both HGU and HGP in response to input from insulin as well as other hormones and nutrients. PMID:25200294

  19. A High Phosphorus Diet Affects Lipid Metabolism in Rat Liver: A DNA Microarray Analysis.

    Science.gov (United States)

    Chun, Sunwoo; Bamba, Takeshi; Suyama, Tatsuya; Ishijima, Tomoko; Fukusaki, Eiichiro; Abe, Keiko; Nakai, Yuji

    2016-01-01

    A high phosphorus (HP) diet causes disorders of renal function, bone metabolism, and vascular function. We previously demonstrated that DNA microarray analysis is an appropriate method to comprehensively evaluate the effects of a HP diet on kidney dysfunction such as calcification, fibrillization, and inflammation. We reported that type IIb sodium-dependent phosphate transporter is significantly up-regulated in this context. In the present study, we performed DNA microarray analysis to investigate the effects of a HP diet on the liver, which plays a pivotal role in energy metabolism. DNA microarray analysis was performed with total RNA isolated from the livers of rats fed a control diet (containing 0.3% phosphorus) or a HP diet (containing 1.2% phosphorus). Gene Ontology analysis of differentially expressed genes (DEGs) revealed that the HP diet induced down-regulation of genes involved in hepatic amino acid catabolism and lipogenesis, while genes related to fatty acid β-oxidation process were up-regulated. Although genes related to fatty acid biosynthesis were down-regulated in HP diet-fed rats, genes important for the elongation and desaturation reactions of omega-3 and -6 fatty acids were up-regulated. Concentrations of hepatic arachidonic acid and eicosapentaenoic acid were increased in HP diet-fed rats. These essential fatty acids activate peroxisome proliferator-activated receptor alpha (PPARα), a transcription factor for fatty acid β-oxidation. Evaluation of the upstream regulators of DEGs using Ingenuity Pathway Analysis indicated that PPARα was activated in the livers of HP diet-fed rats. Furthermore, the serum concentration of fibroblast growth factor 21, a hormone secreted from the liver that promotes fatty acid utilization in adipose tissue as a PPARα target gene, was higher (p = 0.054) in HP diet-fed rats than in control diet-fed rats. These data suggest that a HP diet enhances energy expenditure through the utilization of free fatty acids

  20. A High Phosphorus Diet Affects Lipid Metabolism in Rat Liver: A DNA Microarray Analysis

    Science.gov (United States)

    Chun, Sunwoo; Bamba, Takeshi; Suyama, Tatsuya; Ishijima, Tomoko; Fukusaki, Eiichiro; Abe, Keiko; Nakai, Yuji

    2016-01-01

    A high phosphorus (HP) diet causes disorders of renal function, bone metabolism, and vascular function. We previously demonstrated that DNA microarray analysis is an appropriate method to comprehensively evaluate the effects of a HP diet on kidney dysfunction such as calcification, fibrillization, and inflammation. We reported that type IIb sodium-dependent phosphate transporter is significantly up-regulated in this context. In the present study, we performed DNA microarray analysis to investigate the effects of a HP diet on the liver, which plays a pivotal role in energy metabolism. DNA microarray analysis was performed with total RNA isolated from the livers of rats fed a control diet (containing 0.3% phosphorus) or a HP diet (containing 1.2% phosphorus). Gene Ontology analysis of differentially expressed genes (DEGs) revealed that the HP diet induced down-regulation of genes involved in hepatic amino acid catabolism and lipogenesis, while genes related to fatty acid β-oxidation process were up-regulated. Although genes related to fatty acid biosynthesis were down-regulated in HP diet-fed rats, genes important for the elongation and desaturation reactions of omega-3 and -6 fatty acids were up-regulated. Concentrations of hepatic arachidonic acid and eicosapentaenoic acid were increased in HP diet-fed rats. These essential fatty acids activate peroxisome proliferator-activated receptor alpha (PPARα), a transcription factor for fatty acid β-oxidation. Evaluation of the upstream regulators of DEGs using Ingenuity Pathway Analysis indicated that PPARα was activated in the livers of HP diet-fed rats. Furthermore, the serum concentration of fibroblast growth factor 21, a hormone secreted from the liver that promotes fatty acid utilization in adipose tissue as a PPARα target gene, was higher (p = 0.054) in HP diet-fed rats than in control diet-fed rats. These data suggest that a HP diet enhances energy expenditure through the utilization of free fatty acids

  1. Role of glycolytic intermediate in regulation: Improving lycopene production in Escherichia coli by engineering metabolic control

    Energy Technology Data Exchange (ETDEWEB)

    Farmer, W.R.; Liao, J.C.

    2001-06-01

    Metabolic engineering in the postgenomic era is expected to benefit from a full understanding of the biosynthetic capability of microorganisms as a result of the progress being made in bioinformatics and functional genomics. The immediate advantage of such information is to allow the rational design of novel pathways and the elimination of native reactions that are detrimental or unnecessary for the desired purpose. However, with the ability to manipulate metabolic pathways becoming more effective, metabolic engineering will need to face a new challenge: the reengineering of the regulatory hierarchy that controls gene expression in those pathways. In addition to constructing the genetic composition of a metabolic pathway, they propose that it will become just as important to consider the dynamics of pathways gene expression. It has been widely observed that high-level induction of a recombinant protein or pathway leads to growth retardation and reduced metabolic activity. These phenotypic characteristics result from the fact that the constant demands of production placed upon the cell interfere with its changing requirements for growth. They believe that this common situation in metabolic engineering can be alleviated by designing a dynamic controller that is able to sense the metabolic state of the cell and regulate the expression of the recombinant pathway accordingly. This approach, which is termed metabolic control engineering, involves redesigning the native regulatory circuits and applying them to the recombinant pathway. The general goal of such an effort will be to control the flux to the recombinant pathway adaptively according to the cell's metabolic state. The dynamically controlled recombinant pathway can potentially lead to enhanced production, minimized growth retardation, and reduced toxic by-product formation. The regulation of gene expression in response to the physiological state is also essential to the success of gene therapy. Here they

  2. Synthetic control of a fitness tradeoff in yeast nitrogen metabolism

    Directory of Open Access Journals (Sweden)

    Lee Jack J

    2009-01-01

    Full Text Available Abstract Background Microbial communities are involved in many processes relevant to industrial and medical biotechnology, such as the formation of biofilms, lignocellulosic degradation, and hydrogen production. The manipulation of synthetic and natural microbial communities and their underlying ecological parameters, such as fitness, evolvability, and variation, is an increasingly important area of research for synthetic biology. Results Here, we explored how synthetic control of an endogenous circuit can be used to regulate a tradeoff between fitness in resource abundant and resource limited environments in a population of Saccharomyces cerevisiae. We found that noise in the expression of a key enzyme in ammonia assimilation, Gdh1p, mediated a tradeoff between growth in low nitrogen environments and stress resistance in high ammonia environments. We implemented synthetic control of an endogenous Gdh1p regulatory network to construct an engineered strain in which the fitness of the population was tunable in response to an exogenously-added small molecule across a range of ammonia environments. Conclusion The ability to tune fitness and biological tradeoffs will be important components of future efforts to engineer microbial communities.

  3. [Metabolic control in the critically ill patient an update: hyperglycemia, glucose variability hypoglycemia and relative hypoglycemia].

    Science.gov (United States)

    Pérez-Calatayud, Ángel Augusto; Guillén-Vidaña, Ariadna; Fraire-Félix, Irving Santiago; Anica-Malagón, Eduardo Daniel; Briones Garduño, Jesús Carlos; Carrillo-Esper, Raúl

    Metabolic changes of glucose in critically ill patients increase morbidity and mortality. The appropriate level of blood glucose has not been established so far and should be adjusted for different populations. However concepts such as glucose variability and relative hypoglycemia of critically ill patients are concepts that are changing management methods and achieving closer monitoring. The purpose of this review is to present new data about the management and metabolic control of patients in critical areas. Currently glucose can no longer be regarded as an innocent element in critical patients; both hyperglycemia and hypoglycemia increase morbidity and mortality of patients. Protocols and better instruments for continuous measurement are necessary to achieve the metabolic control of our patients. Copyright © 2016 Academia Mexicana de Cirugía A.C. Publicado por Masson Doyma México S.A. All rights reserved.

  4. A dual control mechanism synchronizes riboflavin and sulphur metabolism in Bacillus subtilis

    Science.gov (United States)

    Pedrolli, Danielle Biscaro; Kühm, Christian; Sévin, Daniel C.; Vockenhuber, Michael P.; Sauer, Uwe; Suess, Beatrix; Mack, Matthias

    2015-01-01

    Flavin mononucleotide (FMN) riboswitches are genetic elements, which in many bacteria control genes responsible for biosynthesis and/or transport of riboflavin (rib genes). Cytoplasmic riboflavin is rapidly and almost completely converted to FMN by flavokinases. When cytoplasmic levels of FMN are sufficient (“high levels”), FMN binding to FMN riboswitches leads to a reduction of rib gene expression. We report here that the protein RibR counteracts the FMN-induced “turn-off” activities of both FMN riboswitches in Bacillus subtilis, allowing rib gene expression even in the presence of high levels of FMN. The reason for this secondary metabolic control by RibR is to couple sulfur metabolism with riboflavin metabolism. PMID:26494285

  5. Computational analysis of storage synthesis in developing Brassica napus L. (oilseed rape) embryos: Flux variability analysis in relation to 13C-metabolic flux analysis

    Energy Technology Data Exchange (ETDEWEB)

    Hay, J.; Schwender, J.

    2011-08-01

    Plant oils are an important renewable resource, and seed oil content is a key agronomical trait that is in part controlled by the metabolic processes within developing seeds. A large-scale model of cellular metabolism in developing embryos of Brassica napus (bna572) was used to predict biomass formation and to analyze metabolic steady states by flux variability analysis under different physiological conditions. Predicted flux patterns are highly correlated with results from prior 13C metabolic flux analysis of B. napus developing embryos. Minor differences from the experimental results arose because bna572 always selected only one sugar and one nitrogen source from the available alternatives, and failed to predict the use of the oxidative pentose phosphate pathway. Flux variability, indicative of alternative optimal solutions, revealed alternative pathways that can provide pyruvate and NADPH to plastidic fatty acid synthesis. The nutritional values of different medium substrates were compared based on the overall carbon conversion efficiency (CCE) for the biosynthesis of biomass. Although bna572 has a functional nitrogen assimilation pathway via glutamate synthase, the simulations predict an unexpected role of glycine decarboxylase operating in the direction of NH4+ assimilation. Analysis of the light-dependent improvement of carbon economy predicted two metabolic phases. At very low light levels small reductions in CO2 efflux can be attributed to enzymes of the tricarboxylic acid cycle (oxoglutarate dehydrogenase, isocitrate dehydrogenase) and glycine decarboxylase. At higher light levels relevant to the 13C flux studies, ribulose-1,5-bisphosphate carboxylase activity is predicted to account fully for the light-dependent changes in carbon balance.

  6. Effects of concurrent training on muscle strength in older adults with metabolic syndrome: A randomized controlled clinical trial.

    Science.gov (United States)

    Agner, Vania Fernanda Clemente; Garcia, Marcia Carvalho; Taffarel, Andre Andriolli; Mourão, Camila Baudini; da Silva, Isabel Paulo; da Silva, Sara Pereira; Peccin, Maria Stella; Lombardi, Império

    Metabolic syndrome is highly prevalent among older adults. Concurrent training comprises muscle strengthening and aerobic exercise. Determine the effects of a concurrent training program on muscle strength, walking function, metabolic profile, cardiovascular risk, use of medications and quality of life among older adults with metabolic syndrome. A randomised, controlled, blind, clinical trial was conducted in the city of Santos, state of São Paulo, Brazil, involving 41 male and female older adults. The participants were randomly allocated to a control group (n = 18) and intervention group (n = 23) and were submitted to the following evaluations: strength - 1 maximum repetition (1MR) for 12 muscle groups; the Six-Minute Walk Test (6MWT); blood concentrations of cholesterol and glucose; the use of medications; and the administration of the SF-36 questionnaire. The intervention was conducted twice a week over a total of 24 sessions of concurrent training: 50 min of strength exercises (40-70% 1MR) and 40 min of walking exercises (70-85% maximum heart rate). Increases in muscle strength were found in the upper and lower limbs in the inter-group analysis and a greater distance travelled on the 6MWT was found in the intervention group (p = 0.001). The intervention group demonstrated a reduction in the consumption of biguanides (p = 0.002). No changes were found regarding metabolic profile, cardiovascular risk or self-perceived quality of life. The findings of this clinical trial can be used for the prescription of concurrent training for older adults with metabolic syndrome for gains in muscle strength and walking distance as well as a reduction in the use of biguanides. Copyright © 2017 Elsevier B.V. All rights reserved.

  7. Antinociceptive effects, metabolism and disposition of ketamine in ponies under target-controlled drug infusion

    International Nuclear Information System (INIS)

    Knobloch, M.; Portier, C.J.; Levionnois, O.L.; Theurillat, R.; Thormann, W.; Spadavecchia, C.; Mevissen, M.

    2006-01-01

    Ketamine is widely used as an anesthetic in a variety of drug combinations in human and veterinary medicine. Recently, it gained new interest for use in long-term pain therapy administered in sub-anesthetic doses in humans and animals. The purpose of this study was to develop a physiologically based pharmacokinetic (PBPk) model for ketamine in ponies and to investigate the effect of low-dose ketamine infusion on the amplitude and the duration of the nociceptive withdrawal reflex (NWR). A target-controlled infusion (TCI) of ketamine with a target plasma level of 1 μg/ml S-ketamine over 120 min under isoflurane anesthesia was performed in Shetland ponies. A quantitative electromyographic assessment of the NWR was done before, during and after the TCI. Plasma levels of R-/S-ketamine and R-/S-norketamine were determined by enantioselective capillary electrophoresis. These data and two additional data sets from bolus studies were used to build a PBPk model for ketamine in ponies. The peak-to-peak amplitude and the duration of the NWR decreased significantly during TCI and returned slowly toward baseline values after the end of TCI. The PBPk model provides reliable prediction of plasma and tissue levels of R- and S-ketamine and R- and S-norketamine. Furthermore, biotransformation of ketamine takes place in the liver and in the lung via first-pass metabolism. Plasma concentrations of S-norketamine were higher compared to R-norketamine during TCI at all time points. Analysis of the data suggested identical biotransformation rates from the parent compounds to the principle metabolites (R- and S-norketamine) but different downstream metabolism to further metabolites. The PBPk model can provide predictions of R- and S-ketamine and norketamine concentrations in other clinical settings (e.g. horses)

  8. Urea and Ammonia Metabolism and the Control of Renal Nitrogen Excretion

    Science.gov (United States)

    Mitch, William E.; Sands, Jeff M.

    2015-01-01

    Renal nitrogen metabolism primarily involves urea and ammonia metabolism, and is essential to normal health. Urea is the largest circulating pool of nitrogen, excluding nitrogen in circulating proteins, and its production changes in parallel to the degradation of dietary and endogenous proteins. In addition to serving as a way to excrete nitrogen, urea transport, mediated through specific urea transport proteins, mediates a central role in the urine concentrating mechanism. Renal ammonia excretion, although often considered only in the context of acid-base homeostasis, accounts for approximately 10% of total renal nitrogen excretion under basal conditions, but can increase substantially in a variety of clinical conditions. Because renal ammonia metabolism requires intrarenal ammoniagenesis from glutamine, changes in factors regulating renal ammonia metabolism can have important effects on glutamine in addition to nitrogen balance. This review covers aspects of protein metabolism and the control of the two major molecules involved in renal nitrogen excretion: urea and ammonia. Both urea and ammonia transport can be altered by glucocorticoids and hypokalemia, two conditions that also affect protein metabolism. Clinical conditions associated with altered urine concentrating ability or water homeostasis can result in changes in urea excretion and urea transporters. Clinical conditions associated with altered ammonia excretion can have important effects on nitrogen balance. PMID:25078422

  9. Integration of a constraint-based metabolic model of Brassica napus developing seeds with 13C-Metabolic Flux Analysis

    Directory of Open Access Journals (Sweden)

    Jordan eHay

    2014-12-01

    Full Text Available The use of large-scale or genome-scale metabolic reconstructions for modeling and simulation of plant metabolism and integration of those models with large-scale omics and experimental flux data is becoming increasingly important in plant metabolic research. Here we report an updated version of bna572, a bottom-up reconstruction of oilseed rape (Brassica napus L.; Brassicaceae developing seeds with emphasis on representation of biomass-component biosynthesis. New features include additional seed-relevant pathways for isoprenoid, sterol, phenylpropanoid, flavonoid, and choline biosynthesis. Being now based on standardized data formats and procedures for model reconstruction, bna572+ is available as a COBRA-compliant Systems Biology Markup Language (SBML model and conforms to the Minimum Information Requested in the Annotation of Biochemical Models (MIRIAM standards for annotation of external data resources. Bna572+ contains 966 genes, 671 reactions, and 666 metabolites distributed among 11 subcellular compartments. It is referenced to the Arabidopsis thaliana genome, with gene-protein-reaction associations resolving subcellular localization. Detailed mass and charge balancing and confidence scoring were applied to all reactions. Using Brassica napus seed specific transcriptome data, expression was verified for 78% of bna572+ genes and 97% of reactions. Alongside bna572+ we also present a revised carbon centric model for 13C-Metabolic Flux Analysis (13C-MFA with all its reactions being referenced to bna572+ based on linear projections. By integration of flux ratio constraints obtained from 13C-MFA and by elimination of infinite flux bounds around thermodynamically infeasible loops based on COBRA loopless methods, we demonstrate improvements in predictive power of Flux Variability Analysis (FVA. Using this combined approach we characterize the difference in metabolic flux of developing seeds of two Brassica napus genotypes contrasting in starch and

  10. Clinical and biochemical heterogeneity between patients with glycogen storage disease type IA: the added value of CUSUM for metabolic control.

    Science.gov (United States)

    Peeks, Fabian; Steunenberg, Thomas A H; de Boer, Foekje; Rubio-Gozalbo, M Estela; Williams, Monique; Burghard, Rob; Rajas, Fabienne; Oosterveer, Maaike H; Weinstein, David A; Derks, Terry G J

    2017-09-01

    To study heterogeneity between patients with glycogen storage disease type Ia (GSD Ia), a rare inherited disorder of carbohydrate metabolism caused by the deficiency of glucose-6-phosphatase (G6Pase). Descriptive retrospective study of longitudinal clinical and biochemical data and long-term complications in 20 GSD Ia patients. We included 11 patients with homozygous G6PC mutations and siblings from four families carrying identical G6PC genotypes. To display subtle variations for repeated triglyceride measurements with respect to time for individual patients, CUSUM-analysis graphs were constructed. Patients with different homozygous G6PC mutations showed important differences in height, BMI, and biochemical parameters (i.e., lactate, uric acid, triglyceride, and cholesterol concentrations). Furthermore, CUSUM-analysis predicts and displays subtle changes in longitudinal blood triglyceride concentrations. Siblings in families also displayed important differences in biochemical parameters (i.e., lactate, uric acid, triglycerides, and cholesterol concentrations) and long-term complications (i.e., liver adenomas, nephropathy, and osteopenia/osteoporosis). Differences between GSD Ia patients reflect large clinical and biochemical heterogeneity. Heterogeneity between GSD Ia patients with homozygous G6PC mutations indicate an important role of the G6PC genotype/mutations. Differences between affected siblings suggest an additional role (genetic and/or environmental) of modifying factors defining the GSD Ia phenotype. CUSUM-analysis can facilitate single-patient monitoring of metabolic control and future application of this method may improve precision medicine for patients both with GSD and remaining inherited metabolic diseases.

  11. Fatty liver associated with metabolic derangement in patients with chronic kidney disease: A controlled attenuation parameter study

    Directory of Open Access Journals (Sweden)

    Chang-Yun Yoon

    2017-03-01

    Full Text Available Background: Hepatic steatosis measured with controlled attenuation parameter (CAP using transient elastography predicts metabolic syndrome in the general population. We investigated whether CAP predicted metabolic syndrome in chronic kidney disease patients. Methods: CAP was measured with transient elastography in 465 predialysis chronic kidney disease patients (mean age, 57.5 years. Results: The median CAP value was 239 (202–274 dB/m. In 195 (41.9% patients with metabolic syndrome, diabetes mellitus was more prevalent (105 [53.8%] vs. 71 [26.3%], P < 0.001, with significantly increased urine albumin-to-creatinine ratio (184 [38–706] vs. 56 [16–408] mg/g Cr, P = 0.003, high sensitivity C-reactive protein levels (5.4 [1.4–28.2] vs. 1.7 [0.6–9.9] mg/L, P < 0.001, and CAP (248 [210–302] vs. 226 [196–259] dB/m, P < 0.001. In multiple linear regression analysis, CAP was independently related to body mass index (β = 0.742, P < 0.001, triglyceride levels (β = 2.034, P < 0.001, estimated glomerular filtration rate (β = 0.316, P = 0.001, serum albumin (β = 1.386, P < 0.001, alanine aminotransferase (β = 0.064, P = 0.029, and total bilirubin (β = −0.881, P = 0.009. In multiple logistic regression analysis, increased CAP was independently associated with increased metabolic syndrome risk (per 10 dB/m increase; odds ratio, 1.093; 95% confidence interval, 1.009–1.183; P = 0.029 even after adjusting for multiple confounding factors. Conclusion: Increased CAP measured with transient elastography significantly correlated with and could predict increased metabolic syndrome risk in chronic kidney disease patients.

  12. 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 ...

  13. Isotopically nonstationary metabolic flux analysis (INST-MFA) of photosynthesis and photorespiration in plants

    Science.gov (United States)

    Photorespiration is a central component of photosynthesis; however to better understand its role it should be viewed in the context of an integrated metabolic network rather than a series of individual reactions that operate independently. Isotopically nonstationary 13C metabolic flux analysis (INST...

  14. Robust Regression Analysis of GCMS Data Reveals Differential Rewiring of Metabolic Networks in Hepatitis B and C Patients

    Directory of Open Access Journals (Sweden)

    Cedric Simillion

    2017-10-01

    Full Text Available About one in 15 of the world’s population is chronically infected with either hepatitis virus B (HBV or C (HCV, with enormous public health consequences. The metabolic alterations caused by these infections have never been directly compared and contrasted. We investigated groups of HBV-positive, HCV-positive, and uninfected healthy controls using gas chromatography-mass spectrometry analyses of their plasma and urine. A robust regression analysis of the metabolite data was conducted to reveal correlations between metabolite pairs. Ten metabolite correlations appeared for HBV plasma and urine, with 18 for HCV plasma and urine, none of which were present in the controls. Metabolic perturbation networks were constructed, which permitted a differential view of the HBV- and HCV-infected liver. HBV hepatitis was consistent with enhanced glucose uptake, glycolysis, and pentose phosphate pathway metabolism, the latter using xylitol and producing threonic acid, which may also be imported by glucose transporters. HCV hepatitis was consistent with impaired glucose uptake, glycolysis, and pentose phosphate pathway metabolism, with the tricarboxylic acid pathway fueled by branched-chain amino acids feeding gluconeogenesis and the hepatocellular loss of glucose, which most probably contributed to hyperglycemia. It is concluded that robust regression analyses can uncover metabolic rewiring in disease states.

  15. Physiology and genetics of metabolic flux control in Zymomonas mobilis. Progress report

    Energy Technology Data Exchange (ETDEWEB)

    Conway, T.

    1992-08-01

    This work seeks to understand the role of gene expression in regulating glycolytic enzyme synthesis in a balance that allows proper glycoltic flux control. The seven genes targeted for study in this laboratory have been cloned and sequenced, and molecular details of regulation have been investigated. Clear that glycolytic enzyme synthesis is coordinated to prevent the build up of toxic metabolic intermediates. The genetic mechanisms responsible for regulating balanced expression of the EntnerDoudoroff and glycolytic genes in Z. mobilis are beginning to be understood. Several layers of genetic control, perhaps in a hierarchal arrangement act in concert to determine the relative abundance of the glycolytic enzymes. These genetic controls involve differential translational efficiency, highly conserved promoter sequences, transcription factors, differential mRNA stabilities, and nucleolytic mRNA processing. The serendipitous cloning of the glucose facilitator, glf, as a result of linkage to several other genes of interest will have a significant impact on the study of Z. mobilis metabolism. The glucose facilitator is being characterized in a genetically reconstituted system in E. coli. Molecular genetic studies indicate that the ratio of glf expression to that of glk, zmf, and edd is carefully regulated, and suggests a critical role in metabolic control. Regulation of glycolytic gene expression is now sufficiently well understood to allow use of the glycolytic genes as tools to manipulate specified enzyme levels for the purpose of analyzing metabolic flux control. The critical genes have been subcloned for stable expression in Z. mobilis and placed under control of a regulated promoter system involving the tac promoter, the lacI repressor, and gene induction in by IPTG. HPLC methods have been developed that allow quantitation of virtually all of the metabolic intermediates in the cell pool.

  16. Autonomous exercise game use improves metabolic control and quality of life in type 2 diabetes patients - a randomized controlled trial.

    Science.gov (United States)

    Kempf, Kerstin; Martin, Stephan

    2013-12-10

    Lifestyle intervention in type 2 diabetes mellitus (T2DM) is effective but needs a special local setting and is costly. Therefore, in a randomized-controlled trial we tested the hypothesis that the autonomous use of the interactive exercise game Wii Fit Plus over a period of 12 weeks improves metabolic control, with HbA1c reduction as the primary outcome, and weight loss, reduction of cardiometabolic risk factors, physical activity and quality of life (secondary outcomes) in T2DM patients. Participants (n = 220) were randomized into an intervention and a control group. The intervention group was provided with a Wii console, a balance board and the exercise game Wii Fit Plus for 12 weeks. The control group remained under routine care and received the items 12 weeks later. At baseline and after 12 weeks (and for the control group additionally after 12 weeks of intervention) the participants' health parameters, medication, physical activity and validated questionnaires for quality of life (PAID, SF12, WHO-5, CES-D) were requested and compared in a complete case analysis using the Mann-Whitney test and the Wilcoxon signed rank test. 80% of participants completed the 12-week study. Patients in the intervention group significantly improved HbA1c (from 7.1 ± 1.3% to 6.8 ± 0.9%; -0.3 ± 1.1%; p = 0.0002) in comparison to the control group (from 6.8 ± 0.9% to 6.7 ± 0.7%; -0.1 ± 0.5%) and also significantly reduced fasting blood glucose (from 135.8 ± 38.9 mg/dl to 126.6 ± 36.6 mg/dl; p = 0.04), weight (from 97.6 ± 19.2 kg to 96.3 ± 18.7 kg; p game intervention. In this trial a low-threshold intervention with the interactive exercise game Wii Fit Plus was able to motivate T2DM patients to improve physical activity, glucometabolic control and quality of life. ClinicalTrials.gov NCT01735643.

  17. Insulin receptor substrate signaling controls cardiac energy metabolism and heart failure.

    Science.gov (United States)

    Guo, Cathy A; Guo, Shaodong

    2017-06-01

    The heart is an insulin-dependent and energy-consuming organ in which insulin and nutritional signaling integrates to the regulation of cardiac metabolism, growth and survival. Heart failure is highly associated with insulin resistance, and heart failure patients suffer from the cardiac energy deficiency and structural and functional dysfunction. Chronic pathological conditions, such as obesity and type 2 diabetes mellitus, involve various mechanisms in promoting heart failure by remodeling metabolic pathways, modulating cardiac energetics and impairing cardiac contractility. Recent studies demonstrated that insulin receptor substrates 1 and 2 (IRS-1,-2) are major mediators of both insulin and insulin-like growth factor-1 (IGF-1) signaling responsible for myocardial energetics, structure, function and organismal survival. Importantly, the insulin receptor substrates (IRS) play an important role in the activation of the phosphatidylinositide-3-dependent kinase (PI-3K) that controls Akt and Foxo1 signaling cascade, regulating the mitochondrial function, cardiac energy metabolism and the renin-angiotensin system. Dysregulation of this branch in signaling cascades by insulin resistance in the heart through the endocrine system promotes heart failure, providing a novel mechanism for diabetic cardiomyopathy. Therefore, targeting this branch of IRS→PI-3K→Foxo1 signaling cascade and associated pathways may provide a fundamental strategy for the therapeutic and nutritional development in control of metabolic and cardiovascular diseases. In this review, we focus on insulin signaling and resistance in the heart and the role energetics play in cardiac metabolism, structure and function. © 2017 Society for Endocrinology.

  18. Metabolic transistor strategy for controlling electron transfer chain activity in Escherichia coli.

    Science.gov (United States)

    Wu, Hui; Tuli, Leepika; Bennett, George N; San, Ka-Yiu

    2015-03-01

    A novel strategy to finely control a large metabolic flux by using a "metabolic transistor" approach was established. In this approach a small change in the level or availability of an essential component for the process is controlled by adding a competitive reaction that affects a precursor or an intermediate in its biosynthetic pathway. The change of the basal level of the essential component, considered as a base current in a transistor, has a large effect on the flux through the major pathway. In this way, the fine-tuning of a large flux can be accomplished. The "metabolic transistor" strategy was applied to control electron transfer chain function by manipulation of the quinone synthesis pathway in Escherichia coli. The achievement of a theoretical yield of lactate production under aerobic conditions via this strategy upon manipulation of the biosynthetic pathway of the key participant, ubiquinone-8 (Q8), in an E. coli strain provides an in vivo, genetically tunable means to control the activity of the electron transfer chain and manipulate the production of reduced products while limiting consumption of oxygen to a defined amount. Copyright © 2015 International Metabolic Engineering Society. Published by Elsevier Inc. All rights reserved.

  19. Dietary intake and metabolic control of children aged six to ten with ...

    African Journals Online (AJOL)

    Objectives: The objective of this study was to assess the dietary intake and metabolic control of children with type 1 diabetes. Design: A cross-sectional observational study was carried out. Subjects: A total of 30 subjects whose ages ranged from six to ten years were included in the study. Setting: The study was conducted at ...

  20. Dietary intake and metabolic control of children aged six to ten with ...

    African Journals Online (AJOL)

    six to ten with type 1 diabetes mellitus in KwaZulu-Natal. Introduction. In South Africa the leading ... the ages of six and ten years. Abstract. Objectives: The objective of this study was to assess the dietary intake and metabolic control of children with type 1 diabetes. ... three snacks in between. Dietary intake. Dietary data were ...

  1. The effect of metabolic control on hemodynamics in short-term insulin-dependent diabetic patients

    DEFF Research Database (Denmark)

    Mathiesen, E R; Hilsted, J; Feldt-Rasmussen, B

    1985-01-01

    Hemodynamics variables (heart rate, arterial blood pressure, cardiac output, hepato-splanchnic blood flow, forearm blood flow, and plasma catecholamines) were measured during good (median blood glucose 4.7 mmol/L) and poor (median blood glucose 16.3 mmol/L) metabolic control in eight young, short...

  2. Cognitive Maturity, Stressful Events and Metabolic Control in Adolescents with Diabetes.

    Science.gov (United States)

    Ingersoll, Gary M.; And Others

    Management of insulin dependent diabetes mellitus (IDDM) is a complex task that requires the adolescent with IDDM recognize the interaction between diet, exercise, stress, emotions, and insulin dosage. With regularity, however, adolescents with IDDM are shown to be in less good metabolic control than younger children or young adults. The study…

  3. Muscle insulin sensitivity and glucose metabolism are controlled by the intrinsic muscle clock

    DEFF Research Database (Denmark)

    Dyar, Kenneth A.; Ciciliot, Stefano; Wright, Lauren E.

    2014-01-01

    Circadian rhythms control metabolism and energy homeostasis, but the role of the skeletal muscle clock has never been explored. We generated conditional and inducible mouse lines with muscle-specific ablation of the core clock gene Bmal1. Skeletal muscles from these mice showed impaired insulin-s...

  4. SIRT4 Is a Lysine Deacylase that Controls Leucine Metabolism and Insulin Secretion

    DEFF Research Database (Denmark)

    Anderson, Kristin A; Huynh, Frank K; Fisher-Wellman, Kelsey

    2017-01-01

    in leucine oxidation, and we show a primary role for SIRT4 in controlling this pathway in mice. Furthermore, we find that dysregulated leucine metabolism in SIRT4KO mice leads to elevated basal and stimulated insulin secretion, which progressively develops into glucose intolerance and insulin resistance...

  5. The origin of modern metabolic networks inferred from phylogenomic analysis of protein architecture.

    Science.gov (United States)

    Caetano-Anollés, Gustavo; Kim, Hee Shin; Mittenthal, Jay E

    2007-05-29

    Metabolism represents a complex collection of enzymatic reactions and transport processes that convert metabolites into molecules capable of supporting cellular life. Here we explore the origins and evolution of modern metabolism. Using phylogenomic information linked to the structure of metabolic enzymes, we sort out recruitment processes and discover that most enzymatic activities were associated with the nine most ancient and widely distributed protein fold architectures. An analysis of newly discovered functions showed enzymatic diversification occurred early, during the onset of the modern protein world. Most importantly, phylogenetic reconstruction exercises and other evidence suggest strongly that metabolism originated in enzymes with the P-loop hydrolase fold in nucleotide metabolism, probably in pathways linked to the purine metabolic subnetwork. Consequently, the first enzymatic takeover of an ancient biochemistry or prebiotic chemistry was related to the synthesis of nucleotides for the RNA world.

  6. Proteome analysis of schizophrenia patients Wernicke's area reveals an energy metabolism dysregulation

    Directory of Open Access Journals (Sweden)

    Marangoni Sérgio

    2009-04-01

    Full Text Available Abstract Background Schizophrenia is likely to be a consequence of DNA alterations that, together with environmental factors, will lead to protein expression differences and the ultimate establishment of the illness. The superior temporal gyrus is implicated in schizophrenia and executes functions such as the processing of speech, language skills and sound processing. Methods We performed an individual comparative proteome analysis using two-dimensional gel electrophoresis of 9 schizophrenia and 6 healthy control patients' left posterior superior temporal gyrus (Wernicke's area – BA22p identifying by mass spectrometry several protein expression alterations that could be related to the disease. Results Our analysis revealed 11 downregulated and 14 upregulated proteins, most of them related to energy metabolism. Whereas many of the identified proteins have been previously implicated in schizophrenia, such as fructose-bisphosphate aldolase C, creatine kinase and neuron-specific enolase, new putative disease markers were also identified such as dihydrolipoyl dehydrogenase, tropomyosin 3, breast cancer metastasis-suppressor 1, heterogeneous nuclear ribonucleoproteins C1/C2 and phosphate carrier protein, mitochondrial precursor. Besides, the differential expression of peroxiredoxin 6 (PRDX6 and glial fibrillary acidic protein (GFAP were confirmed by western blot in schizophrenia prefrontal cortex. Conclusion Our data supports a dysregulation of energy metabolism in schizophrenia as well as suggests new markers that may contribute to a better understanding of this complex disease.

  7. Association of metabolically healthy obesity with depressive symptoms: pooled analysis of eight studies.

    Science.gov (United States)

    Jokela, M; Hamer, M; Singh-Manoux, A; Batty, G D; Kivimäki, M

    2014-08-01

    The hypothesis of metabolically healthy obesity posits that adverse health effects of obesity are largely avoided when obesity is accompanied by a favorable metabolic profile. We tested this hypothesis with depressive symptoms as the outcome using cross-sectional data on obesity, metabolic health and depressive symptoms. Data were extracted from eight studies and pooled for individual-participant meta-analysis with 30,337 men and women aged 15-105 years (mean age=46.1). Clinic measures included height, weight and metabolic risk factors (high blood pressure, high triglycerides, low high-density lipoprotein cholesterol, high C-reactive protein and high glycated hemoglobin). Depressive symptoms were assessed using clinical interview or standardized rating scales. The pooled sample comprised 7673 (25%) obese participants (body mass index ⩾30 kg m(-2)). Compared to all non-obese individuals, the OR for depressive symptoms was higher in metabolically unhealthy obese individuals with two or more metabolic risk factors (1.45; 95% confidence interval (CI)=1.30, 1.61) and for metabolically healthy obese with ⩽1 metabolic risk factor (1.19; 95% CI=1.03, 1.37), adjusted for sex, age and race/ethnicity. Metabolically unhealthy obesity was associated with higher depression risk (OR=1.23; 95% CI=1.05, 1.45) compared with metabolically healthy obesity. These associations were consistent across studies with no evidence for heterogeneity in estimates (all I(2)-valuesobese persons with a favorable metabolic profile have a slightly increased risk of depressive symptoms compared with non-obese, but the risk is greater when obesity is combined with an adverse metabolic profile. These findings suggest that metabolically healthy obesity is not a completely benign condition in relation to depression risk.

  8. Analysis of Aspergillus nidulans metabolism at the genome-scale

    DEFF Research Database (Denmark)

    David, Helga; Ozcelik, İlknur Ş; Hofmann, Gerald

    2008-01-01

    , in an objective and systematic manner. The functional assignments served as a basis to develop a mathematical model, linking 666 genes (both previously and newly annotated) to metabolic roles. The model was used to simulate metabolic behavior and additionally to integrate, analyze and interpret large-scale gene...... expression data concerning a study on glucose repression, thereby providing a means of upgrading the information content of experimental data and getting further insight into this phenomenon in A. nidulans. Conclusion: We demonstrate how pathway modeling of A. nidulans can be used as an approach to improve...

  9. [Prevalence of metabolic syndrome in Chinese children and adolescents: a Meta-analysis].

    Science.gov (United States)

    Ye, Peiyu; Yan, Yinkun; Ding, Wenqing; Dong, Hongbo; Liu, Qin; Huang, Guimin; Mi, Jie

    2015-08-01

    To evaluate the prevalence of metabolic syndrome (MS) in Chinese children and adolescents to provide scientific basis for early prevention of MS in the related populations. Studies on CNKI, Wanfangdata, VIP and PubMed databases on related prevalence of metabolic syndrome in Chinese children and adolescents between 2004-2014 were searched. Quality of literatures was evaluated according to the cross-sectional study standard in Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement. Stata 12.0 software was used to estimate the prevalence of MS, as well as on gender, weight and other factors to make subgroup analysis. According to funnel plot and Egger assess publication bias, sensitivity analysis performed by excluding the impact of any article was generated by the combined effect of the value of literature. This study included 19 papers from the literature (5 in English, 14 in Chinese). According to International Diabetes Federation (IDF), National Cholesterol Education Program III (NCEP III) and The definition and prevention recommends of metabolic syndrome in Chinese children and adolescents (CHN2012), the prevalence rates of MS in Chinese children were seen as 1.8%, 2.6% and 2.0%. According to IDF, the prevalence rates of MS appeared 2.9% in boys and 1.8% in girls, 0.2% in children with normal weight, 4.7% in overweight and 17.3% in obesity. Both the results from NCEPIII and CHN2012 showed that the prevalence rates of MS as boys > girls, obesity > overweight > normal weight. Prevalence of MS in Chinese children and adolescents showed a general trend. Data under different standards showed different prevalence rates. Obesity appeared an important risk factor of MS, suggesting that in order to control obesity in children, attention should be paid to identifying and carrying out effective interventions on children under overweight or obesity.

  10. Metabolic patterns in prion diseases: an FDG PET voxel-based analysis

    International Nuclear Information System (INIS)

    Prieto, Elena; Dominguez-Prado, Ines; Jesus Ribelles, Maria; Arbizu, Javier; Riverol, Mario; Ortega-Cubero, Sara; Rosario Luquin, Maria; Castro, Purificacion de

    2015-01-01

    Clinical diagnosis of human prion diseases can be challenging since symptoms are common to other disorders associated with rapidly progressive dementia. In this context, 18 F-fluorodeoxyglucose (FDG) positron emission tomography (PET) might be a useful complementary tool. The aim of this study was to determine the metabolic pattern in human prion diseases, particularly sporadic Creutzfeldt-Jakob disease (sCJD), the new variant of Creutzfeldt-Jakob disease (vCJD) and fatal familial insomnia (FFI). We retrospectively studied 17 patients with a definitive, probable or possible prion disease who underwent FDG PET in our institution. Of these patients, 12 were diagnosed as sCJD (9 definitive, 2 probable and 1 possible), 1 was diagnosed as definitive vCJD and 4 were diagnosed as definitive FFI. The hypometabolic pattern of each individual and comparisons across the groups of subjects (control subjects, sCJD and FFI) were evaluated using a voxel-based analysis. The sCJD group exhibited a pattern of hypometabolism that affected both subcortical (bilateral caudate, thalamus) and cortical (frontal cortex) structures, while the FFI group only presented a slight hypometabolism in the thalamus. Individual analysis demonstrated a considerable variability of metabolic patterns among patients, with the thalamus and basal ganglia the most frequently affected areas, combined in some cases with frontal and temporal hypometabolism. Patients with a prion disease exhibit a characteristic pattern of brain metabolism presentation in FDG PET imaging. Consequently, in patients with rapidly progressive cognitive impairment, the detection of these patterns in the FDG PET study could orient the diagnosis to a prion disease. (orig.)

  11. Metabolic patterns in prion diseases: an FDG PET voxel-based analysis

    Energy Technology Data Exchange (ETDEWEB)

    Prieto, Elena; Dominguez-Prado, Ines; Jesus Ribelles, Maria; Arbizu, Javier [Clinica Universidad de Navarra, Nuclear Medicine Department, Pamplona (Spain); Riverol, Mario; Ortega-Cubero, Sara; Rosario Luquin, Maria; Castro, Purificacion de [Clinica Universidad de Navarra, Neurology Department, Pamplona (Spain)

    2015-09-15

    Clinical diagnosis of human prion diseases can be challenging since symptoms are common to other disorders associated with rapidly progressive dementia. In this context, {sup 18}F-fluorodeoxyglucose (FDG) positron emission tomography (PET) might be a useful complementary tool. The aim of this study was to determine the metabolic pattern in human prion diseases, particularly sporadic Creutzfeldt-Jakob disease (sCJD), the new variant of Creutzfeldt-Jakob disease (vCJD) and fatal familial insomnia (FFI). We retrospectively studied 17 patients with a definitive, probable or possible prion disease who underwent FDG PET in our institution. Of these patients, 12 were diagnosed as sCJD (9 definitive, 2 probable and 1 possible), 1 was diagnosed as definitive vCJD and 4 were diagnosed as definitive FFI. The hypometabolic pattern of each individual and comparisons across the groups of subjects (control subjects, sCJD and FFI) were evaluated using a voxel-based analysis. The sCJD group exhibited a pattern of hypometabolism that affected both subcortical (bilateral caudate, thalamus) and cortical (frontal cortex) structures, while the FFI group only presented a slight hypometabolism in the thalamus. Individual analysis demonstrated a considerable variability of metabolic patterns among patients, with the thalamus and basal ganglia the most frequently affected areas, combined in some cases with frontal and temporal hypometabolism. Patients with a prion disease exhibit a characteristic pattern of brain metabolism presentation in FDG PET imaging. Consequently, in patients with rapidly progressive cognitive impairment, the detection of these patterns in the FDG PET study could orient the diagnosis to a prion disease. (orig.)

  12. Effects of telephone-based motivational interviewing in lifestyle modification program on reducing metabolic risks in middle-aged and older women with metabolic syndrome: A randomized controlled trial.

    Science.gov (United States)

    Lin, Chia-Huei; Chiang, Shang-Lin; Heitkemper, Margaret McLean; Hung, Yi-Jen; Lee, Meei-Shyuan; Tzeng, Wen-Chii; Chiang, Li-Chi

    2016-08-01

    Lifestyle modification is often difficult for middle-aged and older women living in the community who are at high risk of physical inactivity and metabolic syndrome. To examine the effects of telephone-based motivational interviewing in a 12-week lifestyle modification program on physical activity, MetS, metabolic risks (fasting plasma glucose, blood pressure, triglyceride, high-density lipoprotein, and central obesity), and the number of metabolic risks in community-living middle-aged and older women diagnosed with metabolic syndrome. A randomized controlled trial was conducted. Recruited were 328 middle-aged and older women from a community health center in Taiwan. Eligible women medically diagnosed with metabolic syndrome (n=115) were randomly assigned to one of three groups: The experimental group received an individualized telephone delivered lifestyle modification program that included motivational interviewing delivered by an experienced nurse. The brief group received a single brief lifestyle modification counseling session with a brochure. The usual care group received standard care. Physical activity was assessed with the International Physical Activity Questionnaire and metabolic risks were determined by serum markers and anthropometric measures at pre- and post-intervention. One hundred women completed the study and an intention-to-treat analysis was performed. Generalized estimating equations were used to examine the intervention effects. Women in the experimental group increased physical activity from 1609 to 1892 MET-min/week (β=846, p=.01), reduced the percentage of diagnosed with metabolic syndrome to 81.6% (β=-0.17, p=.003), and decreased the number of metabolic risks from 4.0 to 3.6 (β=-0.50, pMotivational interviewing as a component of an individualized physical activity and lifestyle modification program has positive benefit in reducing metabolic risks in middle-aged and older women. Copyright © 2016 Elsevier Ltd. All rights reserved.

  13. Glucose Metabolic Profile by Visual Assessment Combined with Statistical Parametric Mapping Analysis in Pediatric Patients with Epilepsy.

    Science.gov (United States)

    Zhu, Yuankai; Feng, Jianhua; Wu, Shuang; Hou, Haifeng; Ji, Jianfeng; Zhang, Kai; Chen, Qing; Chen, Lin; Cheng, Haiying; Gao, Liuyan; Chen, Zexin; Zhang, Hong; Tian, Mei

    2017-08-01

    PET with 18 F-FDG has been used for presurgical localization of epileptogenic foci; however, in nonsurgical patients, the correlation between cerebral glucose metabolism and clinical severity has not been fully understood. The aim of this study was to evaluate the glucose metabolic profile using 18 F-FDG PET/CT imaging in patients with epilepsy. Methods: One hundred pediatric epilepsy patients who underwent 18 F-FDG PET/CT, MRI, and electroencephalography examinations were included. Fifteen age-matched controls were also included. 18 F-FDG PET images were analyzed by visual assessment combined with statistical parametric mapping (SPM) analysis. The absolute asymmetry index (|AI|) was calculated in patients with regional abnormal glucose metabolism. Results: Visual assessment combined with SPM analysis of 18 F-FDG PET images detected more patients with abnormal glucose metabolism than visual assessment only. The |AI| significantly positively correlated with seizure frequency ( P glucose metabolism. The only significant contributing variable to the |AI| was the time since last seizure, in patients both with hypometabolism ( P = 0.001) and with hypermetabolism ( P = 0.005). For patients with either hypometabolism ( P glucose metabolic profiles in nonsurgical epilepsy patients. |AI| might be used for evaluation of clinical severity and progress in these patients. Patients with a prolonged period of seizure freedom may have more subtle (or no) metabolic abnormalities on PET. The clinical value of PET might be enhanced by timing the scan closer to clinical seizures. © 2017 by the Society of Nuclear Medicine and Molecular Imaging.

  14. Self-monitoring of blood glucose in non-insulin-treated diabetic patients: a longitudinal evaluation of its impact on metabolic control.

    Science.gov (United States)

    Franciosi, M; Pellegrini, F; De Berardis, G; Belfiglio, M; Di Nardo, B; Greenfield, S; Kaplan, S H; Rossi, M C E; Sacco, M; Tognoni, G; Valentini, M; Nicolucci, A

    2005-07-01

    In the framework of a nationwide outcomes research programme, we assessed the impact of self-monitoring of blood glucose (SMBG) on metabolic control over 3 years in patients with Type 2 diabetes mellitus (DM2) not treated with insulin. The study involved 1896 patients who completed, at 6-month intervals for 3 years, a questionnaire investigating SMBG practice. Clinical information was collected by participating clinicians at the same time intervals. The predictive value of SMBG frequency on long-term metabolic control was estimated using multilevel analysis. The impact of SMBG on metabolic control was also evaluated in distinct and homogeneous subgroups of patients showing different likelihood of performing SMBG, identified using a tree-growing technique (RECPAM). Overall, 22% of the patients were on diet alone and 78% were treated with oral agents; 41% practiced SMBG > or = 1/week (10.3% > or = 1/day). The analysis of metabolic control according to the frequency of SMBG failed to show any significant impact of this practice on HbA1c levels over 3 years. Similarly, changes in SMBG frequency during the study were not related to significant changes in HbA1c levels. RECPAM analysis led to the identification of eight classes, characterized by substantial differences in the likelihood of performing SMBG with a frequency of at least 1/week. Nevertheless, in none of the RECPAM classes identified, did SMBG predict a better metabolic control over 3 years of follow-up. In those RECPAM classes indicating that SMBG was mainly performed to avoid hypoglycaemic episodes, SMBG was associated with a decrease in the frequency of hypoglycaemic episodes during the study. In a large sample of non-insulin-treated Type 2 diabetic patients, the performance and frequency of SMBG did not predict better metabolic control over 3 years. We could not identify any specific subgroups of patients for whom SMBG practice was associated with lower HbA1c levels during the study.

  15. High-throughput metabolic state analysis: The missing link in integrated functional genomics of yeasts

    DEFF Research Database (Denmark)

    Villas-Bôas, Silas Granato; Moxley, Joel. F; Åkesson, Mats Fredrik

    2005-01-01

    The lack of comparable metabolic state assays severely limits understanding the metabolic changes caused by genetic or environmental perturbations. The present study reports the application of a novel derivatization method for metabolome analysis of yeast, coupled to data-mining software that ach......The lack of comparable metabolic state assays severely limits understanding the metabolic changes caused by genetic or environmental perturbations. The present study reports the application of a novel derivatization method for metabolome analysis of yeast, coupled to data-mining software...... that achieve comparable throughput, effort and cost compared with DNA arrays. Our sample workup method enables simultaneous metabolite measurements throughout central carbon metabolism and amino acid biosynthesis, using a standard GC-MS platform that was optimized for this Purpose. As an implementation proof...

  16. Regression of microalbuminuria in type 1 diabetic patients: results of a sequential intervention with improved metabolic control and ACE inhibitors.

    Science.gov (United States)

    Vilarrasa, N; Soler, J; Montanya, E

    2005-06-01

    The objective was to evaluate the effect of improved metabolic control and ACE inhibition used sequentially in the treatment of type 1 diabetic patients with microalbuminuria. We studied 44 consecutive type 1 diabetic patients with microalbuminuria not previously treated with ACE inhibitors. Improved metabolic control (optimisation period) was attempted for 6-12 months and patients with persistent microalbuminuria were subsequently treated with ACE inhibitors. Stepwise logistic regression analysis included the variables age, age at diabetes onset, duration of diabetes, HbA1c, initial albumin excretion rate (AER) and mean blood pressure as predictors of final AER. Thirty per cent of patients regressed to normoalbuminuria after the optimisation period, and 58% of them maintained normal AER 4.5+/-1.3 years later (3-7 years). Patients achieving normoalbuminuria had lower baseline AER (53+/-22 vs. 94+/-63 mg/24 h, p=0.012). The initial AER level was the only factor associated with final AER (r=0.58, p=0.021). Thirty patients with persistent microalbuminuria were treated with ACE inhibitors for two years, 35.5% of whom regressed to normal AER. Patients achieving normoalbuminuria after ACE inhibitor treatment had lower baseline AER (55+/-24 vs. 132+/-75 mg/24 h, p=0.03). The initial AER was the sole predictor of final AER (r=0.51, ptherapy resulted in long-term normalisation of AER in 47.4% of patients. The sequential implementation of improved metabolic control and ACE inhibitor therapy had a long-term beneficial effect in type 1 diabetic patients with microalbuminuria. We propose that type 1 diabetic patients with microalbuminuria could benefit from a period of metabolic improvement before the initiation of ACE inhibitor therapy.

  17. Combined Effects of Ezetimibe and Phytosterols on Cholesterol Metabolism: A Randomized, Controlled Feeding Study in Humans

    Science.gov (United States)

    Lin, Xiaobo; Racette, Susan B.; Lefevre, Michael; Ma, Lina; Spearie, Catherine Anderson; Steger-May, Karen; Ostlund, Richard E.

    2011-01-01

    Background Both ezetimibe and phytosterols inhibit cholesterol absorption. We tested the hypothesis that ezetimibe combined with phytosterols is more effective than ezetimibe alone in altering cholesterol metabolism. Methods and Results Twenty-one mildly hypercholesterolemic subjects completed a randomized, double-blind, placebo-controlled, triple crossover study. Each subject received a phytosterol-controlled diet plus (1) ezetimibe placebo + phytosterol placebo, (2) 10 mg ezetimibe/day + phytosterol placebo, and (3) 10 mg ezetimibe/day + 2.5 g phytosterols/day, for 3 weeks each. All meals were prepared in a metabolic kitchen. Primary outcomes were intestinal cholesterol absorption, fecal cholesterol excretion, and LDL cholesterol levels. The combined treatment resulted in significantly lower intestinal cholesterol absorption (598 mg/day, 95% CI 368 to 828) relative to control (2161 mg/day, 1112 to 3209) and ezetimibe alone (1054 mg/day, 546 to 1561, both P phytosterols averaged 129 (95% CI: 116 to 142), 108 (97 to 119), and 101 (90 to 112) mg/dL (P phytosterols to ezetimibe significantly enhanced the effects of ezetimibe on whole-body cholesterol metabolism and plasma LDL cholesterol. The large cumulative action of combined dietary and pharmacologic treatment on cholesterol metabolism emphasizes the potential importance of dietary phytosterols as adjunctive therapy for the treatment of hypercholesterolemia. PMID:21768544

  18. Equal metabolic control but superior caregiver treatment satisfaction with insulin aspart in preschool children.

    Science.gov (United States)

    Pańkowska, Ewa; Nazim, Joanna; Szalecki, Mieczysław; Urban, Miroslawa

    2010-05-01

    The aim of this study was to compare the metabolic outcomes, safety, and caregiver treatment satisfaction of basal-bolus multiple daily injection (MDI) therapy with mealtime insulin aspart (IAsp) or human insulin (HI) (both with basal NPH insulin), or of continuous subcutaneous infusion (CSII) with IAsp in preschool-age children with type 1 diabetes mellitus. After a 3-week HI MDI run-in, 61 children IAsp MDI or HI MDI or allocated to IAsp CSII for 26 weeks. Efficacy measures were glycated hemoglobin (A1C) and overall metabolic control at study end point. Safety evaluation included hypoglycemia and adverse events. Caregiver treatment satisfaction was evaluated using a World Health Organization questionnaire with 7-point scale answers. A1C level and overall metabolic control remained unchanged in all groups. Minor hypoglycemic episodes were equivalent between groups; few major hypoglycemic events occurred. Caregivers of children receiving IAsp CSII documented a greater increase in treatment satisfaction total scores (P = 0.04 vs. HI MDI and IAsp MDI group) and expressed satisfaction with the frequency of hypoglycemic events. After 26 weeks of treatment with IAsp CSII, IAsp MDI, or HI MDI, all metabolic control parameters remained unchanged and equivalent. Caregiver treatment satisfaction was higher in parents who chose IAsp CSII pump therapy for their children.

  19. Lifestyle Intervention on Metabolic Syndrome and its Impact on Quality of Life: A Randomized Controlled Trial

    Directory of Open Access Journals (Sweden)

    Patrícia Pozas Saboya

    Full Text Available Abstract Background: Lifestyle intervention programs can reduce the prevalence of metabolic syndrome (MetS and, therefore, reduce the risk for cardiac disease, one of the main public health problems nowadays. Objective: The aim of this study was to compare the effects of three types of approach for lifestyle change programs in the reduction of metabolic parameters, and to identify its impact on the quality of life (QOL of individuals with MetS. Methods: A randomized controlled trial included 72 individuals with MetS aged 30-59 years. Individuals were randomized into three groups of multidisciplinary intervention [Standard Intervention (SI - control group; Group Intervention (GI; and Individual Intervention (II] during 12 weeks. The primary outcome was change in the metabolic parameters, and secondarily, the improvement in QOL measures at three moments: baseline, 3 and 9 months. Results: Group and individual interventions resulted in a significant reduction in body mass index, waist circumference, systolic blood pressure at 3 months and the improvement of QOL, although it was significantly associated with the physical functioning domain. However, these changes did not remain 6 months after the end of intervention. Depression and anxiety were significantly associated with worse QOL, although they showed no effect on the response to intervention. Conclusion: Multidisciplinary intervention, especially in a group, might be an effective and economically feasible strategy in the control of metabolic parameters of MetS and improvement of QOL compared to SI, even in a dose-effect relationship.

  20. Dynamic analysis of sugar metabolism in different harvest seasons ...

    African Journals Online (AJOL)

    In pineapple fruits, sugar accumulation plays an important role in flavor characteristics, which varies according to the stage of fruit development. Metabolic changes in the contents of fructose, sucrose and glucose and reducing sugar related to the activities of soluble acid invertase (AI), neutral invertase (NI), sucrose ...

  1. A clustering analysis of lipoprotein diameters in the metabolic syndrome

    Science.gov (United States)

    The presence of smaller low-density lipoproteins (LDL) has been associated with atherosclerosis risk, and the insulin resistance (IR) underlying the metabolic syndrome (MetS). In addition, some research has supported the association of very low-, low- and high-density lipoprotein (VLDL HDL) particle...

  2. Alcohol decreases baseline brain glucose metabolism more in heavy drinkers than controls but has no effect on stimulation-induced metabolic increases

    International Nuclear Information System (INIS)

    Volkow, Nora D.; Fowler, Joanna S.; Wang, Gene-Jack; Kojori, Eshan Shokri; Benveniste, Helene; Tomasi, Dardo

    2015-01-01

    During alcohol intoxication the human brain increases metabolism of acetate and decreases metabolism of glucose as energy substrate. Here we hypothesized that chronic heavy drinking facilitates this energy substrate shift both for baseline and stimulation conditions. To test this hypothesis we compared the effects of alcohol intoxication (0.75g/kg alcohol versus placebo) on brain glucose metabolism during video-stimulation (VS) versus when given with no-stimulation (NS), in 25 heavy drinkers (HD) and 23 healthy controls each of whom underwent four PET- 18 FDG scans. We showed that resting whole-brain glucose metabolism (placebo-NS) was lower in HD than controls (13%, p=0.04); that alcohol (compared to placebo) decreased metabolism more in HD (20±13%) than controls (9±11%, p=0.005) and in proportion to daily alcohol consumption (r=0.36, p=0.01) but found that alcohol did not reduce the metabolic increases in visual cortex from VS in either group. Instead, VS reduced alcohol-induced decreases in whole-brain glucose metabolism (10±12%) compared to NS in both groups (15±13%, p=0.04), consistent with stimulation-related glucose metabolism enhancement. These findings corroborate our hypothesis that heavy alcohol consumption facilitates use of alternative energy substrates (i.e. acetate) for resting activity during intoxication, which might persist through early sobriety, but indicate that glucose is still favored as energy substrate during brain stimulation. Our findings are consistent with reduced reliance on glucose as the main energy substrate for resting brain metabolism during intoxication (presumably shifting to acetate or other ketones) and a priming of this shift in heavy drinkers, which might make them vulnerable to energy deficits during withdrawal

  3. Alcohol decreases baseline brain glucose metabolism more in heavy drinkers than controls but has no effect on stimulation-induced metabolic increases.

    Science.gov (United States)

    Volkow, Nora D; Wang, Gene-Jack; Shokri Kojori, Ehsan; Fowler, Joanna S; Benveniste, Helene; Tomasi, Dardo

    2015-02-18

    During alcohol intoxication, the human brain increases metabolism of acetate and decreases metabolism of glucose as energy substrate. Here we hypothesized that chronic heavy drinking facilitates this energy substrate shift both for baseline and stimulation conditions. To test this hypothesis, we compared the effects of alcohol intoxication (0.75 g/kg alcohol vs placebo) on brain glucose metabolism during video stimulation (VS) versus when given with no stimulation (NS), in 25 heavy drinkers (HDs) and 23 healthy controls, each of whom underwent four PET-(18)FDG scans. We showed that resting whole-brain glucose metabolism (placebo-NS) was lower in HD than controls (13%, p = 0.04); that alcohol (compared with placebo) decreased metabolism more in HD (20 ± 13%) than controls (9 ± 11%, p = 0.005) and in proportion to daily alcohol consumption (r = 0.36, p = 0.01) but found that alcohol did not reduce the metabolic increases in visual cortex from VS in either group. Instead, VS reduced alcohol-induced decreases in whole-brain glucose metabolism (10 ± 12%) compared with NS in both groups (15 ± 13%, p = 0.04), consistent with stimulation-related glucose metabolism enhancement. These findings corroborate our hypothesis that heavy alcohol consumption facilitates use of alternative energy substrates (i.e., acetate) for resting activity during intoxication, which might persist through early sobriety, but indicate that glucose is still favored as energy substrate during brain stimulation. Our findings are consistent with reduced reliance on glucose as the main energy substrate for resting brain metabolism during intoxication (presumably shifting to acetate or other ketones) and a priming of this shift in HDs, which might make them vulnerable to energy deficits during withdrawal. Copyright © 2015 the authors 0270-6474/15/353248-08$15.00/0.

  4. Understanding the control of acyl flux through the lipid metabolic network of plant oil biosynthesis.

    Science.gov (United States)

    Bates, Philip D

    2016-09-01

    Plant oil biosynthesis involves a complex metabolic network with multiple subcellular compartments, parallel pathways, cycles, and pathways that have a dual function to produce essential membrane lipids and triacylglycerol. Modern molecular biology techniques provide tools to alter plant oil compositions through bioengineering, however with few exceptions the final composition of triacylglycerol cannot be predicted. One reason for limited success in oilseed bioengineering is the inadequate understanding of how to control the flux of fatty acids through various fatty acid modification, and triacylglycerol assembly pathways of the lipid metabolic network. This review focuses on the mechanisms of acyl flux through the lipid metabolic network, and highlights where uncertainty resides in our understanding of seed oil biosynthesis. This article is part of a Special Issue entitled: Plant Lipid Biology edited by Kent D. Chapman and Ivo Feussner. Copyright © 2016 Elsevier B.V. All rights reserved.

  5. Thyroid peroxidase antibodies in pregnant women with type 1 diabetes: impact on thyroid function, metabolic control and pregnancy outcome

    DEFF Research Database (Denmark)

    Vestgaard, Marianne; Nielsen, Lene Ringholm; Rasmussen, Åse Krogh

    2008-01-01

    In pregnant women with type 1 diabetes, we evaluated whether the presence of thyroid peroxidase autoantibodies (anti-TPO) was associated with changes in thyroid function, metabolic control and pregnancy outcome.......In pregnant women with type 1 diabetes, we evaluated whether the presence of thyroid peroxidase autoantibodies (anti-TPO) was associated with changes in thyroid function, metabolic control and pregnancy outcome....

  6. Impact of hypothalamic reactive oxygen species in the control of energy metabolism and food intake

    Directory of Open Access Journals (Sweden)

    Anne eDrougard

    2015-02-01

    Full Text Available Hypothalamus is a key area involved in the control of metabolism and food intake via the integrations of numerous signals (hormones, neurotransmitters, metabolites from various origins. These factors modify hypothalamic neurons activity and generate adequate molecular and behavioral responses to control energy balance. In this complex integrative system, a new concept has been developed in recent years, that includes reactive oxygen species (ROS as a critical player in energy balance. ROS are known to act in many signaling pathways in different peripheral organs, but also in hypothalamus where they regulate food intake and metabolism by acting on different types of neurons, including proopiomelanocortin (POMC and agouti-related protein (AgRP/neuropeptide Y (NPY neurons. Hypothalamic ROS release is under the influence of different factors such as pancreatic and gut hormones, adipokines (leptin, apelin,..., neurotransmitters and nutrients (glucose, lipids,.... The sources of ROS production are multiple including NADPH oxidase, but also the mitochondria which is considered as the main ROS producer in the brain. ROS are considered as signaling molecules, but conversely impairment of this neuronal signaling ROS pathway contributes to alterations of autonomic nervous system and neuroendocrine function, leading to metabolic diseases such as obesity and type 2 diabetes.In this review we focus our attention on factors that are able to modulate hypothalamic ROS release in order to control food intake and energy metabolism, and whose deregulations could participate to the development of pathological conditions. This novel insight reveals an original mechanism in the hypothalamus that controls energy balance and identify hypothalamic ROS signaling as a potential therapeutic strategy to treat metabolic disorders.

  7. Metabolism and the Control of Cell Fate Decisions and Stem Cell Renewal

    Science.gov (United States)

    Ito, Kyoko; Ito, Keisuke

    2016-01-01

    Although the stem cells of various tissues remain in the quiescent state to maintain their undifferentiated state, they also undergo cell divisions as required, and if necessary, even a single stem cell is able to provide for lifelong tissue homeostasis. Stem cell populations are precisely controlled by the balance between their symmetric and asymmetric divisions, with their division patterns determined by whether the daughter cells involved retain their self-renewal capacities. Recent studies have reported that metabolic pathways and the distribution of mitochondria are regulators of the division balance of stem cells and that metabolic defects can shift division balance toward symmetric commitment, which leads to stem cell exhaustion. It has also been observed that in asymmetric division, old mitochondria, which are central metabolic organelles, are segregated to the daughter cell fated to cell differentiation, whereas in symmetric division, young and old mitochondria are equally distributed between both daughter cells. Thus, metabolism and mitochondrial biology play important roles in stem cell fate decisions. As these decisions directly affect tissue homeostasis, understanding their regulatory mechanisms in the context of cellular metabolism is critical. PMID:27482603

  8. Metabolic Control of Dendritic Cell Activation and Function: Recent Advances and Clinical Implications

    Directory of Open Access Journals (Sweden)

    Bart eEverts

    2014-05-01

    Full Text Available Dendritic cells (DCs are key regulators of both immunity and tolerance by controlling activation and polarization of effector T helper cell and regulatory T cell responses. Therefore, there is a major focus on developing approaches to manipulate DC function for immunotherapy. It is well known that changes in cellular activation are coupled to profound changes in cellular metabolism. Over the past decade there is a growing appreciation that these metabolic changes also underlie the capacity of immune cells to perform particular functions. This has led to the concept that the manipulation of cellular metabolism can be used to shape innate and adaptive immune responses. While most of our understanding in this area has been gained from studies with T cells and macrophages, evidence is emerging that the activation and function of DCs are also dictated by the type of metabolism these cells commit to. We here discuss these new insights and explore whether targeting of metabolic pathways in DCs could hold promise as a novel approach to manipulate the functional properties of DCs for clinical purposes.

  9. Monitoring and robust adaptive control of fed-batch cultures of microorganisms exhibiting overflow metabolism [abstract

    Directory of Open Access Journals (Sweden)

    Vande Wouwer, A.

    2010-01-01

    Full Text Available Overflow metabolism characterizes cells strains that are likely to produce inhibiting by-products resulting from an excess of substrate feeding and a saturated respiratory capacity. The critical substrate level separating the two different metabolic pathways is generally not well defined. Monitoring of this kind of cultures, going from model identification to state estimation, is first discussed. Then, a review of control techniques which all aim at maximizing the cell productivity of fed-batch fermentations is presented. Two main adaptive control strategies, one using an estimation of the critical substrate level as set-point and another regulating the by-product concentration, are proposed. Finally, experimental investigations of an adaptive RST control scheme using the observer polynomial for the regulation of the ethanol concentration in Saccharomyces cerevisiae fed-batch cultures ranging from laboratory to industrial scales, are also presented.

  10. The Impact of Telemedicine Interventions Involving Routine Transmission of Blood Glucose Data with Clinician Feedback on Metabolic Control in Youth with Type 1 Diabetes: A Systematic Review and Meta-Analysis

    Directory of Open Access Journals (Sweden)

    Palmert MarkR

    2010-07-01

    Full Text Available Our objective was to determine the impact of telemedicine (TM interventions on the management of type 1 diabetes (T1DM in youth. We performed a systematic review of randomized trials that evaluated TM interventions involving transmission of blood glucose data followed by unsolicited scheduled clinician feedback. We found no apparent effect of the TM interventions on hemoglobin A1c (HbA1c, severe hypoglycemia, or diabetic ketoacidosis. The limited data available on patient satisfaction, quality of life, and cost also suggested no differences between groups. It is unlikely that TM interventions, as performed in the assessed studies, had a substantial effect on glycemic control or acute complications. However, it remains possible that there are other benefits of TM not adequately reported, that newer TM strategies may be more effective and that interventions may benefit subgroups of youth, such as those with the poor glycemic control, adolescents, or those living in remote areas.

  11. A kinetic model describes metabolic response to perturbations and distribution of flux control in the benzenoid network of Petunia hybrida.

    Science.gov (United States)

    Colón, Amy Marshall; Sengupta, Neelanjan; Rhodes, David; Dudareva, Natalia; Morgan, John

    2010-04-01

    In recent years there has been much interest in the genetic enhancement of plant metabolism; however, attempts at genetic modification are often unsuccessful due to an incomplete understanding of network dynamics and their regulatory properties. Kinetic modeling of plant metabolic networks can provide predictive information on network control and response to genetic perturbations, which allow estimation of flux at any concentration of intermediate or enzyme in the system. In this research, a kinetic model of the benzenoid network was developed to simulate whole network responses to different concentrations of supplied phenylalanine (Phe) in petunia flowers and capture flux redistributions caused by genetic manipulations. Kinetic parameters were obtained by network decomposition and non-linear least squares optimization of data from petunia flowers supplied with either 75 or 150 mm(2)H(5)-Phe. A single set of kinetic parameters simultaneously accommodated labeling and pool size data obtained for all endogenous and emitted volatiles at the two concentrations of supplied (2)H(5)-Phe. The generated kinetic model was validated using flowers from transgenic petunia plants in which benzyl CoA:benzyl alcohol/phenylethanol benzoyltransferase (BPBT) was down-regulated via RNAi. The determined in vivo kinetic parameters were used for metabolic control analysis, in which flux control coefficients were calculated for fluxes around the key branch point at Phe and revealed that phenylacetaldehyde synthase activity is the primary controlling factor for the phenylacetaldehyde branch of the benzenoid network. In contrast, control of flux through the beta-oxidative and non-beta-oxidative pathways is highly distributed.

  12. Elevated host lipid metabolism revealed by iTRAQ-based quantitative proteomic analysis of cerebrospinal fluid of tuberculous meningitis patients

    Energy Technology Data Exchange (ETDEWEB)

    Mu, Jun [Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing (China); Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing (China); Chongqing Key Laboratory of Neurobiology, Chongqing (China); Yang, Yongtao [Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing (China); Chongqing Key Laboratory of Neurobiology, Chongqing (China); Department of Neurology, Yongchuan Hospital of Chongqing Medical University, Chongqing (China); Chen, Jin; Cheng, Ke; Li, Qi; Wei, Yongdong; Zhu, Dan; Shao, Weihua; Zheng, Peng [Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing (China); Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing (China); Chongqing Key Laboratory of Neurobiology, Chongqing (China); Xie, Peng, E-mail: xiepeng@cqmu.edu.cn [Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing (China); Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing (China); Chongqing Key Laboratory of Neurobiology, Chongqing (China); Department of Neurology, Yongchuan Hospital of Chongqing Medical University, Chongqing (China)

    2015-10-30

    Purpose: Tuberculous meningitis (TBM) remains to be one of the most deadly infectious diseases. The pathogen interacts with the host immune system, the process of which is largely unknown. Various cellular processes of Mycobacterium tuberculosis (MTB) centers around lipid metabolism. To determine the lipid metabolism related proteins, a quantitative proteomic study was performed here to identify differential proteins in the cerebrospinal fluid (CSF) obtained from TBM patients (n = 12) and healthy controls (n = 12). Methods: CSF samples were desalted, concentrated, labelled with isobaric tags for relative and absolute quantitation (iTRAQ™), and analyzed by multi-dimensional liquid chromatography-tandem mass spectrometry (LC-MS/MS). Gene ontology and proteomic phenotyping analysis of the differential proteins were conducted using Database for Annotation, Visualization, and Integrated Discovery (DAVID) Bioinformatics Resources. ApoE and ApoB were selected for validation by ELISA. Results: Proteomic phenotyping of the 4 differential proteins was invloved in the lipid metabolism. ELISA showed significantly increased ApoB levels in TBM subjects compared to healthy controls. Area under the receiver operating characteristic curve analysis demonstrated ApoB levels could distinguish TBM subjects from healthy controls and viral meningitis subjects with 89.3% sensitivity and 92% specificity. Conclusions: CSF lipid metabolism disregulation, especially elevated expression of ApoB, gives insights into the pathogenesis of TBM. Further evaluation of these findings in larger studies including anti-tuberculosis medicated and unmedicated patient cohorts with other center nervous system infectious diseases is required for successful clinical translation. - Highlights: • The first proteomic study on the cerebrospinal fluid of tuberculous meningitis patients using iTRAQ. • Identify 4 differential proteins invloved in the lipid metabolism. • Elevated expression of ApoB gives

  13. The Role of Monoaminergic Neurotransmission for Metabolic Control in the Fruit Fly Drosophila Melanogaster

    Directory of Open Access Journals (Sweden)

    Yong Li

    2017-08-01

    Full Text Available Hormones control various metabolic traits comprising fat deposition or starvation resistance. Here we show that two invertebrate neurohormones, octopamine (OA and tyramine (TA as well as their associated receptors, had a major impact on these metabolic traits. Animals devoid of the monoamine OA develop a severe obesity phenotype. Using flies defective in the expression of receptors for OA and TA, we aimed to decipher the contributions of single receptors for these metabolic phenotypes. Whereas those animals impaired in octß1r, octß2r and tar1 share the obesity phenotype of OA-deficient (tβh-deficient animals, the octß1r, octß2r deficient flies showed reduced insulin release, which is opposed to the situation found in tβh-deficient animals. On the other hand, OAMB deficient flies were leaner than controls, implying that the regulation of this phenotype is more complex than anticipated. Other phenotypes seen in tβh-deficient animals, such as the reduced ability to perform complex movements tasks can mainly be attributed to the octß2r. Tissue-specific RNAi experiments revealed a very complex interorgan communication leading to the different metabolic phenotypes observed in OA or OA and TA-deficient flies.

  14. Metabolic Pathway Signatures Associated with Urinary Metabolite Biomarkers Differentiate Bladder Cancer Patients from Healthy Controls.

    Science.gov (United States)

    Kim, Won Tae; Yun, Seok Joong; Yan, Chunri; Jeong, Pildu; Kim, Ye Hwan; Lee, Il Seok; Kang, Ho Won; Park, Sunghyouk; Moon, Sung Kwon; Choi, Yung Hyun; Choi, Young Deuk; Kim, Isaac Yi; Kim, Jayoung; Kim, Wun Jae

    2016-07-01

    Our previous high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry study identified bladder cancer (BCA)-specific urine metabolites, including carnitine, acylcarnitines, and melatonin. The objective of the current study was to determine which metabolic pathways are perturbed in BCA, based on our previously identified urinary metabolome. A total of 135 primary BCA samples and 26 control tissue samples from healthy volunteers were analyzed. The association between specific urinary metabolites and their related encoding genes was analyzed. Significant alterations in the carnitine-acylcarnitine and tryptophan metabolic pathways were detected in urine specimens from BCA patients compared to those of healthy controls. The expression of eight genes involved in the carnitine-acylcarnitine metabolic pathway (CPT1A, CPT1B, CPT1C, CPT2, SLC25A20, and CRAT) or tryptophan metabolism (TPH1 and IDO1) was assessed by RT-PCR in our BCA cohort (n=135). CPT1B, CPT1C, SLC25A20, CRAT, TPH1, and IOD1 were significantly downregulated in tumor tissues compared to normal bladder tissues (pmetabolic pathways, which were the most perturbed pathways in BCA, were determined.

  15. General metabolism of Laribacter hongkongensis: a genome-wide analysis

    Directory of Open Access Journals (Sweden)

    Curreem Shirly O

    2011-04-01

    Full Text Available Abstract Background Laribacter hongkongensis is associated with community-acquired gastroenteritis and traveler's diarrhea. In this study, we performed an in-depth annotation of the genes and pathways of the general metabolism of L. hongkongensis and correlated them with its phenotypic characteristics. Results The L. hongkongensis genome possesses the pentose phosphate and gluconeogenesis pathways and tricarboxylic acid and glyoxylate cycles, but incomplete Embden-Meyerhof-Parnas and Entner-Doudoroff pathways, in agreement with its asaccharolytic phenotype. It contains enzymes for biosynthesis and β-oxidation of saturated fatty acids, biosynthesis of all 20 universal amino acids and selenocysteine, the latter not observed in Neisseria gonorrhoeae, Neisseria meningitidis and Chromobacterium violaceum. The genome contains a variety of dehydrogenases, enabling it to utilize different substrates as electron donors. It encodes three terminal cytochrome oxidases for respiration using oxygen as the electron acceptor under aerobic and microaerophilic conditions and four reductases for respiration with alternative electron acceptors under anaerobic conditions. The presence of complete tetrathionate reductase operon may confer survival advantage in mammalian host in association with diarrhea. The genome contains CDSs for incorporating sulfur and nitrogen by sulfate assimilation, ammonia assimilation and nitrate reduction. The existence of both glutamate dehydrogenase and glutamine synthetase/glutamate synthase pathways suggests an importance of ammonia metabolism in the living environments that it may encounter. Conclusions The L. hongkongensis genome possesses a variety of genes and pathways for carbohydrate, amino acid and lipid metabolism, respiratory chain and sulfur and nitrogen metabolism. These allow the bacterium to utilize various substrates for energy production and survive in different environmental niches.

  16. Identification of microRNAs controlling hepatic mRNA levels for metabolic genes during the metabolic transition from embryonic to posthatch development in the chicken.

    Science.gov (United States)

    Hicks, Julie A; Porter, Tom E; Liu, Hsiao-Ching

    2017-09-05

    The transition from embryonic to posthatch development in the chicken represents a massive metabolic switch from primarily lipolytic to primarily lipogenic metabolism. This metabolic switch is essential for the chick to successfully transition from the metabolism of stored egg yolk to the utilization of carbohydrate-based feed. However, regulation of this metabolic switch is not well understood. We hypothesized that microRNAs (miRNAs) play an important role in the metabolic switch that is essential to efficient growth of chickens. We used high-throughput RNA sequencing to characterize expression profiles of mRNA and miRNA in liver during late embryonic and early posthatch development of the chicken. This extensive data set was used to define the contributions of microRNAs to the metabolic switch during development that is critical to growth and nutrient utilization in chickens. We found that expression of over 800 mRNAs and 30 miRNAs was altered in the embryonic liver between embryonic day 18 and posthatch day 3, and many of these differentially expressed mRNAs and miRNAs are associated with metabolic processes. We confirmed the regulation of some of these mRNAs by miRNAs expressed in a reciprocal pattern using luciferase reporter assays. Finally, through the use of yeast one-hybrid screens, we identified several proteins that likely regulate expression of one of these important miRNAs. Integration of the upstream regulatory mechanisms governing miRNA expression along with monitoring the downstream effects of this expression will ultimately allow for the construction of complete miRNA regulatory networks associated with the hepatic metabolic switch in chickens. Our findings support a key role for miRNAs in controlling the metabolic switch that occurs between embryonic and posthatch development in the chicken.

  17. Flux analysis uncovers key role of functional redundancy in formaldehyde metabolism.

    Directory of Open Access Journals (Sweden)

    Christopher J Marx

    2005-02-01

    Full Text Available Genome-scale analysis of predicted metabolic pathways has revealed the common occurrence of apparent redundancy for specific functional units, or metabolic modules. In many cases, mutation analysis does not resolve function, and instead, direct experimental analysis of metabolic flux under changing conditions is necessary. In order to use genome sequences to build models of cellular function, it is important to define function for such apparently redundant systems. Here we describe direct flux measurements to determine the role of redundancy in three modules involved in formaldehyde assimilation and dissimilation in a bacterium growing on methanol. A combination of deuterium and (14C labeling was used to measure the flux through each of the branches of metabolism for growth on methanol during transitions into and out of methylotrophy. The cells were found to differentially partition formaldehyde among the three modules depending on the flux of methanol into the cell. A dynamic mathematical model demonstrated that the kinetic constants of the enzymes involved are sufficient to account for this phenomenon. We demonstrate the role of redundancy in formaldehyde metabolism and have uncovered a new paradigm for coping with toxic, high-flux metabolic intermediates: a dynamic, interconnected metabolic loop.

  18. Development of Renewable Biofuels Technology by Transcriptomic Analysis and Metabolic Engineering of Diatoms

    Energy Technology Data Exchange (ETDEWEB)

    Hildebrand, Mark [Univ. of California, San Diego, CA (United States)

    2013-11-18

    There is enormous interest in developing renewable sources of liquid fuels because of depletion of fossil fuel reserves, dependence on foreign sources, and increasing atmospheric CO2 levels. Algae produce neutral lipids that are readily converted into liquid fuels such as biodiesel or JP-8 equivalent, and are attractive sources because they are far more productive than plants (yielding 10 -100’s of time more lipid per land area), and can be grown on non-cultivatable land with non-potable (brackish or salt) water sources. Unicellular algae known as diatoms were the most thoroughly characterized species in the National Renewable Energy Laboratory’s Aquatic Species Program, whose goal was to develop microalgae as renewable fuel sources. Lipid accumulation in microalgae is generally induced by nutrient limitation, which involves a change in environmental conditions. Intrinsic variability in cellular response to environmental changes prevents a high degree of control over the process. Nutrient limitation also inhibits biomass accumulation; therefore a tradeoff between high biomass and lipid production occurs. The goal of this project was to develop metabolic engineering approaches for diatoms to enable induction of lipid accumulation by controllable manipulation of intracellular processes rather than from external environmental conditions, and to manipulate carbon partitioning within the cell between lipid and carbohydrate synthesis to enable both abundant biomass and lipid accumulation. There were two specific objectives for this project; Objective 1:To perform comparative transcriptomic analysis in T. pseudonana and C. cryptica of lipid accumulation resulting from silicon and nitrogen limitation, to identify common and key regulatory steps involved in controlling lipid accumulation and carbon partitioning; and Objective 2: To metabolically engineer the cell to alter carbon partitioning to either trigger lipid induction without the need for nutrient

  19. Metabolic engineering of Synechocystis sp. PCC 6803 for enhanced ethanol production based on flux balance analysis.

    Science.gov (United States)

    Yoshikawa, Katsunori; Toya, Yoshihiro; Shimizu, Hiroshi

    2017-05-01

    Synechocystis sp. PCC 6803 is an attractive host for bio-ethanol production due to its ability to directly convert atmospheric carbon dioxide into ethanol using photosystems. To enhance ethanol production in Synechocystis sp. PCC 6803, metabolic engineering was performed based on in silico simulations, using the genome-scale metabolic model. Comprehensive reaction knockout simulations by flux balance analysis predicted that the knockout of NAD(P)H dehydrogenase enhanced ethanol production under photoautotrophic conditions, where ammonium is the nitrogen source. This deletion inhibits the re-oxidation of NAD(P)H, which is generated by ferredoxin-NADP + reductase and imposes re-oxidation in the ethanol synthesis pathway. The effect of deleting the ndhF1 gene, which encodes NADH dehydrogenase subunit 5, on ethanol production was experimentally evaluated using ethanol-producing strains of Synechocystis sp. PCC 6803. The ethanol titer of the ethanol-producing ∆ndhF1 strain increased by 145%, compared with that of the control strain.

  20. 13C Metabolic Flux Analysis for systematic metabolic engineering of S. cerevisiae for overproduction of fatty acids.

    Directory of Open Access Journals (Sweden)

    Amit Ghosh

    2016-10-01

    Full Text Available Efficient redirection of microbial metabolism into the abundant production of desired bioproducts remains non-trivial. Here we used flux-based modeling approaches to improve yields of fatty acids in S. cerevisiae. We combined 13C labeling data with comprehensive genome-scale models to shed light onto microbial metabolism and improve metabolic engineering efforts. We concentrated on studying the balance of acetyl-CoA, a precursor metabolite for the biosynthesis of fatty acids. A genome-wide acetyl-CoA balance study showed ATP citrate lyase from Y. lipolytica as a robust source of cytoplasmic acetyl-CoA and malate synthase as a desirable target for down-regulation in terms of acetyl-CoA consumption. These genetic modifications were applied to S. cerevisiae WRY2, a strain that is capable of producing 460 mg L of free fatty acids. With the addition of ATP citrate lyase and down-regulation of malate synthase the engineered strain produced 26 per cent more free fatty acids. Further increases in free fatty acid production of 33 per cent were obtained by knocking out the cytoplasmic glycerol-3-phosphate dehydrogenase, which flux analysis had shown was competing for carbon flux upstream with the carbon flux through the acetyl-CoA production pathway in the cytoplasm. In total, the genetic interventions applied in this work increased fatty acid production by 70 per cent.

  1. OpenFLUX: efficient modelling software for 13C-based metabolic flux analysis

    Directory of Open Access Journals (Sweden)

    Nielsen Lars K

    2009-05-01

    Full Text Available Abstract Background The quantitative analysis of metabolic fluxes, i.e., in vivo activities of intracellular enzymes and pathways, provides key information on biological systems in systems biology and metabolic engineering. It is based on a comprehensive approach combining (i tracer cultivation on 13C substrates, (ii 13C labelling analysis by mass spectrometry and (iii mathematical modelling for experimental design, data processing, flux calculation and statistics. Whereas the cultivation and the analytical part is fairly advanced, a lack of appropriate modelling software solutions for all modelling aspects in flux studies is limiting the application of metabolic flux analysis. Results We have developed OpenFLUX as a user friendly, yet flexible software application for small and large scale 13C metabolic flux analysis. The application is based on the new Elementary Metabolite Unit (EMU framework, significantly enhancing computation speed for flux calculation. From simple notation of metabolic reaction networks defined in a spreadsheet, the OpenFLUX parser automatically generates MATLAB-readable metabolite and isotopomer balances, thus strongly facilitating model creation. The model can be used to perform experimental design, parameter estimation and sensitivity analysis either using the built-in gradient-based search or Monte Carlo algorithms or in user-defined algorithms. Exemplified for a microbial flux study with 71 reactions, 8 free flux parameters and mass isotopomer distribution of 10 metabolites, OpenFLUX allowed to automatically compile the EMU-based model from an Excel file containing metabolic reactions and carbon transfer mechanisms, showing it's user-friendliness. It reliably reproduced the published data and optimum flux distributions for the network under study were found quickly ( Conclusion We have developed a fast, accurate application to perform steady-state 13C metabolic flux analysis. OpenFLUX will strongly facilitate and

  2. RENT CONTROL: A COMPARATIVE ANALYSIS

    Directory of Open Access Journals (Sweden)

    Sue-Mari Maass

    2012-11-01

    Full Text Available Recent case law shows that vulnerable, previously disadvantaged private sector tenants are currently facing eviction orders – and consequential homelessness – on the basis that their leases have expired. In terms of the case law it is evident that once their leases have expired, these households do not have access to alternative accommodation. In terms of the Constitution, this group of marginalised tenants have a constitutional right of access to adequate housing and a right to occupy land with legally secure tenure. The purpose of this article is to critically analyse a number of legislative interventions, and specifically rent control, that were imposed in various jurisdictions in order to provide strengthened tenure protection for tenants. The rationale for this analysis is to determine whether the current South African landlord-tenant regime is able to provide adequate tenure protection for vulnerable tenants and therefore in the process of transforming in line with the Constitution. The legal construction of rent control was adopted in pre-1994 South Africa, England and New York City to provide substantive tenure protection for tenants during housing shortages. These statutory interventions in the different private rental markets were justified on the basis that there was a general need to protect tenants against exploitation by landlords. However, the justification for the persistent imposition of rent control in New York City is different since it protects a minority group of financially weak tenants against homelessness. The English landlord-tenant regime highlights the importance of a well-structured social sector that can provide secure, long-term housing options for low-income households who are struggling to access the private rental sector. Additionally, the English rental housing framework shows that if the social sector is functioning as a "safety net" for low-income households, the private sector would be able to uphold

  3. Metabolic Control in Mammalian Fed-Batch Cell Cultures for Reduced Lactic Acid Accumulation and Improved Process Robustness.

    Science.gov (United States)

    Konakovsky, Viktor; Clemens, Christoph; Müller, Markus Michael; Bechmann, Jan; Berger, Martina; Schlatter, Stefan; Herwig, Christoph

    2016-01-11

    Biomass and cell-specific metabolic rates usually change dynamically over time, making the "feed according to need" strategy difficult to realize in a commercial fed-batch process. We here demonstrate a novel feeding strategy which is designed to hold a particular metabolic state in a fed-batch process by adaptive feeding in real time. The feed rate is calculated with a transferable biomass model based on capacitance, which changes the nutrient flow stoichiometrically in real time. A limited glucose environment was used to confine the cell in a particular metabolic state. In order to cope with uncertainty, two strategies were tested to change the adaptive feed rate and prevent starvation while in limitation: (i) inline pH and online glucose concentration measurement or (ii) inline pH alone, which was shown to be sufficient for the problem statement. In this contribution, we achieved metabolic control within a defined target range. The direct benefit was two-fold: the lactic acid profile was improved and pH could be kept stable. Multivariate Data Analysis (MVDA) has shown that pH influenced lactic acid production or consumption in historical data sets. We demonstrate that a low pH (around 6.8) is not required for our strategy, as glucose availability is already limiting the flux. On the contrary, we boosted glycolytic flux in glucose limitation by setting the pH to 7.4. This new approach led to a yield of lactic acid/glucose (Y L/G) around zero for the whole process time and high titers in our labs. We hypothesize that a higher carbon flux, resulting from a higher pH, may lead to more cells which produce more product. The relevance of this work aims at feeding mammalian cell cultures safely in limitation with a desired metabolic flux range. This resulted in extremely stable, low glucose levels, very robust pH profiles without acid/base interventions and a metabolic state in which lactic acid was consumed instead of being produced from day 1. With this contribution

  4. Metabolic Control in Mammalian Fed-Batch Cell Cultures for Reduced Lactic Acid Accumulation and Improved Process Robustness

    Directory of Open Access Journals (Sweden)

    Viktor Konakovsky

    2016-01-01

    Full Text Available Biomass and cell-specific metabolic rates usually change dynamically over time, making the “feed according to need” strategy difficult to realize in a commercial fed-batch process. We here demonstrate a novel feeding strategy which is designed to hold a particular metabolic state in a fed-batch process by adaptive feeding in real time. The feed rate is calculated with a transferable biomass model based on capacitance, which changes the nutrient flow stoichiometrically in real time. A limited glucose environment was used to confine the cell in a particular metabolic state. In order to cope with uncertainty, two strategies were tested to change the adaptive feed rate and prevent starvation while in limitation: (i inline pH and online glucose concentration measurement or (ii inline pH alone, which was shown to be sufficient for the problem statement. In this contribution, we achieved metabolic control within a defined target range. The direct benefit was two-fold: the lactic acid profile was improved and pH could be kept stable. Multivariate Data Analysis (MVDA has shown that pH influenced lactic acid production or consumption in historical data sets. We demonstrate that a low pH (around 6.8 is not required for our strategy, as glucose availability is already limiting the flux. On the contrary, we boosted glycolytic flux in glucose limitation by setting the pH to 7.4. This new approach led to a yield of lactic acid/glucose (Y L/G around zero for the whole process time and high titers in our labs. We hypothesize that a higher carbon flux, resulting from a higher pH, may lead to more cells which produce more product. The relevance of this work aims at feeding mammalian cell cultures safely in limitation with a desired metabolic flux range. This resulted in extremely stable, low glucose levels, very robust pH profiles without acid/base interventions and a metabolic state in which lactic acid was consumed instead of being produced from day 1. With

  5. Clinical and economic analysis of the modern strategies for treating metabolic syndrome

    Directory of Open Access Journals (Sweden)

    Marina Fedorovna Kalashnikova

    2014-04-01

    Full Text Available ObjectiveThe objective of this study was to identify the ways to optimize therapy for metabolic syndrome through complex clinical and economic analysis.MethodsSixty patients with metabolic syndrome were included in the study. The study group (30 subjects with the mean age of 41.0±11 years, 23 females (76.7%, 7 males (23.3% received pharmacotherapy for obesity (orlistat and insulin resistance (metformin, lipid-lowering therapy and antihypertensive therapy, if needed. The control group (30 patients with the mean age of 43.4±9.5 years, 26 females (86.7%, 4 males (13.3% received lipid-lowering and antihypertensive therapy, if needed. All patients underwent clinical and laboratory examination, assessment of depression (Beck Depression Inventory and evaluation of the quality of life using the SF-36 questionnaire at admission to the study and after 6 months of therapy. Complex clinical and economic analyses, including cost-effectiveness and cost-utility analyses and calculation of such indices as “the incremental cost-effectiveness ratio” (ICER, LYG, QALY and “net monetary benefit” (NMB, were conducted based on the results obtained.ResultsImprovement of clinical and laboratory indicators and quality of life in the study group was more significant than that in the control group. The direct medical costs were 33,440.40 RUB for the study group and 18,878.50 RUB for the control group (for 6 months of therapy. The control group CER was 4,016.70, while the study group CER was 3,125.30; ICER was 2,430.90 RUB. LYG was equal to 0.7 and 2.3 years for the control and the study groups, respectively. The QALY measure for the control and study groups was 8.63 and 9.45, respectively. The weighted average total costs for the intended period of living was 498,745.00 RUB for the control group and 457,866.00 RUB for the study group. The control group CUR was 57,792.00 and 54,902.00 RUB/QALY without and with discounting, respectively, while in the study group

  6. Changes in the isozymic pattern of phosphoenolpyruvate : An early step in photoperiodic control of crassulacean acid metabolism level.

    Science.gov (United States)

    Brulfert, J; Arrabaça, M C; Guerrier, D; Queiroz, O

    1979-01-01

    Two major isofunctional forms of phosphoenolpyruvate carboxylase (EC 4.1.1.31) have been separated from the leaves of Kalanchoe blossfeldiana Poelln. Tom Thumb by acrylamide gel electrophoresis and diethylaminoethyl cellulose techniques: one of the forms prevails under long-day treatment (low crassulacean acid metabolism level), the other develops under short-day treatment (high Crassulacean acid metabolism level). Molecular weights are significantly different: 175·10(3) and 186·10(3), respectively. These results indicate that two populations of phosphoenolyruvate carboxylase are present in the plant, one of which is responsible for Crassulacean acid metabolism activity under the control of photoperiod.The Crassulacean acid metabolism appears to depend on the same endogenous clock that governs other photoperiodically controlled events (e.g. flowering). The metabolic and energetic significance of this feature is discussed. It is suggested that modification in isozymic composition could be an early step in the response to photoperiodism at the metabolic level.

  7. Hypoglycemia in pregnant women with type 1 diabetes - Predictors and role of metabolic control

    DEFF Research Database (Denmark)

    Nielsen, L.R.; Johansen, M.; Pedersen-Bjergaard, U.

    2008-01-01

    observational study of 108 consecutive pregnant women with type 1 diabetes was conducted. At 8, 14, 21, 27, and 33 weeks of gestation, patients performed self-monitored plasma glucose (SMPG) (eight/day) for 3 days and completed a questionnaire on nausea, vomiting, hypoglycemia awareness, and history of mild...... awareness or unawareness (3.2 [1.2-8.2]) as independent predictors for severe hypoglycemia. CONCLUSIONS - In pregnancy with type 1 diabetes, the incidence of mild and severe hypoglycemia was highest in early pregnancy, although metabolic control was tighter in the last part of pregnancy. Predictors......OBJECTIVE- In pregnancy with type 1 diabetes, we evaluated occurrence of mild and severe hypoglycemia and analyzed the influence of strict metabolic control, nausea, Vomiting, and other potential predictors of occurrence of severe hypoglycemia. RESEARCH DESIGN AND METHODS- A prospective...

  8. Construction and analysis of a genome-scale metabolic network for Bacillus licheniformis WX-02.

    Science.gov (United States)

    Guo, Jing; Zhang, Hong; Wang, Cheng; Chang, Ji-Wei; Chen, Ling-Ling

    2016-05-01

    We constructed the genome-scale metabolic network of Bacillus licheniformis (B. licheniformis) WX-02 by combining genomic annotation, high-throughput phenotype microarray (PM) experiments and literature-based metabolic information. The accuracy of the metabolic network was assessed by an OmniLog PM experiment. The final metabolic model iWX1009 contains 1009 genes, 1141 metabolites and 1762 reactions, and the predicted metabolic phenotypes showed an agreement rate of 76.8% with experimental PM data. In addition, key metabolic features such as growth yield, utilization of different substrates and essential genes were identified by flux balance analysis. A total of 195 essential genes were predicted from LB medium, among which 149 were verified with the experimental essential gene set of B. subtilis 168. With the removal of 5 reactions from the network, pathways for poly-γ-glutamic acid (γ-PGA) synthesis were optimized and the γ-PGA yield reached 83.8 mmol/h. Furthermore, the important metabolites and pathways related to γ-PGA synthesis and bacterium growth were comprehensively analyzed. The present study provides valuable clues for exploring the metabolisms and metabolic regulation of γ-PGA synthesis in B. licheniformis WX-02. Copyright © 2016 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.

  9. Genome-scale metabolic network of Cordyceps militaris useful for comparative analysis of entomopathogenic fungi.

    Science.gov (United States)

    Vongsangnak, Wanwipa; Raethong, Nachon; Mujchariyakul, Warasinee; Nguyen, Nam Ninh; Leong, Hon Wai; Laoteng, Kobkul

    2017-08-30

    The first genome-scale metabolic network of Cordyceps militaris (iWV1170) was constructed representing its whole metabolisms, which consisted of 894 metabolites and 1,267 metabolic reactions across five compartments, including the plasma membrane, cytoplasm, mitochondria, peroxisome and extracellular space. The iWV1170 could be exploited to explain its phenotypes of growth ability, cordycepin and other metabolites production on various substrates. A high number of genes encoding extracellular enzymes for degradation of complex carbohydrates, lipids and proteins were existed in C. militaris genome. By comparative genome-scale analysis, the adenine metabolic pathway towards putative cordycepin biosynthesis was reconstructed, indicating their evolutionary relationships across eleven species of entomopathogenic fungi. The overall metabolic routes involved in the putative cordycepin biosynthesis were also identified in C. militaris, including central carbon metabolism, amino acid metabolism (glycine, l-glutamine and l-aspartate) and nucleotide metabolism (adenosine and adenine). Interestingly, a lack of the sequence coding for ribonucleotide reductase inhibitor was observed in C. militaris that might contribute to its over-production of cordycepin. Copyright © 2017. Published by Elsevier B.V.

  10. Systems biology analysis of drivers underlying hallmarks of cancer cell metabolism

    Science.gov (United States)

    Zielinski, Daniel C.; Jamshidi, Neema; Corbett, Austin J.; Bordbar, Aarash; Thomas, Alex; Palsson, Bernhard O.

    2017-01-01

    Malignant transformation is often accompanied by significant metabolic changes. To identify drivers underlying these changes, we calculated metabolic flux states for the NCI60 cell line collection and correlated the variance between metabolic states of these lines with their other properties. The analysis revealed a remarkably consistent structure underlying high flux metabolism. The three primary uptake pathways, glucose, glutamine and serine, are each characterized by three features: (1) metabolite uptake sufficient for the stoichiometric requirement to sustain observed growth, (2) overflow metabolism, which scales with excess nutrient uptake over the basal growth requirement, and (3) redox production, which also scales with nutrient uptake but greatly exceeds the requirement for growth. We discovered that resistance to chemotherapeutic drugs in these lines broadly correlates with the amount of glucose uptake. These results support an interpretation of the Warburg effect and glutamine addiction as features of a growth state that provides resistance to metabolic stress through excess redox and energy production. Furthermore, overflow metabolism observed may indicate that mitochondrial catabolic capacity is a key constraint setting an upper limit on the rate of cofactor production possible. These results provide a greater context within which the metabolic alterations in cancer can be understood.

  11. Photoperiodism and enzyme activity: towards a model for the control of circadian metabolic rhythms in the crassulacean Acid metabolism.

    Science.gov (United States)

    Queiroz, O; Morel, C

    1974-04-01

    Metabolic readjustments after a change from long days to short days appear, in Kalanchoe blossfeldiana, to be achieved through the operation of two main mechanisms: variation in enzyme capacity, and circadian rhythmicity. After a lag time, capacity in phosphoenolpyruvate carboxylase and capacity in aspartate aminotransferase increase exponentially and appear to be allometrically linked during 50 to 60 short days; then a sudden fall takes place in the activity of the former. Malic enzyme and alanine aminotransferase behave differently. Thus, the operation of the two sections of the pathway (before and after the malate step) give rise to a continuously changing functional compartmentation in the pathway. Circadian rhythmicity, on the other hand, produces time compartmentation through phase shifts and variation in amplitude, independently for each enzyme. These characteristics suggest that the operation of a so-called biological clock would be involved. We propose the hypothesis that feedback regulation would be more accurate and efficient when applied to an already oscillating, clock-controlled enzyme system.

  12. Role of parenting style in achieving metabolic control in adolescents with type 1 diabetes.

    Science.gov (United States)

    Shorer, Maayan; David, Ravit; Schoenberg-Taz, Michal; Levavi-Lavi, Ifat; Phillip, Moshe; Meyerovitch, Joseph

    2011-08-01

    To examine the role of parenting style in achieving metabolic control and treatment adherence in adolescents with type 1 diabetes. Parents of 100 adolescents with type 1 diabetes completed assessments of their parenting style and sense of helplessness. Parents and patients rated patient adherence to the treatment regimen. Glycemic control was evaluated by HbA(1c) values. An authoritative paternal parenting style predicted better glycemic control and adherence in the child; a permissive maternal parenting style predicted poor adherence. A higher sense of helplessness in both parents predicted worse glycemic control and lesser adherence to treatment. Parental sense of helplessness was a significant predictor of diabetes control after correcting for other confounders (patient age, sex, and treatment method). An authoritative nonhelpless parenting style is associated with better diabetes control in adolescents. Paternal involvement is important in adolescent diabetes management. These results have implications for psychological interventions.

  13. Energy analysis for a sustainable future multi-scale integrated analysis of societal and ecosystem metabolism

    CERN Document Server

    Giampietro, Mario; Sorman, Alevgül H

    2013-01-01

    The vast majority of the countries of the world are now facing an imminent energy crisis, particularly the USA, China, India, Japan and EU countries, but also developing countries having to boost their economic growth precisely when more powerful economies will prevent them from using the limited supply of fossil energy. Despite this crisis, current protocols of energy accounting have been developed for dealing with fossil energy exclusively and are therefore not useful for the analysis of alternative energy sources. The first part of the book illustrates the weakness of existing analyses of energy problems: the science of energy was born and developed neglecting the issue of scale. The authors argue that it is necessary to adopt more complex protocols of accounting and analysis in order to generate robust energy scenarios and effective assessments of the quality of alternative energy sources. The second part of the book introduces the concept of energetic metabolism of modern societies and uses empirical res...

  14. Cardiovascular and metabolic syndrome risk among men with and without erectile dysfunction: case-control study

    OpenAIRE

    Zambon, João Paulo; Mendonça, Rafaela Rosalba de; Wroclawski, Marcelo Langer; Karam Junior, Amir; Santos, Raul D.; Carvalho, José Antonio Maluf de; Wroclawski, Eric Roger

    2010-01-01

    CONTEXT AND OBJECTIVE: Erectile dysfunction has been associated with cardiovascular diseases. The aim here was to evaluate cardiovascular risk through the Framingham Risk Score (FRS) criteria, C-reactive protein (CRP) assays and presence of metabolic syndrome (MS) in men with and without erectile dysfunction diagnosed within a healthcare program. DESIGN AND SETTING: A retrospective case-control study was conducted. The patients were selected from a healthcare program at the Hospital Israelita...

  15. Genetic analysis of metabolic defects in the spontaneously hypertensive rat

    Czech Academy of Sciences Publication Activity Database

    Pravenec, Michal; Zídek, Václav; Musilová, Alena; Šimáková, Miroslava; Kostka, Vlastimil; Mlejnek, Petr; Křen, Vladimír; Křenová, D.; Bílá, V.; Míková, B.; Jáchymová, M.; Horký, K.; Kazdová, L.; St.Lezin, E.; Kurtz, W. T.

    2002-01-01

    Roč. 13, č. 5 (2002), s. 253-258 ISSN 0938-8990 R&D Projects: GA MŠk LN00A079; GA ČR GV204/98/K015; GA ČR GA305/00/1646; GA MŠk NB5299 Grant - others:NIH(US) RO1 HL56028; NIH(US) PO1 HL35018; HHMI(US) 55000331 Institutional research plan: CEZ:AV0Z5011922 Keywords : metabolic defects * spontaneously hypertensive rat Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 2.233, year: 2002

  16. Evaluation of 13C isotopic tracers for metabolic flux analysis in mammalian cells.

    Science.gov (United States)

    Metallo, Christian M; Walther, Jason L; Stephanopoulos, Gregory

    2009-11-01

    (13)C metabolic flux analysis (MFA) is the most comprehensive means of characterizing cellular metabolic states. Uniquely labeled isotopic tracers enable more focused analyses to probe specific reactions within the network. As a result, the choice of tracer largely determines the precision with which one can estimate metabolic fluxes, especially in complex mammalian systems that require multiple substrates. Here we have experimentally determined metabolic fluxes in a tumor cell line, successfully recapitulating the hallmarks of cancer cell metabolism. Using these data, we computationally evaluated specifically labeled (13)C glucose and glutamine tracers for their ability to precisely and accurately estimate fluxes in central carbon metabolism. These methods enabled us to identify the optimal tracer for analyzing individual fluxes, specific pathways, and central carbon metabolism as a whole. [1,2-(13)C(2)]glucose provided the most precise estimates for glycolysis, the pentose phosphate pathway, and the overall network. Tracers such as [2-(13)C]glucose and [3-(13)C]glucose also outperformed the more commonly used [1-(13)C]glucose. [U-(13)C(5)]glutamine emerged as the preferred isotopic tracer for the analysis of the tricarboxylic acid (TCA) cycle. These results provide valuable, quantitative information on the performance of (13)C-labeled substrates and can aid in the design of more informative MFA experiments in mammalian cell culture.

  17. Effects of Korean Red Ginseng on Cardiovascular Risks in Subjects with Metabolic Syndrome: a Double-blind Randomized Controlled Study

    OpenAIRE

    Park, Byoung-Jin; Lee, Yong-Jae; Lee, Hye-Ree; Jung, Dong-Hyuk; Na, Ha-Young; Kim, Hong-Bae; Shim, Jae-Yong

    2012-01-01

    Background This study investigated the effects of Korean red ginseng (KRG) supplementation on metabolic parameters, inflammatory markers, and arterial stiffness in subjects with metabolic syndrome. Methods We performed a randomized, double-blind, placebo-controlled, single-center study in 60 subjects who were not taking drugs that could affect metabolic and vascular functions. Subjects were randomized into either a KRG (4.5 g/d) group or a placebo group for a 12-week study. We collected anthr...

  18. Controllability analysis of decentralised linear controllers for polymeric fuel cells

    Energy Technology Data Exchange (ETDEWEB)

    Serra, Maria; Aguado, Joaquin; Ansede, Xavier; Riera, Jordi [Institut de Robotica i Informatica Industrial, Universitat Politecnica de Catalunya - Consejo Superior de Investigaciones Cientificas, C. Llorens i Artigas 4, 08028 Barcelona (Spain)

    2005-10-10

    This work deals with the control of polymeric fuel cells. It includes a linear analysis of the system at different operating points, the comparison and selection of different control structures, and the validation of the controlled system by simulation. The work is based on a complex non linear model which has been linearised at several operating points. The linear analysis tools used are the Morari resiliency index, the condition number, and the relative gain array. These techniques are employed to compare the controllability of the system with different control structures and at different operating conditions. According to the results, the most promising control structures are selected and their performance with PI based diagonal controllers is evaluated through simulations with the complete non linear model. The range of operability of the examined control structures is compared. Conclusions indicate good performance of several diagonal linear controllers. However, very few have a wide operability range. (author)

  19. A CMI (cell metabolic indicator)-based controller for achieving high growth rate Escherichia coli cultures.

    Science.gov (United States)

    Pepper, Matthew E; Wang, Li; Padmakumar, Ajay; Burg, Timothy C; Harcum, Sarah W; Groff, Richard E

    2014-01-01

    A large fraction of biopharmaceuticals are produced in Escherichia coli, where each new product and strain currently requires a high degree of growth characterization in benchtop and industrial bioreactors to achieve economical production protocols. The capability to use a standard set of sensors to characterize a system quickly without the need to conduct numerous experiments to determine stable growth rate for the strain would significantly decrease development time. This paper presents a cell metabolic indicator (CMI) which provides better insight into the E. coli metabolism than a growth rate value. The CMI is the ratio of the oxygen uptake rate (OUR) of the culture and the base addition rate (BAR) required to keep pH at a desired setpoint. The OUR and BAR are measured using a off-gas sensor and pH probe, respectively, and thus the CMI can be computed online. Experimental results demonstrate the relationship between CMI and the different cell metabolic states. A previously published model is augmented with acid production dynamics, allowing for comparison of the CMI-based controller with an open-loop controller in simulation. The CMI-based controller required little a priori knowledge about the E. coli strain in order to achieve a high growth rate. Since many different types of cells exhibit similar behaviors, the CMI concept can be extended to mammalian and stem cells.

  20. Control of sugar transport and metabolism in Zymomonas mobilis. Final report

    Energy Technology Data Exchange (ETDEWEB)

    Conway, T. [Ohio State Univ., Columbus, OH (United States)

    1995-09-01

    This research deals with the physiology and genetics of sugar transport and metabolic control in Zymomonas mobilis. The specific objectives of the grant as as follows: First, the complex interactions of transcriptional, post-transcriptional and translational control mechanisms on regulation of the glf operon will be investigated. Second, the structure and function of the unique glucose facilitator will be examined by a combination of in vitro and in vivo approaches, making use of the genetically reconstituted system in E. coli. Third, the possibility that physical association or indirect interactions between the glucose facilitator and glucokinase are involved in metabolic control will be analyzed. Fourth, the Z. mobilis glucose transport and phosphorylation system will be utilized to metabolically engineer recombinant E. coli with altered cell pool metabolite profiles. Work on the third and fourth objectives is complete, work on the first and second objectives is progressing nicely. Publication of this work has been admittedly slow, due primarily to a change n location of the research program from the University of Nebraska to The Ohio State University. However, it should be noted that much of the unpublished data outlined below represented completed studies, and are contained in graduate student theses which are being prepared for submission this summer. Since a full year remains in the current funding period, and the new laboratory is now up and running, we fully expect to make reasonable progress on the remaining objectives and to publish the results in a timely fashion.

  1. Interaction of Pubertal Development and Metabolic Control in Adolescents with Type 1 Diabetes Mellitus

    Directory of Open Access Journals (Sweden)

    M. Plamper

    2017-01-01

    Full Text Available Background. In T1DM, delayed pubertal development and reduced final height are associated with inadequate metabolic control. Objective. To assess whether T1DM affects pubertal growth spurt and whether metabolic control during puberty is gender-related. Methods. Using a large multicentre database, longitudinal data from 1294 patients were analysed. Inclusion criteria: complete records of height and HbA1c from the age of seven to 16 years. Exclusion criteria: other significant chronic diseases and medications, T1DM duration less than three months, and initial BMI 97th percentile. Results. Growth velocity (GV was impaired with a significant reduction of peak GV by 1.2 cm in boys. HbA1c increase during male puberty was lower except for a period of 1.5 years. The highest HbA1c increase in boys coincided with maximum growth spurt. In girls, the highest HbA1c increase was observed during late puberty. Even though there is impaired GV, both sexes reach a height at 16 years of age which corresponds to the background population height. Conclusion. Worsening of metabolic control is sex-discordant and associated with gender-specific alterations of GV. However, the vast majority of boys and girls with T1DM seems to reach normal height at the age of 16 years.

  2. Hepatic mTORC1 controls locomotor activity, body temperature, and lipid metabolism through FGF21

    Science.gov (United States)

    Cornu, Marion; Oppliger, Wolfgang; Albert, Verena; Robitaille, Aaron M.; Trapani, Francesca; Quagliata, Luca; Fuhrer, Tobias; Sauer, Uwe; Terracciano, Luigi; Hall, Michael N.

    2014-01-01

    The liver is a key metabolic organ that controls whole-body physiology in response to nutrient availability. Mammalian target of rapamycin (mTOR) is a nutrient-activated kinase and central controller of growth and metabolism that is negatively regulated by the tumor suppressor tuberous sclerosis complex 1 (TSC1). To investigate the role of hepatic mTOR complex 1 (mTORC1) in whole-body physiology, we generated liver-specific Tsc1 (L-Tsc1 KO) knockout mice. L-Tsc1 KO mice displayed reduced locomotor activity, body temperature, and hepatic triglyceride content in a rapamycin-sensitive manner. Ectopic activation of mTORC1 also caused depletion of hepatic and plasma glutamine, leading to peroxisome proliferator–activated receptor γ coactivator-1α (PGC-1α)–dependent fibroblast growth factor 21 (FGF21) expression in the liver. Injection of glutamine or knockdown of PGC-1α or FGF21 in the liver suppressed the behavioral and metabolic defects due to mTORC1 activation. Thus, mTORC1 in the liver controls whole-body physiology through PGC-1α and FGF21. Finally, mTORC1 signaling correlated with FGF21 expression in human liver tumors, suggesting that treatment of glutamine-addicted cancers with mTOR inhibitors might have beneficial effects at both the tumor and whole-body level. PMID:25082895

  3. Metabolic screening and metabolomics analysis in the Intellectual Developmental Disorders Mexico Study

    Directory of Open Access Journals (Sweden)

    Isabel Ibarra-González

    2017-07-01

    Full Text Available Objective. Inborn errors of metabolism (IEM are genetic conditions that are sometimes associated with intellectual  developmental disorders (IDD. The aim of this study is to contribute to the metabolic characterization of IDD of unknown etiology in Mexico. Materials and methods. Metabolic screening using tandem mass spectrometry and fluorometry will be performed to rule out IEM. In addition,target metabolomic analysis will be done to characterize the metabolomic profile of patients with IDD. Conclusion. Identification of new metabolomic profiles associated withIDD of unknown etiology and comorbidities will contribute to the development of novel diagnostic and therapeutic schemes for the prevention and treatment of IDD in Mexico.

  4. Study of Stationary Phase Metabolism Via Isotopomer Analysis of Amino Acids from an Isolated Protein

    Energy Technology Data Exchange (ETDEWEB)

    Shaikh, AfshanS.; Tang, YinjieJ.; Mukhopadhyay, Aindrila; Martin, Hector Garcia; Gin, Jennifer; Benke, Peter; Keasling, Jay D.

    2009-09-14

    Microbial production of many commercially important secondary metabolites occurs during stationary phase, and methods to measure metabolic flux during this growth phase would be valuable. Metabolic flux analysis is often based on isotopomer information from proteinogenic amino acids. As such, flux analysis primarily reflects the metabolism pertinent to the growth phase during which most proteins are synthesized. To investigate central metabolism and amino acids synthesis activity during stationary phase, addition of fully 13C-labeled glucose followed by induction of green fluorescent protein (GFP) expression during stationary phase was used. Our results indicate that Escherichia coli was able to produce new proteins (i.e., GFP) in the stationary phase, and the amino acids in GFP were mostly from degraded proteins synthesized during the exponential growth phase. Among amino acid biosynthetic pathways, only those for serine, alanine, glutamate/glutamine, and aspartate/asparagine had significant activity during the stationary phase.

  5. Differential proteomic analysis reveals novel links between primary metabolism and antibiotic production in Amycolatopsis balhimycina

    DEFF Research Database (Denmark)

    Gallo, G.; Renzone, G.; Alduina, R.

    2010-01-01

    A differential proteomic analysis, based on 2-DE and MS procedures, was performed on Amycolatopsis balhimycina DSM5908, the actinomycete producing the vancomycin-like antibiotic balhimycin. A comparison of proteomic profiles before and during balhimycin production characterized differentially...... available over the World Wide Web as interactive web pages (http://www.unipa.it/ampuglia/Abal-proteome-maps). Functional clustering analysis revealed that differentially expressed proteins belong to functional groups involved in central carbon metabolism, amino acid metabolism and protein biosynthesis......, energetic and redox balance, sugar/amino sugar metabolism, balhimycin biosynthesis and transcriptional regulation or with hypothetical and/or unknown function. Interestingly, proteins involved in the biosynthesis of balhimycin precursors, such as amino acids, amino sugars and central carbon metabolism...

  6. Treatment patterns and risk factor control in patients with and without metabolic syndrome in cardiac rehabilitation

    Directory of Open Access Journals (Sweden)

    Gitt A

    2012-04-01

    Full Text Available Anselm Gitt1, Christina Jannowitz2, Marthin Karoff3, Barbara Karmann2, Martin Horack1, Heinz Völler4,51Institut für Herzinfarktforschung an der Universität Heidelberg, Ludwigshafen,2Medical Affairs, MSD Sharp and Dohme GmbH, Haar, 3Klinik Königsfeld der Deutschen Rentenversicherung Westfalen in Ennepetal (NRW, Klinik der Universität Witten-Herdecke, 4Kardiologie, Klinik am See, Rüdersdorf, 5Center of Rehabilitation Research, University Potsdam, GermanyAim: Metabolic syndrome (MetS is a clustering of factors that are associated with increased cardiovascular risk. We aimed to investigate the proportion of patients with MetS in patients undergoing cardiac rehabilitation (CR, and to describe differences between patients with MetS compared to those without MetS with regard to (1 patient characteristics including demographics, risk factors, and comorbidities, (2 risk factor management including drug treatment, and (3 control status of risk factors at entry to CR and discharge from CR.Methods: Post-hoc analysis of data from 27,904 inpatients (Transparency Registry to Objectify Guideline-Oriented Risk Factor Management registry that underwent a CR period of about 3 weeks were analyzed descriptively in total and compared by their MetS status.Results: In the total cohort, mean age was 64.3 years, (71.7% male, with no major differences between groups. Patients had been referred after a ST elevation of myocardial infarction event in 41.1% of cases, non-ST elevation of myocardial infarction in 21.8%, or angina pectoris in 16.7%. They had received a percutaneous coronary intervention in 55.1% and bypass surgery (coronary artery bypass graft in 39.5%. Patients with MetS (n = 15,819 compared to those without MetS (n = 12,085 were less frequently males, and in terms of cardiac interventions, more often received coronary artery bypass surgery. Overall, statin use increased from 79.9% at entry to 95.0% at discharge (MetS: 79.7% to 95.2%. Patients with Met

  7. A High Phosphorus Diet Affects Lipid Metabolism in Rat Liver: A DNA Microarray Analysis.

    Directory of Open Access Journals (Sweden)

    Sunwoo Chun

    Full Text Available A high phosphorus (HP diet causes disorders of renal function, bone metabolism, and vascular function. We previously demonstrated that DNA microarray analysis is an appropriate method to comprehensively evaluate the effects of a HP diet on kidney dysfunction such as calcification, fibrillization, and inflammation. We reported that type IIb sodium-dependent phosphate transporter is significantly up-regulated in this context. In the present study, we performed DNA microarray analysis to investigate the effects of a HP diet on the liver, which plays a pivotal role in energy metabolism. DNA microarray analysis was performed with total RNA isolated from the livers of rats fed a control diet (containing 0.3% phosphorus or a HP diet (containing 1.2% phosphorus. Gene Ontology analysis of differentially expressed genes (DEGs revealed that the HP diet induced down-regulation of genes involved in hepatic amino acid catabolism and lipogenesis, while genes related to fatty acid β-oxidation process were up-regulated. Although genes related to fatty acid biosynthesis were down-regulated in HP diet-fed rats, genes important for the elongation and desaturation reactions of omega-3 and -6 fatty acids were up-regulated. Concentrations of hepatic arachidonic acid and eicosapentaenoic acid were increased in HP diet-fed rats. These essential fatty acids activate peroxisome proliferator-activated receptor alpha (PPARα, a transcription factor for fatty acid β-oxidation. Evaluation of the upstream regulators of DEGs using Ingenuity Pathway Analysis indicated that PPARα was activated in the livers of HP diet-fed rats. Furthermore, the serum concentration of fibroblast growth factor 21, a hormone secreted from the liver that promotes fatty acid utilization in adipose tissue as a PPARα target gene, was higher (p = 0.054 in HP diet-fed rats than in control diet-fed rats. These data suggest that a HP diet enhances energy expenditure through the utilization of free fatty

  8. Contaminant effects on cellular metabolic differential pressure curve: a quantitative analysis

    Science.gov (United States)

    Milani, Marziale; Ballerini, Monica; Ferraro, Lorenzo; Zabeo, Matteo; Barberis, Massimo; Cannone, Maria; Faraone, Venera

    2002-06-01

    The possibility of using a pressure monitoring system based on differential pressure sensors to detect contaminant effects on cellular cultures metabolic activity is discussed using Saccharomyces cerevisiae cell cultures: differential pressure curves' shape, starting slope and maximum are affected both by physical and chemical contamination. Aim of the present study is the investigation of the effects generated by a 72h exposition of Saccharomyces cerevisiae, human lymphocytes and AHH1 cellular line cultures to 50Hz, 60(mu) T electromagnetic field. No significant differences have been recorded between irradiated and control yeast samples. On other hand irradiated lymphocytes samples, cultures in a PHA medium, grow less than control ones, but exhibit a greater metabolic activity: changes in the exposure system configuration influence neither sample growth differences nor metabolic response variations between control and irradiated samples. Control and irradiated lymphocyte samples, without PHA in culture medium, show the same behavior both during irradiation and metabolic test. AHH1 control and irradiated samples show no difference both in growth percentage during irradiation and in metabolic test. Different cell cultures respond to the same stimulus in different manners.

  9. Dose effects of dietary phytosterols on cholesterol metabolism: a controlled feeding study.

    Science.gov (United States)

    Racette, Susan B; Lin, Xiaobo; Lefevre, Michael; Spearie, Catherine Anderson; Most, Marlene M; Ma, Lina; Ostlund, Richard E

    2010-01-01

    Phytosterol supplementation of 2 g/d is recommended by the National Cholesterol Education Program to reduce LDL cholesterol. However, the effects of different intakes of phytosterol on cholesterol metabolism are uncertain. We evaluated the effects of 3 phytosterol intakes on whole-body cholesterol metabolism. In this placebo-controlled, crossover feeding trial, 18 adults received a phytosterol-deficient diet (50 mg phytosterols/2000 kcal) plus beverages supplemented with 0, 400, or 2000 mg phytosterols/d for 4 wk each, in random order. All meals were prepared in a metabolic kitchen; breakfast and dinner on weekdays were eaten on site. Primary outcomes were fecal cholesterol excretion and intestinal cholesterol absorption measured with stable-isotope tracers and serum lipoprotein concentrations. Phytosterol intakes (diet plus supplements) averaged 59, 459, and 2059 mg/d during the 3 diet periods. Relative to the 59-mg diet, the 459- and 2059-mg phytosterol intakes significantly (P phytosterol dose (-8.9 +/- 2.3%); a trend was observed with the 459-mg/d dose (-5.0 +/- 2.1%; P = 0.077). Dietary phytosterols in moderate and high doses favorably alter whole-body cholesterol metabolism in a dose-dependent manner. A moderate phytosterol intake (459 mg/d) can be obtained in a healthy diet without supplementation. This trial was registered at clinicaltrials.gov as NCT00860054.

  10. Dose effects of dietary phytosterols on cholesterol metabolism: a controlled feeding study123

    Science.gov (United States)

    Lin, Xiaobo; Lefevre, Michael; Spearie, Catherine Anderson; Most, Marlene M; Ma, Lina; Ostlund, Richard E

    2010-01-01

    Background: Phytosterol supplementation of 2 g/d is recommended by the National Cholesterol Education Program to reduce LDL cholesterol. However, the effects of different intakes of phytosterol on cholesterol metabolism are uncertain. Objective: We evaluated the effects of 3 phytosterol intakes on whole-body cholesterol metabolism. Design: In this placebo-controlled, crossover feeding trial, 18 adults received a phytosterol-deficient diet (50 mg phytosterols/2000 kcal) plus beverages supplemented with 0, 400, or 2000 mg phytosterols/d for 4 wk each, in random order. All meals were prepared in a metabolic kitchen; breakfast and dinner on weekdays were eaten on site. Primary outcomes were fecal cholesterol excretion and intestinal cholesterol absorption measured with stable-isotope tracers and serum lipoprotein concentrations. Results: Phytosterol intakes (diet plus supplements) averaged 59, 459, and 2059 mg/d during the 3 diet periods. Relative to the 59-mg diet, the 459- and 2059-mg phytosterol intakes significantly (P phytosterol dose (−8.9 ± 2.3%); a trend was observed with the 459-mg/d dose (−5.0 ± 2.1%; P = 0.077). Conclusions: Dietary phytosterols in moderate and high doses favorably alter whole-body cholesterol metabolism in a dose-dependent manner. A moderate phytosterol intake (459 mg/d) can be obtained in a healthy diet without supplementation. This trial was registered at clinicaltrials.gov as NCT00860054. PMID:19889819

  11. Geniposide regulates glucose-stimulated insulin secretion possibly through controlling glucose metabolism in INS-1 cells.

    Directory of Open Access Journals (Sweden)

    Jianhui Liu

    Full Text Available Glucose-stimulated insulin secretion (GSIS is essential to the control of metabolic fuel homeostasis. The impairment of GSIS is a key element of β-cell failure and one of causes of type 2 diabetes mellitus (T2DM. Although the KATP channel-dependent mechanism of GSIS has been broadly accepted for several decades, it does not fully describe the effects of glucose on insulin secretion. Emerging evidence has suggested that other mechanisms are involved. The present study demonstrated that geniposide enhanced GSIS in response to the stimulation of low or moderately high concentrations of glucose, and promoted glucose uptake and intracellular ATP levels in INS-1 cells. However, in the presence of a high concentration of glucose, geniposide exerted a contrary role on both GSIS and glucose uptake and metabolism. Furthermore, geniposide improved the impairment of GSIS in INS-1 cells challenged with a high concentration of glucose. Further experiments showed that geniposide modulated pyruvate carboxylase expression and the production of intermediates of glucose metabolism. The data collectively suggest that geniposide has potential to prevent or improve the impairment of insulin secretion in β-cells challenged with high concentrations of glucose, likely through pyruvate carboxylase mediated glucose metabolism in β-cells.

  12. Is Palmitoleic Acid a Plausible Nonpharmacological Strategy to Prevent or Control Chronic Metabolic and Inflammatory Disorders?

    Science.gov (United States)

    de Souza, Camila O; Vannice, Gretchen K; Rosa Neto, José C; Calder, Philip C

    2018-01-01

    Although dietary fatty acids can modulate metabolic and immune responses, the effects of palmitoleic acid (16:1n-7) remain unclear. Since this monounsaturated fatty acid is described as a lipokine, studies with cell culture and rodent models have suggested it enhances whole body insulin sensitivity, stimulates insulin secretion by β cells, increases hepatic fatty acid oxidation, improves the blood lipid profile, and alters macrophage differentiation. However, human studies report elevated blood levels of palmitoleic acid in people with obesity and metabolic syndrome. These findings might be reflection of the level or activity of stearoyl-CoA desaturase-1, which synthesizes palmitoleate and is enhanced in liver and adipose tissue of obese patients. The aim of this review is to describe the immune-metabolic effects of palmitoleic acid observed in cell culture, animal models, and humans to answer the question of whether palmitoleic acid is a plausible nonpharmacological strategy to prevent, control, or ameliorate chronic metabolic and inflammatory disorders. Despite the beneficial effects observed in cell culture and in animal studies, there are insufficient human intervention studies to fully understand the physiological effects of palmitoleic acid. Therefore, more human-based research is needed to identify whether palmitoleic acid meets the promising therapeutic potential suggested by the preclinical research. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  13. Proteomic Analysis of Hylocereus polyrhizus Reveals Metabolic Pathway Changes.

    Science.gov (United States)

    Hua, Qingzhu; Zhou, Qianjun; Gan, Susheng; Wu, Jingyu; Chen, Canbin; Li, Jiaqiang; Ye, Yaoxiong; Zhao, Jietang; Hu, Guibing; Qin, Yonghua

    2016-09-28

    Red dragon fruit or red pitaya ( Hylocereus polyrhizus ) is the only edible fruit that contains betalains. The color of betalains ranges from red and violet to yellow in plants. Betalains may also serve as an important component of health-promoting and disease-preventing functional food. Currently, the biosynthetic and regulatory pathways for betalain production remain to be fully deciphered. In this study, isobaric tags for relative and absolute quantitation (iTRAQ)-based proteomic analyses were used to reveal the molecular mechanism of betalain biosynthesis in H. polyrhizus fruits at white and red pulp stages, respectively. A total of 1946 proteins were identified as the differentially expressed between the two samples, and 936 of them were significantly highly expressed at the red pulp stage of H. polyrhizus . RNA-seq and iTRAQ analyses showed that some transcripts and proteins were positively correlated; they belonged to "phenylpropanoid biosynthesis", "tyrosine metabolism", "flavonoid biosynthesis", "ascorbate and aldarate metabolism", "betalains biosynthesis" and "anthocyanin biosynthesis". In betalains biosynthesis pathway, several proteins/enzymes such as polyphenol oxidase, CYP76AD3 and 4,5-dihydroxy-phenylalanine (DOPA) dioxygenase extradiol-like protein were identified. The present study provides a new insight into the molecular mechanism of the betalain biosynthesis at the posttranscriptional level.

  14. Systematic analysis of stability patterns in plant primary metabolism.

    Directory of Open Access Journals (Sweden)

    Dorothee Girbig

    Full Text Available Metabolic networks are characterized by complex interactions and regulatory mechanisms between many individual components. These interactions determine whether a steady state is stable to perturbations. Structural kinetic modeling (SKM is a framework to analyze the stability of metabolic steady states that allows the study of the system Jacobian without requiring detailed knowledge about individual rate equations. Stability criteria can be derived by generating a large number of structural kinetic models (SK-models with randomly sampled parameter sets and evaluating the resulting Jacobian matrices. Until now, SKM experiments applied univariate tests to detect the network components with the largest influence on stability. In this work, we present an extended SKM approach relying on supervised machine learning to detect patterns of enzyme-metabolite interactions that act together in an orchestrated manner to ensure stability. We demonstrate its application on a detailed SK-model of the Calvin-Benson cycle and connected pathways. The identified stability patterns are highly complex reflecting that changes in dynamic properties depend on concerted interactions between several network components. In total, we find more patterns that reliably ensure stability than patterns ensuring instability. This shows that the design of this system is strongly targeted towards maintaining stability. We also investigate the effect of allosteric regulators revealing that the tendency to stability is significantly increased by including experimentally determined regulatory mechanisms that have not yet been integrated into existing kinetic models.

  15. AntDAS: Automatic Data Analysis Strategy for UPLC-QTOF-Based Nontargeted Metabolic Profiling Analysis.

    Science.gov (United States)

    Fu, Hai-Yan; Guo, Xiao-Ming; Zhang, Yue-Ming; Song, Jing-Jing; Zheng, Qing-Xia; Liu, Ping-Ping; Lu, Peng; Chen, Qian-Si; Yu, Yong-Jie; She, Yuanbin

    2017-10-17

    High-quality data analysis methodology remains a bottleneck for metabolic profiling analysis based on ultraperformance liquid chromatography-quadrupole time-of-flight mass spectrometry. The present work aims to address this problem by proposing a novel data analysis strategy wherein (1) chromatographic peaks in the UPLC-QTOF data set are automatically extracted by using an advanced multiscale Gaussian smoothing-based peak extraction strategy; (2) a peak annotation stage is used to cluster fragment ions that belong to the same compound. With the aid of high-resolution mass spectrometer, (3) a time-shift correction across the samples is efficiently performed by a new peak alignment method; (4) components are registered by using a newly developed adaptive network searching algorithm; (5) statistical methods, such as analysis of variance and hierarchical cluster analysis, are then used to identify the underlying marker compounds; finally, (6) compound identification is performed by matching the extracted peak information, involving high-precision m/z and retention time, against our compound library containing more than 500 plant metabolites. A manually designed mixture of 18 compounds is used to evaluate the performance of the method, and all compounds are detected under various concentration levels. The developed method is comprehensively evaluated by an extremely complex plant data set containing more than 2000 components. Results indicate that the performance of the developed method is comparable with the XCMS. The MATLAB GUI code is available from http://software.tobaccodb.org/software/antdas .

  16. Control of Proteobacterial Central Carbon Metabolism by the HexR Transcriptional Regulator. A Case Study in Shewanella oneidensis

    Energy Technology Data Exchange (ETDEWEB)

    Leyn, Semen; Li, Xiaoqing; Zheng, Qijing; Novichkov, Pavel; Reed, Samantha B.; Romine, Margaret F.; Fredrickson, Jim K.; Yang, Chen; Osterman, Andrei L.; Rodionov, Dmitry A.

    2011-08-17

    Bacteria exploit multiple mechanisms for controlling central carbon metabolism (CCM). Thus, a bioinformatic analysis together with some experimental data implicated HexR transcriptional factor as a global CCM regulator in some lineages of Gammaproteobacteria operating as a functional replacement of Cra regulator characteristic of Enterobacteriales. In this study we combined a large-scale comparative genomic reconstruction of HexRcontrolled regulons in 87 species of Proteobacteria with the detailed experimental analysis of HexR regulatory network in Shewanella oneidensis model system. Although nearly all of the HexR-controlled genes are associated with CCM, remarkable variations were revealed in the scale (from 1-2 target operons in Enterobacteriales up to 20 operons in Aeromonadales) and gene content of HexR regulons between 11 compared lineages. A predicted 17-bp pseudo-palindrome with a consensus tTGTAATwwwATTACa, was confirmed as HexR-binding motif for 15 target operons (comprising 30 genes) by in vitro binding assays. The negative effect of the key CCM intermediate, 2-keto-3-deoxy-6- phosphogluconate, on the DNA-regulator complex formation was verified. A dual mode of HexR action on various target promoters, repression of genes involved in catabolic pathways and activation of gluconeogenic genes, was for the first time predicted by the bioinformatc analysis and experimentally verified by changed gene expression pattern in S. oneidensis AhexR mutant. Phenotypic profiling revealed the inability of this mutant to grow on lactate or pyruvate as a single carbon source. A comparative metabolic flux analysis of wild-type and mutant strains of S. oneidensis using 13Clactate labeling and GC-MS analysis confirmed the hypothesized HexR role as a master regulator of gluconeogenic flux from pyruvate via the transcriptional activation of phosphoenolpyruvate synthase (PpsA).

  17. Metabolic responses of upper-body accelerometer-controlled video games in adults.

    Science.gov (United States)

    Stroud, Leah C; Amonette, William E; Dupler, Terry L

    2010-10-01

    Historically, video games required little physical exertion, but new systems utilize handheld accelerometers that require upper-body movement. It is not fully understood if the metabolic workload while playing these games is sufficient to replace routine physical activity. The purpose of this study was to quantify metabolic workloads and estimate caloric expenditure while playing upper-body accelerometer-controlled and classic seated video games. Nineteen adults completed a peak oxygen consumption treadmill test followed by an experimental session where exercising metabolism and ventilation were measured while playing 3 video games: control (CON), low activity (LOW) and high activity (HI). Resting metabolic measures (REST) were also acquired. Caloric expenditure was estimated using the Weir equation. Mean oxygen consumption normalized to body weight for HI condition was greater than LOW, CON, and REST. Mean oxygen consumption normalized to body weight for LOW condition was also greater than CON and REST. Mean exercise intensities of oxygen consumption reserve for HI, LOW, and CON were 25.8% ± 5.1%, 6.4% ± 4.8%, and 0.8% ± 2.4%, respectively. Estimated caloric expenditure during the HI was significantly related to aerobic fitness, but not during other conditions. An active video game significantly elevated oxygen consumption and heart rate, but the increase was dependent on the type of game. The mean oxygen consumption reserve during the HI video game was below recommended international standards for moderate and vigorous activity. Although upper-body accelerometer-controlled video games provided a greater exercising stimulus than classic seated video games, these data suggest they should not replace routine moderate or vigorous exercise.

  18. QT correction formulas and laboratory analysis on patients with metabolic syndrome and diabetes

    Science.gov (United States)

    Wong, Sara; Rivera, Pedro; Rodríguez, María. G.; Severeyn, Érika; Altuve, Miguel

    2013-11-01

    This article presents a study of ventricular repolarization in diabetic and metabolic syndrome subjects. The corrected QT interval (QTc) was estimated using four correction formulas commonly employed in the literature: Bazett, Fridericia, Framingham and Hodges. After extracting the Q, R and T waves from the electrocardiogram of 52 subjects (19 diabetic, 15 with metabolic syndrome and 18 control), using a wavelet-based approach, the RR interval and QT interval were determined. Then, QTc interval was computed using the formulas previously mentioned. Additionally, laboratory test (fasting glucose, cholesterol, triglycerides) were also evaluated. Results show that metabolic syndrome subjects have normal QTc. However, a longer QTc in this population may be a sign of future complication. The corrected QT interval by Fridericia's formula seems to be the most appropriated for metabolic syndrome subjects (low correlation coefficient between RR and QTc). Significant differences were obtained in the blood glucose and triglyceride levels, principally due to the abnormal sugar metabolization of metabolic syndrome and diabetic subjects. Further studies are focused on the acquisition of a larger database of metabolic syndrome and diabetics subjects and the repetition of this study using other populations, like high performance athletes.

  19. Metabolomics reveals the metabolic shifts following an intervention with rye bread in postmenopausal women- a randomized control trial

    Directory of Open Access Journals (Sweden)

    Moazzami Ali A

    2012-10-01

    Full Text Available Abstract Background Epidemiological studies have consistently shown that whole grain (WG cereals can protect against the development of chronic diseases, but the underlying mechanism is not fully understood. Among WG products, WG rye is considered even more potent because of its unique discrepancy in postprandial insulin and glucose responses known as the rye factor. In this study, an NMR-based metabolomics approach was applied to study the metabolic effects of WG rye as a tool to determine the beneficial effects of WG rye on human health. Methods Thirty-three postmenopausal Finnish women with elevated serum total cholesterol (5.0-8.5 mmol/L and BMI of 20–33 kg/m2 consumed a minimum of 20% of their daily energy intake as high fiber WG rye bread (RB or refined wheat bread (WB in a randomized, controlled, crossover design with two 8-wk intervention periods separated by an 8-wk washout period. At the end of each intervention period, fasting serum was collected for NMR-based metabolomics and the analysis of cholesterol fractions. Multilevel partial least squares discriminant analysis was used for paired comparisons of multivariate data. Results The metabolomics analysis of serum showed lower leucine and isoleucine and higher betaine and N,N-dimethylglycine levels after RB than WB intake. To further investigate the metabolic effects of RB, the serum cholesterol fractions were measured. Total- and LDL-cholesterol levels were higher after RB intake than after WB (p Conclusions This study revealed favorable shifts in branched amino acid and single carbon metabolism and an unfavorable shift in serum cholesterol levels after RB intake in postmenopausal women, which should be considered for evaluating health beneficial effects of rye products.

  20. Dimensionality controls cytoskeleton assembly and metabolism of fibroblast cells in response to rigidity and shape.

    Directory of Open Access Journals (Sweden)

    Mirjam Ochsner

    2010-03-01

    Full Text Available Various physical parameters, including substrate rigidity, size of adhesive islands and micro-and nano-topographies, have been shown to differentially regulate cell fate in two-dimensional (2-D cell cultures. Cells anchored in a three-dimensional (3-D microenvironment show significantly altered phenotypes, from altered cell adhesions, to cell migration and differentiation. Yet, no systematic analysis has been performed that studied how the integrated cellular responses to the physical characteristics of the environment are regulated by dimensionality (2-D versus 3-D.Arrays of 5 or 10 microm deep microwells were fabricated in polydimethylsiloxane (PDMS. The actin cytoskeleton was compared for single primary fibroblasts adhering either to microfabricated adhesive islands (2-D or trapped in microwells (3-D of controlled size, shape, and wall rigidity. On rigid substrates (Young's Modulus = 1 MPa, cytoskeleton assembly within single fibroblast cells occurred in 3-D microwells of circular, rectangular, square, and triangular shapes with 2-D projected surface areas (microwell bottom surface area and total surface areas of adhesion (microwell bottom plus wall surface area that inhibited stress fiber assembly in 2-D. In contrast, cells did not assemble a detectable actin cytoskeleton in soft 3-D microwells (20 kPa, regardless of their shapes, but did so on flat, 2-D substrates. The dependency on environmental dimensionality was also reflected by cell viability and metabolism as probed by mitochondrial activities. Both were upregulated in 3-D cultured cells versus cells on 2-D patterns when surface area of adhesion and rigidity were held constant.These data indicate that cell shape and rigidity are not orthogonal parameters directing cell fate. The sensory toolbox of cells integrates mechanical (rigidity and topographical (shape and dimensionality information differently when cell adhesions are confined to 2-D or occur in a 3-D space.

  1. Visual and SPM analysis of regional cerebral glucose metabolism in adult patients with neurofibromatosis

    Energy Technology Data Exchange (ETDEWEB)

    Yoon, Joon Kee; An, Young Sil; Hong, Seon Pyo; Joh, Chul Woo; Yoon, Seok Nam [Ajou University, School of Medicine, Suwon (Korea, Republic of)

    2005-07-01

    We evaluated the regional cerebral glucose metabolism in adult patients with neurofibromatosis (NF) using visual and SPM analysis, and compared with MRI findings. A total of 11 adult patients with NF type I were prospectively included in the study. All patients underwent F-18 FDG PET and brain MRI within 2 month of each other. All hypometabolic areas on PET were determined visually by 2 nuclear medicine physician and compared with MRI findings. SPM analysis was done using 42 normal controls with p = 0.005. Seven of 11 PET images showed 10 hypometabolic areas and 4 of 11 MRIs showed 6 areas of signal change brain parenchyma. Hypometabolic areas were bilateral thalamus (n=5), left temporal cortex (n=4) and dentate nucleus (n=1). In only 2 lesions (thalamus and dentate nucleus), hypometabolic foci were consistently related to signal change on MRI. SPM analysis revealed significantly decreased area in bilateral thalamus and left temporal cortex. F-18 FDG PET revealed significant hypometabolism in bilateral thalamus and left temporal cortex in adult patients with NF, and it might be helpful in understanding developmental abnormality of NF.

  2. Modular Control Flow Analysis for Libraries

    DEFF Research Database (Denmark)

    Probst, Christian W.

    2002-01-01

    One problem in analyzing object oriented languages is that the exact control flow graph is not known statically due to dynamic dispatching. However, this is needed in order to apply the large class of known interprocedural analysis. Control Flow Analysis in the object oriented setting aims at det...... at determining run-time types of variables, thus allowing to possibly targeted method implementations. We present a flow sensitive analysis that allows separate handling of libraries and thereby efficient analysis of whole programs....

  3. Construction of phylogenetic trees by kernel-based comparative analysis of metabolic networks

    Directory of Open Access Journals (Sweden)

    Chang Jeong-Ho

    2006-06-01

    Full Text Available Abstract Background To infer the tree of life requires knowledge of the common characteristics of each species descended from a common ancestor as the measuring criteria and a method to calculate the distance between the resulting values of each measure. Conventional phylogenetic analysis based on genomic sequences provides information about the genetic relationships between different organisms. In contrast, comparative analysis of metabolic pathways in different organisms can yield insights into their functional relationships under different physiological conditions. However, evaluating the similarities or differences between metabolic networks is a computationally challenging problem, and systematic methods of doing this are desirable. Here we introduce a graph-kernel method for computing the similarity between metabolic networks in polynomial time, and use it to profile metabolic pathways and to construct phylogenetic trees. Results To compare the structures of metabolic networks in organisms, we adopted the exponential graph kernel, which is a kernel-based approach with a labeled graph that includes a label matrix and an adjacency matrix. To construct the phylogenetic trees, we used an unweighted pair-group method with arithmetic mean, i.e., a hierarchical clustering algorithm. We applied the kernel-based network profiling method in a comparative analysis of nine carbohydrate metabolic networks from 81 biological species encompassing Archaea, Eukaryota, and Eubacteria. The resulting phylogenetic hierarchies generally support the tripartite scheme of three domains rather than the two domains of prokaryotes and eukaryotes. Conclusion By combining the kernel machines with metabolic information, the method infers the context of biosphere development that covers physiological events required for adaptation by genetic reconstruction. The results show that one may obtain a global view of the tree of life by comparing the metabolic pathway

  4. Flight test trajectory control analysis

    Science.gov (United States)

    Walker, R.; Gupta, N.

    1983-01-01

    Recent extensions to optimal control theory applied to meaningful linear models with sufficiently flexible software tools provide powerful techniques for designing flight test trajectory controllers (FTTCs). This report describes the principal steps for systematic development of flight trajectory controllers, which can be summarized as planning, modeling, designing, and validating a trajectory controller. The techniques have been kept as general as possible and should apply to a wide range of problems where quantities must be computed and displayed to a pilot to improve pilot effectiveness and to reduce workload and fatigue. To illustrate the approach, a detailed trajectory guidance law is developed and demonstrated for the F-15 aircraft flying the zoom-and-pushover maneuver.

  5. Identification of Conserved Moieties in Metabolic Networks by Graph Theoretical Analysis of Atom Transition Networks

    Science.gov (United States)

    Haraldsdóttir, Hulda S.; Fleming, Ronan M. T.

    2016-01-01

    Conserved moieties are groups of atoms that remain intact in all reactions of a metabolic network. Identification of conserved moieties gives insight into the structure and function of metabolic networks and facilitates metabolic modelling. All moiety conservation relations can be represented as nonnegative integer vectors in the left null space of the stoichiometric matrix corresponding to a biochemical network. Algorithms exist to compute such vectors based only on reaction stoichiometry but their computational complexity has limited their application to relatively small metabolic networks. Moreover, the vectors returned by existing algorithms do not, in general, represent conservation of a specific moiety with a defined atomic structure. Here, we show that identification of conserved moieties requires data on reaction atom mappings in addition to stoichiometry. We present a novel method to identify conserved moieties in metabolic networks by graph theoretical analysis of their underlying atom transition networks. Our method returns the exact group of atoms belonging to each conserved moiety as well as the corresponding vector in the left null space of the stoichiometric matrix. It can be implemented as a pipeline of polynomial time algorithms. Our implementation completes in under five minutes on a metabolic network with more than 4,000 mass balanced reactions. The scalability of the method enables extension of existing applications for moiety conservation relations to genome-scale metabolic networks. We also give examples of new applications made possible by elucidating the atomic structure of conserved moieties. PMID:27870845

  6. Risk of metabolic syndrome among children living in metropolitan Kuala Lumpur: A case control study

    Directory of Open Access Journals (Sweden)

    Ismail Mohd N

    2011-05-01

    Full Text Available Abstract Background With the increasing prevalence of childhood obesity, the metabolic syndrome has been studied among children in many countries but not in Malaysia. Hence, this study aimed to compare metabolic risk factors between overweight/obese and normal weight children and to determine the influence of gender and ethnicity on the metabolic syndrome among school children aged 9-12 years in Kuala Lumpur and its metropolitan suburbs. Methods A case control study was conducted among 402 children, comprising 193 normal-weight and 209 overweight/obese. Weight, height, waist circumference (WC and body composition were measured, and WHO (2007 growth reference was used to categorise children into the two weight groups. Blood pressure (BP was taken, and blood was drawn after an overnight fast to determine fasting blood glucose (FBG and full lipid profile, including triglycerides (TG, high-density lipoprotein cholesterol (HDL-C, low-density lipoprotein cholesterol (LDL-C and total cholesterol (TC. International Diabetes Federation (2007 criteria for children were used to identify metabolic syndrome. Results Participants comprised 60.9% (n = 245 Malay, 30.9% (n = 124 Chinese and 8.2% (n = 33 Indian. Overweight/obese children showed significantly poorer biochemical profile, higher body fat percentage and anthropometric characteristics compared to the normal-weight group. Among the metabolic risk factors, WC ≥90th percentile was found to have the highest odds (OR = 189.0; 95%CI 70.8, 504.8, followed by HDL-C≤1.03 mmol/L (OR = 5.0; 95%CI 2.4, 11.1 and high BP (OR = 4.2; 95%CI 1.3, 18.7. Metabolic syndrome was found in 5.3% of the overweight/obese children but none of the normal-weight children (p Conclusions We conclude that being overweight or obese poses a greater risk of developing the metabolic syndrome among children. Indian ethnicity is at higher risk compared to their counterparts of the same age. Hence, primary intervention strategies are

  7. Metabolic Profiling Analysis of the Alleviation Effect of the Fractions of Niuhuang Jiedu Tablet on Realgar Induced Toxicity in Rats

    Directory of Open Access Journals (Sweden)

    Wenfeng Xu

    2018-01-01

    Full Text Available Niuhuang Jiedu Tablet (NJT is a classical formula in treating acute tonsillitis, pharyngitis, and so on. In the formula, significant level of Realgar as a potentially toxic element is contained. Our previous experiments revealed that it was less toxic for combined Realgar in NJT. However, the active fraction of this prescription with toxicity alleviation effect on Realgar was still obscure. NJT was divided into five different polar fractions (NJT-PET, NJT-25, NJT-50, NJT-75, and NJT-95, and we explored the toxicity alleviation effect on Realgar. Based on 1H NMR spectra of urine and serum from rats, PCA and PLS-DA were performed to identify different metabolic profiles. Liver and kidney histopathology examinations and serum clinical chemistry analysis were also performed. With pattern recognition analysis of metabolites in urine and serum, Realgar group showed a clear separation from control group, while the metabolic profiles of NJT-PET, NJT-25, NJT-50, and NJT-95 groups were similar to Realgar group, and the metabolic profiles of NJT and NJT-75 groups were very close to control group. Statistics results were confirmed by the histopathological examination and biochemical assay. The present work indicated that 75% EtOH fraction of NJT was the most valid fraction with the toxicity alleviation effect on Realgar.

  8. Effect of metabolic control on parathyroid hormone secretion in diabetic patients

    Directory of Open Access Journals (Sweden)

    Paula F.J.A.

    2001-01-01

    Full Text Available The metabolic derangement caused by diabetes mellitus may potentially affect bone mineral metabolism. In the present study we evaluated the effect of diabetes metabolic control on parathyroid hormone (PTH secretion during stimulation with EDTA infusion. The study was conducted on 24 individuals, 8 of them normal subjects (group N: glycated hemoglobin - HbA1C = 4.2 ± 0.2%; range = 3.5-5.0%, 8 patients with good and regular metabolic control (group G-R: HbA1C = 7.3 ± 0.4%; range = 6.0-8.5%, and 8 patients with poor metabolic control (group P: HbA1C = 12.5 ± 1.0%; range: 10.0-18.8%. Blood samples were collected at 10-min intervals throughout the study (a basal period of 30 min and a 2-h period of EDTA infusion, 30 mg/kg body weight and used for the determination of ionized calcium, magnesium, glucose and intact PTH. Basal ionized calcium levels were slightly lower in group P (1.19 ± 0.01 mmol/l than in group N (1.21 ± 0.01 mmol/l and group G-R (1.22 ± 0.01 mmol/l. After EDTA infusion, the three groups presented a significant fall in calcium, but with no significant difference among them at any time. Basal magnesium levels and levels determined during EDTA infusion were significantly lower (P<0.01 in group P than in group N. The induction of hypocalcemia caused an elevation in PTH which was similar in groups N and G-R but significantly higher than in group P throughout the infusion period (+110 min, N = 11.9 ± 2.1 vs G-R = 13.7 ± 1.6 vs P = 7.5 ± 0.7 pmol/l; P<0.05 for P vs N and G-R. The present results show that PTH secretion is impaired in patients with poorly controlled diabetes.

  9. Randomised controlled trial: Effects of aerobic exercise training programme on indices of adiposity and metabolic markers in hypertension

    International Nuclear Information System (INIS)

    Lamina, S.; Okoye, C.G.

    2013-01-01

    Objective: To investigate the effects of interval training programme on blood pressure, maximal oxygen consumption, indices of adiposity and metabolic markers in black African men with essential hypertension. Methods: The study was conducted at Murtala Muhammed Specialist Hospital, Kano, Nigeria, from October 24, 2007 to February 24, 2009. It comprised 245 male patients with mild to moderate (systolic blood pressure 140-179 and diastolic blood pressure 90-109 mmHg) essential hypertension who were age-matched and grouped into experimental and control groups. The experimental group was involved in an 8-week training programme of between 45 and 60 minutes, while the controls remained sedentary during the period. Cardiovascular parameters, maximal oxygen consumption, per cent body fat, waist-to-hip ratio, body mass index, fasting blood sugar, total cholesterol, triglyceride, high density lipoprotein, low density lipoprotein and artherogenic index were assessed. Analysis of co-variance and Pearson correlation tests were used in data analysis which was done using SPSS 16. Results: The study had 140 (57.1%) cases with a mean age of 58.90+-7.35 years, and 105 (42.9%) controls with a mean age of 58.27+-6.24 years. It revealed significant increased effect of interval training programme on maximal oxygen consumption and high-density lipoprotein. There was significant reduction in on all the other controls. Changes in maximal oxygen consumption as a result of interval training significantly and negatively correlated with the other variables except high-density lipoprotein. Conclusions: The therapeutic role of interval exercise training on blood pressure reduction may be mediated through elevation of high-density lipoprotein, reduction of other markers of metabolism, and reduction in bodyweight and fatness. (author)

  10. [Controlling arachidonic acid metabolic network: from single- to multi-target inhibitors of key enzymes].

    Science.gov (United States)

    Liu, Ying; Chen, Zheng; Shang, Er-chang; Yang, Kun; Wei, Deng-guo; Zhou, Lu; Jiang, Xiao-lu; He, Chong; Lai, Lu-hua

    2009-03-01

    Inflammatory diseases are common medical conditions seen in disorders of human immune system. There is a great demand for anti-inflammatory drugs. There are major inflammatory mediators in arachidonic acid metabolic network. Several enzymes in this network have been used as key targets for the development of anti-inflammatory drugs. However, specific single-target inhibitors can not sufficiently control the network balance and may cause side effects at the same time. Most inflammation induced diseases come from the complicated coupling of inflammatory cascades involving multiple targets. In order to treat these complicated diseases, drugs that can intervene multi-targets at the same time attracted much attention. The goal of this review is mainly focused on the key enzymes in arachidonic acid metabolic network, such as phospholipase A2, cyclooxygenase, 5-lipoxygenase and eukotriene A4 hydrolase. Advance in single target and multi-targe inhibitors is summarized.

  11. Effect of oral cinnamon intervention on metabolic profile and body composition of Asian Indians with metabolic syndrome: a randomized double -blind control trial.

    Science.gov (United States)

    Gupta Jain, Sonal; Puri, Seema; Misra, Anoop; Gulati, Seema; Mani, Kalaivani

    2017-06-12

    Nutritional modulation remains central to the management of metabolic syndrome. Intervention with cinnamon in individuals with metabolic syndrome remains sparsely researched. We investigated the effect of oral cinnamon consumption on body composition and metabolic parameters of Asian Indians with metabolic syndrome. In this 16-week double blind randomized control trial, 116 individuals with metabolic syndrome were randomized to two dietary intervention groups, cinnamon [6 capsules (3 g) daily] or wheat flour [6 capsules (2.5 g) daily]. Body composition, blood pressure and metabolic parameters were assessed. Significantly greater decrease [difference between means, (95% CI)] in fasting blood glucose (mmol/L) [0.3 (0.2, 0.5) p = 0.001], glycosylated haemoglobin (mmol/mol) [2.6 (0.4, 4.9) p = 0.023], waist circumference (cm) [4.8 (1.9, 7.7) p = 0.002] and body mass index (kg/m2 ) [1.3 (0.9, 1.5) p = 0.001] was observed in the cinnamon group compared to placebo group. Other parameters which showed significantly greater improvement were: waist-hip ratio, blood pressure, serum total cholesterol, low-density lipoprotein cholesterol, serum triglycerides, and high-density lipoprotein cholesterol. Prevalence of defined metabolic syndrome was significantly reduced in the intervention group (34.5%) vs. the placebo group (5.2%). A single supplement intervention with 3 g cinnamon for 16 weeks resulted in significant improvements in all components of metabolic syndrome in a sample of Asian Indians in north India. The clinical trial was retrospectively registered (after the recruitment of the participants) in ClinicalTrial.gov under the identification number: NCT02455778 on 25th May 2015.

  12. 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...

  13. Social Competence and Parental Support as Mediators of the Link between Stress and Metabolic Control in Adolescents with Insulin-Dependent Diabetes Mellitus.

    Science.gov (United States)

    Hanson, Cindy L.; And Others

    1987-01-01

    Measured metabolic control, adherence, life stress, social competence, and parental support in adolescents (N=104) with insulin-dependent diabetes mellitus. Found that stress was directly associated with metabolic control, independent of the link between adherence and metabolic control. Social competence buffered negative association between…

  14. Metabolic flux ratio analysis and multi-objective optimization revealed a globally conserved and coordinated metabolic response of E. coli to paraquat-induced oxidative stress.

    Science.gov (United States)

    Shen, Tie; Rui, Bin; Zhou, Hong; Zhang, Ximing; Yi, Yin; Wen, Han; Zheng, Haoran; Wu, Jihui; Shi, Yunyu

    2013-01-27

    The ability of a microorganism to adapt to changes in the environment, such as in nutrient or oxygen availability, is essential for its competitive fitness and survival. The cellular objective and the strategy of the metabolic response to an extreme environment are therefore of tremendous interest and, thus, have been increasingly explored. However, the cellular objective of the complex regulatory structure of the metabolic changes has not yet been fully elucidated and more details regarding the quantitative behaviour of the metabolic flux redistribution are required to understand the systems-wide biological significance of this response. In this study, the intracellular metabolic flux ratios involved in the central carbon metabolism were determined by fractional (13)C-labeling and metabolic flux ratio analysis (MetaFoR) of the wild-type E. coli strain JM101 at an oxidative environment in a chemostat. We observed a significant increase in the flux through phosphoenolpyruvate carboxykinase (PEPCK), phosphoenolpyruvate carboxylase (PEPC), malic enzyme (MEZ) and serine hydroxymethyltransferase (SHMT). We applied an ε-constraint based multi-objective optimization to investigate the trade-off relationships between the biomass yield and the generation of reductive power using the in silico iJR904 genome-scale model of E. coli K-12. The theoretical metabolic redistribution supports that the trans-hydrogenase pathway should not play a direct role in the defence mounted by E. coli against oxidative stress. The agreement between the measured ratio and the theoretical redistribution established the significance of NADPH synthesis as the goal of the metabolic reprogramming that occurs in response to oxidative stress. Our work presents a framework that combines metabolic flux ratio analysis and multi-objective optimization to investigate the metabolic trade-offs that occur under varied environmental conditions. Our results led to the proposal that the metabolic response of E

  15. Metabolic benefits of dietary prebiotics in human subjects: a systematic review of randomised controlled trials.

    Science.gov (United States)

    Kellow, Nicole J; Coughlan, Melinda T; Reid, Christopher M

    2014-04-14

    Complex relationships exist between the gut microflora and their human hosts. Emerging evidence suggests that bacterial dysbiosis within the colon may be involved in the pathogenesis of the metabolic syndrome, type 2 diabetes and CVD. The use of dietary prebiotic supplements to restore an optimal balance of intestinal flora may positively affect host metabolism, representing a potential treatment strategy for individuals with cardiometabolic disorders. The present review aimed to examine the current evidence supporting that dietary prebiotic supplementation in adults has beneficial effects on biochemical parameters associated with the development of metabolic abnormalities including obesity, glucose intolerance, dyslipidaemia, hepatic steatosis and low-grade chronic inflammation. Between January 2000 and September 2013, eight computer databases were searched for randomised controlled trials published in English. Human trials were included if at least one group received a dietary prebiotic intervention. In the present review, twenty-six randomised controlled trials involving 831 participants were included. Evidence indicated that dietary prebiotic supplementation increased self-reported feelings of satiety in healthy adults (standardised mean difference -0.57, 95% CI -1.13, -0.01). Prebiotic supplementation also significantly reduced postprandial glucose (-0.76, 95% CI -1.41, -0.12) and insulin (-0.77, 95% CI -1.50, -0.04) concentrations. The effects of dietary prebiotics on total energy intake, body weight, peptide YY and glucagon-like peptide-1 concentrations, gastric emptying times, insulin sensitivity, lipids, inflammatory markers and immune function were contradictory. Dietary prebiotic consumption was found to be associated with subjective improvements in satiety and reductions in postprandial glucose and insulin concentrations. Additional evidence is required before recommending prebiotic supplements to individuals with metabolic abnormalities. Large

  16. Association of sedentary behaviour with metabolic syndrome: a meta-analysis.

    Directory of Open Access Journals (Sweden)

    Charlotte L Edwardson

    Full Text Available In recent years there has been a growing interest in the relationship between sedentary behaviour (sitting and health outcomes. Only recently have there been studies assessing the association between time spent in sedentary behaviour and the metabolic syndrome. The aim of this study is to quantify the association between sedentary behaviour and the metabolic syndrome in adults using meta-analysis.Medline, Embase and the Cochrane Library were searched using medical subject headings and key words related to sedentary behaviours and the metabolic syndrome. Reference lists of relevant articles and personal databases were hand searched. Inclusion criteria were: (1 cross sectional or prospective design; (2 include adults ≥ 18 years of age; (3 self-reported or objectively measured sedentary time; and (4 an outcome measure of metabolic syndrome. Odds Ratio (OR and 95% confidence intervals for metabolic syndrome comparing the highest level of sedentary behaviour to the lowest were extracted for each study. Data were pooled using random effects models to take into account heterogeneity between studies. Ten cross-sectional studies (n = 21393 participants, one high, four moderate and five poor quality, were identified. Greater time spent sedentary increased the odds of metabolic syndrome by 73% (OR 1.73, 95% CI 1.55-1.94, p<0.0001. There were no differences for subgroups of sex, sedentary behaviour measure, metabolic syndrome definition, study quality or country income. There was no evidence of statistical heterogeneity (I(2 = 0.0%, p = 0.61 or publication bias (Eggers test t = 1.05, p = 0.32.People who spend higher amounts of time in sedentary behaviours have greater odds of having metabolic syndrome. Reducing sedentary behaviours is potentially important for the prevention of metabolic syndrome.

  17. Shifts in metabolic hydrogen sinks in the methanogenesis-inhibited ruminal fermentation: a meta-analysis

    Directory of Open Access Journals (Sweden)

    Emilio M. Ungerfeld

    2015-02-01

    Full Text Available Maximizing the flow of metabolic hydrogen ([H] in the rumen away from CH4 and towards volatile fatty acids (VFA would increase the efficiency of ruminant production and decrease its environmental impact. The objectives of this meta-analysis were: i To quantify shifts in metabolic hydrogen sinks when inhibiting ruminal methanogenesis in vitro; and ii To understand the variation in shifts of metabolic hydrogen sinks among experiments and between batch and continuous cultures systems when methanogenesis is inhibited. Batch (28 experiments, N=193 and continuous (16 experiments, N=79 culture databases of experiments with at least 50% inhibition in CH4 production were compiled. Inhibiting methanogenesis generally resulted in less fermentation and digestion in most batch culture, but not in most continuous culture, experiments. Inhibiting CH4 production in batch cultures resulted in redirection of metabolic hydrogen towards propionate and H2 but not butyrate. In continuous cultures, there was no overall metabolic hydrogen redirection towards propionate or butyrate, and H2 as a proportion of metabolic hydrogen spared from CH4 production was numerically smaller compared to batch cultures. Dihydrogen accumulation was affected by type of substrate and methanogenesis inhibitor, with highly fermentable substrates resulting in greater redirection of metabolic hydrogen towards H2 when inhibiting methanogenesis, and some oils causing small or no H2 accumulation. In both batch and continuous culture, there was a decrease in metabolic hydrogen recovered as the sum of propionate, butyrate, CH4 and H2 when inhibiting methanogenesis, and it is speculated that as CH4 production decreases metabolic hydrogen could be increasingly incorporated into formate, microbial biomass, and, perhaps, reductive acetogenesis in continuous cultures. Energetic benefits of inhibiting methanogenesis depended on the inhibitor and its concentration and on the in vitro system.

  18. Noninvasive analysis of metabolic changes following nutrient input into diverse fish species, as investigated by metabolic and microbial profiling approaches

    Directory of Open Access Journals (Sweden)

    Taiga Asakura

    2014-10-01

    Full Text Available An NMR-based metabolomic approach in aquatic ecosystems is valuable for studying the environmental effects of pharmaceuticals and other chemicals on fish. This technique has also contributed to new information in numerous research areas, such as basic physiology and development, disease, and water pollution. We evaluated the microbial diversity in various fish species collected from Japan’s coastal waters using next-generation sequencing, followed by evaluation of the effects of feed type on co-metabolic modulations in fish-microbial symbiotic ecosystems in laboratory-scale experiments. Intestinal bacteria of fish in their natural environment were characterized (using 16S rRNA genes for trophic level using pyrosequencing and noninvasive sampling procedures developed to study the metabolism of intestinal symbiotic ecosystems in fish reared in their environment. Metabolites in feces were compared, and intestinal contents and feed were annotated based on HSQC and TOCSY using SpinAssign and network analysis. Feces were characterized by species and varied greatly depending on the feeding types. In addition, feces samples demonstrated a response to changes in the time series of feeding. The potential of this approach as a non-invasive inspection technique in aquaculture is suggested.

  19. Metabolic syndrome in patients with bipolar disorder: comparison with major depressive disorder and non-psychiatric controls.

    Science.gov (United States)

    Silarova, Barbora; Giltay, Erik J; Van Reedt Dortland, Arianne; Van Rossum, Elisabeth F C; Hoencamp, Erik; Penninx, Brenda W J H; Spijker, Annet T

    2015-04-01

    We aimed to investigate the prevalence of the metabolic syndrome (MetS) and its individual components in subjects with bipolar disorder (BD) compared to those with major depressive disorder (MDD) and non-psychiatric controls. We examined 2431 participants (mean age 44.3±13.0, 66.1% female), of whom 241 had BD; 1648 had MDD; and 542 were non-psychiatric controls. The MetS was ascertained according to NCEP ATP III criteria. Multivariable analyses were adjusted for age, sex, ethnicity, level of education, smoking status and severity of depressive symptoms, and in the case of BD subjects, also for psychotropic medication use. Subjects with BD had a significantly higher prevalence of MetS when compared to subjects with MDD and non-psychiatric controls (28.4% vs. 20.2% and 16.5%, respectively, ppsychiatric controls). The differences between BD subjects with controls could partly be ascribed to a higher mean waist circumference (91.0 cm vs. 88.8, respectively, p=0.03). In stratified analysis, the differences in the prevalence of MetS between patients with BD and MDD were found in symptomatic but not in asymptomatic cases. This study confirms a higher prevalence of MetS in patients with BD compared to both MDD patients and controls. Specifically at risk are patients with a higher depression score and abdominal obesity. Copyright © 2015 Elsevier Inc. All rights reserved.

  20. Thyroid peroxidase antibodies in pregnant women with type 1 diabetes: impact on thyroid function, metabolic control and pregnancy outcome

    DEFF Research Database (Denmark)

    Vestgaard, Marianne; Nielsen, Lene Ringholm; Rasmussen, Åse Krogh

    2008-01-01

    In pregnant women with type 1 diabetes, we evaluated whether the presence of thyroid peroxidase autoantibodies (anti-TPO) was associated with changes in thyroid function, metabolic control and pregnancy outcome....

  1. A randomized placebo-controlled study on the effects of pioglitazone on cortisol metabolism in polycystic ovary syndrome

    DEFF Research Database (Denmark)

    Glintborg, Dorte; Hermann, Anne Pernille; Hagen, Claus

    2009-01-01

    OBJECTIVE: To investigate possible effects of insulin-sensitizing treatment on cortisol metabolism in insulin-resistant patients with polycystic ovary syndrome (PCOS). DESIGN: Randomized placebo-controlled study. SETTING: Academic tertiary care medical center. PATIENT(S): Thirty insulin...

  2. Comparing metabolic control and complications in type 2 diabetes in two Pacific Islands at baseline and following diabetes care intervention

    Directory of Open Access Journals (Sweden)

    Si Thu Win Tin

    2016-06-01

    Conclusions: This study indicates improved metabolic control but little change in diabetes complications 15 months after intervention. Efforts to improve and evaluate the ongoing quality and accessibility of diabetes care in Pacific Island settings need to be further strengthened.

  3. Pathway analysis of Pichia pastoris to elucidate methanol metabolism and its regulation for production of recombinant proteins.

    Science.gov (United States)

    Unrean, Pornkamol

    2014-01-01

    This research rationally analyzes metabolic pathways of Pichia pastoris to study the metabolic flux responses of this yeast under methanol metabolism. A metabolic model of P. pastoris was constructed and analyzed by elementary mode analysis (EMA). EMA was used to comprehensively identify the cell's metabolic flux profiles and its underlying regulation mechanisms for the production of recombinant proteins from methanol. Change in phenotypes and flux profiles during methanol adaptation with varying feed mixture of glycerol and methanol was examined. EMA identified increasing and decreasing fluxes during the glycerol-methanol metabolic shift, which well agreed with experimental observations supporting the validity of the metabolic network model. Analysis of all the identified pathways also led to the determination of the metabolic capacities as well as the optimum metabolic pathways for recombinant protein synthesis during methanol induction. The network sensitivity analysis revealed that the production of proteins can be improved by manipulating the flux ratios at the pyruvate branch point. In addition, EMA suggested that protein synthesis is optimum under hypoxic culture conditions. The metabolic modeling and analysis presented in this study could potentially form a valuable knowledge base for future research on rational design and optimization of P. pastoris by determining target genes, pathways, and culture conditions for enhanced recombinant protein synthesis. The metabolic pathway analysis is also of considerable value for production of therapeutic proteins by P. pastoris in biopharmaceutical applications. © 2013 American Institute of Chemical Engineers.

  4. Systematic analysis of rice (Oryza sativa) metabolic responses to herbivory.

    Science.gov (United States)

    Alamgir, Kabir Md; Hojo, Yuko; Christeller, John T; Fukumoto, Kaori; Isshiki, Ryutaro; Shinya, Tomonori; Baldwin, Ian T; Galis, Ivan

    2016-02-01

    Plants defend against attack from herbivores by direct and indirect defence mechanisms mediated by the accumulation of phytoalexins and release of volatile signals, respectively. While the defensive arsenals of some plants, such as tobacco and Arabidopsis are well known, most of rice's (Oryza sativa) defence metabolites and their effectiveness against herbivores remain uncharacterized. Here, we used a non-biassed metabolomics approach to identify many novel herbivory-regulated metabolic signatures in rice. Most were up-regulated by herbivore attack while only a few were suppressed. Two of the most prominent up-regulated signatures were characterized as phenolamides (PAs), p-coumaroylputrescine and feruloylputrescine. PAs accumulated in response to attack by both chewing insects, i.e. feeding of the lawn armyworm (Spodoptera mauritia) and the rice skipper (Parnara guttata) larvae, and the attack of the sucking insect, the brown planthopper (Nilaparvata lugens, BPH). In bioassays, BPH insects feeding on 15% sugar solution containing p-coumaroylputrescine or feruloylputrescine, at concentrations similar to those elicited by heavy BPH attack in rice, had a higher mortality compared to those feeding on sugar diet alone. Our results highlight PAs as a rapidly expanding new group of plant defence metabolites that are elicited by herbivore attack, and deter herbivores in rice and other plants. © 2015 John Wiley & Sons Ltd.

  5. Control of Secreted Protein Gene Expression and the Mammalian Secretome by the Metabolic Regulator PGC-1α.

    Science.gov (United States)

    Minsky, Neri; Roeder, Robert G

    2017-01-06

    Secreted proteins serve pivotal roles in the development of multicellular organisms, acting as structural matrix, extracellular enzymes, and signal molecules. However, how the secretome is regulated remains incompletely understood. Here we demonstrate, unexpectedly, that peroxisome proliferator-activated receptor γ coactivator 1-α (PGC-1α), a critical transcriptional co-activator of metabolic gene expression, functions to down-regulate the expression of diverse genes encoding secreted molecules and extracellular matrix components to modulate the secretome. Using cell lines, primary cells, and mice, we show that both endogenous and exogenous PGC-1α down-regulate the expression of numerous genes encoding secreted molecules. Mechanistically, results obtained using mRNA stability measurements as well as intronic RNA expression analysis are consistent with a transcriptional effect of PGC-1α on the expression of genes encoding secreted proteins. Interestingly, PGC-1α requires the central heat shock response regulator heat shock factor protein 1 (HSF1) to affect some of its targets, and both factors co-reside on several target genes encoding secreted molecules in cells. Finally, using a mass spectrometric analysis of secreted proteins, we demonstrate that PGC-1α modulates the secretome of mouse embryonic fibroblasts. Our results define a link between a key pathway controlling metabolic regulation and the regulation of the mammalian secretome. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  6. Quality control analysis at the hospital

    International Nuclear Information System (INIS)

    Kristensen, K.

    1979-01-01

    Quality control analysis is an integral part of quality assurance. In a system as with radiopharmaceuticals where part of the finishing of the product takes place at individual hospitals, the need for quality control analysis at the hospital can be discussed. Data are presented that stresses the importance of quality control by the manufacturer as a basis for limitation of such work at hospitals. A simplified programme is proposed

  7. Simple anthropometric measures correlate with metabolic risk indicators as strongly as magnetic resonance imaging-measured adipose tissue depots in both HIV-infected and control subjects.

    Science.gov (United States)

    Scherzer, Rebecca; Shen, Wei; Bacchetti, Peter; Kotler, Donald; Lewis, Cora E; Shlipak, Michael G; Heymsfield, Steven B; Grunfeld, Carl

    2008-06-01

    Studies in persons without HIV infection have compared percentage body fat (%BF) and waist circumference as markers of risk for the complications of excess adiposity, but only limited study has been conducted in HIV-infected subjects. We compared anthropometric and magnetic resonance imaging (MRI)-based adiposity measures as correlates of metabolic complications of adiposity in HIV-infected and control subjects. The study was a cross-sectional analysis of 666 HIV-positive and 242 control subjects in the Fat Redistribution and Metabolic Change in HIV Infection (FRAM) study assessing body mass index (BMI), waist (WC) and hip (HC) circumferences, waist-to-hip ratio (WHR), %BF, and MRI-measured regional adipose tissue. Study outcomes were 3 metabolic risk variables [homeostatic model assessment (HOMA), triglycerides, and HDL cholesterol]. Analyses were stratified by sex and HIV status and adjusted for demographic, lifestyle, and HIV-related factors. In HIV-infected and control subjects, univariate associations with HOMA, triglycerides, and HDL were strongest for WC, MRI-measured visceral adipose tissue, and WHR; in all cases, differences in correlation between the strongest measures for each outcome were small (r HDL, WC appeared to be the best anthropometric correlate of metabolic complications, whereas, for triglycerides, the best was WHR. Relations of simple anthropometric measures with HOMA, triglycerides, and HDL cholesterol are approximately as strong as MRI-measured whole-body adipose tissue depots in both HIV-infected and control subjects.

  8. Metabolic analysis of knee synovial fluid as a potential diagnostic approach for osteoarthritis.

    Science.gov (United States)

    Mickiewicz, Beata; Kelly, Jordan J; Ludwig, Taryn E; Weljie, Aalim M; Wiley, J Preston; Schmidt, Tannin A; Vogel, Hans J

    2015-11-01

    Osteoarthritis (OA) is a leading cause of chronic joint pain in the older human population. Diagnosis of OA at an earlier stage may enable the development of new treatments to one day effectively modify the progression and prognosis of the disease. In this work, we explore whether an integrated metabolomics approach could be utilized for the diagnosis of OA. Synovial fluid (SF) samples were collected from symptomatic chronic knee OA patients and normal human cadaveric knee joints. The samples were analyzed using (1)H nuclear magnetic resonance (NMR) spectroscopy and gas chromatography-mass spectrometry (GC-MS) followed by multivariate statistical analysis. Based on the metabolic profiles, we were able to distinguish OA patients from the controls and validate the statistical models. Moreover, we have integrated the (1)H NMR and GC-MS results and we found that 11 metabolites were statistically important for the separation between OA and normal SF. Additionally, statistical analysis showed an excellent predictive ability of the constructed metabolomics model (area under the receiver operating characteristic curve = 1.0). Our findings indicate that metabolomics might serve as a promising approach for the diagnosis and prognosis of degenerative changes in the knee joint and should be further validated in clinical settings. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

  9. Desomorphine (Krokodil): An overview of its chemistry, pharmacology, metabolism, toxicology and analysis.

    Science.gov (United States)

    Florez, Diego Hernando Ângulo; Dos Santos Moreira, Ana Maria; da Silva, Pedro Rafael; Brandão, Ricardo; Borges, Marcella Matos Cordeiro; de Santana, Fernando José Malagueño; Borges, Keyller Bastos

    2017-04-01

    "Krokodil" or "Crocodile" is an illegal homemade desomorphine drug obtained from chemical reactions of commercial codeine drugs with several other powerful and highly toxic chemical agents increasing its addiction and hallucinogenic effects when compared with other morphine analogues. This paper summarizes a complete review about an old drug called desomorphine (Krokodil), presenting its chemistry, pharmacology, metabolism, toxicology and analysis. It is of particular interest and concern because this cheaper injectable semisynthetic opioid drug has been largely used in recent years for recreational purposes in several Eastern European as well as North and South American countries, despite known damage to health that continuous use might induce. These injuries are much stronger and more aggressive than morphine's, infecting and rotting skin and soft tissue to the bone of addicts at the point of injection in less than three years, which, in most cases, evolves to death. On this basis, it is imperative that literature reviews focus on the chemistry, pharmacology, toxicology and analysis of dangerous Krokodil to find strategies for rapid and effective determination to mitigate its adverse effects on addicts and prevent consumption. It is crucial to know the symptoms and consequences of the use of Krokodil, as well as METHODS: for identification and quantification of desomorphine, contaminants and metabolites, which can help the forensic work of diagnosis and propose actions to control and eradicate this great danger to public health around the world. Copyright © 2017 Elsevier B.V. All rights reserved.

  10. A Transcript-Specific eIF3 Complex Mediates Global Translational Control of Energy Metabolism

    Directory of Open Access Journals (Sweden)

    Meera Shah

    2016-08-01

    Full Text Available The multi-subunit eukaryotic translation initiation factor eIF3 is thought to assist in the recruitment of ribosomes to mRNA. The expression of eIF3 subunits is frequently disrupted in human cancers, but the specific roles of individual subunits in mRNA translation and cancer remain elusive. Using global transcriptomic, proteomic, and metabolomic profiling, we found a striking failure of Schizosaccharomyces pombe cells lacking eIF3e and eIF3d to synthesize components of the mitochondrial electron transport chain, leading to a defect in respiration, endogenous oxidative stress, and premature aging. Energy balance was maintained, however, by a switch to glycolysis with increased glucose uptake, upregulation of glycolytic enzymes, and strict dependence on a fermentable carbon source. This metabolic regulatory function appears to be conserved in human cells where eIF3e binds metabolic mRNAs and promotes their translation. Thus, via its eIF3d-eIF3e module, eIF3 orchestrates an mRNA-specific translational mechanism controlling energy metabolism that may be disrupted in cancer.

  11. α/β-Hydrolase Domain 6 in the Ventromedial Hypothalamus Controls Energy Metabolism Flexibility

    Directory of Open Access Journals (Sweden)

    Alexandre Fisette

    2016-10-01

    Full Text Available α/β-Hydrolase domain 6 (ABHD6 is a monoacylglycerol hydrolase that degrades the endocannabinoid 2-arachidonoylglycerol (2-AG. Although complete or peripheral ABHD6 loss of function is protective against diet-induced obesity and insulin resistance, the role of ABHD6 in the central control of energy balance is unknown. Using a viral-mediated knockout approach, targeted endocannabinoid measures, and pharmacology, we discovered that mice lacking ABHD6 from neurons of the ventromedial hypothalamus (VMHKO have higher VMH 2-AG levels in conditions of endocannabinoid recruitment and fail to physiologically adapt to key metabolic challenges. VMHKO mice exhibited blunted fasting-induced feeding and reduced food intake, energy expenditure, and adaptive thermogenesis in response to cold exposure, high-fat feeding, and dieting (transition to a low-fat diet. Our findings identify ABHD6 as a regulator of the counter-regulatory responses to major metabolic shifts, including fasting, nutrient excess, cold, and dieting, thereby highlighting the importance of ABHD6 in the VMH in mediating energy metabolism flexibility.

  12. Effect of fruit and vegetable concentrates on endothelial function in metabolic syndrome: A randomized controlled trial

    Directory of Open Access Journals (Sweden)

    Ma Yingying

    2011-06-01

    Full Text Available Abstract Background and Objective Dehydrated fruit and vegetable concentrates provide an accessible form of phytonutrient supplementation that may offer cardioprotective effects. This study assessed the effects of two blends of encapsulated juice powder concentrates (with and without added berry powders on endothelial function in persons with metabolic syndrome, a risk factor for type 2 diabetes and cardiovascular disease. Methods Randomized, double blind, placebo controlled crossover clinical trial with three treatment arms. 64 adults with metabolic syndrome were enrolled and received 8-week sequences of each blend of the concentrates and placebo. The primary outcome measure was change in endothelial function (assessed as flow-mediated dilatation of the brachial artery 2 hr after consuming a 75 g glucose load, after 8-weeks of daily consumption (sustained or 2 hr after consumption of a single dose (acute. Secondary outcome measures included plasma glucose, serum insulin, serum lipids, and body weight. Results No significant between-group differences in endothelial function with daily treatment for 8 weeks were seen. No other significant treatment effects were discerned in glucose, insulin, lipids, and weight. Conclusion Encapsulated fruit and vegetable juice powder concentrates did not alter insulin or glucose measures in this sample of adults with metabolic syndrome. Trial Registration clinicaltrials.gov NCT01224743

  13. The Relationship between Metabolic Control and Growth in Children with Type I Diabetes Mellitus in Southwest of Iran

    Directory of Open Access Journals (Sweden)

    Shide Assar

    2015-01-01

    Full Text Available Background. Metabolic control is an important factor in growth of children with type I diabetes. This study assessed the relationship between growth and metabolic control in such children. Materials and Methods. 83 children with diabetes were studied. They were examined for weight and height gain and HbA1C was quantified every 3 months for one year. The growth process was studied in patients who were divided into 3 groups according to their HbA1C amounts, consisting of good, intermediate, and poor metabolic control. Results. Mean age of cases was 7.6 ± 2. The presenting sign at the onset of disease was diabetic ketoacidosis in 44.6%. The average HbA1C amount was 8.89%. The average weight SDS at diagnosis was −0.18 and at the end of the study was 0.45 (P<0.001. The average height SDS at diagnosis was −0.04 and at the end of the study was −0.07 (P=0.64. A significant difference in weight SDS changes was only seen between patients with good and poor metabolic control (P=0.04. Conclusion. Poor metabolic control can decrease height growth but has minimal influence on weight. Metabolic control was not the only predictive factor of physical growth in children with diabetes.

  14. Clinical analysis of the relationship between cystatin C and metabolic syndrome in the elderly.

    Science.gov (United States)

    Liu, Ping; Sui, Shujian; Xu, Dongling; Xing, Xiaowei; Liu, Caixia

    2014-01-01

    Studies have shown that both cystatin C and metabolic syndrome (MetS) are associated with inflammation. We set out to investigate the correlation between serum cystatin C levels and MetS in the elderly. This prospective study was conducted in 380 elderly individuals, including 135 patients with MetS, 142 patients with metabolic disturbance (MetD), and 103 healthy elderly individuals (control group). Waist-hip ratio, waist circumference, waist-height ratio, body mass index (BMI), fasting plasma glucose (FPG), hemoglobin A1c (HbA1c), low-density lipoprotein cholesterol (LDL-C), triglycerides (TG), high-density lipoprotein (HDL-C), systolic blood pressure (SBP), diastolic blood pressure (DBP), pulse pressure and cystatin C were measured and their mutual relations were analyzed. The higher the MetS scores, the higher the serum cystatin C concentration in these patients. Serum cystatin C concentration was closely related to waist-hip ratio, waist circumference, waist-height ratio, BMI, TG, FPG, and blood pressure, not related to LDL-C levels, and negatively correlated with HDL-C levels. Logistic regression analysis indicated that cystatin C, waist-height ratio, waist circumference, FPG, TG, SBP and pulse pressure were significantly associated with MetS (OR between cystatin C and MetS 2.164, 95% CI 1.136-8.259). Cystatin C was significantly associated with MetS in the elderly. As MetS scores rose, serum cystatin C levels increased. Copyright © 2013 Sociedade Portuguesa de Cardiologia. Published by Elsevier España. All rights reserved.

  15. Exogenous auxin regulates multi-metabolic network and embryo development, controlling seed secondary dormancy and germination in Nicotiana tabacum L.

    Science.gov (United States)

    Li, Zhenhua; Zhang, Jie; Liu, Yiling; Zhao, Jiehong; Fu, Junjie; Ren, Xueliang; Wang, Guoying; Wang, Jianhua

    2016-02-09

    Auxin was recognized as a secondary dormancy phytohormone, controlling seed dormancy and germination. However, the exogenous auxin-controlled seed dormancy and germination remain unclear in physiological process and gene network. Tobacco seeds soaked in 1000 mg/l auxin solution showed markedly decreased germination compared with that in low concentration of auxin solutions and ddH2O. Using an electron microscope, observations were made on the seeds which did not unfold properly in comparison to those submerged in ddH2O. The radicle traits measured by WinRHIZO, were found to be also weaker than the other treatment groups. Quantified by ELISA, there was no significant difference found in β-1,3glucanase activity and abscisic acid (ABA) content between the seeds imbibed in gradient concentration of auxin solution and those soaked in ddH2O. However, gibberellic acid (GA) and auxin contents were significantly higher at the time of exogenous auxin imbibition and were gradually reduced at germination. RNA sequencing (RNA-seq), revealed that the transcriptome of auxin-responsive dormancy seeds were more similar to that of the imbibed seeds when compared with primary dormancy seeds by principal component analysis. The results of gene differential expression analysis revealed that auxin-controlled seed secondary dormancy was associated with flavonol biosynthetic process, gibberellin metabolic process, adenylyl-sulfate reductase activity, thioredoxin activity, glutamate synthase (NADH) activity and chromatin regulation. In addition, auxin-responsive germination responded to ABA, auxin, jasmonic acid (JA) and salicylic acid (SA) mediated signaling pathway (red, far red and blue light), glutathione and methionine (Met) metabolism. In this study, exogenous auxin-mediated seed secondary dormancy is an environmental model that prevents seed germination in an unfavorable condition. Seeds of which could not imbibe normally, and radicles of which also could not develop normally and

  16. [DiabeTIC website: a pilot study of satisfaction and impact on metabolic control].

    Science.gov (United States)

    Carral San Laureano, Florentino; Ayala Ortega, María del Carmen; Jiménez Millán, Ana Isabel; Piñero Zaldivar, Antonia; García Calzado, Concepción; Prieto Ferrón, Matilde; Silva Rodríguez, Juan José

    2013-10-01

    To evaluate satisfaction and short-term impact on metabolic control of diabetes monitoring through the DiabeTIC website. A prospective, uncontrolled intervention study was conducted in 32 patients aged 29.7±9.7 years (65% female) incorporated to the telemedicine platform DiabeTIC between March and September 2012. All patients completed a satisfaction questionnaire in the first month, and impact on metabolic control was evaluated at three and six months. In the satisfaction survey conducted in the first month of follow-up, the following mean scores (0-10) were obtained: overall impression with the platform: 8.6±1.8; ease of use: 8.1±1.5; intuitive navigation: 6.7±3.0; value of measurements: 9.1±1.1; importance of the platform in diabetes management: 9.5±0.9; sense of security: 9.5±0.8; value of the library: 9.4±1.1; value of messages: 9.1±1.4, and recommendation to use the platform: 9.4±0.9. Glycosilated hemoglobin concentrations significantly improved at six months as compared to study start (7.0±0.8 versus 8.1±1.9; p=0.007). Nine patients were discharged from DiabeTIC before completing six months of follow-up. Patients with diabetes monitored through the DiabeTIC website report a high degree of satisfaction, showing improved metabolic control at short-term follow-up. Copyright © 2012 SEEN. Published by Elsevier Espana. All rights reserved.

  17. Effect of growth regulators on 'Brookfield' apple gas diffusion and metabolism under controlled atmosphere storage

    Directory of Open Access Journals (Sweden)

    Auri Brackmann

    2014-05-01

    Full Text Available The objective of this work was to evaluate the effect of growth regulators on gas diffusion and on metabolism of 'Brookfield' apple, and to determine their correlation with quality characteristics of fruit stored in controlled atmosphere. A completely randomized design was used with four replicates. After eight months of storage, the effects of water (control, aminoethoxyvinylglycine (AVG, AVG + ethephon, AVG + naphthaleneacetic acid (NAA, ethephon + NAA, sole NAA, 1-MCP, ethylene absorption by potassium permanganate (ABS, AVG + ABS, and of AVG + 1-MCP - applied at different rates and periods - were evaluated on: gas diffusion rate, ethylene production, respiratory rate, internal ethylene concentration, internal CO2 content, mealiness, and intercellular space. Fruit from the control and sole NAA treatments had the highest mealiness occurrence. Growth regulators significantly changed the gaseous diffusion through the pulp of 'Brookfield' apple, mainly in the treatment AVG + ABS, which kept the highest gas diffusion rate. NAA spraying in the field, with or without another growth regulator, increased ripening metabolism by rising ethylene production and respiration rate, and reduced gas diffusion during shelf life. AVG spraying cannot avoid the ethephon effect during the ripening process, and reduces both the internal space and mealiness incidence, but it is not able to induce ethylene production or to increase respiration rates.

  18. Mitochondrial metabolism and the control of vascular smooth muscle cell proliferation

    Directory of Open Access Journals (Sweden)

    Mario eChiong

    2014-12-01

    Full Text Available Differentiation and dedifferentiation of vascular smooth muscle cells (VSMCs are essential processes of vascular development. VSMCs have biosynthetic, proliferative and contractile roles in the vessel wall. Alterations in the differentiated state of the VSMCs play a critical role in the pathogenesis of a variety of cardiovascular diseases, including atherosclerosis, hypertension and vascular stenosis. This review provides an overview of the current state of knowledge of molecular mechanisms involved in the control of VSMC proliferation, with particular focus on mitochondrial metabolism. Mitochondrial activity can be controlled by regulating mitochondrial dynamics, i.e. mitochondrial fusion and fission, and by regulating mitochondrial calcium handling through the interaction with the endoplasmic reticulum (ER. Alterations in both VSMC proliferation and mitochondrial function can be triggered by dysregulation of mitofusin-2, a small GTPase associated with mitochondrial fusion and mitochondrial-ER interaction. Several lines of evidence highlight the relevance of mitochondrial metabolism in the control of VSMC proliferation, indicating a new area to be explored in the treatment of vascular diseases.

  19. Metabolic control and bone health in adolescents with type 1 diabetes

    Directory of Open Access Journals (Sweden)

    Mohan Subburaman

    2011-10-01

    Full Text Available Abstract Background Adults with type 1 diabetes (T1D have decreased bone mineral density (BMD and increased fracture risk, yet the etiologies remain elusive. Early detection of derangements in bone biomarkers during adolescence could lead to timely recognition. In adolescents with T1D, we evaluated the relationships between metabolic control, BMD, and bone anabolic and turnover markers. Methods Cross-sectional study of 57 adolescent subjects with T1D who had HbA1c consistently ≥ 9% (Poor Control, PC n = 27 or Results There were no differences between HbA1c groups in BMD, components of the IGF system, or 25-hydroxyvitamin D status. The prevalence of 25-hydroxyvitamin D abnormalities was similar to that seen in the general adolescent population. Few patients met the recommended dietary allowance (RDA for vitamin D or calcium. Conclusions These data provide no evidence of association between degree of metabolic control and BMD in adolescents with T1D. Adolescents with T1D have a high prevalence of serum 25-hydroxyvitamin D abnormalities. Longitudinal studies are needed to evaluate the predictive value of vitamin D abnormalities on fracture risk.

  20. Control Flow Analysis for BioAmbients

    DEFF Research Database (Denmark)

    Nielson, Flemming; Nielson, Hanne Riis; Priami, C.

    2007-01-01

    This paper presents a static analysis for investigating properties of biological systems specified in BioAmbients. We exploit the control flow analysis to decode the bindings of variables induced by communications and to build a relation of the ambients that can interact with each other. We...... eventually apply our analysis to an example of gene regulation by positive feedback taken from the literature....

  1. The Mitochondrial Permeability Transition Pore Regulator Cyclophilin D Exhibits Tissue-Specific Control of Metabolic Homeostasis.

    Directory of Open Access Journals (Sweden)

    Rhianna C Laker

    Full Text Available The mitochondrial permeability transition pore (mPTP is a key regulator of mitochondrial function that has been implicated in the pathogenesis of metabolic disease. Cyclophilin D (CypD is a critical regulator that directly binds to mPTP constituents to facilitate the pore opening. We previously found that global CypD knockout mice (KO are protected from diet-induced glucose intolerance; however, the tissue-specific function of CypD and mPTP, particularly in the control of glucose homeostasis, has not been ascertained. To this end, we performed calcium retention capacity (CRC assay to compare the importance of CypD in the liver versus skeletal muscle. We found that liver mitochondria are more dependent on CypD for mPTP opening than skeletal muscle mitochondria. To ascertain the tissue-specific role of CypD in metabolic homeostasis, we generated liver-specific and muscle-specific CypD knockout mice (LKO and MKO, respectively and fed them either a chow diet or 45% high-fat diet (HFD for 14 weeks. MKO mice displayed similar body weight gain and glucose intolerance compared with wild type littermates (WT, whereas LKO mice developed greater visceral obesity, glucose intolerance and pyruvate intolerance compared with WT mice. These findings demonstrate that loss of muscle CypD is not sufficient to alter whole body glucose metabolism, while the loss of liver CypD exacerbates obesity and whole-body metabolic dysfunction in mice fed HFD.

  2. [Risk factors for metabolic syndrome in a case control study in Temuco, Chile].

    Science.gov (United States)

    Philco L, Patricia; Serón S, Pamela; Muñoz N, Sergio; Navia B, Pilar; Lanas Z, Fernando

    2012-03-01

    Metabolic syndrome is becoming an important public health problem in affluent societies. To identify factors associated to metabolic syndrome in a Southern Chilean city. Using a case control design, 200 participants, aged 35 to 70 years with at least three criteria for metabolic syndrome according to the National Cholesterol Education Program (NCEP_ATPIII) and 200 subjects with less than three criteria, were studied. Both groups were compared in terms of ethnic background, educational level, family history of diabetes and coronary artery disease, menopausal status, smoking, stress and depression, physical activity, changes in body mass index in the last five years and diet. Among subjects aged more than 54 years, among males and among overweight individuals, having a Mapuche origin was a risk factor with odds ratios (OR) of 7.2; 88 and 3.9 respectively. Among subjects aged more than 54 years, among women and among overweight individuals, a family history of diabetes was a risk factor with OR of 17.7; 3.2 and 3.9 respectively. Among subjects aged more than 54 years and among women a change in body mass index of more than three points was a risk factor with OR of 12.5 and 7.4, respectively. Depression also was a risk factor among subjects aged more than 54 years (OR 3.3). Regular consumption of wine was a protective factor among participants of more than 54 years, with an OR of 0.17. The risk factors for metabolic syndrome detected in this group of participants, were having a Mapuche origin, a family history of diabetes mellitus and depression. Wine consumption was associated with a lower risk.

  3. The essential YycFG two-component system controls cell wall metabolism in Bacillus subtilis

    DEFF Research Database (Denmark)

    Bisicchia, Paola; Noone, David; Lioliou, Efthimia

    2007-01-01

    Adaptation of bacteria to the prevailing environmental and nutritional conditions is often mediated by two-component signal transduction systems (TCS). The Bacillus subtilis YycFG TCS has attracted special attention as it is essential for viability and its regulon is poorly defined. Here we show...... that YycFG is a regulator of cell wall metabolism. We have identified five new members of the YycFG regulon: YycF activates expression of yvcE, lytE and ydjM and represses expression of yoeB and yjeA. YvcE(CwlO) and LytE encode endopeptidase-type autolysins that participate in peptidoglycan synthesis...... to lysozyme digestion and YdjM is also predicted to have a role in cell wall metabolism. A genetic analysis shows that YycFG essentiality is polygenic in nature, being a manifestation of disrupted cell wall metabolism caused by aberrant expression of a number of YycFG regulon genes....

  4. A global evolutionary and metabolic analysis of human obesity gene risk variants.

    Science.gov (United States)

    Castillo, Joseph J; Hazlett, Zachary S; Orlando, Robert A; Garver, William S

    2017-09-05

    It is generally accepted that the selection of gene variants during human evolution optimized energy metabolism that now interacts with our obesogenic environment to increase the prevalence of obesity. The purpose of this study was to perform a global evolutionary and metabolic analysis of human obesity gene risk variants (110 human obesity genes with 127 nearest gene risk variants) identified using genome-wide association studies (GWAS) to enhance our knowledge of early and late genotypes. As a result of determining the mean frequency of these obesity gene risk variants in 13 available populations from around the world our results provide evidence for the early selection of ancestral risk variants (defined as selection before migration from Africa) and late selection of derived risk variants (defined as selection after migration from Africa). Our results also provide novel information for association of these obesity genes or encoded proteins with diverse metabolic pathways and other human diseases. The overall results indicate a significant differential evolutionary pattern for the selection of obesity gene ancestral and derived risk variants proposed to optimize energy metabolism in varying global environments and complex association with metabolic pathways and other human diseases. These results are consistent with obesity genes that encode proteins possessing a fundamental role in maintaining energy metabolism and survival during the course of human evolution. Copyright © 2017. Published by Elsevier B.V.

  5. Effects of low-fat milk consumption on metabolic and atherogenic biomarkers in Korean adults with the metabolic syndrome: a randomised controlled trial.

    Science.gov (United States)

    Lee, Y J; Seo, J A; Yoon, T; Seo, I; Lee, J H; Im, D; Lee, J H; Bahn, K-N; Ham, H S; Jeong, S A; Kang, T S; Ahn, J H; Kim, D H; Nam, G E; Kim, N H

    2016-08-01

    Previous studies of the health effects of low-fat milk or dairy consumption on the metabolic syndrome have yielded inconsistent results. The present study aimed to investigate the effects of low-fat milk consumption on traits associated with the metabolic syndrome, as well as inflammatory and atherogenic biomarkers, in Korean adults with the metabolic syndrome. Overweight Koreans with the metabolic syndrome (n = 58) were recruited and randomly assigned to either the low-fat milk or control group. The low-fat milk group was instructed to consume two packs of low-fat milk per day (200 mL twice daily) for 6 weeks, and the control group was instructed to maintain their habitual diet. Clinical investigations were conducted during the screening visit, on study day 0, and after 6 weeks. No significant differences in changes in body mass index, blood pressure, lipid profile and adiponectin levels, as well as levels of inflammatory markers, oxidative stress markers and atherogenic markers, were found between the low-fat milk and control groups. However, compared to the controls, significant favourable decreases in serum soluble vascular adhesion molecule-1 and endothelin-1 levels were found in the 12 subjects with high blood pressure and in the 18 subjects with hypertriglyceridaemia in the low-fat milk group. The present study did not demonstrate an overall beneficial effect of low-fat milk consumption in subjects with the metabolic syndrome. However, low-fat milk consumption may have a favourable effect on atherogenic markers in subjects with high blood pressure or hypertriglyceridaemia. © 2016 The British Dietetic Association Ltd.

  6. Functional roles of FgLaeA in controlling secondary metabolism, sexual development, and virulence in Fusarium graminearum.

    Directory of Open Access Journals (Sweden)

    Hee-Kyoung Kim

    Full Text Available Fusarium graminearum, the causal agent of Fusarium head blight in cereal crops, produces mycotoxins such as trichothecenes and zearalenone in infected plants. Here, we focused on the function of FgLaeA in F. graminearum, a homolog of Aspergillus nidulans LaeA encoding the global regulator for both secondary metabolism and sexual development. Prior to gene analysis, we constructed a novel luciferase reporter system consisting of a transgenic F. graminearum strain expressing a firefly luciferase gene under control of the promoter for either TRI6 or ZEB2 controlling the biosynthesis of these mycotoxins. Targeted deletion of FgLaeA led to a dramatic reduction of luminescence in reporter strains, indicating that FgLaeA controls the expression of these transcription factors in F. graminearum; reduced toxin accumulation was further confirmed by GC-MS analysis. Overexpression of FgLaeA caused the increased production of trichothecenes and additional metabolites. RNA seq-analysis revealed that gene member(s belonging to ~70% of total tentative gene clusters, which were previously proposed, were differentially expressed in the ΔFgLaeA strain. In addition, ΔFgLaeA strains exhibited an earlier induction of sexual fruiting body (perithecia formation and drastically reduced disease symptoms in wheat, indicating that FgLaeA seems to negatively control perithecial induction, but positively control virulence toward the host plant. FgLaeA was constitutively expressed under both mycotoxin production and sexual development conditions. Overexpression of a GFP-FgLaeA fusion construct in the ΔFgLaeA strain restored all phenotypic changes to wild-type levels and led to constitutive expression of GFP in both nuclei and cytoplasm at different developmental stages. A split luciferase assay demonstrated that FgLaeA was able to interact with FgVeA, a homolog of A. nidulans veA. Taken together, these results demonstrate that FgLaeA, a member of putative FgVeA complex

  7. Multiobjective flux balancing using the NISE method for metabolic network analysis.

    Science.gov (United States)

    Oh, Young-Gyun; Lee, Dong-Yup; Lee, Sang Yup; Park, Sunwon

    2009-01-01

    Flux balance analysis (FBA) is well acknowledged as an analysis tool of metabolic networks in the framework of metabolic engineering. However, FBA has a limitation for solving a multiobjective optimization problem which considers multiple conflicting objectives. In this study, we propose a novel multiobjective flux balance analysis method, which adapts the noninferior set estimation (NISE) method (Solanki et al., 1993) for multiobjective linear programming (MOLP) problems. NISE method can generate an approximation of the Pareto curve for conflicting objectives without redundant iterations of single objective optimization. Furthermore, the flux distributions at each Pareto optimal solution can be obtained for understanding the internal flux changes in the metabolic network. The functionality of this approach is shown by applying it to a genome-scale in silico model of E. coli. Multiple objectives for the poly(3-hydroxybutyrate) [P(3HB)] production are considered simultaneously, and relationships among them are identified. The Pareto curve for maximizing succinic acid production vs. maximizing biomass production is used for the in silico analysis of various combinatorial knockout strains. This proposed method accelerates the strain improvement in the metabolic engineering by reducing computation time of obtaining the Pareto curve and analysis time of flux distribution at each Pareto optimal solution. (c) 2009 American Institute of Chemical Engineers Biotechnol. Prog., 2009.

  8. Dynamic analysis of sugar metabolism in different harvest seasons ...

    African Journals Online (AJOL)

    user

    2011-04-04

    Apr 4, 2011 ... sugars and reducing sugars of pineapple treated by methyl jasmonate (MeJA) on chilling injuries were not significantly different from that of the control pineapple. Liu et al. (2009) reported that the flavor in summer pineapple fruit was better than that of the winter fruit. Joomwong (2006) showed that the fruit ...

  9. Analysis of Chinese hamster ovary cell metabolism through a combined computational and experimental approach.

    Science.gov (United States)

    Chen, Ning; Bennett, Mark H; Kontoravdi, Cleo

    2014-12-01

    Optimization of cell culture processes can benefit from the systematic analysis of experimental data and their organization in mathematical models, which can be used to decipher the effect of individual process variables on multiple outputs of interest. Towards this goal, a kinetic model of cytosolic glucose metabolism coupled with a population-level model of Chinese hamster ovary cells was used to analyse metabolic behavior under batch and fed-batch cell culture conditions. The model was parameterized using experimental data for cell growth dynamics, extracellular and intracellular metabolite profiles. The results highlight significant differences between the two culture conditions in terms of metabolic efficiency and motivate the exploration of lactate as a secondary carbon source. Finally, the application of global sensitivity analysis to the model parameters highlights the need for additional experimental information on cell cycle distribution to complement metabolomic analyses with a view to parameterize kinetic models.

  10. Stray light analysis and control

    CERN Document Server

    Fest, Eric

    2013-01-01

    Stray light is defined as unwanted light in an optical system, a familiar concept for anyone who has taken a photograph with the sun in or near their camera's field of view. This book addresses stray light terminology, radiometry, and the physics of stray light mechanisms, such as surface roughness scatter and ghost reflections. The most-efficient ways of using stray light analysis software packages are included. The book also demonstrates how the basic principles are applied in the design, fabrication, and testing phases of optical system development.

  11. Negative Affectivity Predicts Lower Quality of Life and Metabolic Control in Type 2 Diabetes Patients: A Structural Equation Modeling Approach.

    Science.gov (United States)

    Conti, Chiara; Di Francesco, Giulia; Fontanella, Lara; Carrozzino, Danilo; Patierno, Chiara; Vitacolonna, Ester; Fulcheri, Mario

    2017-01-01

    Introduction: It is essential to consider the clinical assessment of psychological aspects in patients with Diabetes Mellitus (DM), in order to prevent potentially adverse self-management care behaviors leading to diabetes-related complications, including declining levels of Quality of Life (QoL) and negative metabolic control. Purpose : In the framework of Structural Equation Modeling (SEM), the specific aim of this study is to evaluate the influence of distressed personality factors as Negative Affectivity (NA) and Social Inhibition (SI) on diabetes-related clinical variables (i.e., QoL and glycemic control). Methods: The total sample consists of a clinical sample, including 159 outpatients with Type 2 Diabetes Mellitus (T2DM), and a control group composed of 102 healthy respondents. All participants completed the following self- rating scales: The Type D Scale (DS14) and the World Health Organization QoL Scale (WHOQOLBREF). Furthermore, the participants of the clinical group were assessed for HbA1c, disease duration, and BMI. The observed covariates were BMI, gender, and disease duration, while HbA1c was considered an observed variable. Results: SEM analysis revealed significant differences between groups in regards to the latent construct of NA and the Environmental dimension of QoL. For the clinical sample, SEM showed that NA had a negative impact on both QoL dimensions and metabolic control. Conclusions: Clinical interventions aiming to improve medication adherence in patients with T2DM should include the psychological evaluation of Type D Personality traits, by focusing especially on its component of NA as a significant risk factor leading to negative health outcomes.

  12. Effect of testosterone treatment on glucose metabolism in men with type 2 diabetes: a randomized controlled trial.

    Science.gov (United States)

    Gianatti, Emily J; Dupuis, Philippe; Hoermann, Rudolf; Strauss, Boyd J; Wentworth, John M; Zajac, Jeffrey D; Grossmann, Mathis

    2014-08-01

    To determine whether testosterone therapy improves glucose metabolism in men with type 2 diabetes (T2D) and lowered testosterone. We conducted a randomized, double-blind, parallel, placebo-controlled trial in 88 men with T2D, aged 35-70 years with an HbA1c ≤8.5% (69 mmol/mol), and a total testosterone level, measured by immunoassay, of ≤12.0 nmol/L (346 ng/dL). Participants were randomly assigned to 40 weeks of intramuscular testosterone undecanoate (n = 45) or matching placebo (n = 43). All study subjects were included in the primary analysis. Seven men assigned to testosterone and six men receiving placebo did not complete the study. Main outcome measures were insulin resistance by homeostatic model assessment (HOMA-IR, primary outcome) and glycemic control by HbA1c (secondary outcome). Testosterone therapy did not improve insulin resistance (mean adjusted difference [MAD] for HOMA-IR compared with placebo -0.08 [95% CI -0.31 to 0.47; P = 0.23]) or glycemic control (MAD HbA1c 0.36% [0.0-0.7]; P = 0.05), despite a decrease in fat mass (MAD -2.38 kg [-3.10 to -1.66]; P Testosterone therapy reduced subcutaneous (MAD -320 cm(3) [-477 to -163]; P Testosterone therapy does not improve glucose metabolism or visceral adiposity in obese men with moderately controlled T2D and modest reductions in circulating testosterone levels typical for men with T2D. © 2014 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

  13. Negative Affectivity Predicts Lower Quality of Life and Metabolic Control in Type 2 Diabetes Patients: A Structural Equation Modeling Approach

    Directory of Open Access Journals (Sweden)

    Chiara Conti

    2017-05-01

    Full Text Available Introduction: It is essential to consider the clinical assessment of psychological aspects in patients with Diabetes Mellitus (DM, in order to prevent potentially adverse self-management care behaviors leading to diabetes-related complications, including declining levels of Quality of Life (QoL and negative metabolic control.Purpose: In the framework of Structural Equation Modeling (SEM, the specific aim of this study is to evaluate the influence of distressed personality factors as Negative Affectivity (NA and Social Inhibition (SI on diabetes-related clinical variables (i.e., QoL and glycemic control.Methods: The total sample consists of a clinical sample, including 159 outpatients with Type 2 Diabetes Mellitus (T2DM, and a control group composed of 102 healthy respondents. All participants completed the following self- rating scales: The Type D Scale (DS14 and the World Health Organization QoL Scale (WHOQOLBREF. Furthermore, the participants of the clinical group were assessed for HbA1c, disease duration, and BMI. The observed covariates were BMI, gender, and disease duration, while HbA1c was considered an observed variable.Results: SEM analysis revealed significant differences between groups in regards to the latent construct of NA and the Environmental dimension of QoL. For the clinical sample, SEM showed that NA had a negative impact on both QoL dimensions and metabolic control.Conclusions: Clinical interventions aiming to improve medication adherence in patients with T2DM should include the psychological evaluation of Type D Personality traits, by focusing especially on its component of NA as a significant risk factor leading to negative health outcomes.

  14. Selective androgen receptor modulators: in vitro and in vivo metabolism and analysis

    NARCIS (Netherlands)

    Rijke, de E.; Essers, M.L.; Rijk, J.C.W.; Thevis, M.; Bovee, T.F.H.; Ginkel, van L.A.; Sterk, S.S.

    2013-01-01

    For future targeted screening in National Residue Control Programmes, the metabolism of seven SARMs, from the arylpropionamide and the quinolinone classes, was studied in vitro using S9 bovine liver enzymes. Metabolites were detected and identified with ultra-performance liquid chromatography (UPLC)

  15. The relationship between epicardial fat and indices of obesity and the metabolic syndrome: a systematic review and meta-analysis.

    Science.gov (United States)

    Rabkin, Simon W

    2014-02-01

    Epicardial fat (epicardial adipose tissue, EAT) has been implicated in the pathogenesis of coronary artery disease (CAD). The objective of this study was to examine the relationship between EAT and generalized obesity, central or visceral adipose tissue (VAT), and the components of the metabolic syndrome--systolic blood pressure (SBP), triglycerides (TGs), high-density lipoprotein cholesterol (HDL-C), and fasting blood glucose (FBG)--that are linked to CAD. A systematic review of the literature, following meta-analysis guidelines, was conducted until May, 2013, using the search strategy "Obesity" OR "abdominal obesity" OR "metabolic syndrome" OR "metabolic syndrome X" AND "epicardial fat". Thirty-eight studies fulfilled the criteria. There was a highly significant (Pcorrelation between EAT and body mass index (BMI), waist circumference (WC), or VAT. The correlation between EAT and VAT was significantly (Pcorrelation between EAT and WC, which in turn was significantly greater than the correlation between EAT and BMI. Overall, EAT was 7.5 ± 0.1 mm in thickness in the metabolic syndrome (n=427) compared to 4.0 ± 0.1 mm in controls (n=301). EAT correlated significantly (PHDL, and FBG, but the strength of the association was less than one-half of the relationship of EAT to indices of obesity. The results of multivariate analysis were less consistent but show a relationship between EAT and metabolic syndrome independent of BMI. In summary, the very strong correlation between EAT and VAT suggests a relationship between these two adipose tissue depots. Measurement of EAT can be useful to indicate VAT. Whereas EAT correlates significantly with each of the components of the metabolic syndrome- SBP, TGs, HDL, or FBG-the magnitude of the relationship is considerably and significantly less than the relationship of EAT to BMI. These data show the strong relationship between EAT and BMI but especially with WC and VAT. They also demonstrate the smaller magnitude of the

  16. [Plasma fatty acid metabolic profiles for traditional Chinese medicine syndrome differentiation in diabetic patients using uncorrelated linear discriminant analysis].

    Science.gov (United States)

    Xu, Wenjuan; Zhang, Liangxiao; Huang, Yuhong; Yang, Qianxu; Xiao, Hongbin; Zhang, Deqin

    2012-09-01

    Diabetes is a common metabolic syndrome which presents a serious threat to human health. Traditional Chinese medicine (TCM) has been widely paid attention to its advantages and characteristics in the diagnosis and the treatment of diabetes. A strategy of classifying five TCM syndromes in diabetes (Qi-deficiency, Yin-deficiency, Qi- and Yin-deficiency, Damp heat and Blood stasis) was employed based on plasma fatty acid metabolic profiles, lipid metabolism indicators and chemometrics methods. Using orthogonal signal correction-partial least squares (OSC-PLS) method, the five syndromes were obviously distinguished from those of the health control, which confirmed there existed metabolite differences in different traditional Chinese medicine syndromes. Furthermore, a new method, uncorrelated linear discriminant analysis (ULDA), was applied in the discrimination of health control, TCM deficiency syndromes (Qi-deficiency, Yin-deficiency, Qi- and Yin-deficiency) and TCM empirical syndromes (Damp heat, Blood stasis), which demonstrated better clustering results, the correct rate reached 95.7%. The four potential biomarkers, C20: 2, C20: 5, triglycerides (TG) and high density lipoprotein (HDL), performed large contributions to the classification which can provide important information assisting TCM clinical diagnosis.

  17. Environmental impact analysis of nitrogen cross-media metabolism: A case study of municipal solid waste treatment system in China.

    Science.gov (United States)

    Wen, Zongguo; Bai, Weinan; Zhang, Wenting; Chen, Chen; Fei, Fan; Chen, Bin; Huang, Yi

    2018-03-15

    Municipal Solid Waste Treatment System (MSWTS) contributes a lot to urban metabolism optimization and pollution control of nitrogen. An analysis framework for cross-media metabolism of nitrogen was developed for MSWTS to study the systematic effects of nitrogen metabolism in MSWTS on ecosystem quality. Then cross-media distribution of pollutants was calculated in landfill, composting, incineration and anaerobic digestion, respectively. Sixty three percent to 82% of the original inputs ended up in the natural environment using the former three technologies (landfill, composting and incineration), which was attributed to cross-media migration. Anaerobic digestion should be highlighted due to its overall desirable removal efficiency. Critical processes related to nitrogen cross-media migration were identified to analyze the overall environmental impacts sensitivities. Positive effects emerged in liquid-solid interface migration of nitrogen through sewage collection and treatment technology processes, while the incineration flue gas treatment witnessed negative effects in gas-liquid interface migration. Overall, the environmental impact sensitivity levels of nitrogen cross-media migration under critical processes were as follows: incineration>landfill>composting>anaerobic digestion. Therefore, the environment is most sensitively affected by incineration and its processes. The present study is of great significance to optimize environmental management by shifting the management mode from single environmental medium quality control to systematic ecosystem quality improvement. Copyright © 2017 Elsevier B.V. All rights reserved.

  18. Altered post-mortem metabolism identified in very fast chilled lamb M. longissimus thoracis et lumborum using metabolomic analysis.

    Science.gov (United States)

    Warner, Robyn D; Jacob, Robin H; Rosenvold, Katja; Rochfort, Simone; Trenerry, Craige; Plozza, Tim; McDonagh, Matthew B

    2015-10-01

    The aim of this experiment was to use metabolomic techniques to investigate the energy metabolism in lamb M. longissimus thoracis et lumborum subjected to very fast chilling (VFC) post-mortem. The tissue was prepared by 2 different operators and subjected to very fast chilling (less than 0°C within 1.5h of slaughter) or typical chilling regimes (Control; 0°C within 22h of slaughter). Non-targeted metabolomic analysis ((1)H NMR) and targeted analysis ((31)P NMR, HPLC-PDA and HPLC-MS/MS) were used to examine the change in muscle metabolites post-mortem. One VFC treatment, which resulted in a colder core temperature and more tender meat, had higher levels of glycolytic intermediate metabolites pre-rigor as well as more of the end-products of adenosine and nicotine nucleotide metabolism pre-rigor, relative to conventionally chilled treatments. In conclusion, VFC to less than 0°C within 1.5h of slaughter causes considerable changes in metabolism and rigor onset, which are associated with tender meat. Crown Copyright © 2015. Published by Elsevier Ltd. All rights reserved.

  19. Phylogenetic and functional analysis of metagenome sequence from high-temperature archaeal habitats demonstrate linkages between metabolic potential and geochemistry

    Directory of Open Access Journals (Sweden)

    William P. Inskeep

    2013-05-01

    Full Text Available Geothermal habitats in Yellowstone National Park (YNP provide an unparalled opportunity to understand the environmental factors that control the distribution of archaea in thermal habitats. Here we describe, analyze and synthesize metagenomic and geochemical data collected from seven high-temperature sites that contain microbial communities dominated by archaea relative to bacteria. The specific objectives of the study were to use metagenome sequencing to determine the structure and functional capacity of thermophilic archaeal-dominated microbial communities across a pH range from 2.5 to 6.4 and to discuss specific examples where the metabolic potential correlated with measured environmental parameters and geochemical processes occurring in situ. Random shotgun metagenome sequence (~40-45 Mbase Sanger sequencing per site was obtained from environmental DNA extracted from high-temperature sediments and/or microbial mats and subjected to numerous phylogenetic and functional analyses. Analysis of individual sequences (e.g., MEGAN and G+C content and assemblies from each habitat type revealed the presence of dominant archaeal populations in all environments, 10 of whose genomes were largely reconstructed from the sequence data. Analysis of protein family occurrence, particularly of those involved in energy conservation, electron transport and autotrophic metabolism, revealed significant differences in metabolic strategies across sites consistent with differences in major geochemical attributes (e.g., sulfide, oxygen, pH. These observations provide an ecological basis for understanding the distribution of indigenous archaeal lineages across high temperature systems of YNP.

  20. Phylogenetic and Functional Analysis of Metagenome Sequence from High-Temperature Archaeal Habitats Demonstrate Linkages between Metabolic Potential and Geochemistry.

    Science.gov (United States)

    Inskeep, William P; Jay, Zackary J; Herrgard, Markus J; Kozubal, Mark A; Rusch, Douglas B; Tringe, Susannah G; Macur, Richard E; Jennings, Ryan deM; Boyd, Eric S; Spear, John R; Roberto, Francisco F

    2013-01-01

    Geothermal habitats in Yellowstone National Park (YNP) provide an unparalleled opportunity to understand the environmental factors that control the distribution of archaea in thermal habitats. Here we describe, analyze, and synthesize metagenomic and geochemical data collected from seven high-temperature sites that contain microbial communities dominated by archaea relative to bacteria. The specific objectives of the study were to use metagenome sequencing to determine the structure and functional capacity of thermophilic archaeal-dominated microbial communities across a pH range from 2.5 to 6.4 and to discuss specific examples where the metabolic potential correlated with measured environmental parameters and geochemical processes occurring in situ. Random shotgun metagenome sequence (∼40-45 Mb Sanger sequencing per site) was obtained from environmental DNA extracted from high-temperature sediments and/or microbial mats and subjected to numerous phylogenetic and functional analyses. Analysis of individual sequences (e.g., MEGAN and G + C content) and assemblies from each habitat type revealed the presence of dominant archaeal populations in all environments, 10 of whose genomes were largely reconstructed from the sequence data. Analysis of protein family occurrence, particularly of those involved in energy conservation, electron transport, and autotrophic metabolism, revealed significant differences in metabolic strategies across sites consistent with differences in major geochemical attributes (e.g., sulfide, oxygen, pH). These observations provide an ecological basis for understanding the distribution of indigenous archaeal lineages across high-temperature systems of YNP.

  1. Comparative functional genomic analysis of two Vibrio phages reveals complex metabolic interactions with the host cell

    Directory of Open Access Journals (Sweden)

    Dimitrios Skliros

    2016-11-01

    Full Text Available Sequencing and annotation was performed for two giant double stranded DNA bacteriophages, φGrn1 and φSt2 of the Myoviridae family, considered to be of great interest for phage therapy against Vibrios in aquaculture live feeds. In addition, phage-host metabolic interactions and exploitation was studied by transcript profiling of selected viral and host genes. Comparative genomic analysis with other giant Vibrio phages was also performed to establish the presence and location of homing endonucleases highlighting distinct features for both phages. Phylogenetic analysis revealed that they belong to the schizoT4like clade. Although many reports of newly sequenced viruses have provided a large set of information, basic research related to the shift of the bacterial metabolism during infection remains stagnant. The function of many viral protein products in the process of infection is still unknown. Genome annotation identified the presence of several viral ORFs participating in metabolism, including a Sir2/cobB (sirtuin protein and a number of genes involved in auxiliary NAD+ and nucleotide biosynthesis, necessary for phage DNA replication. Key genes were subsequently selected for detail study of their expression levels during infection. This work suggests a complex metabolic interaction and exploitation of the host metabolic pathways and biochemical processes, including a possible post-translational protein modification, by the virus during infection.

  2. Metabolic Profiling of Dividing Cells in Live Rodent Brain by Proton Magnetic Resonance Spectroscopy (1HMRS) and LCModel Analysis

    DEFF Research Database (Denmark)

    Park, June-Hee; Lee, Hedok; Makaryus, Rany

    2014-01-01

    RATIONALE: Dividing cells can be detected in the live brain by positron emission tomography or optical imaging. Here we apply proton magnetic resonance spectroscopy (1HMRS) and a widely used spectral fitting algorithm to characterize the effect of increased neurogenesis after electroconvulsive......-PDGF mice, when compared to normal brain tissue in the control mice. CONCLUSIONS: Metabolic profiling using 1HMRS in combination with LCModel analysis did not reveal correlation between Lip13a+Lip13b spectral signatures and an increase in neurogenesis in adult rat hippocampus after ECS. However, increases...

  3. Control of (pre-analytical aspects in immunoassay measurements of metabolic hormones in rodents

    Directory of Open Access Journals (Sweden)

    Maximilian Bielohuby

    2018-04-01

    Full Text Available The measurement of circulating hormones by immunoassay remains a cornerstone in preclinical endocrine research. For scientists conducting and interpreting immunoassay measurements of rodent samples, the paramount aim usually is to obtain reliable and meaningful measurement data in order to draw conclusions on biological processes. However, the biological variability between samples is not the only variable affecting the readout of an immunoassay measurement and a considerable amount of unwanted or unintended variability can be quickly introduced during the pre-analytical and analytical phase. This review aims to increase the awareness for the factors ‘pre-analytical’ and ‘analytical’ variability particularly in the context of immunoassay measurement of circulating metabolic hormones in rodent samples. In addition, guidance is provided how to gain control over these variables and how to avoid common pitfalls associated with sample collection, processing, storage and measurement. Furthermore, recommendations are given on how to perform a basic validation of novel single and multiplex immunoassays for the measurement of metabolic hormones in rodents. Finally, practical examples from immunoassay measurements of plasma insulin in mice address the factors ‘sampling site and inhalation anesthesia’ as frequent sources of introducing an unwanted variability during the pre-analytical phase. The knowledge about the influence of both types of variability on the immunoassay measurement of circulating hormones as well as strategies to control these variables are crucial, on the one hand, for planning and realization of metabolic rodent studies and, on the other hand, for the generation and interpretation of meaningful immunoassay data from rodent samples.

  4. The Effects of Mindfulness-Based Interventions on Diabetes-Related Distress, Quality of Life, and Metabolic Control Among Persons with Diabetes: A Meta-Analytic Review.

    Science.gov (United States)

    Bogusch, Leah M; O'Brien, William H

    2018-04-04

    Mindfulness-based interventions (MBIs) have improved psychological outcomes for multiple chronic health conditions, including diabetes. A meta-analytic review of the literature was conducted on all located studies (n = 14) investigating MBIs that targeted diabetes-related distress (DRD) and diabetes-related outcomes among people with Type 1 and Type 2 diabetes. PsychInfo, PubMed, Medline, and Web of Science were searched for MBIs that were designed to improve DRD and other secondary outcomes, including quality of life and measures of metabolic control. A meta-analysis of these outcomes uncovered small-to-moderate effect sizes for intervention studies measuring pretreatment to posttreatment changes in DRD and metabolic control among treatment group participants. However, the pretreatment to follow-up comparisons for DRD and metabolic control were small and unreliable. For control groups, all pre-treatment to post-treatment and pre-treatment to follow-up comparisons were unreliable for all outcomes. A moderate effect size for treatment-control comparisons was found for intervention studies measuring quality of life outcomes at posttreatment, but not at follow-up comparisons. All other effect sizes for treatment-control comparisons were unreliable. Limitations and implications for MBIs among individuals with diabetes are discussed.

  5. Robustness analysis of chiller sequencing control

    International Nuclear Information System (INIS)

    Liao, Yundan; Sun, Yongjun; Huang, Gongsheng

    2015-01-01

    Highlights: • Uncertainties with chiller sequencing control were systematically quantified. • Robustness of chiller sequencing control was systematically analyzed. • Different sequencing control strategies were sensitive to different uncertainties. • A numerical method was developed for easy selection of chiller sequencing control. - Abstract: Multiple-chiller plant is commonly employed in the heating, ventilating and air-conditioning system to increase operational feasibility and energy-efficiency under part load condition. In a multiple-chiller plant, chiller sequencing control plays a key role in achieving overall energy efficiency while not sacrifices the cooling sufficiency for indoor thermal comfort. Various sequencing control strategies have been developed and implemented in practice. Based on the observation that (i) uncertainty, which cannot be avoided in chiller sequencing control, has a significant impact on the control performance and may cause the control fail to achieve the expected control and/or energy performance; and (ii) in current literature few studies have systematically addressed this issue, this paper therefore presents a study on robustness analysis of chiller sequencing control in order to understand the robustness of various chiller sequencing control strategies under different types of uncertainty. Based on the robustness analysis, a simple and applicable method is developed to select the most robust control strategy for a given chiller plant in the presence of uncertainties, which will be verified using case studies

  6. Pathway analysis of kidney cancer using proteomics and metabolic profiling

    Directory of Open Access Journals (Sweden)

    Fiehn Oliver

    2006-11-01

    Full Text Available Abstract Background Renal cell carcinoma (RCC is the sixth leading cause of cancer death and is responsible for 11,000 deaths per year in the US. Approximately one-third of patients present with disease which is already metastatic and for which there is currently no adequate treatment, and no biofluid screening tests exist for RCC. In this study, we have undertaken a comprehensive proteomic analysis and subsequently a pathway and network approach to identify biological processes involved in clear cell RCC (ccRCC. We have used these data to investigate urinary markers of RCC which could be applied to high-risk patients, or to those being followed for recurrence, for early diagnosis and treatment, thereby substantially reducing mortality of this disease. Results Using 2-dimensional electrophoresis and mass spectrometric analysis, we identified 31 proteins which were differentially expressed with a high degree of significance in ccRCC as compared to adjacent non-malignant tissue, and we confirmed some of these by immunoblotting, immunohistochemistry, and comparison to published transcriptomic data. When evaluated by several pathway and biological process analysis programs, these proteins are demonstrated to be involved with a high degree of confidence (p values Conclusion Extensive pathway and network analysis allowed for the discovery of highly significant pathways from a set of clear cell RCC samples. Knowledge of activation of these processes will lead to novel assays identifying their proteomic and/or metabolomic signatures in biofluids of patient at high risk for this disease; we provide pilot data for such a urinary bioassay. Furthermore, we demonstrate how the knowledge of networks, processes, and pathways altered in kidney cancer may be used to influence the choice of optimal therapy.

  7. Improving production of ?-lactam antibiotics by Penicillium chrysogenum : Metabolic engineering based on transcriptome analysis

    NARCIS (Netherlands)

    Veiga, T.

    2012-01-01

    In Chapters 2-5 of this thesis, the applicability of transcriptome analysis to guide metabolic engineering strategies in P. chrysogenum is explored by investigating four cellular processes that are of potential relevance for industrial production of ?-lactam antibiotics: - Regulation of secondary

  8. An update on psoriasis and metabolic syndrome: A meta-analysis of observational studies.

    Directory of Open Access Journals (Sweden)

    Sanminder Singh

    Full Text Available The relationship between psoriasis and metabolic syndrome is not well understood. Though multiple epidemiologic studies have suggested a link between psoriasis and metabolic syndrome, there is a lack of a comprehensive meta-analysis synthesizing the results of all available observational studies to date. In this meta-analysis, we examined global data on the relationship between psoriasis and odds of metabolic syndrome by searching for studies published between 1946-2016. Specifically, we analyzed the results from 35 observational studies from 20 countries with 1,450,188 total participants, of which 46,714 were psoriasis patients. The pooled odds ratio based on random effects analysis was 2.14 (95% CI 1.84-2.48. Publication bias was present, as evidenced by an Egger test and graphical visualization through a funnel plot (p = 0.001. Based on this comprehensive meta-analysis, psoriasis patients have higher odds of having metabolic syndrome when compared with the general population.

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

    Indian Academy of Sciences (India)

    2015-09-28

    Sep 28, 2015 ... genome-scale metabolic model of rice leaf using Flux Balance Analysis to investigate whether it has potential .... is number of reactions. In steady state. S.v = 0. (2) where v is the flux vector of reactions (Kauffman et al. 2003). Objective function is. Z = w.v. (3). 820 .... All the reactions are not included.

  10. Gene Coexpression Analysis Reveals Complex Metabolism of the Monoterpene Alcohol Linalool in Arabidopsis FlowersW

    NARCIS (Netherlands)

    Ginglinger, J.F.; Boachon, B.; Hofer, R.; Paetz, C.; Kollner, T.G.; Miesch, L.; Lugan, R.; Baltenweck, R.; Mutterer, J.; Ullman, P.; Verstappen, F.W.A.; Bouwmeester, H.J.

    2013-01-01

    The cytochrome P450 family encompasses the largest family of enzymes in plant metabolism, and the functions of many of its members in Arabidopsis thaliana are still unknown. Gene coexpression analysis pointed to two P450s that were coexpressed with two monoterpene synthases in flowers and were thus

  11. Tumour xenograft detection through quantitative analysis of the metabolic profile of urine in mice

    Energy Technology Data Exchange (ETDEWEB)

    Moroz, Jennifer [Department of Physics, University of Alberta, 11322-89 Avenue, Edmonton, Alberta T6G 2G7 (Canada); Turner, Joan [Department of Experimental Oncology, University of Alberta, Cross Cancer Institute, 11560 University Avenue, Edmonton, Alberta T6G 1Z2 (Canada); Slupsky, Carolyn [Department of Nutrition, University of California, One Shields Avenue, Davis, CA 95616-8598 (United States); Fallone, Gino; Syme, Alasdair, E-mail: alasdair.syme@albertahealthservices.ca [Department of Oncology, University of Alberta, Cross Cancer Institute, 11560 University Avenue, Edmonton, Alberta T6G 1Z2 (Canada)

    2011-02-07

    The metabolic content of urine from NIH III nude mice (n = 22) was analysed before and after inoculation with human glioblastoma multiforme (GBM) cancer cells. An age- and gender-matched control population (n = 14) was also studied to identify non-tumour-related changes. Urine samples were collected daily for 6 weeks, beginning 1 week before cell injection. Metabolite concentrations were obtained via targeted profiling with Chenomx Suite 5.1, based on nuclear magnetic resonance (NMR) spectra acquired on an Oxford 800 MHz cold probe NMR spectrometer. The Wilcoxon rank sum test was used to evaluate the significance of the change in metabolite concentration between the two time points. Both the metabolite concentrations and the ratios of pairs of metabolites were studied. The complicated inter-relationships between metabolites were assessed through partial least-squares discriminant analysis (PLS-DA). Receiver operating characteristic (ROC) curves were generated for all variables and the area under the curve (AUC) calculated. The data indicate that the number of statistically significant changes in metabolite concentrations was more pronounced in the tumour-bearing population than in the control animals. This was also true of the ratios of pairs of metabolites. ROC analysis suggests that the ratios were better able to differentiate between the pre- and post-injection samples compared to the metabolite concentrations. PLS-DA models produced good separation between the populations and had the best AUC results (all models exceeded 0.937). These results demonstrate that metabolomics may be used as a screening tool for GBM cells grown in xenograft models in mice.

  12. NMR metabolic analysis of samples using fuzzy K-means clustering.

    Science.gov (United States)

    Cuperlović-Culf, Miroslava; Belacel, Nabil; Culf, Adrian S; Chute, Ian C; Ouellette, Rodney J; Burton, Ian W; Karakach, Tobias K; Walter, John A

    2009-12-01

    The global analysis of metabolites can be used to define the phenotypes of cells, tissues or organisms. Classifying groups of samples based on their metabolic profile is one of the main topics of metabolomics research. Crisp clustering methods assign each feature to one cluster, thereby omitting information about the multiplicity of sample subtypes. Here, we present the application of fuzzy K-means clustering method for the classification of samples based on metabolomics 1D (1)H NMR fingerprints. The sample classification was performed on NMR spectra of cancer cell line extracts and of urine samples of type 2 diabetes patients and animal models. The cell line dataset included NMR spectra of lipophilic cell extracts for two normal and three cancer cell lines with cancer cell lines including two invasive and one non-invasive cancers. The second dataset included previously published NMR spectra of urine samples of human type 2 diabetics and healthy controls, mouse wild type and diabetes model and rat obese and lean phenotypes. The fuzzy K-means clustering method allowed more accurate sample classification in both datasets relative to the other tested methods including principal component analysis (PCA), hierarchical clustering (HCL) and K-means clustering. In the cell line samples, fuzzy clustering provided a clear separation of individual cell lines, groups of cancer and normal cell lines as well as non-invasive and invasive tumour cell lines. In the diabetes dataset, clear separation of healthy controls and diabetics in all three models was possible only by using the fuzzy clustering method.

  13. Tumour xenograft detection through quantitative analysis of the metabolic profile of urine in mice

    International Nuclear Information System (INIS)

    Moroz, Jennifer; Turner, Joan; Slupsky, Carolyn; Fallone, Gino; Syme, Alasdair

    2011-01-01

    The metabolic content of urine from NIH III nude mice (n = 22) was analysed before and after inoculation with human glioblastoma multiforme (GBM) cancer cells. An age- and gender-matched control population (n = 14) was also studied to identify non-tumour-related changes. Urine samples were collected daily for 6 weeks, beginning 1 week before cell injection. Metabolite concentrations were obtained via targeted profiling with Chenomx Suite 5.1, based on nuclear magnetic resonance (NMR) spectra acquired on an Oxford 800 MHz cold probe NMR spectrometer. The Wilcoxon rank sum test was used to evaluate the significance of the change in metabolite concentration between the two time points. Both the metabolite concentrations and the ratios of pairs of metabolites were studied. The complicated inter-relationships between metabolites were assessed through partial least-squares discriminant analysis (PLS-DA). Receiver operating characteristic (ROC) curves were generated for all variables and the area under the curve (AUC) calculated. The data indicate that the number of statistically significant changes in metabolite concentrations was more pronounced in the tumour-bearing population than in the control animals. This was also true of the ratios of pairs of metabolites. ROC analysis suggests that the ratios were better able to differentiate between the pre- and post-injection samples compared to the metabolite concentrations. PLS-DA models produced good separation between the populations and had the best AUC results (all models exceeded 0.937). These results demonstrate that metabolomics may be used as a screening tool for GBM cells grown in xenograft models in mice.

  14. Role of resting metabolic rate and energy expenditure in hunger and appetite control: a new formulation.

    Science.gov (United States)

    Blundell, John E; Caudwell, Phillipa; Gibbons, Catherine; Hopkins, Mark; Naslund, Erik; King, Neil; Finlayson, Graham

    2012-09-01

    A long-running issue in appetite research concerns the influence of energy expenditure on energy intake. More than 50 years ago, Otto G. Edholm proposed that "the differences between the intakes of food [of individuals] must originate in differences in the expenditure of energy". However, a relationship between energy expenditure and energy intake within any one day could not be found, although there was a correlation over 2 weeks. This issue was never resolved before interest in integrative biology was replaced by molecular biochemistry. Using a psychobiological approach, we have studied appetite control in an energy balance framework using a multi-level experimental system on a single cohort of overweight and obese human subjects. This has disclosed relationships between variables in the domains of body composition [fat-free mass (FFM), fat mass (FM)], metabolism, gastrointestinal hormones, hunger and energy intake. In this Commentary, we review our own and other data, and discuss a new formulation whereby appetite control and energy intake are regulated by energy expenditure. Specifically, we propose that FFM (the largest contributor to resting metabolic rate), but not body mass index or FM, is closely associated with self-determined meal size and daily energy intake. This formulation has implications for understanding weight regulation and the management of obesity.

  15. Role of resting metabolic rate and energy expenditure in hunger and appetite control: a new formulation

    Directory of Open Access Journals (Sweden)

    John E. Blundell

    2012-09-01

    Full Text Available A long-running issue in appetite research concerns the influence of energy expenditure on energy intake. More than 50 years ago, Otto G. Edholm proposed that “the differences between the intakes of food [of individuals] must originate in differences in the expenditure of energy”. However, a relationship between energy expenditure and energy intake within any one day could not be found, although there was a correlation over 2 weeks. This issue was never resolved before interest in integrative biology was replaced by molecular biochemistry. Using a psychobiological approach, we have studied appetite control in an energy balance framework using a multi-level experimental system on a single cohort of overweight and obese human subjects. This has disclosed relationships between variables in the domains of body composition [fat-free mass (FFM, fat mass (FM], metabolism, gastrointestinal hormones, hunger and energy intake. In this Commentary, we review our own and other data, and discuss a new formulation whereby appetite control and energy intake are regulated by energy expenditure. Specifically, we propose that FFM (the largest contributor to resting metabolic rate, but not body mass index or FM, is closely associated with self-determined meal size and daily energy intake. This formulation has implications for understanding weight regulation and the management of obesity.

  16. Zinc Status Biomarkers and Cardiometabolic Risk Factors in Metabolic Syndrome: A Case Control Study

    Science.gov (United States)

    Freitas, Erika P. S.; Cunha, Aline T. O.; Aquino, Sephora L. S.; Pedrosa, Lucia F. C.; Lima, Severina C. V. C.; Lima, Josivan G.; Almeida, Maria G.; Sena-Evangelista, Karine C. M.

    2017-01-01

    Metabolic syndrome (MS) involves pathophysiological alterations that might compromise zinc status. The aim of this study was to evaluate zinc status biomarkers and their associations with cardiometabolic factors in patients with MS. Our case control study included 88 patients with MS and 37 controls. We performed clinical and anthropometric assessments and obtained lipid, glycemic, and inflammatory profiles. We also evaluated zinc intake, plasma zinc, erythrocyte zinc, and 24-h urinary zinc excretion. The average zinc intake was significantly lower in the MS group (p 0.05) between the two groups. We found significantly higher erythrocyte zinc concentration in the MS group (p < 0.001) independent from co-variable adjustments. Twenty-four hour urinary zinc excretion was significantly higher in the MS group (p = 0.008), and adjustments for age and sex explained 21% of the difference (R2 = 0.21, p < 0.001). There were significant associations between zincuria and fasting blood glucose concentration (r = 0.479), waist circumference (r = 0.253), triglyceride concentration (r = 0.360), glycated hemoglobin concentration (r = 0.250), homeostatic model assessment—insulin resistance (r = 0.223), and high-sensitivity C-reactive protein concentration (r = 0.427) (all p < 0.05) in the MS group. Patients with MS had alterations in zinc metabolism mainly characterized by an increase in erythrocyte zinc and higher zincuria. PMID:28241426

  17. Zinc Status Biomarkers and Cardiometabolic Risk Factors in Metabolic Syndrome: A Case Control Study

    Directory of Open Access Journals (Sweden)

    Erika P. S. Freitas

    2017-02-01

    Full Text Available Metabolic syndrome (MS involves pathophysiological alterations that might compromise zinc status. The aim of this study was to evaluate zinc status biomarkers and their associations with cardiometabolic factors in patients with MS. Our case control study included 88 patients with MS and 37 controls. We performed clinical and anthropometric assessments and obtained lipid, glycemic, and inflammatory profiles. We also evaluated zinc intake, plasma zinc, erythrocyte zinc, and 24-h urinary zinc excretion. The average zinc intake was significantly lower in the MS group (p < 0.001. Regression models indicated no significant differences in plasma zinc concentration (all p > 0.05 between the two groups. We found significantly higher erythrocyte zinc concentration in the MS group (p < 0.001 independent from co-variable adjustments. Twenty-four hour urinary zinc excretion was significantly higher in the MS group (p = 0.008, and adjustments for age and sex explained 21% of the difference (R2 = 0.21, p < 0.001. There were significant associations between zincuria and fasting blood glucose concentration (r = 0.479, waist circumference (r = 0.253, triglyceride concentration (r = 0.360, glycated hemoglobin concentration (r = 0.250, homeostatic model assessment—insulin resistance (r = 0.223, and high-sensitivity C-reactive protein concentration (r = 0.427 (all p < 0.05 in the MS group. Patients with MS had alterations in zinc metabolism mainly characterized by an increase in erythrocyte zinc and higher zincuria.

  18. Consistency Analysis of Genome-Scale Models of Bacterial Metabolism: A Metamodel Approach.

    Science.gov (United States)

    Ponce-de-Leon, Miguel; Calle-Espinosa, Jorge; Peretó, Juli; Montero, Francisco

    2015-01-01

    Genome-scale metabolic models usually contain inconsistencies that manifest as blocked reactions and gap metabolites. With the purpose to detect recurrent inconsistencies in metabolic models, a large-scale analysis was performed using a previously published dataset of 130 genome-scale models. The results showed that a large number of reactions (~22%) are blocked in all the models where they are present. To unravel the nature of such inconsistencies a metamodel was construed by joining the 130 models in a single network. This metamodel was manually curated using the unconnected modules approach, and then, it was used as a reference network to perform a gap-filling on each individual genome-scale model. Finally, a set of 36 models that had not been considered during the construction of the metamodel was used, as a proof of concept, to extend the metamodel with new biochemical information, and to assess its impact on gap-filling results. The analysis performed on the metamodel allowed to conclude: 1) the recurrent inconsistencies found in the models were already present in the metabolic database used during the reconstructions process; 2) the presence of inconsistencies in a metabolic database can be propagated to the reconstructed models; 3) there are reactions not manifested as blocked which are active as a consequence of some classes of artifacts, and; 4) the results of an automatic gap-filling are highly dependent on the consistency and completeness of the metamodel or metabolic database used as the reference network. In conclusion the consistency analysis should be applied to metabolic databases in order to detect and fill gaps as well as to detect and remove artifacts and redundant information.

  19. KAT2B Is Required for Pancreatic Beta Cell Adaptation to Metabolic Stress by Controlling the Unfolded Protein Response.

    Science.gov (United States)

    Rabhi, Nabil; Denechaud, Pierre-Damien; Gromada, Xavier; Hannou, Sarah Anissa; Zhang, Hongbo; Rashid, Talha; Salas, Elisabet; Durand, Emmanuelle; Sand, Olivier; Bonnefond, Amélie; Yengo, Loic; Chavey, Carine; Bonner, Caroline; Kerr-Conte, Julie; Abderrahmani, Amar; Auwerx, Johan; Fajas, Lluis; Froguel, Philippe; Annicotte, Jean-Sébastien

    2016-05-03

    The endoplasmic reticulum (ER) unfolded protein response (UPR(er)) pathway plays an important role in helping pancreatic β cells to adapt their cellular responses to environmental cues and metabolic stress. Although altered UPR(er) gene expression appears in rodent and human type 2 diabetic (T2D) islets, the underlying molecular mechanisms remain unknown. We show here that germline and β cell-specific disruption of the lysine acetyltransferase 2B (Kat2b) gene in mice leads to impaired insulin secretion and glucose intolerance. Genome-wide analysis of Kat2b-regulated genes and functional assays reveal a critical role for Kat2b in maintaining UPR(er) gene expression and subsequent β cell function. Importantly, Kat2b expression is decreased in mouse and human diabetic β cells and correlates with UPR(er) gene expression in normal human islets. In conclusion, Kat2b is a crucial transcriptional regulator for adaptive β cell function during metabolic stress by controlling UPR(er) and represents a promising target for T2D prevention and treatment. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  20. Gene expression analysis of starch metabolism using mRNAseq and the potato genome sequence

    DEFF Research Database (Denmark)

    Sønderkær, Mads; Kloosterman, Bjorn; Bachem, Christian

    2010-01-01

    starch yield than presently possible, detailed knowledge about starch metabolism is crucial. Accumulation of carbohydrates in the form of starch in potato tubers is the result of both anabolic and catabolic processes. These processes are highly redundant in terms of gene isoforms and multiple metabolic......, starch synthesis takes place not only in tubers but also in leaves in the form of transient starch during the day, which is consumed in the absence of photosynthesis during the night. This poster will present the results of a transcriptome analysis based on the draft potato genome sequence v3. Samples...

  1. Combined treatment with melatonin and insulin improves glycemic control, white adipose tissue metabolism and reproductive axis of diabetic male rats.

    Science.gov (United States)

    Oliveira, Ariclecio Cunha de; Andreotti, Sandra; Sertie, Rogério António Laurato; Campana, Amanda Baron; de Proença, André Ricardo Gomes; Vasconcelos, Renata Prado; Oliveira, Keciany Alves de; Coelho-de-Souza, Andrelina Noronha; Donato-Junior, José; Lima, Fábio Bessa

    2018-04-15

    Melatonin treatment has been reported to be capable of ameliorating metabolic diabetes-related abnormalities but also to cause hypogonadism in rats. We investigated whether the combined treatment with melatonin and insulin can improve insulin resistance and other metabolic disorders in rats with streptozotocin-induced diabetes during neonatal period and the repercussion of this treatment on the hypothalamic-pituitary-gonadal axis. At the fourth week of age, diabetic animals started an 8-wk treatment with only melatonin (0.2 mg/kg body weight) added to drinking water at night or associated with insulin (NHP, 1.5 U/100 g/day) or only insulin. Animals were then euthanized, and the subcutaneous (SC), epididymal (EP), and retroperitoneal (RP) fat pads were excised, weighed and processed for adipocyte isolation for morphometric analysis as well as for measuring glucose uptake, oxidation, and incorporation of glucose into lipids. Hypothalamus was collected for gene expression and blood samples were collected for biochemical assays. The treatment with melatonin plus insulin (MI) was capable of maintaining glycemic control. In epididymal (EP) and subcutaneous (SC) adipocytes, the melatonin plus insulin (MI) treatment group recovered the insulin responsiveness. In the hypothalamus, melatonin treatment alone promoted a significant reduction in kisspeptin-1, neurokinin B and androgen receptor mRNA levels, in relation to control group. Combined treatment with melatonin and insulin promoted a better glycemic control, improving insulin sensitivity in white adipose tissue (WAT). Indeed, melatonin treatment reduced hypothalamic genes related to reproductive function. Copyright © 2017. Published by Elsevier Inc.

  2. Metabolic Markers or Conditions Preceding Parkinson’s Disease: A Case-Control Study

    Science.gov (United States)

    Savica, Rodolfo; Grossardt, Brandon R.; Ahlskog, J. Eric; Rocca, Walter A.

    2013-01-01

    Background Several metabolic markers or conditions have been explored as possible risk or protective factors for Parkinson’s disease (PD); however, results remain conflicting. We further investigated these associations using a case-control study design. Methods We used the medical records-linkage system of the Rochester Epidemiology Project to identify 196 subjects who developed PD in Olmsted County, MN, from 1976 through 1995. Each incident case was matched by age (± 1 year) and sex to a general population control. We reviewed the complete medical records of cases and controls in the medical records-linkage system to abstract information about body mass index (BMI), cholesterol levels, hypertension, and diabetes mellitus preceding the onset of PD (or the index year). Results There were no significant differences between cases and controls for the metabolic markers or conditions investigated. No significant associations were found using 2 cut-offs for BMI levels (BMI ≥ 25 or BMI ≥ 30 kg/m2) and 3 cut-offs for cholesterol levels (> 200, > 250, or > 300 mg/dl). A diagnosis of hypertension or the documented use of anti-hypertensive medications were not significantly associated with the subsequent risk of PD (odds ratio [OR], 1.00; 95% confidence interval [CI], 0.65–1.54; P = .99), nor was a diagnosis of diabetes mellitus or the use of glucose-lowering medications (OR, 0.77; 95% CI, 0.37–1.57; P =.47). Conclusions Our study, based on historical information from a records-linkage system, does not support an association between BMI, cholesterol levels, hypertension, or diabetes mellitus and later development of PD. PMID:22674432

  3. Quantitative Multilevel Analysis of Central Metabolism in Developing Oilseeds of Oilseed Rape during in Vitro Culture.

    Science.gov (United States)

    Schwender, Jörg; Hebbelmann, Inga; Heinzel, Nicolas; Hildebrandt, Tatjana; Rogers, Alistair; Naik, Dhiraj; Klapperstück, Matthias; Braun, Hans-Peter; Schreiber, Falk; Denolf, Peter; Borisjuk, Ljudmilla; Rolletschek, Hardy

    2015-07-01

    Seeds provide the basis for many food, feed, and fuel products. Continued increases in seed yield, composition, and quality require an improved understanding of how the developing seed converts carbon and nitrogen supplies into storage. Current knowledge of this process is often based on the premise that transcriptional regulation directly translates via enzyme concentration into flux. In an attempt to highlight metabolic control, we explore genotypic differences in carbon partitioning for in vitro cultured developing embryos of oilseed rape (Brassica napus). We determined biomass composition as well as 79 net fluxes, the levels of 77 metabolites, and 26 enzyme activities with specific focus on central metabolism in nine selected germplasm accessions. Overall, we observed a tradeoff between the biomass component fractions of lipid and starch. With increasing lipid content over the spectrum of genotypes, plastidic fatty acid synthesis and glycolytic flux increased concomitantly, while glycolytic intermediates decreased. The lipid/starch tradeoff was not reflected at the proteome level, pointing to the significance of (posttranslational) metabolic control. Enzyme activity/flux and metabolite/flux correlations suggest that plastidic pyruvate kinase exerts flux control and that the lipid/starch tradeoff is most likely mediated by allosteric feedback regulation of phosphofructokinase and ADP-glucose pyrophosphorylase. Quantitative data were also used to calculate in vivo mass action ratios, reaction equilibria, and metabolite turnover times. Compounds like cyclic 3',5'-AMP and sucrose-6-phosphate were identified to potentially be involved in so far unknown mechanisms of metabolic control. This study provides a rich source of quantitative data for those studying central metabolism. © 2015 American Society of Plant Biologists. All Rights Reserved.

  4. Quantitative Multilevel Analysis of Central Metabolism in Developing Oilseeds of Oilseed Rape During In Vitro Culture

    Energy Technology Data Exchange (ETDEWEB)

    Schwender, Jorg [Brookhaven National Lab. (BNL), Upton, NY (United States); Hebbelmann, Inga [Brookhaven National Lab. (BNL), Upton, NY (United States); Heinzel, Nicholas [Leibniz Inst. of Plant Genetics and Crop Plant Research, Gatersleben (Germany); Hildebrandt, Tatjana [Univ. of Hannover (Germany); Rogers, Alistair [Brookhaven National Lab. (BNL), Upton, NY (United States); Naik, Dhiraj [Brookhaven National Lab. (BNL), Upton, NY (United States); Indian Inst. of Advanced Research Koba, Gujarat (India); Klapperstuck, Matthias [Monash Univ., Melbourne, VIC (Australia); Braun, Hans -Peter [Univ. of Hannover (Germany); Schreiber, Falk [Monash Univ., Melbourne, VIC (Australia); Univ. Halle-Wittenberg, Melbourne (Australia); Denolf, Peter [Bayer CropScience (Belgium); Borisjuk, Ljudmilla [Leibniz Inst. of Plant Genetics and Crop Plant Research, Gatersleben (Germany); Rolletschek, Hardy [Leibniz Inst. of Plant Genetics and Crop Plant Research, Gatersleben (Germany)

    2015-07-01

    Seeds provide the basis for many food, feed, and fuel products. Continued increases in seed yield, composition, and quality require an improved understanding of how the developing seed converts carbon and nitrogen supplies into storage. Current knowledge of this process is often based on the premise that transcriptional regulation directly translates via enzyme concentration into flux. In an attempt to highlight metabolic control, we explore genotypic differences in carbon partitioning for in vitro cultured developing embryos of oilseed rape (Brassica napus). We determined biomass composition as well as 79 net fluxes, the levels of 77 metabolites, and 26 enzyme activities with specific focus on central metabolism in nine selected germplasm accessions. We observed a tradeoff between the biomass component fractions of lipid and starch. With increasing lipid content over the spectrum of genotypes, plastidic fatty acid synthesis and glycolytic flux increased concomitantly, while glycolytic intermediates decreased. The lipid/starch tradeoff was not reflected at the proteome level, pointing to the significance of (posttranslational) metabolic control. Enzyme activity/flux and metabolite/flux correlations suggest that plastidic pyruvate kinase exerts flux control and that the lipid/starch tradeoff is most likely mediated by allosteric feedback regulation of phosphofructokinase and ADP-glucose pyrophosphorylase. Also, quantitative data were used to calculate in vivo mass action ratios, reaction equilibria, and metabolite turnover times. Compounds like cyclic 3',5'-AMP and sucrose-6-phosphate were identified to potentially be involved in so far unknown mechanisms of metabolic control. This study provides a rich source of quantitative data for those studying central metabolism..

  5. Reconstruction and analysis of a genome-scale metabolic model for Scheffersomyces stipitis

    Directory of Open Access Journals (Sweden)

    Balagurunathan Balaji

    2012-02-01

    Full Text Available Abstract Background Fermentation of xylose, the major component in hemicellulose, is essential for economic conversion of lignocellulosic biomass to fuels and chemicals. The yeast Scheffersomyces stipitis (formerly known as Pichia stipitis has the highest known native capacity for xylose fermentation and possesses several genes for lignocellulose bioconversion in its genome. Understanding the metabolism of this yeast at a global scale, by reconstructing the genome scale metabolic model, is essential for manipulating its metabolic capabilities and for successful transfer of its capabilities to other industrial microbes. Results We present a genome-scale metabolic model for Scheffersomyces stipitis, a native xylose utilizing yeast. The model was reconstructed based on genome sequence annotation, detailed experimental investigation and known yeast physiology. Macromolecular composition of Scheffersomyces stipitis biomass was estimated experimentally and its ability to grow on different carbon, nitrogen, sulphur and phosphorus sources was determined by phenotype microarrays. The compartmentalized model, developed based on an iterative procedure, accounted for 814 genes, 1371 reactions, and 971 metabolites. In silico computed growth rates were compared with high-throughput phenotyping data and the model could predict the qualitative outcomes in 74% of substrates investigated. Model simulations were used to identify the biosynthetic requirements for anaerobic growth of Scheffersomyces stipitis on glucose and the results were validated with published literature. The bottlenecks in Scheffersomyces stipitis metabolic network for xylose uptake and nucleotide cofactor recycling were identified by in silico flux variability analysis. The scope of the model in enhancing the mechanistic understanding of microbial metabolism is demonstrated by identifying a mechanism for mitochondrial respiration and oxidative phosphorylation. Conclusion The genome

  6. Early detection of metabolic and energy disorders by thermal time series stochastic complexity analysis.

    Science.gov (United States)

    Lutaif, N A; Palazzo, R; Gontijo, J A R

    2014-01-01

    Maintenance of thermal homeostasis in rats fed a high-fat diet (HFD) is associated with changes in their thermal balance. The thermodynamic relationship between heat dissipation and energy storage is altered by the ingestion of high-energy diet content. Observation of thermal registers of core temperature behavior, in humans and rodents, permits identification of some characteristics of time series, such as autoreference and stationarity that fit adequately to a stochastic analysis. To identify this change, we used, for the first time, a stochastic autoregressive model, the concepts of which match those associated with physiological systems involved and applied in male HFD rats compared with their appropriate standard food intake age-matched male controls (n=7 per group). By analyzing a recorded temperature time series, we were able to identify when thermal homeostasis would be affected by a new diet. The autoregressive time series model (AR model) was used to predict the occurrence of thermal homeostasis, and this model proved to be very effective in distinguishing such a physiological disorder. Thus, we infer from the results of our study that maximum entropy distribution as a means for stochastic characterization of temperature time series registers may be established as an important and early tool to aid in the diagnosis and prevention of metabolic diseases due to their ability to detect small variations in thermal profile.

  7. Early detection of metabolic and energy disorders by thermal time series stochastic complexity analysis

    Energy Technology Data Exchange (ETDEWEB)

    Lutaif, N.A. [Departamento de Clínica Médica, Faculdade de Ciências Médicas, Universidade Estadual de Campinas, Campinas, SP (Brazil); Palazzo, R. Jr [Departamento de Telemática, Faculdade de Engenharia Elétrica e Computação, Universidade Estadual de Campinas, Campinas, SP (Brazil); Gontijo, J.A.R. [Departamento de Clínica Médica, Faculdade de Ciências Médicas, Universidade Estadual de Campinas, Campinas, SP (Brazil)

    2014-01-17

    Maintenance of thermal homeostasis in rats fed a high-fat diet (HFD) is associated with changes in their thermal balance. The thermodynamic relationship between heat dissipation and energy storage is altered by the ingestion of high-energy diet content. Observation of thermal registers of core temperature behavior, in humans and rodents, permits identification of some characteristics of time series, such as autoreference and stationarity that fit adequately to a stochastic analysis. To identify this change, we used, for the first time, a stochastic autoregressive model, the concepts of which match those associated with physiological systems involved and applied in male HFD rats compared with their appropriate standard food intake age-matched male controls (n=7 per group). By analyzing a recorded temperature time series, we were able to identify when thermal homeostasis would be affected by a new diet. The autoregressive time series model (AR model) was used to predict the occurrence of thermal homeostasis, and this model proved to be very effective in distinguishing such a physiological disorder. Thus, we infer from the results of our study that maximum entropy distribution as a means for stochastic characterization of temperature time series registers may be established as an important and early tool to aid in the diagnosis and prevention of metabolic diseases due to their ability to detect small variations in thermal profile.

  8. Early detection of metabolic and energy disorders by thermal time series stochastic complexity analysis

    Directory of Open Access Journals (Sweden)

    N.A. Lutaif

    2014-01-01

    Full Text Available Maintenance of thermal homeostasis in rats fed a high-fat diet (HFD is associated with changes in their thermal balance. The thermodynamic relationship between heat dissipation and energy storage is altered by the ingestion of high-energy diet content. Observation of thermal registers of core temperature behavior, in humans and rodents, permits identification of some characteristics of time series, such as autoreference and stationarity that fit adequately to a stochastic analysis. To identify this change, we used, for the first time, a stochastic autoregressive model, the concepts of which match those associated with physiological systems involved and applied in male HFD rats compared with their appropriate standard food intake age-matched male controls (n=7 per group. By analyzing a recorded temperature time series, we were able to identify when thermal homeostasis would be affected by a new diet. The autoregressive time series model (AR model was used to predict the occurrence of thermal homeostasis, and this model proved to be very effective in distinguishing such a physiological disorder. Thus, we infer from the results of our study that maximum entropy distribution as a means for stochastic characterization of temperature time series registers may be established as an important and early tool to aid in the diagnosis and prevention of metabolic diseases due to their ability to detect small variations in thermal profile.

  9. Early detection of metabolic and energy disorders by thermal time series stochastic complexity analysis

    International Nuclear Information System (INIS)

    Lutaif, N.A.; Palazzo, R. Jr; Gontijo, J.A.R.

    2014-01-01

    Maintenance of thermal homeostasis in rats fed a high-fat diet (HFD) is associated with changes in their thermal balance. The thermodynamic relationship between heat dissipation and energy storage is altered by the ingestion of high-energy diet content. Observation of thermal registers of core temperature behavior, in humans and rodents, permits identification of some characteristics of time series, such as autoreference and stationarity that fit adequately to a stochastic analysis. To identify this change, we used, for the first time, a stochastic autoregressive model, the concepts of which match those associated with physiological systems involved and applied in male HFD rats compared with their appropriate standard food intake age-matched male controls (n=7 per group). By analyzing a recorded temperature time series, we were able to identify when thermal homeostasis would be affected by a new diet. The autoregressive time series model (AR model) was used to predict the occurrence of thermal homeostasis, and this model proved to be very effective in distinguishing such a physiological disorder. Thus, we infer from the results of our study that maximum entropy distribution as a means for stochastic characterization of temperature time series registers may be established as an important and early tool to aid in the diagnosis and prevention of metabolic diseases due to their ability to detect small variations in thermal profile

  10. Metabolomics analysis of metabolic effects of nicotinamide phosphoribosyltransferase (NAMPT inhibition on human cancer cells.

    Directory of Open Access Journals (Sweden)

    Vladimir Tolstikov

    Full Text Available Nicotinamide phosphoribosyltransferase (NAMPT plays an important role in cellular bioenergetics. It is responsible for converting nicotinamide to nicotinamide adenine dinucleotide, an essential molecule in cellular metabolism. NAMPT has been extensively studied over the past decade due to its role as a key regulator of nicotinamide adenine dinucleotide-consuming enzymes. NAMPT is also known as a potential target for therapeutic intervention due to its involvement in disease. In the current study, we used a global mass spectrometry-based metabolomic approach to investigate the effects of FK866, a small molecule inhibitor of NAMPT currently in clinical trials, on metabolic perturbations in human cancer cells. We treated A2780 (ovarian cancer and HCT-116 (colorectal cancer cell lines with FK866 in the presence and absence of nicotinic acid. Significant changes were observed in the amino acids metabolism and the purine and pyrimidine metabolism. We also observed metabolic alterations in glycolysis, the citric acid cycle (TCA, and the pentose phosphate pathway. To expand the range of the detected polar metabolites and improve data confidence, we applied a global metabolomics profiling platform by using both non-targeted and targeted hydrophilic (HILIC-LC-MS and GC-MS analysis. We used Ingenuity Knowledge Base to facilitate the projection of metabolomics data onto metabolic pathways. Several metabolic pathways showed differential responses to FK866 based on several matches to the list of annotated metabolites. This study suggests that global metabolomics can be a useful tool in pharmacological studies of the mechanism of action of drugs at a cellular level.

  11. A tissue-specific approach to the analysis of metabolic changes in Caenorhabditis elegans.

    Directory of Open Access Journals (Sweden)

    Jürgen Hench

    Full Text Available The majority of metabolic principles are evolutionarily conserved from nematodes to humans. Caenorhabditis elegans has widely accelerated the discovery of new genes important to maintain organismic metabolic homeostasis. Various methods exist to assess the metabolic state in worms, yet they often require large animal numbers and tend to be performed as bulk analyses of whole worm homogenates, thereby largely precluding a detailed studies of metabolic changes in specific worm tissues. Here, we have adapted well-established histochemical methods for the use on C. elegans fresh frozen sections and demonstrate their validity for analyses of morphological and metabolic changes on tissue level in wild type and various mutant strains. We show how the worm presents on hematoxylin and eosin (H&E stained sections and demonstrate their usefulness in monitoring and the identification of morphological abnormalities. In addition, we demonstrate how Oil-Red-O staining on frozen worm cross-sections permits quantification of lipid storage, avoiding the artifact-prone fixation and permeabilization procedures of traditional whole-mount protocols. We also adjusted standard enzymatic stains for respiratory chain subunits (NADH, SDH, and COX to monitor metabolic states of various C. elegans tissues. In summary, the protocols presented here provide technical guidance to obtain robust, reproducible and quantifiable tissue-specific data on worm morphology as well as carbohydrate, lipid and mitochondrial energy metabolism that cannot be obtained through traditional biochemical bulk analyses of worm homogenates. Furthermore, analysis of worm cross-sections overcomes the common problem with quantification in three-dimensional whole-mount specimens.

  12. Transcriptome Analysis of Sucrose Metabolism during Bulb Swelling and Development in Onion (Allium cepa L.

    Directory of Open Access Journals (Sweden)

    Yi Liang

    2016-09-01

    Full Text Available Allium cepa L. is a widely cultivated and economically significant vegetable crop worldwide, with beneficial dietary and health-related properties, but its sucrose metabolism is still poorly understood. To analyze sucrose metabolism during bulb swelling, and the development of sweet taste in onion, a global transcriptome profile of onion bulbs was undertaken at three different developmental stages, using RNA-seq. A total of 79,376 unigenes, with a mean length of 678 bp, was obtained. In total, 7% of annotated Clusters of Orthologous Groups (COG were involved in carbohydrate transport and metabolism. In the Kyoto Encyclopedia of Genes and Genomes (KEGG database, starch and sucrose metabolism (147, 2.40% constituted the primary metabolism pathway in the integrated library. The expression of sucrose transporter genes was greatest during the early-swelling stage, suggesting that sucrose transporters participated in sucrose metabolism mainly at an early stage of bulb development. A gene-expression analysis of the key enzymes of sucrose metabolism suggested that sucrose synthase, cell wall invertase and invertase were all likely to participate in the hydrolysis of sucrose, generating glucose and fructose. In addition, trehalose was hydrolyzed to two molecules of glucose by trehalase. From 15 to 40 days after swelling (DAS, both the glucose and fructose contents of bulbs increased, whereas the sucrose content decreased. The growth rate between 15 and 30 DAS was slower than that between 30 and 40 DAS, suggesting that the latter was a period of rapid expansion. The dataset generated by our transcriptome profiling will provide valuable information for further research.

  13. Metabolomics analysis of metabolic effects of nicotinamide phosphoribosyltransferase (NAMPT) inhibition on human cancer cells.

    Science.gov (United States)

    Tolstikov, Vladimir; Nikolayev, Alexander; Dong, Sucai; Zhao, Genshi; Kuo, Ming-Shang

    2014-01-01

    Nicotinamide phosphoribosyltransferase (NAMPT) plays an important role in cellular bioenergetics. It is responsible for converting nicotinamide to nicotinamide adenine dinucleotide, an essential molecule in cellular metabolism. NAMPT has been extensively studied over the past decade due to its role as a key regulator of nicotinamide adenine dinucleotide-consuming enzymes. NAMPT is also known as a potential target for therapeutic intervention due to its involvement in disease. In the current study, we used a global mass spectrometry-based metabolomic approach to investigate the effects of FK866, a small molecule inhibitor of NAMPT currently in clinical trials, on metabolic perturbations in human cancer cells. We treated A2780 (ovarian cancer) and HCT-116 (colorectal cancer) cell lines with FK866 in the presence and absence of nicotinic acid. Significant changes were observed in the amino acids metabolism and the purine and pyrimidine metabolism. We also observed metabolic alterations in glycolysis, the citric acid cycle (TCA), and the pentose phosphate pathway. To expand the range of the detected polar metabolites and improve data confidence, we applied a global metabolomics profiling platform by using both non-targeted and targeted hydrophilic (HILIC)-LC-MS and GC-MS analysis. We used Ingenuity Knowledge Base to facilitate the projection of metabolomics data onto metabolic pathways. Several metabolic pathways showed differential responses to FK866 based on several matches to the list of annotated metabolites. This study suggests that global metabolomics can be a useful tool in pharmacological studies of the mechanism of action of drugs at a cellular level.

  14. Inulin controls inflammation and metabolic endotoxemia in women with type 2 diabetes mellitus: a randomized-controlled clinical trial.

    Science.gov (United States)

    Dehghan, Parvin; Gargari, Bahram Pourghassem; Jafar-Abadi, Mohammad Asghari; Aliasgharzadeh, Akbar

    2014-02-01

    There is limited evidence on the effects of prebiotics on inflammation. Therefore, the aim of this study was to evaluate the effects of inulin supplementation on inflammatory indices and metabolic endotoxemia in patients with type 2 diabetes mellitus. The participants included diabetic females (n = 49). They were divided into an intervention group (n = 24) as well as a control group (n = 25) and received 10 g/d inulin or maltodextrin for 8 weeks, respectively. Fasting blood sugar (FBS), HbA1c, insulin, high-sensitive C-reactive protein (hs-CRP), tumor necrosis factor-alpha (TNF-α), interleukin-10 (IL-10), and plasma lipopolysaccharide (LPS) were measured pre and post intervention. Inulin-supplemented patients exhibited a significant decrease in FBS (8.5%), HbA1c (10.4%), fasting insulin (34.3%), homeostasis model assessment of insulin resistance (HOMA-IR) (39.5%), hs-CRP (35.6%), TNF-α (23.1%), and LPS (27.9%) compared with the maltodextrin group (p metabolic endotoxemia in women with type 2 diabetes.

  15. A comparative analysis of metal transportomes from metabolically versatile Pseudomonas

    Directory of Open Access Journals (Sweden)

    Rodrigue Agnes

    2008-09-01

    Full Text Available Abstract Background The availability of complete genome sequences of versatile Pseudomonas occupying remarkably diverse ecological niches enabled to gain insights into their adaptative assets. The objective of this study was to analyze the complete genetic repertoires of metal transporters (metal transportomes from four representative Pseudomonas species and to identify metal transporters with "Genomic Island" associated features. Methods A comparative metal transporter inventory was built for the following four Pseudomonas species: P.putida (Ppu KT2440, P.aeruginosa (Pae PA01, P.fluorescens (Pfl Pf-5 and P.syringae (Psypv.tomato DC3000 using TIGR-CMR and Transport DB. Genomic analysis of essential and toxic metal ion transporters was accomplished from the above inventory. Metal transporters with "Genomic Island" associated features were identified using Islandpath analysis. Results Dataset cataloguing has been executed for 262 metal transporters from the four spp. Additional metal ion transporters belonging to NiCoT, Ca P-type ATPase, Cu P-type ATPases, ZIP and MgtC families were identified. In Psy DC3000, 48% of metal transporters showed strong GI features while it was 45% in Ppu KT2440. In Pfl Pf-5 and Pae PA01 only 26% of their metal transporters exhibited GI features. Conclusion Our comparative inventory of 262 metal transporters from four versatile Pseudomonas spp is the complete suite of metal transportomes analysed till date in a prokaryotic genus. This study identified differences in the basic composition of metal transportomes from Pseudomonas occupying diverse ecological niches and also elucidated their novel features. Based on this inventory we analysed the role of horizontal gene transfer in expansion and variability of metal transporter families.

  16. Comparative analysis of Salmonella genomes identifies a metabolic network for escalating growth in the inflamed gut.

    Science.gov (United States)

    Nuccio, Sean-Paul; Bäumler, Andreas J

    2014-03-18

    The Salmonella genus comprises a group of pathogens associated with illnesses ranging from gastroenteritis to typhoid fever. We performed an in silico analysis of comparatively reannotated Salmonella genomes to identify genomic signatures indicative of disease potential. By removing numerous annotation inconsistencies and inaccuracies, the process of reannotation identified a network of 469 genes involved in central anaerobic metabolism, which was intact in genomes of gastrointestinal pathogens but degrading in genomes of extraintestinal pathogens. This large network contained pathways that enable gastrointestinal pathogens to utilize inflammation-derived nutrients as well as many of the biochemical reactions used for the enrichment and biochemical discrimination of Salmonella serovars. Thus, comparative genome analysis identifies a metabolic network that provides clues about the strategies for nutrient acquisition and utilization that are characteristic of gastrointestinal pathogens. IMPORTANCE While some Salmonella serovars cause infections that remain localized to the gut, others disseminate throughout the body. Here, we compared Salmonella genomes to identify characteristics that distinguish gastrointestinal from extraintestinal pathogens. We identified a large metabolic network that is functional in gastrointestinal pathogens but decaying in extraintestinal pathogens. While taxonomists have used traits from this network empirically for many decades for the enrichment and biochemical discrimination of Salmonella serovars, our findings suggest that it is part of a "business plan" for growth in the inflamed gastrointestinal tract. By identifying a large metabolic network characteristic of Salmonella serovars associated with gastroenteritis, our in silico analysis provides a blueprint for potential strategies to utilize inflammation-derived nutrients and edge out competing gut microbes.

  17. Unraveling the metabolism of HEK-293 cells using lactate isotopomer analysis.

    Science.gov (United States)

    Henry, Olivier; Jolicoeur, Mario; Kamen, Amine

    2011-03-01

    HEK-293 is the most extensively used human cell line for the production of viral vectors and is gaining increasing attention for the production of recombinant proteins by transient transfection. To further improve the metabolic characterization of this cell line, we have performed cultures using ¹³C-labeled substrates and measured the resulting mass isotopomer distributions in lactate by LC/MS. Simultaneous metabolite and isotopomer balancing allowed improvement and validation of the metabolic model and quantification of key intracellular pathways. We have determined the amounts of glucose carbon channeled through the PPP, incorporated into the TCA cycle for energy production and lipids biosynthesis, as well as the cytosolic and mitochondrial malic enzyme fluxes. Our analysis also revealed that glutamine did not significantly contribute to lactate formation. An improved and quantitative understanding of the central carbon metabolism is greatly needed to pursue the rational development of engineering approaches at both the cellular and process levels.

  18. MetaboTools: A Comprehensive Toolbox for Analysis of Genome-Scale Metabolic Models

    Science.gov (United States)

    Aurich, Maike K.; Fleming, Ronan M. T.; Thiele, Ines

    2016-01-01

    Metabolomic data sets provide a direct read-out of cellular phenotypes and are increasingly generated to study biological questions. Previous work, by us and others, revealed the potential of analyzing extracellular metabolomic data in the context of the metabolic model using constraint-based modeling. With the MetaboTools, we make our methods available to the broader scientific community. The MetaboTools consist of a protocol, a toolbox, and tutorials of two use cases. The protocol describes, in a step-wise manner, the workflow of data integration, and computational analysis. The MetaboTools comprise the Matlab code required to complete the workflow described in the protocol. Tutorials explain the computational steps for integration of two different data sets and demonstrate a comprehensive set of methods for the computational analysis of metabolic models and stratification thereof into different phenotypes. The presented workflow supports integrative analysis of multiple omics data sets. Importantly, all analysis tools can be applied to metabolic models without performing the entire workflow. Taken together, the MetaboTools constitute a comprehensive guide to the intra-model analysis of extracellular metabolomic data from microbial, plant, or human cells. This computational modeling resource offers a broad set of computational analysis tools for a wide biomedical and non-biomedical research community. PMID:27536246

  19. Gene-based mapping and pathway analysis of metabolic traits in dairy cows.

    Directory of Open Access Journals (Sweden)

    Ngoc-Thuy Ha

    Full Text Available The metabolic adaptation of dairy cows during the transition period has been studied intensively in the last decades. However, until now, only few studies have paid attention to the genetic aspects of this process. Here, we present the results of a gene-based mapping and pathway analysis with the measurements of three key metabolites, (1 non-esterified fatty acids (NEFA, (2 beta-hydroxybutyrate (BHBA and (3 glucose, characterizing the metabolic adaptability of dairy cows before and after calving. In contrast to the conventional single-marker approach, we identify 99 significant and biologically sensible genes associated with at least one of the considered phenotypes and thus giving evidence for a genetic basis of the metabolic adaptability. Moreover, our results strongly suggest three pathways involved in the metabolism of steroids and lipids are potential candidates for the adaptive regulation of dairy cows in their early lactation. From our perspective, a closer investigation of our findings will lead to a step forward in understanding the variability in the metabolic adaptability of dairy cows in their early lactation.

  20. Reconciliation of genome-scale metabolic reconstructions for comparative systems analysis.

    Directory of Open Access Journals (Sweden)

    Matthew A Oberhardt

    2011-03-01

    Full Text Available In the past decade, over 50 genome-scale metabolic reconstructions have been built for a variety of single- and multi- cellular organisms. These reconstructions have enabled a host of computational methods to be leveraged for systems-analysis of metabolism, leading to greater understanding of observed phenotypes. These methods have been sparsely applied to comparisons between multiple organisms, however, due mainly to the existence of differences between reconstructions that are inherited from the respective reconstruction processes of the organisms to be compared. To circumvent this obstacle, we developed a novel process, termed metabolic network reconciliation, whereby non-biological differences are removed from genome-scale reconstructions while keeping the reconstructions as true as possible to the underlying biological data on which they are based. This process was applied to two organisms of great importance to disease and biotechnological applications, Pseudomonas aeruginosa and Pseudomonas putida, respectively. The result is a pair of revised genome-scale reconstructions for these organisms that can be analyzed at a systems level with confidence that differences are indicative of true biological differences (to the degree that is currently known, rather than artifacts of the reconstruction process. The reconstructions were re-validated with various experimental data after reconciliation. With the reconciled and validated reconstructions, we performed a genome-wide comparison of metabolic flexibility between P. aeruginosa and P. putida that generated significant new insight into the underlying biology of these important organisms. Through this work, we provide a novel methodology for reconciling models, present new genome-scale reconstructions of P. aeruginosa and P. putida that can be directly compared at a network level, and perform a network-wide comparison of the two species. These reconstructions provide fresh insights into the

  1. Reconciliation of Genome-Scale Metabolic Reconstructions for Comparative Systems Analysis

    Science.gov (United States)

    Martins dos Santos, Vítor A. P.; Papin, Jason A.

    2011-01-01

    In the past decade, over 50 genome-scale metabolic reconstructions have been built for a variety of single- and multi- cellular organisms. These reconstructions have enabled a host of computational methods to be leveraged for systems-analysis of metabolism, leading to greater understanding of observed phenotypes. These methods have been sparsely applied to comparisons between multiple organisms, however, due mainly to the existence of differences between reconstructions that are inherited from the respective reconstruction processes of the organisms to be compared. To circumvent this obstacle, we developed a novel process, termed metabolic network reconciliation, whereby non-biological differences are removed from genome-scale reconstructions while keeping the reconstructions as true as possible to the underlying biological data on which they are based. This process was applied to two organisms of great importance to disease and biotechnological applications, Pseudomonas aeruginosa and Pseudomonas putida, respectively. The result is a pair of revised genome-scale reconstructions for these organisms that can be analyzed at a systems level with confidence that differences are indicative of true biological differences (to the degree that is currently known), rather than artifacts of the reconstruction process. The reconstructions were re-validated with various experimental data after reconciliation. With the reconciled and validated reconstructions, we performed a genome-wide comparison of metabolic flexibility between P. aeruginosa and P. putida that generated significant new insight into the underlying biology of these important organisms. Through this work, we provide a novel methodology for reconciling models, present new genome-scale reconstructions of P. aeruginosa and P. putida that can be directly compared at a network level, and perform a network-wide comparison of the two species. These reconstructions provide fresh insights into the metabolic similarities

  2. Transcriptome analysis of carbohydrate metabolism during bulblet formation and development in Lilium davidii var. unicolor.

    Science.gov (United States)

    Li, XueYan; Wang, ChunXia; Cheng, JinYun; Zhang, Jing; da Silva, Jaime A Teixeira; Liu, XiaoYu; Duan, Xin; Li, TianLai; Sun, HongMei

    2014-12-19

    The formation and development of bulblets are crucial to the Lilium genus since these processes are closely related to carbohydrate metabolism, especially to starch and sucrose metabolism. However, little is known about the transcriptional regulation of both processes. To gain insight into carbohydrate-related genes involved in bulblet formation and development, we conducted comparative transcriptome profiling of Lilium davidii var. unicolor bulblets at 0 d, 15 d (bulblets emerged) and 35 d (bulblets formed a basic shape with three or four scales) after scale propagation. Analysis of the transcriptome revealed that a total of 52,901 unigenes with an average sequence size of 630 bp were generated. Based on Clusters of Orthologous Groups (COG) analysis, 8% of the sequences were attributed to carbohydrate transport and metabolism. The results of KEGG pathway enrichment analysis showed that starch and sucrose metabolism constituted the predominant pathway among the three library pairs. The starch content in mother scales and bulblets decreased and increased, respectively, with almost the same trend as sucrose content. Gene expression analysis of the key enzymes in starch and sucrose metabolism suggested that sucrose synthase (SuSy) and invertase (INV), mainly hydrolyzing sucrose, presented higher gene expression in mother scales and bulblets at stages of bulblet appearance and enlargement, while sucrose phosphate synthase (SPS) showed higher expression in bulblets at morphogenesis. The enzymes involved in the starch synthetic direction such as ADPG pyrophosphorylase (AGPase), soluble starch synthase (SSS), starch branching enzyme (SBE) and granule-bound starch synthase (GBSS) showed a decreasing trend in mother scales and higher gene expression in bulblets at bulblet appearance and enlargement stages while the enzyme in the cleavage direction, starch de-branching enzyme (SDBE), showed higher gene expression in mother scales than in bulblets. An extensive transcriptome

  3. From elementary flux modes to elementary flux vectors: Metabolic pathway analysis with arbitrary linear flux constraints

    Science.gov (United States)

    Klamt, Steffen; Gerstl, Matthias P.; Jungreuthmayer, Christian; Mahadevan, Radhakrishnan; Müller, Stefan

    2017-01-01

    Elementary flux modes (EFMs) emerged as a formal concept to describe metabolic pathways and have become an established tool for constraint-based modeling and metabolic network analysis. EFMs are characteristic (support-minimal) vectors of the flux cone that contains all feasible steady-state flux vectors of a given metabolic network. EFMs account for (homogeneous) linear constraints arising from reaction irreversibilities and the assumption of steady state; however, other (inhomogeneous) linear constraints, such as minimal and maximal reaction rates frequently used by other constraint-based techniques (such as flux balance analysis [FBA]), cannot be directly integrated. These additional constraints further restrict the space of feasible flux vectors and turn the flux cone into a general flux polyhedron in which the concept of EFMs is not directly applicable anymore. For this reason, there has been a conceptual gap between EFM-based (pathway) analysis methods and linear optimization (FBA) techniques, as they operate on different geometric objects. One approach to overcome these limitations was proposed ten years ago and is based on the concept of elementary flux vectors (EFVs). Only recently has the community started to recognize the potential of EFVs for metabolic network analysis. In fact, EFVs exactly represent the conceptual development required to generalize the idea of EFMs from flux cones to flux polyhedra. This work aims to present a concise theoretical and practical introduction to EFVs that is accessible to a broad audience. We highlight the close relationship between EFMs and EFVs and demonstrate that almost all applications of EFMs (in flux cones) are possible for EFVs (in flux polyhedra) as well. In fact, certain properties can only be studied with EFVs. Thus, we conclude that EFVs provide a powerful and unifying framework for constraint-based modeling of metabolic networks. PMID:28406903

  4. Prenatal Programming by Testosterone of Hypothalamic Metabolic Control Neurones in the Ewe

    Science.gov (United States)

    Sheppard, Kayla M.; Padmanabhan, Vasantha; Coolen, Lique M.; Lehman, Michael N.

    2013-01-01

    Ewes treated prenatally with testosterone (T) develop metabolic deficits, including insulin resistance, in addition to reproductive dysfunctions that collectively mimic polycystic ovarian syndrome (PCOS), a common endocrine disease in women. We hypothesised that metabolic deficits associated with prenatal T excess involve alterations in arcuate nucleus (ARC) neurones that contain either agouti-related peptide (AgRP) or proopiomelanocortin (POMC). Characterization of these neurones in the ewe showed that immunoreactive AgRP and POMC neurones were present in separate populations in the ARC, that AgRP and POMC neurones co-expressed either neuropeptide Y or cocaine- and amphetamine-regulated transcript, respectively, and that each population had a high degree of colocalization with androgen receptors. Examination of the effect of prenatal T exposure on the number of AgRP and POMC neurones in adult ewes showed that prenatal T excess significantly increased the number of AgRP but, not POMC neurones compared to controls; this increase was restricted to the middle division of the ARC, was mimicked by prenatal treatment with dihydrotestosterone, a non-aromatizable androgen, and was blocked by co-treatment of prenatal T with the anti-androgen, flutamide. The density of AgRP fibre immunoreactivity in the preoptic area, paraventricular nucleus, lateral hypothalamus and dorsomedial hypothalamic nucleus was also increased by prenatal T exposure. Thus, ewes that were exposed to androgens during foetal life showed alterations in the number of AgRP-immunoreactive neurones and the density of fibre immunoreactivity in their projection areas, suggestive of permanent prenatal programming of metabolic circuitry that may, in turn, contribute to insulin resistance and increased risk of obesity in this model of PCOS. PMID:21418339

  5. Delicate Metabolic Control and Coordinated Stress Response Critically Determine Antifungal Tolerance of Candida albicans Biofilm Persisters.

    Science.gov (United States)

    Li, Peng; Seneviratne, Chaminda J; Alpi, Emanuele; Vizcaino, Juan A; Jin, Lijian

    2015-10-01

    Candida infection has emerged as a critical health care burden worldwide, owing to the formation of robust biofilms against common antifungals. Recent evidence shows that multidrug-tolerant persisters critically account for biofilm recalcitrance, but their underlying biological mechanisms are poorly understood. Here, we first investigated the phenotypic characteristics of Candida biofilm persisters under consecutive harsh treatments of amphotericin B. The prolonged treatments effectively killed the majority of the cells of biofilms derived from representative strains of Candida albicans, Candida glabrata, and Candida tropicalis but failed to eradicate a small fraction of persisters. Next, we explored the tolerance mechanisms of the persisters through an investigation of the proteomic profiles of C. albicans biofilm persister fractions by liquid chromatography-tandem mass spectrometry. The C. albicans biofilm persisters displayed a specific proteomic signature, with an array of 205 differentially expressed proteins. The crucial enzymes involved in glycolysis, the tricarboxylic acid cycle, and protein synthesis were markedly downregulated, indicating that major metabolic activities are subdued in the persisters. It is noteworthy that certain metabolic pathways, such as the glyoxylate cycle, were able to be activated with significantly increased levels of isocitrate lyase and malate synthase. Moreover, a number of important proteins responsible for Candida growth, virulence, and the stress response were greatly upregulated. Interestingly, the persisters were tolerant to oxidative stress, despite highly induced intracellular superoxide. The current findings suggest that delicate metabolic control and a coordinated stress response may play a crucial role in mediating the survival and antifungal tolerance of Candida biofilm persisters. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  6. Novel Strategy for Non-Targeted Isotope-Assisted Metabolomics by Means of Metabolic Turnover and Multivariate Analysis

    Directory of Open Access Journals (Sweden)

    Yasumune Nakayama

    2014-08-01

    Full Text Available Isotope-labeling is a useful technique for understanding cellular metabolism. Recent advances in metabolomics have extended the capability of isotope-assisted studies to reveal global metabolism. For instance, isotope-assisted metabolomics technology has enabled the mapping of a global metabolic network, estimation of flux at branch points of metabolic pathways, and assignment of elemental formulas to unknown metabolites. Furthermore, some data processing tools have been developed to apply these techniques to a non-targeted approach, which plays an important role in revealing unknown or unexpected metabolism. However, data collection and integration strategies for non-targeted isotope-assisted metabolomics have not been established. Therefore, a systematic approach is proposed to elucidate metabolic dynamics without targeting pathways by means of time-resolved isotope tracking, i.e., “metabolic turnover analysis”, as well as multivariate analysis. We applied this approach to study the metabolic dynamics in amino acid perturbation of Saccharomyces cerevisiae. In metabolic turnover analysis, 69 peaks including 35 unidentified peaks were investigated. Multivariate analysis of metabolic turnover successfully detected a pathway known to be inhibited by amino acid perturbation. In addition, our strategy enabled identification of unknown peaks putatively related to the perturbation.

  7. Kinematics Control and Analysis of Industrial Robot

    Science.gov (United States)

    Zhu, Tongbo; Cai, Fan; Li, Yongmei; Liu, Wei

    2018-03-01

    The robot’s development present situation, basic principle and control system are introduced briefly. Research is mainly focused on the study of the robot’s kinematics and motion control. The structural analysis of a planar articulated robot (SCARA) robot is presented,the coordinate system is established to obtain the position and orientation matrix of the end effector,a method of robot kinematics analysis based on homogeneous transformation method is proposed, and the kinematics solution of the robot is obtained.Establishment of industrial robot’s kinematics equation and formula for positive kinematics by example. Finally,the kinematic analysis of this robot was verified by examples.It provides a basis for structural design and motion control.It has active significance to promote the motion control of industrial robot.

  8. BEYOND GLYCEMIC CONTROL IN DIABETES MELLITUS: EFFECTS OF INCRETIN-BASED THERAPY ON BONE METABOLISM

    Directory of Open Access Journals (Sweden)

    ELENA eCECCARELLI

    2013-06-01

    Full Text Available Diabetes mellitus (DM and osteoporosis (OP are common disorders with a significant health burden, and an increase in fracture risk has been described both in type 1 (T1DM and in type 2 (T2DM diabetes. The pathogenic mechanisms of impaired skeletal strength in diabetes remain to be clarified in details and they are only in part reflected by a variation in bone mineral density (BMD. In T2DM, the occurrence of low bone turnover together with a decreased osteoblast activity and compromised bone quality has been shown. Of note, some antidiabetic drugs (e.g. tiazolidinediones, insulin may deeply affect bone metabolism. In addition, the recently introduced class of incretin-based drugs (i.e. GLP-1 receptor agonists and DPP-4 inhibitors is expected to exert potentially beneficial effects on bone health, possibly due to a bone anabolic activity of GLP-1, that can be either direct or indirect through the involvement of thyroid C cells.Here we will review the established as well as the putative effects of incretin hormones and of incretin-based drugs on bone metabolism, both in preclinical models and in man, taking into account that such therapeutic strategy may be effective not only to achieve a good glycemic control, but also to improve bone health in diabetic patients.

  9. Exercise-stimulated interleukin-15 is controlled by AMPK and regulates skin metabolism and aging

    Science.gov (United States)

    Crane, Justin D; MacNeil, Lauren G; Lally, James S; Ford, Rebecca J; Bujak, Adam L; Brar, Ikdip K; Kemp, Bruce E; Raha, Sandeep; Steinberg, Gregory R; Tarnopolsky, Mark A

    2015-01-01

    Aging is commonly associated with a structural deterioration of skin that compromises its barrier function, healing, and susceptibility to disease. Several lines of evidence show that these changes are driven largely by impaired tissue mitochondrial metabolism. While exercise is associated with numerous health benefits, there is no evidence that it affects skin tissue or that endocrine muscle-to-skin signaling occurs. We demonstrate that endurance exercise attenuates age-associated changes to skin in humans and mice and identify exercise-induced IL-15 as a novel regulator of mitochondrial function in aging skin. We show that exercise controls IL-15 expression in part through skeletal muscle AMP-activated protein kinase (AMPK), a central regulator of metabolism, and that the elimination of muscle AMPK causes a deterioration of skin structure. Finally, we establish that daily IL-15 therapy mimics some of the anti-aging effects of exercise on muscle and skin in mice. Thus, we elucidate a mechanism by which exercise confers health benefits to skin and suggest that low-dose IL-15 therapy may prove to be a beneficial strategy to attenuate skin aging. PMID:25902870

  10. Basal metabolic rate in children with chronic kidney disease and healthy control children.

    Science.gov (United States)

    Anderson, Caroline E; Gilbert, Rodney D; Elia, Marinos

    2015-11-01

    Meeting energy requirements of children with chronic kidney disease (CKD) is paramount to optimising growth and clinical outcome, but little information on this subject has been published. In this study, we examined basal metabolic rate (BMR; a component of energy expenditure) with the aim to determine whether it is related to kidney function independently of weight, height and lean body mass (LBM). Twenty children with CKD and 20 healthy age- and gender-matched control children were studied on one occasion. BMR was measured by indirect open circuit calorimetry and predicted by the Schofield equation. Estimated glomerular filtration rate (eGFR) was related to BMR and adjusted for weight, height, age and LBM measured by skinfold thickness. The adjusted BMR of children with CKD did not differ significantly from that of healthy subjects (1296 ± 318 vs.1325 ± 178 kcal/day; p = 0.720). Percentage of predicted BMR also did not differ between the two groups (102 ± 12% vs. 99 ± 14%; p = 0.570). Within the CKD group, eGFR (mean 33.7 ± 20.5 mL/min/m(2)) was significantly related to BMR (β 0.3, r = 0.517, p = 0.019) independently of nutritional status and LBM. It seems reasonable to use estimated average requirement as the basis of energy prescriptions for children with CKD (mean CKD stage 3 disease). However, those who were sicker had significantly lower metabolic rates.

  11. The Deubiquitylase MATH-33 Controls DAF-16 Stability and Function in Metabolism and Longevity.

    Science.gov (United States)

    Heimbucher, Thomas; Liu, Zheng; Bossard, Carine; McCloskey, Richard; Carrano, Andrea C; Riedel, Christian G; Tanasa, Bogdan; Klammt, Christian; Fonslow, Bryan R; Riera, Celine E; Lillemeier, Bjorn F; Kemphues, Kenneth; Yates, John R; O'Shea, Clodagh; Hunter, Tony; Dillin, Andrew

    2015-07-07

    FOXO family transcription factors are downstream effectors of Insulin/IGF-1 signaling (IIS) and major determinants of aging in organisms ranging from worms to man. The molecular mechanisms that actively promote DAF16/FOXO stability and function are unknown. Here we identify the deubiquitylating enzyme MATH-33 as an essential DAF-16 regulator in IIS, which stabilizes active DAF-16 protein levels and, as a consequence, influences DAF-16 functions, such as metabolism, stress response, and longevity in C. elegans. MATH-33 associates with DAF-16 in cellulo and in vitro. MATH-33 functions as a deubiquitylase by actively removing ubiquitin moieties from DAF-16, thus counteracting the action of the RLE-1 E3-ubiquitin ligase. Our findings support a model in which MATH-33 promotes DAF-16 stability in response to decreased IIS by directly modulating its ubiquitylation state, suggesting that regulated oscillations in the stability of DAF-16 protein play an integral role in controlling processes such as metabolism and longevity. Copyright © 2015 Elsevier Inc. All rights reserved.

  12. CD47 Receptor Globally Regulates Metabolic Pathways That Control Resistance to Ionizing Radiation.

    Science.gov (United States)

    Miller, Thomas W; Soto-Pantoja, David R; Schwartz, Anthony L; Sipes, John M; DeGraff, William G; Ridnour, Lisa A; Wink, David A; Roberts, David D

    2015-10-09

    Modulating tissue responses to stress is an important therapeutic objective. Oxidative and genotoxic stresses caused by ionizing radiation are detrimental to healthy tissues but beneficial for treatment of cancer. CD47 is a signaling receptor for thrombospondin-1 and an attractive therapeutic target because blocking CD47 signaling protects normal tissues while sensitizing tumors to ionizing radiation. Here we utilized a metabolomic approach to define molecular mechanisms underlying this radioprotective activity. CD47-deficient cells and cd47-null mice exhibited global advantages in preserving metabolite levels after irradiation. Metabolic pathways required for controlling oxidative stress and mediating DNA repair were enhanced. Some cellular energetics pathways differed basally in CD47-deficient cells, and the global declines in the glycolytic and tricarboxylic acid cycle metabolites characteristic of normal cell and tissue responses to irradiation were prevented in the absence of CD47. Thus, CD47 mediates signaling from the extracellular matrix that coordinately regulates basal metabolism and cytoprotective responses to radiation injury. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  13. CD47 Receptor Globally Regulates Metabolic Pathways That Control Resistance to Ionizing Radiation*

    Science.gov (United States)

    Miller, Thomas W.; Soto-Pantoja, David R.; Schwartz, Anthony L.; Sipes, John M.; DeGraff, William G.; Ridnour, Lisa A.; Wink, David A.; Roberts, David D.

    2015-01-01

    Modulating tissue responses to stress is an important therapeutic objective. Oxidative and genotoxic stresses caused by ionizing radiation are detrimental to healthy tissues but beneficial for treatment of cancer. CD47 is a signaling receptor for thrombospondin-1 and an attractive therapeutic target because blocking CD47 signaling protects normal tissues while sensitizing tumors to ionizing radiation. Here we utilized a metabolomic approach to define molecular mechanisms underlying this radioprotective activity. CD47-deficient cells and cd47-null mice exhibited global advantages in preserving metabolite levels after irradiation. Metabolic pathways required for controlling oxidative stress and mediating DNA repair were enhanced. Some cellular energetics pathways differed basally in CD47-deficient cells, and the global declines in the glycolytic and tricarboxylic acid cycle metabolites characteristic of normal cell and tissue responses to irradiation were prevented in the absence of CD47. Thus, CD47 mediates signaling from the extracellular matrix that coordinately regulates basal metabolism and cytoprotective responses to radiation injury. PMID:26311851

  14. Multidisciplinary Treatment of the Metabolic Syndrome Lowers Blood Pressure Variability Independent of Blood Pressure Control.

    Science.gov (United States)

    Marcus, Yonit; Segev, Elad; Shefer, Gabi; Sack, Jessica; Tal, Brurya; Yaron, Marianna; Carmeli, Eli; Shefer, Lili; Margaliot, Miri; Limor, Rona; Gilad, Suzan; Sofer, Yael; Stern, Naftali

    2016-01-01

    Blood pressure (BP) variability (BPV) contributes to target organ damage independent of BP. The authors examined the effect of a 1-year multidisciplinary intervention on BPV in patients with the metabolic syndrome (MetS) as defined by criteria from the Third Report of the Adult Treatment Panel. Forty-four nondiabetic patients underwent clinical and biochemical profiling, 24-hour ambulatory BP monitoring (ABPM), body composition, carotid intima-media thickness, and carotid-femoral pulse wave velocity (PWV). The intervention targeted all MetS components. BPV was assessed by the standard deviation of daytime systolic BP derived from ABPM. Patients with low and high BPV (lower or higher than the median daytime standard deviation of 11.6 mm Hg) did not differ in regards to systolic and diastolic BP, age, fasting glucose, glycated hemoglobin, and body mass index, but the high-variability group had higher values of low-density lipoprotein and leg fat. The 1-year intervention resulted in weight reduction but not BP-lowering. BPV declined in the high-variability group in association with lowering of PWV, C-reactive protein, glycated hemoglobin, alanine aminotransferase, asymmetric dimethylarginine, and increased high-density lipoprotein cholesterol. A multidisciplinary intervention independent of BP-lowe